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Dr KK Aggarwal

President, Heart Care Foundation of India; Sr Consultant and Dean Medical Education, Moolchand Medcity; Member, Delhi Medical Council; Past President, Delhi Medical Association; Past President, IMA New Delhi Branch; Past Hony Director. IMA AKN Sinha Institute, Chairman IMA Academy of Medical Specialities & Hony Finance Secretary National IMA; Editor-in-Chief IJCP Group of Publications & Hony Visiting Professor (Clinical Research) DIPSAR

22 February 2011, Tuesday

Dear Colleague,

New Drug Policy A formal proposal to create India’s first ever antibiotic policy will be submitted to the Union health ministry soon. Under the proposal, several drugs will now be sold only against prescription while several others would be available only for hospital use and not in pharmacies. The policy calls for the creation of a new schedule under the Drugs and Cosmetics Act called Schedule HX which will be mentioned on the label of the drug itself as a direction to consumers and physicians. Schedule H will denote those drugs which would be given only on prescription while Schedule X denotes those drugs which will have to be kept under lock and key in hospitals. A Schedule HX drug would come with a label warning, “Dangerous to take this preparation except in accordance with medical advice and not to be sold on retail without prescription of a registered medical practitioner.” Schedule HX would have two parts. Part A of Schedule HX (only to tertiary hospitals) would include 16 drugs like Moxifloxacin, Meropenem, Imipenem, Ertapenem, Doripenem, Colistin, Linezolid and Cefpirome. Part B of Schedule HX (against prescription only) would include 75 drugs like Gentamicin, Amikacin, Pencillin, Oxacilin, Zolpidem, Cefalexin, Norfloxacin, Cefaclor and Cefdinir. Dr KK Aggarwal Editor-in-Chief

national news

Infertility Update

Certificate Courses in 2D and 3D Echocardiography/ Fellowship Diploma in Non Invasive Cardiology

How Many People are Affected by Infertility? Estimates are that one in six couples is affected by some measure of infertility. However, that number may be very deceptive. Many couples choose to lead child–free lives rather than look for treatment for their infertility, and we believe they are rarely included in infertility estimates. Others suffer frequent pregnancy losses which are, in a way, a form of infertility and are not technically considered “infertile” because they are able to conceive. INCIID is in the process of creating a survey designed to provide new insights about who is infertile, what kinds of infertility they are experiencing, what kinds of treatments have been successful for specific diagnoses, and much more. This survey will be conducted online, and is expected to be a source of important clinical information for practitioners as well as consumers.

Cashless facility for patients Moolchand is proud to have been selected by India’s leading insurance companies (National Insurance Company Ltd., United India Insurance Company Ltd., The New India Assurance Company Ltd. and The Oriental Insurance Company Ltd.) to extend cashless facility for patients. Bird flu strikes India again NEW DELHI: Bird flu has struck the country again. This time at the State Duck Breeding Farm in Agartala that has been ordered to cull all poultry within a radius of three kilometres of the farm. The State will also impose a ban on movement of poultry and its products and order closure of all poultry egg market and outlets within a radius of 10 km. With this, India has lost its bird flu– free status that it acquired in June 2, 2010. It will now inform international authorities about the development. The Centre advised the Tripura government to cull all birds in the State farm after the High Security Animal Disease Laboratory in Bhopal confirmed that samples collected from the farm tested positive for H5 strain of Avian Influenza. The State government had reported “unusual deaths” of poultry on February 15. (Source: The Hindu, Feb 19, 2011) Contact Dr KK Aggarwal, Moolchand Medcity email: Medi Finance Update

Dr. Kaberi Banerjee, Infertility and IVF Specialist Max Hospital; Director Precious Baby Foundation

Thyroid Update Some Drugs that alter Thyroid Function 

Dopamine (even short–term)



Individual Mediclaim policies  

Anesthesia, blood, oxygen, operation theatre charges, surgical appliances, medicines and drugs, diagnostic materials and X-ray, dialysis, chemotherapy, radiotherapy, cost of pacemaker, artificial limbs and cost of organs and similar expenses. Pre and post hospitalization expenses.

High–dose glucocorticoids (>20mg/day prednisone, >100mg/ day hydrocortisone, >4 mg/day dexamethasone) Furosemide and some NSAIDS displace T4 from binding proteins, decreasing serum T4 levels. Dr. Neelam Mohan, Director Pediatric Gastroenterology, Hepatology and Liver Transplantation, Medanta – The Medicity

Online Submission

Volume 13, Number 10, February 2011

An IJCP Group Publication

Contents From the Desk of Group Editor-in-Chief

Now MRI-safe Pacemaker Dr KK Aggarwal Group Editor-in-Chief IJCP Group

Dr Praveen Chandra Guest Editor, AJCC praveen.chandra@

Assistant Editor: Dr Nagendra Chouhan

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IJCP Editorial Board Dr Alka Kriplani, Asian Journal of Obs & Gynae Practice Dr VP Sood, Asian Journal of Ear, Nose and Throat Dr Praveen Chandra, Asian Journal of Clinical Cardiology


KK Aggarwal

original article

Cardiovascular Risk Factors in North Indian Population in South India vs Native South Indian Population


Vijay Viswanathan, Shabana T, Arut Selvi D, Satyavani K, Vigneswari A, Parthiban M

Review Article

Role of Omega-3 Fatty Acids in Cardiovascular Disease


KK Aggarwal, Rajiv Garg

Clinical Study

Comparison of Left Ventricular Function by Doppler Imaging in Diabetics with and without Systemic HT 287 PR Gupta, Dharmendra Jain, Kamaljeet, Dilip, Vivek, Vikas, Deba

Dr Swati Y Bhave, Asian Journal of Paediatric Practice Dr Vijay Viswanathan, The Asian Journal of Diabetology Dr KMK Masthan, Indian Journal of Multidisciplinary Dentistry Dr M Paul Anand, Dr SK Parashar, Cardiology Dr CR Anand Moses, Dr Sidhartha Das, Dr Ramachandran, Dr Samith A Shetty, Diabetology Dr Ajay Kumar, Gastroenterology Dr Koushik Lahiri, Dermatology Dr Georgi Abraham, Nephrology

Clinical REview

Peripartum Cardiomyopathy


Vijay Garg, Satyendra Sharma, Arvind Pancholia, SB Gawarikar

Dr Sidharth Kumar Das, Rheumatology Dr V Nagarajan, Neurology Dr Thankam Verma, Dr Kamala Selvaraj, Obs and Gyne

Advisory Bodies Heart Care Foundation of India Overseas Indian Peoples Foundation

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From eMedinewS


Volume 13, Number 10, February 2011

Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Pvt. Ltd. and Published at Daryacha, 39, Hauz Khas Village New Delhi - 110 016 E-mail:

Dr. Good and Dr. Bad Situation:

A patient with hypertension had nonresponding cough.

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Stop ACE inhibitors

Take an X–ray

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The commonest cause of cough in a patient with high blood pressure is the intake of ACE inhibitors. Lesson:

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Now MRI-safe Pacemaker


cardiac pacemaker, Revo MRI SureScan pacemaker, made by Medtronic that is MRI-safe has won FDA approval. MRI produces powerful magnetic forces that react with ferric metals and induce electrical currents in electronic components. MRI machines also emit radiofrequency energy that may interact with pacemakers. As a result, MRI scans can disrupt pacemaker settings or cause wires to overheat, resulting in unintended heart stimulation, device electrical failure or tissue damage. Until now, most MRI scans have been contraindicated for patients with pacemakers. About half of such patients have conditions that would ordinarily call for MRI scans. Among the features included in the Revo MRI product is a function to be switched on prior to undergoing an MRI to eliminate problems associated with induced currents and radiofrequency emissions. The FDA’s approval is conditional meaning that it is safe with MRI scans under certain conditions. The major clinical trial published last month only tested the device with MRI machines of no more than 1.5 Tesla and the scanning isocenters were located above the cervical spine or below the thoracic spine. In the trial, 464 patients received the Revo device and were randomized 1:1 to receive an MRI or not. No scan-related complications were seen in patients who had the scans. The Revo MRI SureScan pacemaker must be used with special leads designed for the system.

Dr KK Aggarwal

Padma Shri and Dr BC Roy National Awardee Sr Physician and Cardiologist, Moolchand Medcity President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS Chairman Ethical Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) Krishan Kumar Aggarwal (Facebook)

Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011


Original Article

Cardiovascular Risk Factors in North Indian Population in South India vs Native South Indian Population Vijay Viswanathan,* Shabana T**, Arut Selvi D†, Satyavani K‡, Vigneswari A**, Parthiban M#

Abstract Background: The regional variation in the prevalence of noncommunicable diseases (NCDs) within India is well-established. The diet pattern plays a major role and it is an established modifiable risk factor for most of the NCDs. Objective: To compare the prevalence of risk factors of cardiovascular diseases (CVDs) in a Gujarati vegetarian community settled in Chennai with a native nonvegetarian population in Chennai. Subject and Methods: This cross-sectional study was conducted among 288 individuals (M:F-141:147) aged 20 years and above. Among them 134 were North Indians and 154 were South Indians. Details on Sociodemographic status, behavioral risk factors anthropometric, blood pressure measurements, dietary assessment and physical activity details were recorded. Fasting venous blood was collected, glucose and lipid profile were estimated by using standard procedures. Prevalence of abnormalities was calculated using cutoff values. Results: The prevalence of obesity (>25 kg/m2) was higher among North Indians (55.2 vs 42.2%, p = 0.037) whereas waist circumference was higher among South Indians. The total cholesterol (≥200 mg/dl) and the LDL-C (≥100 mg/dl) was higher among North Indians but triglycerides (>150 mg/dl) and low HDL-C (<40 mg/dl in male and <50 mg/dl in female) was higher among SI. The prevalence of diabetes was similar. The difference in the prevalence of IFG was statistically significant (3 vs 18.2%, p < 0.001).The prevalence of hypertension was 39% in North Indians and 28.8% in South Indians (p = 0.092). Conclusion: The difference in the prevalence of cardiovascular risk factors clearly denotes the requirement of a region and culture specific lifestyle intervention. Key words: CVD risk factors, North Indians, South Indians


iabetes and cardiovascular diseases (CVDs) evolved as global epidemics.1,2 Emergence of noncommunicable diseases (NCDs), especially CVD, emphasize enormous burden in terms of morbidity and mortality in developing countries like India, where the health systems face the brunt from infectious diseases as well.3,4 Evidence has shown explicitly that there is regional disparity in the prevalence of NCD risk factors like overweight and obesity, dysglycemia, dyslipidemia, hypertension, etc.

Director and Head Prof. M Viswanathan Diabetes Research Centre and MV Hospital for Diabetes **Epidemiologist † Postgraduate ‡ Assistant Director (Research) Dept. of Epidemiology, Diabetes Research Centre # ­ Dept. of Biochemistry, Diabetes Research Centre Address for correspondence Dr Vijay Viswanathan Director and Head Prof. M Viswanathan Diabetes Research Centre and MV Hospital for Diabetes (WHO Collaborating Centre for Research, Education and Training in Diabetes) No- 4, Main Road Royapuram - 600 013 Chennai E-mail *


within the country due to widespread regional variations, social and cultural differences, lifestyle and environmental patterns existing among the population.5,6 Despite the wide geographical variations in the prevalence of these risk factors, the two complex diseases, diabetes and CVD show stronger association. Inter-regional differences in lifestyle and environment provides an opportunity to explore the effect of environmental factors on disease patterns among the ethnic communities, thus possibly describing the complexity in gene-environment interactions. In India, diet patterns, tobacco consumption and activity levels are influenced by ethnicity and geographic location. Rural-urban differences exist in the prevalence of cardiovascular risk factors.7,8 Industrialization, urbanization, rural-urban migration resulting in acculturation, plays a causative role in the early development of cardiovascular risk factors. Nevertheless, the multifactorial etiology of CVD is incomplete without the mention of genetic role. Irrespective of all other modifiable risk factors, genetic predisposition, which is nonmodifiable, plays a potential role in the development of CVD.9 The present study explores the effect of lifestyle pattern on cardiovascular risk factors Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Original ARticle and diabetes between two communities: A migrated but typical North Indian vegetarian community settled in Chennai and the native South Indian nonvegetarian population. Subjects and Methods A cross-sectional study was conducted among 288 subjects (141 males and 147 females) aged above 20 years with similar socioeconomic status. The study groups comprised of pure vegetarian North Indian Gujarati population settled in Chennai (Group 1, n = 134 subjects) and the comparative group had 154 subjects who were natives of South India and resided in the same locality with nonvegetarian dietary habits (Group 2). The two study groups were selected from the same residential area by using random sampling technique. A semi-structured questionnaire was administered to collect demographic characteristics, socioeconomic status; behavioral risk factors such as smoking, alcohol consumption, diet pattern and physical activity. A written informed consent was obtained from all the study subjects. The study protocol was approved by the Institutional Review Board. Anthropometric measurements such as height, weight, waist circumference were recorded. Height was recorded using stadiometer with an accuracy of 0.5 cm. Weight was recorded by using Krupps weighing machine with an accuracy of 0.5 kg. Body mass index (BMI kg/m2) was calculated. Waist circumference was measured in centimeters with the help of measuring tape placed at the mid point between the lowest costal margin and the iliac crest. Blood pressure measurements were taken at a relaxed condition in a sitting posture using sphygmomanometer. Out of 5 ml of fasting venous blood sample collected, 2 ml was aliquoted in fluoride tube and 3 ml in gel tube to estimate the plasma glucose and serum lipid profile, respectively. Plasma glucose was estimated by glucose oxidase-peroxidase method. All the biochemical estimations were done by using enzymatic procedures within five hours using Hitachi 917 auto analyzer. According to American Diabetes Association (ADA) criteria, the fasting plasma glucose (FPG) value of >125 mg/dl was diagnosed as diabetes and FPG value between 100-125 mg/dl was diagnosed as impaired fasting glucose (IFG).10 The total cholesterol >200 mg/dl; triglyceride >150 mg/dl; high-density Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

lipoprotein cholesterol (HDL-C) Male <40 mg/dl: Female <50 mg/dl; low-density lipoprotein cholesterol (LDL- C) >100 mg/dl were considered as dyslipidemia.11 Blood pressure measurements more than 130 mmHg (systolic) and 85 mmHg (diastolic) were considered as hypertension.12 BMI more than 25 kg/m2 was considered as obese.13 Scores were given based on the level of the physical activity such as standing (1), house hold activities (2), walking (3) and regular exercises (4). Then the scores were multiplied by the respective duration of the physical activity in minutes. The study subjects were categorized as sedentary, if the score is (<300), moderately active (300-600) and heavy activity, if the score is above 600. Statistical Analysis

SPSS Version 10.0 was used for statistical analysis. Mean and standard deviations were estimated for continuous variables. Prevalences were reported in percentages. Students â&#x20AC;&#x2DC;tâ&#x20AC;&#x2122; test/Chi-square test was used as relevant to test the statistical significance with a p < 0.05. Results Among the 288 study subjects, 134 were North Indians with vegetarian diet habit and the remaining 154 were south Indian nonvegetarian population. The sociodemographic and anthropometric details are shown in Table 1. The study groups had similar mean age and income status. Literacy levels were higher among North Indians than the South Indians. Tobacco consumption in the form of smoking cigarettes and alcohol habits were significantly higher among the South Indian population. More than 50% of the study population was sedentary in both the study groups. Table 2 shows the anthropometric, biochemical and hemodynamic details of the study groups. BMI was similar in both the groups. Waist circumference was higher among South Indian population. Increased mean values of biochemical risk factors like mean plasma glucose, triglycerides and lower mean values of HDL-C levels were seen among the nonvegetarian South Indian population whereas, the vegetarian North Indian population had higher mean total cholesterol and LDL-C. Both the systolic and diastolic blood pressure values were similar in both the study groups. 275

Original ARticle Table 1. Sociodemographic and Habitual Risk Factor Details of the Study Groups

Table 2. Anthropometric, Biochemical and Hemodynamic Details of the Study Groups



North Indian group (n = 134)

South Indian group (n = 154)

43.8 ± 9.9

42.4 ± 9.1



Mean Age (in years)   Gender (M:F) Education status

Values are n (%) Values are n (%)

South Indian group

(n = 134)

(n = 154)

mean ± SD BMI (kg/m2)

25 ± 6.1

24.3 ± 5.2

1 (0.8)

27 (17.5)*

Waist circumference (cms)


74 (55.2)

105 (68.2)


80.8 ± 15.8

85.2 ± 12.1#

  Graduation and above

59 (44.0)

22 (14.3)*


77.5 ± 19.6

83 ± 12.9#

FPG (mg/dl)

83.7 ± 9.2

103.8 ± 46.5*


83 (61.9)

112 (72.7)

Total cholesterol (mg/dl)

185.7± 46.3

156.8 ± 45.5*


36 (26.9)

35 (22.7)

Triglycerides (mg/dl)

107.8 ± 51.5

139.8 ± 95.3*


15 (11.2)

7 (4.5)

LDL-C (mg/dl)

112.0 ± 38.3

88.5 ± 33.4*

HDL-C (mg/dl)

50.7 ± 12.8

40.7 ± 11.4*

4 (3.0)

36 (23.4)*

VLDL-C (mg/dl)

21.7 ± 10.2

26.3 ± 15.9#

14 (10.4)

27 (17.5)

Blood pressure (mmHg)


71 (52.9)

80 (51.9)

126 ± 16.9

120 ± 12.3


39 (29.1)

60 (38.9)

80 ± 8.7

76 ± 8.6


24 (17.9)

14 (9.1)#

  Carbohydrate (gs)

271 ± 45.2

331.6 ± 63.8*

  Protein (gs)

52.8 ± 8.3

52.5 ± 11.9

  Fat (gs)

43.1 ± 5.5

46.5 ± 5.7*

1,687.4 ± 233.1

1,983.4 ± 337.3*


Income/Month (INR)

Habits   Smoking   Alcohol consumption  Physical activity

Dietary details

Total calorie intake (kcal)

*P < 0.001, #P = 0.005: (North Indians vs South Indians)

Table 3 shows the prevalence of cardiovascular risk factors in the study groups. Other important findings of the study are higher levels of obesity among the North Indians inspite of similar prevalence of abnormal waist circumference between the two groups. The results indicate that the South Indian group had higher prevalence of the prediabetes condition IFG, hypertriglyceridemia and lower HDL-C, which were statistically significant. The only risk factors that were significantly higher among the North Indian population were obesity and hypercholesterolemia. Prevalence of hypertension was also higher in this group but was nonsignificant. The prevalence of diabetes was similar in both the study groups (p = 0.088). Dietary Assessment Qualitative details of the diet pattern obtained from the surveyed population showed the characteristic 276

North Indian group

  Systolic   Diastolic

* P < 0.001, P = 0.005: (North Indians vs South Indians) #

nature of food consumption and distinct difference in diet habits among the two groups. The North Indian population consumed wheat as main cereal, consumed only vegetables and had increased oil and ghee intake. Whilst the South Indian population consumed rice as the main cereal with mixed diet consisting of vegetables, meat, fish and chicken (Appendix 1). Consumption of carbohydrate and fat content was significantly higher among South Indians than North Indians (p < 0.001). Protein consumption was similar between the groups. Overall, the total calorie intake was higher in South Indians than North Indians. (p < 0.001) (Table 1). Discussion The shift towards chronic NCDs is apparent in the developed world and this epidemiological transition is currently being witnessed in the developing world.14 Lifestyle patterns exert a major influence on health as a whole.15 Major changes in lifestyle has led to increasing rates of diabetes, hypertension and dyslipidemia. The present study compared the prevalence of diabetes and cardiovascular risk factors of two different communities by ethnicity and lifestyle within the same geographical Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Original ARticle Table 3. Prevalence of Diabetes and Cardiovascular Risk Factors in the Study Groups NCD and its risk factors

North Indian group

South Indian group

p value






  (Fasting 100-125 mg/dl)


























Diabetes   (Fasting >125 mg/dl) Impaired fasting glucose

High cholesterol   (>200 mg/dl) High LDL-C   (>100 mg/dl) Low HDL-C   (<40 mg/dl-Male;   <50 mg/dl-Female) High triglycerides   (>150 mg/dl) Obesity   (BMI >25 kg/m2) Waist circumference (cms)   (Male ≥90, Female ≥80)

Appendix 1. Diet Pattern of the Study Groups North Indians

South Indians

Morning drink

Tea: 1 cup/Savories

Coffee/Tea: 1 cup


Khichdi/Roti/Idly/Dosa with Chutney/Ghee/Sweet Sambar/Pickles

Idly/Dosa/Poori/Pongal Upma/Rice Porridge with Sambar/Coconut Chutney/Onion Chutney/ Tomato Chutney

Mid-morning drink Tea: 1 Cup/Savories/Biscuits/Milk Sweets/Boiled Groundnuts



Roti with Ghee/Dhal/Vegetables/Curd/Papad/Pickles/ Butter Milk

Rice with Sambar/ Rasam/Vegetables/Appalam/ Pickles/Fish/Mutton/Chicken/Egg

Evening drink


Coffee: 1 Cup/Tea: 1 Cup/Bhajji/Vadai


Roti/Bhelpuri/Khichdi with Ghee/Pickles/Sweets

Rice/Chappati/Idly/Dosa with Sambar/Vegetables/ Rasam/Appalam/Pickles/Fish/Chicken

Bedtime drink

Milk: 1 cup/Fruits


region. The results showed some differences in the prevalence of cardiovascular risk factors in two different communities which varied by lifestyle. An important finding of this study was that the differences seen in the prevalence of cardiovascular risk factors between age-matched and income-matched two different communities. Dyslipidemia in terms of Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

hypertriglyceridemia and low HDL-C and dysglycemia was widespread among the former while the North Indians had only hypercholesterolemia. This may be attributed to the pattern of diet consumed and their habits and in depth diet studies are required to determine the cause and association. The diet details recorded in this study showed that North Indians consumed wheat as main cereal and only vegetables, 277

Original ARticle with increased oil and ghee intake while South Indians consumed rice as main cereal with mixed diet of vegetables, fish, meat and chicken. The pattern of lipid abnormality seen in both the groups was different. North Indians had higher prevalence of hypertension and hypercholesterolemia despite their vegetarian dietary habits. The North Indians showed high mean cholesterol and LDL-C, which may be due to regular intake of sweets and milk products (ghee) which is their traditional diet. The South Indians showed low level of mean HDL-C and high triglycerides coupled with higher proportion of dysglycemia, which are the most common features of metabolic syndrome. The prevalence of diabetes was similar in both the groups. It is well-known that Indians in different parts of the country have both diverse lifestyles and social structures, accordingly marked variations are noted in this study. It is worth mentioning that even though obesity levels were lower among the south Indian community, they had higher prevalence of cardiovascular abnormalities making the group vulnerable to high morbidity and mortality due to heart diseases. A similar study done much earlier among Gujarati community settled in Delhi and the natives of Delhi also found similar results that the Gujarati population had lesser abnormalities than the native Delhites.16 These findings suggest the possible effects and role of environment and dietary factors in disease and health. Along with industrialization, a rapid nutritional transition is also occurring in India. The traditional diet pattern is being replaced by refined foods, diet rich in fats and simple sugars, low in minerals and fiber.17,18 Bradford Hill and Rothman are pioneers in causality and by their way, valid epidemiological studies are required to study the disease patterns among different ethnic groups in India and to conceptualize the complex gene environment interactions.19 Thus, establishing the specific temporality among the specific populations and ethnic groups paves the way for focused primary prevention activities rather than generalizing the prevention notes. A cost-effective preventive strategy should be focused on reducing these risk factors in the whole population. One of the limitations of the study is that it is a small sized study and the sampling is from a residential area and should not be assumed to represent the prevalence of these risk factors in the city as a whole. 278

Conclusion The South Indians are at higher risk for CVDs due to high prevalence of the metabolic and biochemical abnormalities among them. Also, the study ascertains that different disease pattern exist among different communities within India owing to differences in lifestyle patterns and ethnicity. It is necessary to assess the prevalence of risk factors state-wise and formulate cultural and region-specific prevention strategy in India to curb the epidemic of NCDs. Creating awareness about lifestyle modification with moderate daily physical activity and healthy diet in general is essential. Acknowledgement We are grateful to all the study subjects who were very cooperative during the entire process of data collection. We thank our team members for the blood collection and other procedures done at the field level. We would like to acknowledge the help rendered by Ms. Sheela Paul, Ms. Malini, Ms. Ruth Annapoorni for doing the diet assessment. This manuscript was presented in 38th Annual Scientific Meeting RSSDI 2010 conference held in Cochin on 20th November.

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Original ARticle 8. Yusuf S, Reddy S, Ă&#x201D;unpuu S, Anand S. Global burden of cardiovascular diseases: Part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies. Circulation 2001;104(23):2855-64. 9. North KE, Howard BV, Welty TK, Best LG, Lee ET, Yeh JL, et al. Genetic and environmental contributions to cardiovascular disease risk in American Indians the strong heart family study. Am J Epidemiol 2003;157(4): 303-14. 10. American Diabetes Association. Diagnosis and classiďŹ cation of diabetes mellitus. Diabetes Care 2010;33 (Suppl 1):S62-9. 11. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001;285(12):2486-97. 12. Ogden LG, He J, Lydick E, Whelton PK. Longterm absolute benefit of lowering blood pressure in hypertensive patients according to the JNC-VI risk stratification. Hypertension 2000;35(2):539-43. 13. The Asia Pacific perspective: Redefining obesity and its treatment. Regional Office for the Western Pacific of the World Health Organization. World Health Organization, International Association for the Study of

Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Obesity and International Obesity Task Force, Health Communications Australia 2000:22-9. 14. Nugent R. chronic diseases in developing countries: health and economic burdens. Ann N Y Acad Sci 2008;1136:70-9. 15. Willett WC, Koplan JP, Nugent R, Dusenbury C, Puska P, GazianoTA. Prevention of chronic disease by means of diet and lifestyle changes. In: Disease Control Priorities in Developing Countries. 2nd edition, Jameson DT, Breman JG, Measham AR, et al. (Eds.), World Bank: Washington DC 2006. Chapter 44. 16. Chadha SL, Gopinath N, Ramachandran K. Epidemiological study of coronary heart disease in Gujaratis in Delhi (India). Indian J Med Res 1992;96: 115-21. 17. Lang T. The public health impact of globalization of food trade. In: Diet, Nutrition and Chronic Disease: Lessons from Contrasting Worlds. Shetty PS, Mc Pherson K, (Eds.), Wiky, Chichester, UK 1997: 173-87. 18. Reddy KS, Yusuf S. Emerging epidemic of cardiovascular disease in developing countries. Circulation 1998;97(6): 596-601. 19. Ruth Bonita, Robert Beaglehole, Tord Kjellstrom: Textbook of Basic Epidemiology. WHO Publications, 2006.





Review Article

Role of Omega-3 Fatty Acids in Cardiovascular Disease KK Aggarwal*, Rajiv Garg**

Abstract There is a large and increasing global burden of cardiovascular disease (CVD). The Indian subcontinent may be one of the regions with the highest burden of CVD in the world. With affluence and urbanization, fat intake, especially saturated fat is increasing. Vitamins have beneficial effects which are useful to the heart, but do not provide the all-round cardioprotection that is required. Hence, there is a perceived need of nutritional supplement that is rich in these essential nutrients. Studies have shown multifactorial cardioprotective actions of w-3 fatty acids. A cardioceutical contains all the essential nutrients viz. vitamins, minerals including w-3 fatty acids in the right proportion that will provide all-round protection to the heart. Key words: Cardiovascular disease, dietary fat, cardioceutical, omega-3 fatty acids

Prevalence of Cardiovascular Disease There is a large and increasing global burden of cardiovascular disease (CVD). About 14 million individuals died of cardiovascular disease in 1990; this is projected to rise to about 25 million by 2020. An estimated 30.9% of all deaths in 1998, as well as 10.3% of the total disease related burden, in terms of disabilityadjusted life year (DALY) loss were attributable to CVD.1 The Indian subcontinent may be one of the regions with the highest burden of CVD in the world.2 With industrialization, the major causes of death and disability, in the more advanced societies, have shifted from a large number of nutritional deficiencies and infectious diseases, to degenerative diseases such as CVD, cancer and diabetes. This shift has been termed â&#x20AC;&#x2DC;the epidemiologic transitionâ&#x20AC;&#x2122;. Noncommunicable diseases (NCDs) predominate, with the highest mortality caused by atherosclerotic CVD, most commonly ischemic heart disease and atherothrombotic stroke, especially at ages below 50 years. This phase is found in urban India.1 The Global Burden of Diseases (GBD) study reported the estimated mortality from coronary heart disease

*Dr KK Aggarwal Senior Physician and Cardiologist, Moolchand Medcity, New Delhi **Dr Rajiv Garg Senior Medical Specialist and Head, Dept. of Medicine ESI Hospital, Noida Address for correspondence Dr KK Aggarwal Senior Physician and Cardiologist Moolchand Medcity, New Delhi E-mail:

Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

(CHD) in India at 1.6 million in the year 2000. About 64 million cases of CVD are likely in the year 2015, of which nearly 61 million would be CHD cases (the remaining would include stroke, rheumatic heart disease and congenital heart diseases). Deaths from this group of diseases are likely to be 3.4 million. CHD is more prevalent in Indian urban populations and there is a clear declining gradient in its prevalence from semi-urban to rural populations. The Indian Council of Medical Research-World Health Organization (ICMR-WHO) study on Burden of Disease reviewed literature till 2003 on NCDs and noted the weighted average prevalence for ischemic heart disease to be 6.4% in urban areas and 2.5% in rural areas.3 By the year 2020, CVD is likely to be the largest cause of disability and death in India.4 Besides the high rate of CHD mortality in the Indian subcontinent, CHD also manifests almost 10 years earlier on average in this region compared with the rest of the world. In Western countries where CVD is considered a disease of the aged, 23% of CVD deaths occur below 70-year of age versus 52% of CVD deaths occurring among people under 70-year of age in India.2 Dietary Fats Play a Role in Promoting Cardiovascular Disease With affluence and urbanization, fat intake, especially saturated fat, is increasing with reduced intake of dietary fiber. This dietary profile is a major factor for the high prevalence of CHD in urban population in India.5 Consumption of trans-fatty acids (TFAs) increases levels of low-density liproprotein (LDL) 281

Review Article cholesterol and reduces high-density liporotein (HDL) cholesterol. Several studies have established that it is the type of fat and not total amount of fat that predicts serum cholesterol levels and determining the risk of CHD. Replacement of dietary saturated fat with unsaturated fats (mono- or polyunsaturated fats) significantly lowers the plasma-cholesterol and LDL cholesterol levels and is more effective in lowering risk of CHD than merely reducing total fat consumption.6 Recommendations have therefore emphasized on â&#x20AC;&#x2DC;taking the right fat, since type of fat is more important than total fatâ&#x20AC;&#x2122;. Most Indians usually consume a plantbased diet which contains lot of legumes. Legumes are rich in phytates. The major concern about the presence of phytate in the diet is its negative effect on mineral absorption.7 Presence of oxalates and phytates in plantbased diets may limit the bioavailability of nutrients such as calcium, iron and zinc from vegetarian diets.8

Emergence of a Category of Cardioceuticals

Nutrients and Cardioprotection Lifestyle practices can have an obvious impact on the prevention of CVD. Diet is the cornerstone of all prevention efforts. There is impressive data about how individual dietary factors, including nutrients and foods, and dietary patterns alter multiple CVD risk factors.9 Observational data have suggested strong associations between carotenoids, folic acid and vitamin E, and decreased CVD risk.10 Some good-quality cohort studies have reported an association between vitamin supplements and lower risk for CVD.11 Observational studies have also reported inverse associations of CVD with dietary intake or plasma concentrations of w-3 fatty acids, suggesting that w-3 fatty acids supplementation might exert protective effects on CVD.12 A study published in the Journal of Nutrition suggested that certain nutrients (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], oleic acid folic acid and vitamins A, B6, D and E) when taken together may have beneficial effects on risk factors and clinical variables in patients that suffered from myocardial infarction (MI) in a cardiac rehabilitation program.13

Dietary N-6 and N-3 Fatty Acid Balance and Cardiovascular Disease

Do Multivitamins Suffice in Providing Cardioprotection?

Vitamins exert their beneficial effects due to their antioxidant properties. While these effects are useful to the heart, they do not provide the all-round cardioprotection that is required. Hence, there is a perceived need of nutritional supplement that is rich in these essential nutrients. 282

A cardioceutical contains all the essential nutrients including vitamins, minerals, w-3 fatty acids and other antioxidants like a-lipoic acid and coenzyme Q10 in the right proportion that will provide all-round protection to the heart. The most evident long-term benefits of a cardioceutical are the prevention of the risk factors of the heart. The cardioceutical focuses on improvement of different parameters that contribute to a healthy heart such as increasing oxygen supply, protection of artery walls and prevention of clots, antioxidation, maintaining healthy rhythm of the heart and lowering of cholesterol. Cardioceuticals therefore would subsequently reduce the cost of treatment in the highrisk patients by reducing need for re-hospitalization, improve the quality of living and reduce the mortality rates in the high-risk population.

N-6 PUFAs (polyunsaturated fatty acids) may compete with n-3 PUFAs for common metabolic enzymes and thereby increase the production of prothrombotic rather than antithrombotic, aggregatory and inflammatory leukotrienes, thromboxanes, and prostaglandins and thus attenuate benefits. These data have raised concerns that n-6 PUFAs may counteract the potential cardiovascular benefits of n-3 PUFAs.14 Hence, the distinct functions of these two PUFAs makes the balance between dietary n-6 and n-3 fatty acids an important consideration influencing cardiovascular health.15 Western diets are deficient in w-3 fatty acids, and have excessive amounts of w-6 fatty acids compared with the diet on which human beings evolved and their genetic patterns were established. Excessive amounts of w-6 PUFAs and a very high w-6/w-3 ratio, as is found in todayâ&#x20AC;&#x2122;s Western diets, promote the pathogenesis of many diseases, including CVD.16 Human beings evolved on a diet with a ratio of w-6 to w-3 essential fatty acids (EFA) of approximately 1 whereas in Western diets the ratio is 15/1-16.7/1. An w-6 to w-3 ratio exceeding 5:1 is now known to favor atherogenesis.17 Indian diets tend to be very high in w-6 w-3 ratio.18 Most Indians consume w-6 and w-3 fatty acids in a ratio of 30-70:1.19 Asian Indians have a low intake of monounsaturated fatty acid (MUFA), n-3 PUFA and fiber and high intake of fats, saturated fats, carbohydrates and TFAs.20 Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Review Article Role of w-3 Fatty Acids in Cardiovascular Disease w-3 fatty acids are essential PUFA as they cannot be synthesized ‘de novo’ in the body and must therefore be obtained from the diet or supplementation. The three major types of w-3 fatty acids obtained from foods and used by the body, are EPA and DHA and a-linolenic acid (ALA). ALA is converted to EPA and DHA, which are the two w-3 fatty acids more readily used by the body.21 Fish and fish oil are rich sources of w-3 fatty acids, specifically EPA and DHA, which are present in fatty fish. ALA is present in seeds and oils (flaxseed), green leafy vegetables and nuts and beans (such as walnuts and soybeans).22 Evidence for Cardioprotection

w-3 Fatty Acids and CAD Primary prevention of CAD

There are no randomized controlled trial (RCT) to show that w-3 fatty acids reduce the risk of cardiovascular events and mortality in a primary prevention population. An 18% decrease in cardiovascular events in 80% of patients in the Japan EPA Lipid Intervention Study (JELIS) trial without documented coronary artery disease (CAD) provides evidence supporting a beneficial effect of w-3 fatty acids in primary prevention.23 Two large prospective cohort studies, the Physicians’ Health Study and the Nurses’ Health Study demonstrated some cardiovascular benefit.21 Physicians’ Health Study: The US Physicians’ Health Study was a survey of about 20,000 male physicians, aged 40-84 years and who had no prior MI, cerebrovascular disease and cancer at baseline. Neither dietary fish consumption nor n-3 fatty acid intake was found to be associated with a reduced risk of total MI, nonsudden cardiac death or total cardiovascular mortality. But, men who ate fish at least once per week had a 50% decrease in the risk for sudden death and a significant reduction in all-cause mortality.24 A reanalysis of the US Physicians’ Health Study observed a significant inverse relationship between blood levels of w-3 fatty acids and the risk of sudden death in men among men without evidence of prior CVD.22 Nurses’ Health Study: The US Nurses’ Health Study provides data about the protective effects of fish and ALA in women.25 The study analyzed the diets of 84,688 healthy female nurses aged 34-59 years and found that higher consumption of fish and w-3 fatty acids is associated with a lower risk of CHD, particularly CHD-related deaths.22 Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Secondary prevention of CAD

DART Trial: The Diet and Reinfarction Trial (DART)26 was one of the first studies to investigate a relationship between dietary intake of w-3 fatty acids and secondary prevention of MI. In this study, 1,015 men were advised to eat at least two servings of fatty fish per week, and 1,018 men were not so advised.22 This study reported a 29% reduction (p < 0.05) in all-cause mortality over a 2-year period in men who recovered from the MI. However, no difference between the two groups was found concerning total CVD events, probably because of the higher incidence of nonfatal MIs in subjects advised to increase their fish intake. The greatest benefit was found in fatal MIs (reduction by 33%, p < 0.01).27 The Indian Experiment of Infarct Survival: The Indian Experiment of Infarct Survival, a double-blinded placebocontrolled, RCT, was the first secondary prevention prospective study to examine the effect of w-3 fatty acid supplements on clinical events and suggested that fish oil and mustard oil, possibly due to the presence of n-3 fatty acids, may provide rapid protective effects in patients with acute MI. The trial randomized 4,360 patients to three arms within 24 hours of an acute MI: a) Fish oil capsules (providing 1.8 g of EPA and DHA daily), b) a mustard oil group (providing 2.9 g ALA daily) and c) a placebo group. At 1-year follow-up, total cardiac events (24.5% and 28% vs 34.7%, p < 0.01) as well as nonfatal MIs group (13.0% and 15.0% vs 25.4%, p < 0.05) after 1-year were significantly reduced in both the fish oil and the mustard oil group versus the placebo group. Total cardiac deaths showed no significant reduction in the mustard oil group; but, fish oil group had significantly less cardiac deaths compared with the placebo group (11.4% vs 22.0%).28 The Lyon Diet Heart Study: The Lyon Diet Heart Study, a single blinded RCT, compared the impact of a Mediterranean diet (rich in ALA) with a standard postinfarction diet in 423 people who survived a first MI. The treatment group received a Mediterranean diet (more fish, cereals, fresh fruits) (rich in ALA), whereas the control group continued their routine diet. Nonfatal MIs and CHD deaths declined considerably in the treated group at end of the 46 months follow-up period.29 Figures 1 and 2 show event-free survival. GISSI-Prevenzione Study: The GISSI-Prevenzione Study concluded that n-3 PUFA resulted in a clinically important benefit in secondary prevention of CVD and that vitamin E had no benefit after MI. In the study, 283

Review Article

100 Experimental

90 80


70 60

p = 0.0001

50 40

90 Percent without event

Percent without event




70 60 50


p = 0.0002


1 2 3 4 5 Year

Figure 1. Cumulative survival without nonfatal infarction and without major secondary endpoints.

1 2 3 4 5 Year

Figure 2. Cumulative survival without nonfatal infarction, without major secondary endpoints, and without minor secondary endpoints.

11,324 patients with known CHD were randomized to receive either vitamin E (300 mg), w-3 fatty acids (850 mg, both or neither). After 3.5 years, w-3 fatty acids supplementation reduced the primary endpoint (the cumulative rate of all-cause death, nonfatal MI and nonfatal stroke and the cumulative rate of CVD death, nonfatal MI and nonfatal stroke) by 15%, all-cause mortality by 20% and induced a marked reduction of 45% in sudden cardiac death (Fig. 3).30 JELIS Trial: In the JELIS, administration of 1.8 g/day of highly purified EPA capsules in 18,645 patients (14,981 in primary prevention and 3,664 in secondary prevention) with hypercholesterolemia taking low doses of various statins led to a significant decrease in the incidence of major coronary events (MCEs), mainly due to a decrease in unstable angina (hazard ratio for MCEs and unstable angina of 0.81 and 0.76, respectively).31







w-3 fatty acids -35%

-32% -45%


-9% NS

4 2 0

All deaths

CV death

Cardiac death

CHD death

Sudden death

2. MI

Figure 3. GISSI-Prevention Trial: 3.5 years post-MI patients.


w-3 Fatty Acids and Hyperlipidemia w-3 fatty acids lower plasma triglycerides by inhibiting very-low-density lipoprotein (VLDL) cholesterol and triglyceride synthesis in the liver. A review of human studies concluded that ~4 g/day of w-3 fatty acids reduced serum triglyceride concentrations by 25-30%, increased serum LDL cholesterol levels by 5-10%, and increased HDL cholesterol levels by 1-3%.22,32 In a RCT of patients with persistent hypertriglyceridemia, patients who received simvastatin (10-40 mg daily) + w-3 fatty acids (1 g). Omacor had 20-30% decreases in serum triglyceride and 30-40% decreases in VLDL cholesterol levels than those receiving simvastatin and placebo.33 w-3 Fatty Acids and Hypertension w-3 fatty acids have a dose response hypotensive effect in patients with hypertension and have little to no effect in normotensive patients.22 A meta-analysis reported that daily consumption of 5.6 g of w-3 fatty acids by hypertensive subjects resulted in a blood pressure reduction of 3.4/2.0 mmHg.34 Similarly, Appel et al found a decrease of 5.5/3.5 mmHg in blood pressure in untreated hypertensive subjects after the administration of â&#x2030;Ľ3 g w-3 fatty acids daily.35 DHA seems to be more effective than EPA in lowering blood pressure.27 w-3 Fatty Acids and Arrhythmias Research has shown that w-3 fatty acids decrease risk of arrhythmias, which can lead to sudden death.36,37 A large study of more than 5,000 men and women by Mozaffarian et al showed that high dietary fish intake was associated with lower heart rate, slower atrial ventricular conduction and a significantly less chances of having a prolonged QT interval.38 w-3 Fatty Acids and Heart Failure Another beneficial action of w-3 fatty acids is their ability to lower the risk of heart failure (HF). One major cause of congestive heart failure (CHF) is MI or heart attack which is an irreversible injury to heart muscle. The Cardiovascular Health Study, involving 4,738 men and women â&#x2030;Ľ65 years of age, found an inverse association of baked or broiled fish intake and incident CHF.39 Data from the ARIC (Atherosclerosis Risk In Community) study corroborated this beneficial effect.40 The recent GISSI-HF trial of adults (mean age 67/68) with confirmed CHF (NYHA Class II-IV gave confirmatory evidence that long-term administration of 1 g/day of w-3 fatty acids in patients with CHF reduced all-cause Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Review Article mortality by 9% and hospitalization for CVDs by 8% (Fig. 4).41 The placebo-controlled trial of nearly 7,000 patients with Class II-IV HF who were randomized to 1 g of w-3 PUFA (850-882 mg EPA and DHA as ethyl esters in the average ratio of 1:1.2), rosuvastatin (10 mg daily), both or dual placebo. This therapy was safe and well-tolerated; improvements in clinical outcomes were additive to that of other well-established HF therapies, including b-blockers, angiotensin-converting enzyme inhibitor/angiotensin receptor blockers and aldosterone receptor blockers. w-3 Fatty Acids and Endothelial Dysfunction Endothelial dysfunction is an imbalance between the vasoconstriction and vasodilatation components and is an early and crucial instigating event in atherosclerosis and heart disease.42 It occurs much earlier than the onset of symptomatic disease. Several clinical trials have demonstrated that fish oil consumption also lowers circulating markers of endothelial dysfunction, such as E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1).43,44 Another recent trial found that greater intake of w-3 fatty acids had a clear correlation with lower levels of blood markers associated with dangerous endothelial dysfunction showing lower levels of inflammation and endothelial activation.45

Probability of all cause death or admission for cardiovascular reasons

w-3 Fatty Acids Regress Blockage w-3 fatty acids have antiatherosclerotic effect i.e. they may reduce chronic progression of atherosclerosis. Modest but statistically significant effects of fish oil supplementation on progression of coronary, but not carotid, atherosclerosis have been noted.46,47 Patients


Placebo w-3 PUFA


with CAD who took about 1.5 g of w-3 fatty acids per day for two years had less progression and more regression of CAD on coronary angiography than did comparable patients who ingested a placebo. These patients also experienced fewer cardiovascular events.46 In a study in Japanese patients with type 2 diabetes, EPA had less progression of both mean and maximal intimal-medial thickness.48 Mechanism of Cardioprotective Action

w-3 fatty acid consumption protect against both the pathological processes leading to the CVD (i.e. atherosclerosis) and the processes that ultimately cause death (e.g., MI and stroke). They reduce both fasting and postprandial plasma triacylglycerol concentrations and also decrease chemoattractant, growth factor and adhesion molecule production and so could down-regulate processes leading to leukocyte and smooth muscle migration into the vessel wall intima. Due to their anti-inflammatory action, they decrease inflammatory processes within the vessel wall, which are now recognized to be a major contributory factor in the atherosclerosis. w-3 fatty acids cause endothelial relaxation and promote arterial compliance, which might be related to altered nitric oxide production (Table 1).49 Antithrombotic and antiarrhythmic effects are considered to confer strong protective effect against acute cardiovascular events, especially those that are fatal. Recently, the antiinflammatory effects also contribute in the protective effects towards acute cardiovascular events.50 Table 1. Mechanisms of Cardioprotective Effects of w-3 Fatty Acids50,51 Antithrombogenic

Inhibit platelet aggregation


Inhibit intimal hyperplasia


Improve membrane fluidity, prevent atrial fibrillation, reduce susceptibility of heart to ventricular arrhythmias


Reduce production of w-6 pro-inflammatory eicosanoid, reduce C-reactive protein

Improve endothelial function

Direct effect on endothelial vasomotor function

Improve lipid parameters and cardiovascular risk parameters

Hypotriglyceridemic; inhibit synthesis of hepatic TGs and VLDL leading to lower TG levels; raise HDL levels, lower apolipoprotein levels


Mild lowering of blood pressure

0.5 0.4 0.3 0.2 0.1 0



12 18

24 30 36 42 48

Time since randomization (months)


Figure 4. Kaplan-Meier curves for time to all-cause death or admission to hospital for cardiovascular reasons.

Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011


Review Article Daily Recommendations for w-3 Intake21 The AHA recommends an intake of at least two servings of oily fish per week, in addition to vegetable oils (flaxseed, walnut, canola and soybean oils) which are rich in ALA. In patients with documented CVD an average intake of approximately 1 g of EPA + DHA is recommended. This can be either via diet (e.g. fatty fish), or if dietary intake is insufficient then as a supplement in consultation with a physician. NICE recommends that following MI, patients should consume at least 7 g of w-3 fatty acids per week obtained from 2-4 portions of oily fish. If these patients are not achieving this level of w-3 intake then the prescription of at least 1 g of w-3-acid ethyl ester treatment (licensed for secondary prevention post-MI) should be considered for upto four years. Initiation of such supplementation has been recommended within three months of patients having had a MI, but not in those who have had a MI longer than three months prior.

Conclusion Preventing the occurrence of CVD with nutritional interventions is a therapeutic strategy that has recently garnered great attention. These nutrients also reduce cardiovascular morbidity and mortality. The increased use of w-3 fatty acids is one such nutritional strategy that may have notable cardiovascular benefits. w-3 fatty acids have a multi-factorial mode of action in CVD.21 While the therapeutic actions of w-3 PUFA are largely characterized by their ability to lower serum triglycerides, they have other cardioprotection mechanisms including reduced platelet aggregation, antithrombotic and fibrinolytic activities, antiarrhythmic effects, reduced blood viscosity and anti-inflammatory properties.52 Trials have shown a favorable modifying effect of these fatty acids on various risk factors for CVD. They have been proven to be effective in secondary prevention of MI, including sudden death as well as in primary prevention. Hence, given the public health importance of the epidemic of CVD, which accounts for nearly one-half of all deaths in the developed and developing world, dietary increases in w-3 PUFA consumption should be encouraged for all individuals, especially those at risk of developing CVD. References 1. 2.


Yusuf S, et al. Circulation 2001;104:2746-53. Goyal A, Yusuf S. Indian J Med Res 2006;124:235-44.

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52.

Shah B, Mathur P. Indian J Med Res 2010;132:634-42. Goenka S, et al. Curr Sci 2009;97(3):367-77. Misra A, et al. Eur J Clin Nutr 2001;55:727-34. Hu FB, et al. J Am Clin Nutr 2001;20(1):5-19. Greiner R, et al. Journal für Ernährungsmedizin 2006; 8(3):18-28. Jonnalagadda SS, Diwan S. J Am Coll Nutr 2002;21(5): 372-80. Kris-Etherton PM, et al. J Nutr 2008;138(9): 1746S-1751S. Lichtenstein AH. J Lipid Res 2009;50(Suppl):S429-33. Morris CD, Corson S. Ann Intern Med 2003;139(1): 56-70. Galan P, et al. BMJ 2010;341:c6273. Carrero JJ, et al. J Nutr 2007;137(2):384-90. Mozaffarian D, et al. Circulation 2005;111(2):157-64. Wijendran V, Hoyes KC. Annu Rev Nutr 2004;24: 597-615. Simopoulos AP. Exp Biol Med (Maywood) 2008;233(6): 674-88. Sudha V, et al. Indian J Med Res 2004;120:4-8. Bamji MS. Curr Sci 2006;90(12):1590-1. Singh M. Indian J Pediatr 2005;72(3):239-42. Misra A, et al. Br J Nutr 2008;101(4):1-9. Kandasamy N, et al. Br J Diab Vasc Dis 2008;8(3):121-8. Covington MB. Am Fam Physician 2004;70:133-40. Lee JH, et al. Mayo Clin Proc 2008;83(3):324-32. Albert CM, et al. JAMA 1998;279:23-8. Hu FB, et al. JAMA 2002;287:1815-21. Burr ML, et al. Lancet 1989;2:757-61. Gazi I, et al. Hellenic J Cardiol 2006;47:223-31. Singh RB, et al. Cardiovasc Drugs Ther 1997;11:485-91. de Lorgeril M, et al. Circulation 1999;99(6):779-85. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet 1999;354:447-55. Yokoyama M, et al. Lancet 2007;369(9567):1090-8. Harris WS. Am J Clin Nutr 1997;65:1645S-1654S. Durrington PN, et al. Heart 2001;85:544-8. Morris MC, et al. Circulation 1993;88:523-33. Appel LJ, et al. Arch Intern Med 1993;153:1429-38. O’Keefe JH Jr, et al. Am J Cardiol 2006;97:1127-30. Geelen A, et al. Am J Clin Nutr 2005;81:416-20. Mozaffarian D, et al. J Am Coll Cardiol 2006;48:478-84. Mozaffarian D, et al. J Am Coll Cardiol 2005;45:2015-21. Yamagishi K, et al. Am Heart J 2008;156:965-74. Tavazzi L, et al. Lancet 2008;372:1223-30. Eid HM, et al. Nutr Metab (Lond) 2006;3:4. Robinson JG, Stone NJ. Am J Cardiol 2006;98:39i. James MJ, et al. Am J Clin Nutr 2000;71:343S. Lopez-Garcia E, et al. J Nutr 2004;134(7):1806-11. Von Schacky C, et al. Ann Intern Med 1999;130:554. Angerer P, et al. Cardiovasc Res 2002;54:183. Mita T, et al. Atherosclerosis 2007;191:162-7. Calder PC. Clin Sci 2004;107:1-11. Kris-Etherton PM, et al. Circulation 2002;106:2747-57. Schwalfenberg G. Can Fam Physician 2006;52:734-40. Patel JV, et al. Vasc Health Risk Manag 2009;5:801-1.

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Clinical Study

Comparison of Left Ventricular Function by Doppler Imaging in Diabetics with and without Systemic HT PR Gupta*, Dharmendra Jain**, Kamaljeet†, Dilip‡, Vivek‡, Vikas‡, Deba#

Abstract Diabetes mellitus (DM) and hypertension (HT) are known risk factors for myocardial dysfunction. Uptill now the main focus was on systolic dysfunction but subtle diastolic relaxation abnormalities which appear earlier are overlooked. In our study we compared left ventricular (LV) function by Doppler imaging in patients with DM with and without systemic HT. We divided patients in four groups: HT, DM, HT + DM and controls. Age and ejection fraction were comparable in all groups and we concluded that diastolic dysfunction was detected with conventional Doppler in HT and HT + diabetes. But conventional Doppler was unable to detect diastolic dysfunction in DM while tissue Doppler imaging was able to detect diastolic dysfunction in all groups hence, we concluded tissue Doppler imaging is better modality for detection of early diastolic abnormalities. Key words: Diastolic dysfunction, conventional Doppler, tissue Doppler imaging


iabetes mellitus (DM) and hypertension (HT) are important risk factors for the development of coronary heart disease. Till date, all the emphasis has been on systolic function and its implication as clinical outcome. Many patients with DM, with or without HT have normal left ventricular (LV) systolic function but still they complains of dyspnea, peripheral edema, raised jugular venous pressure (JVP) and other sign and symptoms of congestive heart failure. Therefore, there is need for assessment of diastolic dysfunction in diabetes and HT with normal LV systolic function. DM is an established risk factor for cardiovascular events especially the development of congestive heart failure.1 It has been suggested that impairment of LV function in patients with DM is due to concomitant risk factors such as arterial HT or diffuse peripheral and coronary atherosclerosis.2 However, actual mechanisms remain unclear and evidence has accumulated for the existence of a distinct diabetic cardiomyopathy. Impairment of LV diastolic function in patients with DM has been described using digitized M-mode and

*Professor and Head, Dept. of Cardiology Banaras Hindu University, Varanasi **Consultant † Attending Consultant Dept. of Cardiology, Max Hospital, New Delhi ‡ Senior Resident # Junior Resident, Dept. of Cardiology, Banaras Hindu University, Varanasi

Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Doppler echocardiography. Some of the previous studies had established an association of diabetes and diastolic dysfunction while some have found no association between DM and diastolic dysfunction. Most of the previous studies have used conventional Doppler to estimate diastolic dysfunction. Therefore, in our study we have used in addition to conventional Doppler echocardiography, tissue Doppler imaging for assessment of LV function - a new technique that is independent of loading conditions. Our study demonstrated the early appearance of both LV systolic and diastolic dysfunction in diabetic patients at rest and the contributory effect of diabetes to myocardial impairment produced by HT, as well as the high usefulness of tissue Doppler imaging in detection and quantitation of myocardial dysfunction in diabetics. This method was superior to other echocardiographic techniques. Material and Methods The study was conducted on patients who presented to the OPD or were admitted as inpatient either in Cardiology ward or the Coronary Care Unit of Sir Sunderlal Hospital - Banaras Hindu University, Varanasi between February 2008 to July 2009. Three types of patients were included in the study: Hypertensive first time diagnosed not under treatment, diabetic, hypertensive + diabetic. Age- and sex-matched controls were also taken. A detailed clinical history was taken and physical 287

Clinical Study examination was performed. Treadmill test (TMT) was done in all patients and only those patients whose TMT was negative for inducible myocardial ischemia were registered for the study. History of ischemic chest pain, poor quality echocardiographic imaging, valvular or congenital heart disease, decreased LV ejection fraction i.e., <55%, endocrine disorder other than diabetes, absence of stable sinus rhythm, renal impairment with serum creatinine >2.5 mg/dl, conductive or rhythm disturbances on ECG were excluded from the study. All study participants underwent standard ECG with Doppler studies using Seimen’s Acuson CV70 machine with a 2.5 MHz transducer. The measurements of LV dimension and wall thickness were performed from 2-dimensionally targeted M-mode tracings. LV mass was calculated by standard formula and indexed for body surface area to obtain the LV mass index. LV ejection fraction was estimated using Simpson’s biplane method and LV Teich (M) method. LV fractional shortening was derived from standard formula. Conventional Doppler measurements was done with the transducer in the apical position. The sample value is placed at the tip of the mitral valve leaflet and by using pulse-wave Doppler, the inflow pattern of mitral valve was evaluated. The early flow coincident with mitral E-wave peak velocity was noted. Along with E-wave second wave A-wave peak velocity was noted and ratio of E’/A’ was calculated. Calculation of Deceleration Time

Deceleration time (DT) is a commonly used parameter to assess diastolic dysfunction. The slope of descending limb of E-wave was measured and DT was calculated. Measurement of DT of E-wave is problematic when E-wave decay curve is not linear, in these instances, using the midportion of E-wave deceleration is most appropriate for determining slope. Many individuals have a Ski slope E-wave in which there is a short rapid decline is E-wave velocity followed by a more gradual slope. In this instance ignoring the initial steep decline and measuring the midportion of the E-wave is the appropriate methodology. In many instances the E-wave velocity does not decline fully to a velocity of 0 m/s and hence the true time points for DT cannot be determined, standard practice is to extrapolate the DT from the more proximal portions of the E-wave. 288

Tissue Doppler Imaging

Tissue Doppler imaging was performed in apical views 4 and 2 chambers and in parasternal short axis view to assess the function of longitudinal and circumferential myocardial fibers. The sampling window was positioned as parallel as possible with the myocardial segment of interest to ensure that the optimal angles of imaging the sample values were located in the central part of the basal and mid-segments in each apical view and mid-anteroseptal and posterior segments in the parasternal short axis view. Mean values of peak systolic velocities and peak early and peak late diastolic velocities obtained form the basal segments served as a measure of global myocardial function. For the mid and basal segments, we estimated the mean peak systolic velocity, mean peak early/peak late diastolic velocity by keeping the sample values in central part of mid and basal segments. Data were analyzed using standard statistical software SPSS (Version 12.0). The statistical analysis was done using analysis of variance (ANOVA) and Boneferoni test was used for group comparison. Chi-square test was used to analyze qualitative data. P < 0.05 was considered as statistically significant. Results In group 1 (hypertensive group) there were 20 patients, out of which seven (35%) were females. Mean age in group 1 was 55.40 ± 4.59 years. In group 2, only diabetic patients were included with mean age 57.60 ± 8.15 years; there was 10 patients in diabetes group with only two (20%) female patients. In group 3 (n = 20), both diabetic and hypertensive patients were included with mean age 55.35 ± 6.74 years. There were seven (35%) female patients in this group. In group 4, 20 controls with four females (20.0%) was included with mean age of 56.20 ± 4.37 years. In group 1, the mean systolic BP was 161.0 ± 11.26 mmHg and mean diastolic BP was 100.40 ± 7.38 mmHg. In group 2, mean systolic BP was 120.20 ± 8.76 mmHg and mean diastolic BP was 77.80 ± 7.80 mmHg. In group 3, mean systolic BP was 153.30 ± 10.34 mmHg and mean diastolic BP was 97.80 ± 8.60 mmHg. Mean systolic BP in control group was 122.27 ± 8.31 mmHg and mean diastolic BP was 79.60 ± 6.64 mmHg. On statistical analysis, age in all four groups was comparable. Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Clinical Study Mean LV ejection fraction in HT group was 66.77 ± 3.66%; mean LV ejection fraction in diabetes group was 64.00 ± 3.52%; mean LV ejection fraction in diabetic and HT group was 65.15 ± 4.17% and mean LV ejection fraction in control group was 63.93 ± 4.38%. On comparing each group with control and group 1 with group 3 and group 2 and group 3, p value was not statistically significant indicating there was no impact of HT and DM on ejection fraction. In HT group, LV mass index was 145.5 ± 8.7 g/m2 while in control group, it was 98.60 ± 8.63 g/m2 (p < 0.001). In diabetes group, LV mass index was 95.50 ± 7.51 g/m2 (p = NS). In HT + diabetes group mean LV mass index was 151.35 ± 8.13 g/m2 (p < 0.001). On comparison with control there was significant increase in LV mass index in hypertensive group; greater increase was in HT + diabetes group. Comparison of the diabetic with HT + diabetes group (p < 0.001) concluded that DM by itself does not increase LV mass index. HT increases LV mass index and greatest increase was in HT + diabetes group (Table 1).

Table 1. LV Mass Index Group

No. of cases

LV mass index (g/m2) (mean ± SD)

Group 1 (Hypertension)


145.55 ± 8.73

Group 2 (Diabetes)


95.50 ± 7.51

Group 3 (Hypertension + Diabetes)


151.35 ± 8.13

Group 4 (Control)


98.60 ± 8.63

F = 193.57; p < 0.001

Group Comparison (Bonferroni Test) Group

p value

Group 1 vs Group 4


Group 2 vs Group 4


Group 3 vs Group 4


Group 2 vs Group 3


Group 1 vs Group 3


Table 2: Early Mitral Flow (E)/Late Mitral Flow (A) Group

No. of cases

E’/A’ (mean ± SD)

Group 1 (Hypertension)


0.82 ± 0.2233

Group 2 (Diabetes)


1.12 ± 0.2198

In HT group, E’/A’ was 0.82 ± 0.22 while in the control group, E’/A’ was 1.15 ± 0.15 (p < 0.001). In DM group, E’/A’ ratio was 1.12 ± 0.21 comparing with control (p = NS). In HT + diabetes group, E’/A’ ratio was 0.76 ± 0.15 when compared with controls (p < 0.001). On comparing HT with HT + diabetes group (p = NS), HT was associated with decrease in E’/A’ ratio which was more pronounced in HT with diabetic. But independently only DM was not associated with significant change in E’/A’ ratio (Table 2).

Group 3 (Hypertension + Diabetes)


0.76 ± 0.1574

Group 4 (Control)


1.15 ± 0.1500

Mean DT in HT group was 209.00 ± 23.07 msec while in control group it was 173.47 ± 24.34 msec on comparison (p < 0.001). Mean DT in diabetes group was 200.00 ± 18.8 msec as compared with control (p = 0.05). Mean DT in HT + diabetes group was 233.20 ± 24.23 msec on comparing with control (p < 0.001). On comparing DM with HT + diabetes group, p value was significant (p = 0.003). On comparing HT with diabetic + HT group (p < 0.001). DT is increased in HT. It is not significantly increased in diabetic patient. In cases with both HT + DM, DT is increased to greatest extent (Table 3).

it was 7.62 ± 0.74 (p < 0.001). MPSV in DM group was again 6.33 ± 0.42 both of these were significantly less than control group (p < 0.001). In HT + diabetes group, velocity was least i.e. 5.79 ± 0.49 and was again significantly less than control group (p < 0.001). On comparing DM with HT + diabetes group and HT with diabetic + hypertensive group results were insignificant. Mean positive systolic velocity in basal segments was significantly decreased in patients with diabetes, HT and diabetes + HT (Table 4).

MPSV (mean peak systolic velocity) in hypertensive group was 6.33 ± 0.93 cm/s while in control group

E’ (mean peak early myocardial diastolic velocity) in hypertensive group was 6.14 ± 0.82 cm/sec as

Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

F = 17.780; p < 0.001

Group Comparison (Bonferroni Test) Group

p value

Group 1 vs Group 4


Group 2 vs Group 4


Group 3 vs Group 4


Group 2 vs Group 3


Group 1 vs Group 3



Clinical Study Table 3. Deceleration Time Group

No. of cases

Deceleration time (msec) (mean ± SD)

Group 1 (Hypertension)


209.00 ± 23.07

Group 2 (Diabetes)


200.00 ± 18.80

Group 3 (Hypertension + Diabetes)


233.20 ± 24.23

Group 4 (Control)


173.47 ± 24.34

F = 19.346; p < 0.001

Group Comparison (Bonferroni Test) Group

p value

Group 1 vs Group 4


Group 2 vs Group 4


Group 3 vs Group 4


Group 2 vs Group 3


Group 1 vs Group 3


Table 4. Mean Peak Systolic Velocity (Basal Segments) Group

No. of cases

MPSV (Basal) (cm/sec) (mean ± SD)

Group 1 (Hypertension)


6.33 ± 0.93

Group 2 (Diabetes)


6.33 ± 0.42

Group 3 (Hypertension + Diabetes)


5.79 ± 0.49

Group 4 (Control)


7.62 ± 0.74

F = 19.758; p < 0.001

Group Comparison (Bonferroni Test)

MPSV (mid segment) in HT group was 4.72 ± 0.86 cm/sec which was significantly less than in control group in which it was 6.44 ± 0.42 cm/sec (p < 0.001). MPSV in diabetes group was 4.74 ± 0.48 which was significantly less than in control group (p < 0.001). MPSV in HT + diabetes group was 4.49 ± 0.39 cm/sec, which was least in all groups and was significantly less than control group (p < 0.001). While MPSV in HT + diabetes group was not significantly different than HT or DM group. E’ (mid segment) in HT group was 4.85 ± 0.67 cm/sec which was significantly less in control group in which it was 6.30 ± 0.41 cm/sec (p < 0.001). E’ (mid) in diabetes group was 5.22 ± 0.58 cm/ sec, which was significantly less than control group (p < 0.001). E’ (mid) in HT + DM group was


p value

Group 1 vs Group 4


Table 5. Mean Peak Early Myocardial Diastolic Velocity E’/Late Myocardial Diastolic Velocity A’

Group 2 vs Group 4



Group 3 vs Group 4


Group 2 vs Group 3


Group 1 vs Group 3


comparing with control in which it was 7.64 ± 1.01 cm/sec, it was significantly decreased (p < 0.001). E’ in DM group was 6.63 ± 0.38 cm/sec as comparing with control it was also decreased (p < 0.001). E’ in HT + diabetes group was 4.79 ± 0.61 cm/sec which was least in all study groups and was significantly less than control (p < 0.001). In both HT and diabetes groups E’ was significantly less than control while E’ was least in HT + diabetes group. 290

In HT group E’/A’ was 0.90 ± 0.18 while in control group E’/A’ was 1.21 ± 0.16 on comparison, E’/A’ was significantly decreased in HT group versus control group (p < 0.001). In diabetes group, E’/A’ was 1.11 ± 0.21 which was not significantly different than control group (p = 1.000). In HT + diabetes group, E’/A’ was 0.76 ± 0.11 which was very significantly less than control group (p < 0.001). On comparing DM group with HT + DM group, E’/A’ was significantly less in combination group (HT + DM) (p < 0.001); while E’/A’ was not significantly different in HT and HT + DM group (p = 0.06) (Table 5).

No. of cases

E’/A’ (Basal) (mean ± SD)

Group 1 (Hypertension)


0.901 ± 0.1857

Group 2 (Diabetes)


1.119 ± 0.2162

Group 3 (Hypertension + Diabetes)


0.761 ± 0.1156

Group 4 (Control)


1.211 ± 0.1663

F = 24.343; p < 0.001

Group Comparison (Bonferroni Test) Group

p value

Group 1 vs Group 4


Group 2 vs Group 4


Group 3 vs Group 4


Group 2 vs Group 3


Group 1 vs Group 3


Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Clinical Study 3.77 ± 0.55 cm/sec, which was significantly less than control group (p = 0.001). On comparing HT + DM group with DM or HT, velocities were significantly less in HT + DM group (p < 0.001). E’/A’ (mid segment) was 0.89 ± 0.19 in HT group which was significantly less than control group in which it was 1.15 ± 0.15 (p < 0.001). E’/A’ (mid) was 1.09 ± 0.20 in DM group which was not significantly different than control group (p = 1.000). E’/A’ in HT + DM group was 0.77 ± 0.11, which was significantly less than control group (p < 0.001). E’/A’ in HT + DM group was significantly less than DM group (p < 0.001) while E’/A’ was insignificantly different in HT and HT + DM group (p = 0.15). Discussion The present study represents assessment of LV diastolic filling in adults having DM with or without HT in a population-based sample of middle-aged and older adults. The present study reveals association between DM and diastolic filling that is independent of age, BP and systolic function. The filling pattern in hypertensive is compared to controls and impact of HT + DM as LV filling pattern is also studied. In our study, LV mass index in diabetes group (95.50 ± 7.5 gm/m2) was not significantly different than controls (98.60 ± 8.63 gm/m2). Kosmala et al3 in their study showed similar finding. In hypertensive group, LV mass index was 145.55 ± 8.73 gm/m2 and significantly more than control and was greatest in HT + DM group. Kosmala et al3 in their study showed similar findings. Liu4 in 2001, showed similar findings that LV mass index was indifferent in control versus DM group and greatest increase was in HT + DM group, while in HT group, LV mass index was increased to moderate range.

Study showed similar findings with HT group and HT + DM group but they showed by DT and E’/A’ ratio significant impairment in LV relaxation in DM group their findings might be different in DM group from our study as they included patients mainly with poor glycemic control and with microvascular complication. Shapiro et al5 proved the association of diastolic filling abnormalities with DM. They was also concluded that the abnormality of relaxation was more severe in the combined DM + HT group, suggesting additive deleterious effect on active LV relaxation in early diastole when both these conditions are present. MPSV was comparable in HT and DM group but was significantly less than control group. MPSV was least in hypertensive + diabetic combined group indicating additive effect of each on impaired ventricular relaxation. Kosmala et al3 in their study in 2004, also found that longitudinal systolic myocardial function evidenced by decreased MPSV was reduced in all the patient groups being most severely affected in the DM + HT group. Velocities in the mid-segments were again reduced in DM group and HT group as compared with control and velocities were least in HT + DM group. Velocities in each group was less in mid segment as compared to basal segment. Similar findings was established by Kosmala et al3 in 2004. E’ is reduced in both HT and DM group as compared with control and was least in HT + DM group, concluding that diastolic dysfunction is present in DM group, HT group and HT + DM combination group, with diastolic dysfunction being most severe in combination group. Kosmala et al3 in their study confirmed same findings.

In our study, E’/A’ ratio was comparable in DM and control group. E’/A’ ratio was less in HT group and was least in HT + DM group. Kosmola et al3 in their study showed similar trend.

Gul et al6 proposed that both septal E’ and lateral E’ velocities were significantly lower in diabetes than in control group. E’ in mid-segments reveals similar trend in all groups but overall velocities in mid- segments were less than basal segments in all groups.

DT was insignificantly different between control and DM group and DT was increased significantly in HT group and was maximal in HT + DM group. Kosmola et al3 in their study found similar comparable findings. Liu et al4 in their Strong Heart

E’/A’ ratio was not significantly different in control group and diabetes group. E’/A’ ratio was reduced in HT group significantly and was least in combination (HT and DM) group. Similar findings were proposed by Kosmala et al3 in 2004.

Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011


Clinical Study The present study demonstrates the absence of significant difference in LV structure and function between DM group and healthy control subjects when analyzed by conventional Doppler methods as transmitral inflow pattern and DT but when analyzed with tissue Doppler as MPSV and Eâ&#x20AC;&#x2122; there is significant impairment in LV function in DM as compared to controls. DM is associated in most cases with HT, obesity and high prevalence of coronary artery disease and microangiopathic complications, which are known to impair LV diastolic function. Nevertheless, some studies have demonstrated an impairment in LV diastolic function in diabetic patients independent of HT and coronary artery disease, suggesting that this abnormality could be an early manifestation of a specific diabetic cardiomyopathy.7 Most of these studies have been performed in small sample sized population. While some studies reported significant abnormalities of diastolic function (Annonu AK et al),8 others demonstrated no differences from healthy control subjects.9 By the way, evidence of an intrinsic diastolic dysfunction in DM remains questionable. Tissue Doppler imaging (TDI) is a new ultrasound method that records regional systolic and diastolic velocities with in the myocardium. A good correlation has been found between the initial diastolic peak velocity and ventricular relaxation measurements obtained through invasive methods.10 Previous studies have shown that the early diastolic velocity recorded at the mitral annulus is reduced in patients with relaxation abnormality and is sensitive to change not identified by conventional mitral Doppler index (Severino S et al).11 To date, only few studies have used this new Doppler method in the assessment of subclinical myocardial disease in DM.12 Fang et al12 have recently reported that regional diastolic myocardial function (peak early diastolic velocity obtained at the septal annulus) is significantly reduced in a population of diabetic patients compared with controls. The observation that DM was associated with abnormal LV diastolic filling suggests that hyperglycemia may contribute to the pathogenetic mechanism of abnormal ventricular relaxation in DM. Interstitial accumulation of advanced glycated end products (AGEs) which 292

include collagen, elastin and other connective tissue proteins as well as fibrosis in the myocardium have been reported in human diabetic heart which can increase end diastolic stiffness as well as LV mass. Quantization of fibrosis in hypertensive, diabetes and hypertensive diabetic heart has revealed the lowest proportion in hypertensive hearts and the highest in hypertensive diabetic hearts with diabetic hearts in the mid range.13 Another factor linking DM and abnormal LV relaxation may be the presence of coronary artery disease, although that may be the etiology in some cases. All of our subjects had negative stress ECG and normal wall motion with ejection fraction >55%. Our study confirms and substantially extends previous findings by revealing additional cardiovascular abnormalities associated with DM. DM is associated with abnormal LV relaxation similar to the well-known impaired relaxation associated with HT. Abnormal LV relaxation seen in DM independent of other factors, may contribute to the increase incidence of congestive heart failure despite normal LV ejection fraction, thereby being another cause of clinical cardiovascular morbidity. In addition, reduced mitral Eâ&#x20AC;&#x2122;/Aâ&#x20AC;&#x2122; ratio is independently associated with increased all cause mortality as well as cardiovascular morbidity.14 Abnormal LV filling pattern suggests that degree of hyperglycemia may play a role in the pathogenesis of diastolic dysfunction in DM. A prospective trial is needed to determine whether better glycemic control will improve LV structure and function in adults with DM. Conclusion Conventional Doppler can detect diastolic dysfunction in HT and HT + diabetes group while in diabetes group conventional Doppler was not able to detect diastolic dysfunction. While tissue Doppler imaging was able to detect LV diastolic dysfunction in diabetic mellitus, HT and DM + HT group. References 1. Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham Heart Study. JAMA 1979;241(19):2035-8. 2. Ruderman NB, Haudenschild C. Diabetes as an atherogenic factor (review). Prog Cardiovasc Dis 1974;26:373-412. Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Clinical Study 3. Kosmala W, et al. Comparison of left ventricular function by tissue Doppler imaging in patients with diabetes mellitus without systemic hypertension versus diabetic mellitus with systemic hypertension. Am J Cardiol 2004;94(3):395-9.

9. Romanens M, Fankhauser S, Saner B, Saner H. No evidence for systolic or ventricular dysfunction at rest in selected long-term type I diabetes mellitus. Eur 1999;(2):169-75.

4. Liu JE, Palmieri V, Roman MJ, Bella JN, Fabsitz R, Howard BV, et al. The impact of diabetes on left ventricular filling pattern in normotensive and hypertensive adults: the strong Heart Study. J Am Coll Cardiol 2001;37(7):1943-9.

10. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, QuiĹ&#x2C6;ones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997;30(6):1527-33.

5. Shapiro LM. Echocardiographic features of impaired ventricular function in diabetes mellitus. Br Heart J 1982;47(3):439-44. 6. Gul K, Celebi AS, Kacmaz F, Ozcan OC, Ostan I, Berker D, et al. Tissue Doppler imaging must be performed to detect early left ventricular dysfunction in patients with type and diabetes mellitus. Eur J Echocardiogr 2009;10(7):841-6. 7. Raev DC. Which left ventricular function is impaired earlier in the evolution of diabetic cardiomyopathy? An echocardiographic study of young type I diabetic patients. Diabetes Care 1994;17(7):633-9. 8. Annonu AK, Fattah AA, Mokhtar MS, Ghareeb S, Elhendy A. Left ventricular systolic and diastolic functional abnormalities in asymptomatic patients with non-insulin-dependent diabetes mellitus. J Am Soc Echocardiogr 2001;14(9):885-91.

Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Michaud L, diastolic left patients with J Heart Fail

11. Severino S, Caso P, Galderisi M, De Simone L, Petrocelli A, de Divitiis O, et al. Use of pulsed Doppler tissue imaging to assess regional left ventricular diastolic dysfunction in hypertrophic cardiomyopathy. Am J Cardiol 1998;82(11):1394-8. 12. Fang ZY, Yuda S, Anderson V, Short L, Case C, Marwick TH. Echocardiographic detection of early diabetic myocardial disease. J Am Coll Cardiol 2003;41(4): 611-7. 13. Van Hoeven KV, Factor SM. A comparison of the pathological spectrum of hypertensive, diabetic, and hypertensive-diabetic heart disease. Circulation 1990;82(3):848-55. 14. Bella JN, Palmieri V, Roman MJ, et al. Prognostic significance of abnormal peak early to late diastolic filling ratio in middle-aged to elderly American Indians: the Strong Heart Study (abstr). J Am Coll Cardiol 2000;35:293A.





Clinical Review

Peripartum Cardiomyopathy Vijay Garg*, Satyendra Sharma**, Arvind Pancholiaâ&#x20AC; , SB Gawarikar*

Abstract Peripartum cardiomyopathy (PPCM) is characterized by left ventricular dysfunction and symptoms of heart failure (HF) that can arise in the last trimester of pregnancy or upto five months after delivery. Many theories has been proposed as possible etiological factor but none has been proved. While it can affect women of all races, it is more prevalent in some countries. Echocardiography is gold standard for diagnosis. Angiotensin-converting enzyme inhibitors (ACEIs) are the first-line therapy after delivery. Newer treatment with bromocriptine, pentoxifylline, needs large trials. Key words: Heart failure, cardiomyopathy, pregnancy, postpartum period


eripartum cardiomyopathy (PPCM) is a rare but life-threatening condition that occurs in previously healthy women during peripartum period. It is characterized by left ventricular dysfunction and symptoms of heart failure (HF) that can arise in the last trimester of pregnancy or upto five months after delivery. PPCM is a diagnosis of exclusion, wherein patients have no prior history of heart disease and there are no other known possible causes of HF. Echocardiogram is used to both diagnose and monitor the effectiveness of treatment for PPCM.1-5 PPCM is responsible for overall 4% causes of dilated cardiomyopathy (DCM). Etiology Many nutritional disorders have been suggested as causes, but other than salt overload, none has been validated by epidemiological studies. An increased prevalence of myocarditis has been found in case series and in a small case-control study. Abnormal myocardial biopsy findings were associated with a worse long-term prognosis for recovery. More recent data have found

*Professor **Assistant Professor Dept. of Medicine RD Gardi Medical College, Surasa, Ujjain â&#x20AC;  Head Dept. of Medicine Arihant Hospital and Research Centre, Indore Address for correspondence Dr Vijay Garg Professor, Dept. of Medicine RD Gardi Medical College Agar Road, Surasa, Ujjain - 456 006 (MP)


a similar incidence of myocarditis in women with PPCM, when compared to those with the idiopathic type. However, a study that found myocarditis in 62% of 44 women with PPCM found that the finding did not correlate with survival. Recent studies have found lower levels of selenium in patients with PPCM. Autoantibodies against myocardial proteins have been identified in patients with PPCM but not in those with idiopathic cardiomyopathy. Case reports and anecdotal experience have documented ejection fractions as low as 10-15% in patients with severe pre-eclampsia, with subsequent normalization of echocardiograms within 3-6 months. Pre-eclampsia has been listed as a risk factor, but it may be the cause in some cases. Noncardiogenic pulmonary edema has many causes, all of which must be considered.6 A study in 2005 found that eight of 26 patients had viral etiology. Parvovirus B19, human herpes virus 6, Epstein-Barr virus, and human cytomegalovirus were detected after molecular analysis of myocardial biopsy specimens.7 Other possible etiological factors are recent discovery of an oxidative stress-cathepsin, D-16-kDa, prolactin cascade in experimental and human PPCM, relaxin, immune complexes, cardiac nitric oxide (NO) synthase and cardiac dystrophin. Incidence It is estimated that the incidence of PPCM in the United States is between one in 1,300-4,000 live births.1,8,9 While it can affect women of all races, it is more prevalent in some countries; for example, estimates suggest that PPCM occurs at rates of one in 1,000 live births in South African Bantus, and as Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Clinical Review high as one in 300 in Haiti.9,10 Some studies assert that PPCM may be slightly more prevalent among older women who have had higher numbers of liveborn children and among women of older and younger extremes of childbearing age.8,10 However, one-quarter to one-third of PPCM patients are young women who have given birth for the first time.2,3,9-12 Clinical Presentation Symptoms: Paroxysmal nocturnal dyspnea, dyspnea on exertion, cough, orthopnea, chest pain, abdominal discomfort, palpitation. Signs: Tachypnea, tachycardia, edema, cardiomegaly, gallop rhythm, systolic murmur. Unfortunately, patients and clinicians sometimes dismiss early symptoms because they appear to be typical of normal pregnancy. Delays in diagnosis and treatment of PPCM are associated with increased morbidity and mortality.1,3-5,10,13,14 It is paramount that clinicians hold a high suspicion of PPCM in any perior postpartum patient where unusual or unexplained symptoms or presentations occur.1,3,7,15,16 Criteria for Diagnosis

The following four criteria must be present.  Development of heart failure in the last month of pregnancy, or within five months postpartum  Absence of a determinable cause for cardiac failure  Absence of heart disease before last month of pregnancy  Left ventricular impairment demonstrated on Echo

Differential Diagnosis  Pregnancy-induced hypertension (PIH): However, heart failure associated with PIH represents a diastolic failure versus systolic in PPCM.  Pulmonary embolism: Usually ruled out by CXR. If still suspicious than spiral CT scan is useful. Management Delivery of Fetus

It will reduce the hemodynamic stress. Compensated patients may undergo vaginal delivery with appropriate monitoring. In those with more significant hemodynamic compromise, consideration should be given to elective cesarean with invasive hemodynamic monitoring of the mother. Sequential combined epidural anesthesia is better than conventional epidural or spinal technique or general anesthesia.17 Advantages of a regional technique include: Vasodilation which is beneficial in isolated left ventricular dysfunction, prevention of thromboembolic events and reduced epinephrine and norepinephrine levels. Pharmacotherapy 

Investigations EKG shows sinus tachycardia, nonspecific ST changes and left ventricular hypertrophy. Two-dimensional echocardiogram: Shows dilated cardiomyopathy. Chest X-ray: Cardiomegaly and pulmonary edema Lab: CBC, BNP, TSH, ferritin Cardiac MRI: May be used as a complementary tool for diagnosis of PPCM. It can measure global/or segmental myocardial contraction. If PPCM is persistent after initial therapy, then cardiac catheterization or myocardial biopsy are useful. Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Drugs useful during pregnancy: Diuretics, digoxin, b-blockers, nitrates. Drugs useful in postpartum period: Angiotensinconverting enzyme inhibitor (ACEI)/ARBs (angiotensin receptor blockers), diuretics, digoxin, b-blockers, nitrates. Anticoagulants in PPCM: Risk of thromboembolic complications increases during pregnancy and cardioembolic complications further increased due to dilated chambers, akinetic myocardium and in the presence of atrial fibrillation (AF). So consider anticoagulation in patients with left ventricular ejection fraction (LVEF) <20% and in AF. Immunosuppressive and immunomodulatory therapy: In one retrospective study, six PPCM patients and 11 controls were treated with intravenous immunoglobulins (IVIG). All six patients treated with IVIG (2 g/kg) showed improvement in EF as compared to only 4/11 controls. IVIG markedly reduced the level of inflammatory markers like thioredoxin (All patients had diagnosis of myocarditis and dilated cardiomyopathy).18 But in IMAC trial, IVIG did not show any improvement in outcome. In a series of 18 patients 295

Clinical Review

from John Hopkins treated with prednisolone and azathioprine, resolution was seen in nine of 10 treated patients.19 But in Myocarditis Treatment Trial, immunosuppressives did not prove efficacy. So immunosuppressants are not yet fully proven and they can be considered in patients with proven myocarditis. Viral etiology should be ruled out before starting the immunosuppressive therapy. Bromocriptine: Increased prolactin secretion is considered to have a proapoptotic effect due to expression of cardiac cathepsin-D and based on this concept, inhibitors of prolactin secretion may represent a novel therapy for PPCM but it needs to have a large randomized control trial to prove it. More recently, the use of bromocriptine was successful in preventing left ventricular dysfunction in subsequent pregnancies of women known to have had PPCM.20 A randomized, controlled multicenter trial is going on in Germany to evaluate the efficacy and safety of bromocriptine in PPCM. Cabergoline: It is a strong and long-lasting antagonist of prolactin secretion. Rapid recovery has been seen in a patient of PPCM after use of cabergoline.²¹ Pentoxifylline: In a small prospective study it improved LVSF, and symptoms when added to conventional therapy. Pentoxifylline has been used due to its capacity to reduce production of tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP) and Fas/Apo-1 (a marker of apoptosis), but further studies are needed to clarify its effects. Levosimendan: A calcium-sensitizing drug with additional vasodilating properties, has been successfully used for treatment of a woman with PPCM.²² Cardiac transplantation: Patients with severe HF despite maximal drug therapy need cardiac transplantation to survive. Cardiac transplant patients should be strongly advised against future pregnancies because of increased risk of hypertension, pre-eclampsia and preterm labor.23

How Long to Treat?

Patients with PPCM who recover normal left ventricular systolic function at rest or with low-dose dobutamine can be allowed to taper and then discontinue HF treatment in 6-12 months. 296

Prognosis For those women whose left ventricular function does not recover, mortality estimates range from 10 to 50%. Most deaths occur within three months postpartum. Death is usually caused by: Progressive pump failure, arrhythmias and thromboembolic events.24,25 In an Indian study,13 20 patients of PPCM were followed for 14 months postpartum and several factors for deterioration found: Age >30, high parity, later onset of symptoms following pregnancy and worse echo findings on initial examination. Predictors of recovery: Left ventricular size at the time of presentation is the best predictor of recovery. Marked left ventricular dilatation during systole (>55 mm) is predictor of poor recovery. Activity and follow-up: Women should be encouraged to remain as active as their functional status allows. Aerobic activities and heavy lifting are discouraged for at least the first six months. Breastfeeding is strongly discouraged in more symptomatically limited patients. Left ventricular function assessment by echocardiogram should be repeated at six months postdelivery. Risks of subsequent pregnancies: Opinions widely vary but most experts agree that patients should avoid future pregnancy, if left ventricular dysfunction persists for more than six months. Recommendations for further pregnancies: If left ventricular function has recovered fully than subsequent pregnancy is not contraindicated, although risk is low. If left ventricular function is recovered partially than perform dobutamine stress Echo. If it is normal than no contraindication but if it is abnormal, pregnancy is contraindicated. If left ventricular function is not recovered at all than it is an absolute contraindication for pregnancy. Conclusion PPCM is a rare but life-threatening cardiomyopathy. Echocardiography is the gold standard for the diagnosis. Incidence of major adverse event (MAE) is higher in women with LVEF (≤25%). Diagnosis is often delayed and preceded by MAE. Increased awareness of PPCM is required for early diagnosis and aggressive therapy in an attempt to prevent complications. ACEIs are the first-line therapy after delivery. Anticoagulants are important. Immunoglobulins and, immunosuppressants Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Clinical Review are controversial. Newer treatment with bromocriptine, pentoxifylline, needs large trials. Risk of recurrence should lead to discouragement of further pregnancies even after an apparent recovery. References 1. Pearson GD, Veille JC, Rahimtoola S, Hsia J, Oakley CM, Hosenpud JD, et al. Peripartum cardiomyopathy. National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review. JAMA 2000;283(9):1183-8. 2. Elkayam U, Akhter MW, Singh HS, Khan S, Bitar F, Hameed A, et al. Pregnancy-associated cardiomyopathy: clinical characteristics and a comparison between early and late presentation. Circulation 2005;111(16):2050-5. 3. Sliwa K, Fett J, Elkayam U. Peripartum cardiomyopathy. Lancet 2006;368:687-93. 4. Murali S, Baldisseri MR. Peripartum cardiomyopathy. Crit Care Med 2005;33(10 Suppl):S340-6. 5. Phillips SD, Warnes CA. Peripartum cardiomyopathy: current therapeutic perspectives. Curr Treat Options Cardiovasc Med 2004;6(6):481-8. 6. Billieux MH, Petignat P, Fior A, Mhawech P, Blouin JL, Dahoun S, et al. Pre-eclampsia and peripartum cardiomyopathy in molar pregnancy: clinical implication for maternally imprinted genes. Ultrasound Obstet Gynecol 2004;23(4):398-401. 7. Bultmann BD, Klingel K, Näbauer M, Wallwiener D, Kandolf R. High prevalence of viral genomes and inflammation in peripartum cardiomyopathy. Am J Obstet Gynecol 2005;193(2):363-5. 8. Mielniczuk LM, Williams K, Davis DR, Tang AS, Lemery R, Green MS, et al. Frequency of peripartum cardiomyopathy. Am J Cardiol 2006; 97(12):1765-8. 9. Fett JD, Christie LG, Carraway RD, Murphy JG. Fiveyear prospective study of the incidence and prognosis of peripartum cardiomyopathy at a single institution. Mayo Clin Proc 2005;80(12):1602-6. 10. Desai D, Moodley J, Naidoo D. Peripartum cardiomyopathy: experiences at King Edward VIII Hospital, Durban, South Africa and a review of the literature. Top Doct 1995;25(3):118-23. 11. Sliwa K, Förster O, Libhaber E, Fett J, Sundstrom JB, Hilfiker-Kleiner D, et al. Peripartum cardiomyopathy: inflammatory markers as predictors of outcome in 100 prospectively studied patients. Eur Heart J 2006;27(4): 441-6. 12. Sliwa K, Skudicky D, Bergemann A, Cnady G, Puren A, Sareli P. Peripartum cardiomyopathy: analysis of clinical outcome, left ventricular function, plasma levels of cytokines and Fas/APO-1. J Am Coll Cardiol 2000;35(3):701-5. Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

13. Elkayam U, Tummala PP, Rao K, Akhter MW, Karaalp IS, Wani OR, et al. Maternal and fetal outcomes of subsequent pregnancies in women with peripartum cardiomyopathy. N Engl J Med 2001;344(21):1567-71. 14. Fett JD, Christie LG, Carraway RD, Ansari AA, Sundstrom JB, Murphy JG. Unrecognized peripartum cardiomyopathy in Haitian women. Int J Gynaecol Obstet 2005;90(2): 161-6. 15. Fussell KM, Awad JA, Ware LB. Case of fulminant hepatic failure due to unrecognized peripartum cardiomyopathy. Crit Care Med 2005;33(4):891-3. 16. Lasinska-Kowara M, Dudziak M, Suchorzewska J. Two cases of postpartum cardiomyopathy initially misdiagnosed for pulmonary embolism. Can J Anaesth 2001;48(8): 773-7. 17. Kumari I, Kumar S, Gupta S. Sequential combined spinal epidural anaesthesia for caesarian section in peripartum cardiomyopathy. Indian J Anaesth 2007;51(2):137-9. 18. McNamara DM, Rosenblum WD, Janosko KM, Villaneuva FS, Demetris AJ, Murali S, et al. Intravenous immune globulin in the therapy of myocarditis and acute cardiomyopathy. Circulation 1997;95(11):2476-8. 19. Midei MG, DeMent SH, Feldman AM, Hutchins GM, Baughman KL. Peripartum myocarditis and cardiomyopathy. Circulation 1990;81(3):922-8. 20. Hilfiker-Kleiner D, Kaminsk K, Podewski E, Bonda T, Schafer A, Sliwa K, et al. A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy. Cell 2007;128(3):589-600. 21. de Jong JS, Rieteveld K, van Lochem LT, Bouma BJ. Rapid left ventricular recovery after cabergoline treatment in a patient with peripartum cardiomyopathy. Eur J Heart Fail 2009;11(2):220-2. 22. Successful Use of Lovesimendan in cardiomyopathy. Sidney Benlolo, MD Cecile Lefoll, MD Vahan Katchatouryan,. MD. Didier Payen, MD. phD. and Alexandre Mebazaa, MD. phD From the Department of Anesthesiology and Critical Care Medicine, Hospital Lariboisiere, Assistance pubilique-Hospitaux de paris, Institute Federatif de Recherche 06, Paris, France. 23. Scott JR, Wagoner LE, Olsen SL, Taylor DO, Renlund DG. Pregnancy in heart transplant recipients: management and outcome. Obstet Gynecol 1993;82(3):324-7. 24. O’Connell JB, Costanzo-Nordin MR, Subramanian R, Robinson JA, Walis DE, Scanlon PJ, et al. Peripartum cardiomyopathy: clinical, hemodynamic, histologic and prognostic characteristics. J Am Coll Cardiol 1986;8(2): 52-9. 25. Witlin AG, Mabie WC, Sibai BM. Peripartum cardiomyopathy: an aminous diagnosis. Am J Obstet Gynecol 1997;176(1 pt 1):182-8.


Emedinews Section

From eMedinewS

Carotid Stenting, Surgery Equal for Longâ&#x20AC;&#x201C; term Stroke Prevention

LVADs may Help Certain Patients Recover Heart Function

For carotid stenosis, stenting and surgery are on par with each other for long-term stroke prevention in real-world practice, according to a study published in the Journal of the American College of Cardiology.

WebMD (1/31, Goodman) reported that an implantable pump that assists with the work of a weakened heart may, in rare cases, help some people recover a significant amount of heart function, according to research published the Journal of the American College of Cardiology. The study summarizes international research on recipients of left ventricular assist devices, or LVADs, including 1,092 LVAD patients enrolled in a government-funded registry.

Novel Agent Cuts Stroke in Hard-to-treat Afibrillation In patients with atrial fibrillation who canâ&#x20AC;&#x2122;t take vitamin K antagonist therapy, the experimental anticoagulant apixaban is superior to aspirin for preventing stroke or systemic embolism, final results of the AVERROES trial confirmed. New Guidelines do not Recommend Routine Screening for Carotid Stenosis New practice guidelines from the American Stroke Association/American Heart Association, the American College of Cardiology and other professional groups do not recommend routine screening for carotid artery stenosis in asymptomatic patients who have no signs of or risk factors for atherosclerosis. According to the guidelines, in asymptomatic patients with peripheral arterial disease, coronary artery disease or an atherosclerotic aortic aneurysm, or for those who have at least two risk factors for stroke, Duplex ultrasonography might be considered. The guidelines have been published at the same time in the Journal of the American College of Cardiology, Circulation and Stroke. Standard Clopidogrel Loading-dose Good for Asian STEMI Patients Undergoing PCI According to a study reported in the January 18 online issue of the American Heart Journal, a high loading dose of clopidogrel (600 mg) is unnecessary in Asian patients with ST-segment elevation myocardial infarction (STEMI) who are undergoing primary percutaneous intervention (PCI). The standard 300-mg dose is just as safe and effective for these patients. 298

What is the Role of Spirometry in Diagnosis of Asthma? While spirometry offers objective and sensitive criteria, by no means are these specific to a diagnosis of asthma. Spirometric findings are thus, to be interpreted in concert with the clinical setting. In children below 7-8 years, spirometry is difficult to perform. It is technician-dependent and reproducibility of test results is poor. Spirometric results only reflect the lung function on the day of testing and may thus be normal since asthma is a dynamic condition. The procedure is expensive and the equipment is not widely available. For all these reasons, the consensus group of Indian Academy of Pediatrics feels that spirometry has a very restricted role in the diagnosis of asthma in the Indian setting. However, in a typical case, an obstructive defect is present in the form of normal forced vital capacity (FVC), reduced FEV1, and reduced forced expiratory flow more than 25-75% of the FVC (FEF25-75%) The flow-volume loop can be concave. Documentation of reversibility of airway obstruction after bronchodilator therapy is central to the definition of asthma. FEF25-75% is a sensitive indicator of obstruction and may be the only abnormality in a child with mild disease.

Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

emedinews section Seniors’ Heart Health can be Improved with Exercise Good news for seniors: Heart health can be improved even at a late age. A study conducted at the University of British Columbia showed that seniors with high blood cholesterol, type 2 diabetes and high cholesterol were able to improve the stiffness in their arteries by 20% after three months. Adults between the ages of 65 and 83 were broken into two groups, one did no exercise and the other rode stationary bicycles and performed vigorous exercise on treadmills three days a week. Seniors reported feeling better and cutting back on medication. Gastric Bypass Surgery may Stabilize, Partially Reverse Obesity-related Heart Abnormalities Severely obese patients who have gastric bypass surgery (GBS) can expect obesity-related heart abnormalities to stabilize or partially reverse, according to research published in the Journal of the American College of Cardiology.

Abstract of the Day RESPeRATE: Nonpharmacological Treatment of Hypertension

Systemic hypertension has been well-documented as a major risk factor for premature cardiovascular morbidity and mortality. Reduction of high blood pressure (BP) by nonpharmacological means is widely recommended, either as a primary prevention therapy or as an adjunctive treatment with antihypertensive drugs. RESPeRATE is a commercially available electronic device that presents a novel nonpharmacological approach to the treatment of hypertension. RESPeRATEguided slow-paced breathing aimed at achieving a respiratory frequency of <10 breaths per minute has been shown, in multiple studies, to reduce BP in hypertensive individuals by improving the autonomic balance through respiratory control. Sharma M, Frishman WH, Gandhi K. Cardiol Rev 2011;19(2):47-51.

Traffic Noise may Increase Stroke Risk in Older Individuals Many people who live in cities or near highways are accustomed to a lullaby of cars whizzing by, but that noise may put them at increased risk of stroke, according to a study published in the European Heart Journal. Stress-reduction Therapy may Help Heart Disease Patients Reducing anxiety decreases heart attacks, deaths and other cardiovascular events, research suggests. A stress management program based on cognitive behavioral therapy may reduce the risk of heart attack, stroke and death in patients with heart disease, Swedish researchers report. About 30% of heart attacks may be linked to ‘psychosocial factors,’ including chronic stressors such as poverty or emotional problems, such as depression and hostility, the authors note in the Jan. 24 issue of the Archives of Internal Medicine.

Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

International Medical Science Academy (IMSA) Update Atrial Fibrillation: Lenient versus Strict Rate Control

A randomized trial in patients with atrial fibrillation compared a lenient rate control strategy (resting heart rate <110 beats per minute) with a strict rate-control strategy (resting heart rate <80 beats per minute and heart rate during moderate exercise <110 beats per minute). There was no significant difference in the primary composite outcome at three years, but nearly nine times as many visits were required to achieve the strict rate control targets.


Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767). Asian Journal of Clinical Cardiology strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so. The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript. Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper. Covering letter -

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The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper. Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors. Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

Manuscript - Three complete sets of the manuscript should be submitted and preferably with a CD; typed double spaced throughout (including references, tables and legends to figures).



The manuscript should be arranged as follow: Covering letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, Results, Discussion, References, Tables, Legends to Figures and Figures.


All pages should be numbered consecutively beginning with the title page.

departments and institutions where the work was performed, name of the corresponding authors, acknowledgment of financial support and abbreviations used. - The title should be of no more than 80 characters and should represent the major theme of the manuscript. A subtitle can be added if necessary. - A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included. - The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page. - A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text. Summary - The summary of not more than 200 words. It must convey the essential features of the paper. - It should not contain abbreviations, footnotes or references. Introduction - The introduction should state why the study was carried out and what were its specific aims/objectives. Methods - These should be described in sufficient detail to permit evaluation and duplication of the work by others. - Ethical guidelines followed by the investigations should be described. Statistics The following information should be given: - The statistical universe i.e., the population from which the sample for the study is selected. - Method of selecting the sample (cases, subjects, etc. from the statistical universe). - Method of allocating the subjects into different groups. - Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques.

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors.


Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the


Confidence intervals for the measurements should be provided wherever appropriate.

Results These should be concise and include only the tables and figures necessary to enhance the understanding of the text.

Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

Discussion -

This should consist of a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g. practicality and cost.

References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses). At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution. Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes. Q. J. Expt. Physiol. 1955;40:89-111.

Figures - Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat. - All photomicrographs should indicate the magnification of the print. - Special features should be indicated by arrows or letters which contrast with the background. - The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen. - Color illustrations will be accepted if they make a contribution to the understanding of the article. -

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Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as ‘Fig.’. Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected summary, etc.)_______________________________ 2. Total number of pages ________________________ 3. Number of tables ____________________________ 4. Number of figures ___________________________ 5. Special requests _____________________________


6. Suggestions for reviewers (name and postal address)

Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

Indian 1.____________Foreign 1._ _______________


2._ _______________

Articles in Books


3._ _______________

Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.


4._ _______________

Tables -

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Legends - These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text. -

The legend must include enough information to permit interpretation of the figure without reference to the text.

Asian Journal of Clinical Cardiology, Vol. 13, No. 10, February 2011

7. All authors’ signatures________________________ 8. Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

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