- Email: [email protected]
Risk Factors for Coronary Artery Disease in Indians
Original Article
Risk Factors for Coronary Artery Disease in Indians Col DS Jaswal*, Col TK Saha+, Col N Aggarwal# Abstract Background: A case control study was carried out to study the emerging risk factors for coronary artery disease in Indians. Methods: The diagnosis of coronary artery disease was based on correlation of clinical, biochemical, electrocardiography, echocardiography, treadmill testing and coronary arteriography findings. The study comprised 100 cases of coronary artery disease (acute coronary syndrome and chronic coronary artery disease) and 100 controls in two tertiary care service hospitals. The subjects were evaluated for total plasma homocysteine, insulin, C-reactive protein (CRP), lipoprotein fibrinogen and antichlamydial anti-bodies. Result: Male to female ratio was 10:1 in study group with similar predominance of males in controls. Mean age of the cases was 47 years (range 25-59 years) and that of controls was 43 years (range 23-56 years). 64% cases had acute coronary syndrome and 34% had chronic coronary artery disease. In the coronary artery disease population, 76% cases had hyperhomocyteinemia, 9% hyperinsulinaemia, 11% abnormal CRP values, 23% abnormal lipoprotein (a) levels, 40% IgG anti-chlamydial anti-bodies and only 11% had Ig M anti-chlamydial antibodies. In the control population, 72% had hyperhomocystinaemia and 6% hyperinsulinaemia while 23 % and 9% controls had IgG and IgM anti chlamydial antibodies respectively. In control group 19% cases had abnormal lipoprotein(a) levels and only 2% had abnormal C reactive protein values. Significant correlation of CAD was seen with CRP values and Ig G anti-chlamydial antibodies. Both the study group and controls had higher homocysteine levels than that observed in some Indian and Western studies. Conclusion: High C reactive protein levels and Ig G anti-chlamydial antibodies are associated with coronary artery disease in Indians. Insulin, lipoprotein A, fibrinogen, lgM anti-chlamydial antibodies and higher levels of total plasma homocysteine have no significant association with coronary artery disease. MJAFI 2008; 64 : 317-319 Key Words: Emerging risk factors; Coronary artery disease
Introduction oronary artery disease (CAD) is the largest killer in developed countries and is rapidly becoming one in developing countries [1-4]. Conventional risk factors do not explain all cases of CAD in the Indian population. The increasing frequency of CAD in the young (CADY) suggests the possible role of non-conventional risk factors. The new risk factors implicated in CAD include thrombogenic factors, insulin resistance, lipid disorders, infection, inflammation and psycho-social factors. There is paucity of data on emerging risk factors for CAD in Indians. The present study was undertaken to evaluate the same in the two subsets of CAD patients viz acute coronary syndrome (ACS) and chronic CAD.
C
Material and Methods The study was carried out in two tertiary care hospitals over a period of two years, involving a total of 100 cases (both ACS and chronic CAD). Equal number of controls were enrolled from those found normal on evaluation for CAD or admitted for management of unrelated disabilities. An informed consent was taken from all the subjects for study.
History, physical examination, electrocardiography (ECG), chest radiograph, haemogram and metabolic profile were done in all cases. Echocardiography and treadmill test (TMT) were done as indicated. Coronary arteriography (CART) was done in suspected cases of acute coronary syndromes. The grading of CAD was based on standard criteria of American Heart Association [5]. Patients with renal disease, liver disease, diabetes mellitus, respiratory or heart failure, and those on drugs influencing glucose or lipid metabolism were excluded. Plasma total homocysteine (tHcy), lipoprotein (a) [Lp (a)], C reactive protein (CRP) and insulin levels were measured. Antichlamydial antibodies were determined by enzyme-linked immunosorbent assay (ELISA) technique. Fibrinogen was estimated by clot assay method (Spin React SA kit). Student’s ‘t’ test was used to compare continuous variables. One way analysis of variance (ANOVA) was used for comparison between the subgroups. Categorical variables were compared using Chi square test. Results The mean age of the patients was 47 years ( range 25-59) and that of controls 43 years (range 23-56) . Male: female ratio
*Senior Advisor (Medicine), Military Hospital, Meerut. +Senior Advisor (Pathology & Biochemistry),Base Hospital, Delhi Cantt. #Senior Advisor (Medicine & Cardiology), INHS Asvini, Mumbai. Received : 24.10.2005; Accepted : 18.10.2007
E-mail : [email protected]
318
Jaswal, Saha and Aggarwal
was 10:1 in study group with similar predominance in controls. The subjects were a mix of middle and upper middle socioeconomic strata. 64% cases had ACS and the rest chronic CAD. 60%, 20% and 12% cases had single, double and triplevessel disease respectively. In 8% cases CART was noncontributory. The results of total plasma homocysteine (tHcy), insulin, CRP, Lp (a), fibrinogen and anti-chlamydial antibodies are shown in Fig.1. Mean tHcy values were significantly higher in study group than controls (34.14μ mol/L vs 24.85μmol/L) though the proportions having abnormal tHcy did not differ significantly 76% vs 72% (p>0.05). The insulin levels did not differ significantly in study group and controls (p> 0.05). Abnormal CRP values were seen in 11% cases and 2% controls (p< 0.05). The CRP levels did not correlate with the extent of disease. Lp (a) values were abnormal in 23% cases and 19% controls (p> 0.05). Higher levels of Lp (a) were associated with multiple vessel disease. 21% cases and 12% controls had abnormal fibrinogen values (p> 0.05). Their levels did not correlate with extent of disease. The Ig G anti- chlamydial antibodies levels were significantly higher in study group whereas no difference was seen for Ig M anti- chlamydial antibodies (Table 1).
Discussion The incidence of CAD in younger age group has been rising in India [6]. Majority of CAD cases lack conventional risk factors while those with conventional risk factors do not develop significant CAD. A strong graded association has been found between plasma total homocysteine (tHcy) levels and overall Table 1 Prevalence of emerging risk factors for CAD Variables tHcy(>15μmol/L) Insulin (>25mU/L) CRP (>8 μg/mL) Lp(a) (>30mg/dL) Fibrinogen (>350mg/dL) Anti-chlamydial IgG + Anti-chlamydial IgM +
ACS (% of cases)
Chronic CAD (% of cases)
‘p’ value
51 9 5 18 14 28 5
24 0 6 7 7 12 6
>0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
Fig. 1 : Prevalence of emerging risk factors for CAD
mortality in patients with angiographically confirmed CAD but a causal relationship has not been proven between tHcy and mortality [7]. Conflicting reports exist about association of tHcy with CAD [8-14]. The present study found no correlation of CAD with tHcy, though it shows higher levels of tHcy in Indian population. This may be due to genetic differences and/or nutritional deficiencies of Vit B12, folic acid and Vit B6. Similar findings have been reported by other Indian workers [8,9,13]. In young patients from North India manifesting with CAD, a high prevalence of metabolic syndrome (hypertension, obesity, impaired glucose tolerance (IGT), hyperinsulinaemia and dyslipidaemia) has been reported [15]. Insulin resistance is also reported in the middleaged or elderly CAD cases [16]. The present study showed no significant difference in fasting insulin levels in CAD cases and controls in contrast to the findings of Misra et al [17]. Our study documented raised levels of CRP which have been directly correlated with incidence of coronary events, suggesting the presence of an inflammatory process in unstable CAD [18,19]. Persistent inflammation in atherosclerotic coronary artery related probably to infection, oxidised lipid, free radicals or products of reninangiotensin system (RAS) is considered an important factor for CAD. Some viruses [cytomegalovirus (CMV), herpes simplex virus (HSV)] and Chlamydia have been reported in atherosclerotic region though the issue is not yet settled [20]. We found IgG anti-chlamydial antibody in a significant number of patients of CAD suggesting a link between the two. Lp (a) has been implicated in pathogenesis of CAD as it increases the risk of thrombosis and atherosclerosis by competing with plasminogen for cell surface binding, thereby reducing the formation of endogenous tissue plasminogen activator [21,22]. In contrast to the study by Vasisht et al [23], this study found no association between Lp(a) and CAD. Some workers [18,19,24] have documented increased incidence of acute coronary syndromes associated with higher baseline concentrations of fibrinogen, however we could not show such association. Psycho-social factors such as
Fig. 2 : Prevalence of some new emerging risk factors in acute coronary syndrome and chronic CAD MJAFI, Vol. 64, No. 4, 2008
Emerging Risk Factors for Coronary Artery Disease
stress, type A personality, depression and hostility have emerged as significant risk factors for CAD. They probably act via neuro - endocrine mechanisms, vasospasm and non-compliance with therapy [25]. To conclude we found an association between coronary artery disease and raised levels of serum CRP and Ig G anti-chlamydial antibodies. Acknowledgements The authors are grateful to Col AT Kalghatgi, Senior Advisor (Pathology), Col DK Mishra, Senior Advisor (Pathology & Haematology) and Mr DR Basannar (Scientist D) for their assistance. Conflicts of Interest This study has been funded by research grants from the O/o DGAFMS. Intellectual Contribution of Author Study Conceptt : Col DS Jaswal, Col N Aggarwal, Col TK Saha Drafting & Manuscript Revision : Col DS Jaswal, Col N Aggarwal, Col TK Saha Study Supervision : Col DS Jaswal, Col N Aggarwal
References 1. Gupta R, Prakash H, Majumdar S, Sharma S, Gupta VP. Prevalence of coronary heart disease and coronary risk factors in an urban population of Rajasthan. Indian Heart J 1995; 47: 331-8. 2. World Health Report 2002.Reducing Risk Promoting Healthy Life. Geneva WHO 2002. 3. AHA Statistical Fact Sheet. International Cardiovascular Disease Statistics. American Heart Association, 2003. 4. Gupta R, Gupta VP. Meta-analysis of coronary heart disease prevalence in India. Indian Heart J 1996; 48: 241-5.
319 11. Majumdar S, Kumar S, Banerjee S, et al. Serum homocysteine level as a risk factor for premature CAD amongst Indians.(Abstract) Indian Heart J 2001; 53 : 565. 12. Puri A, Gupta OK, Dwivedi RN, et al. Plasma homocysteine as a coronary risk factor in young hyperlipidemic patients. (Abstract) Indian Heart J 2001; 53: 568. 13. Deepa R, Velmurugan K, Saravanan G, Karkuzhali K, Dwarakanath V, Mohan V. Absence of association between serum homocysteine levels and coronary artery disease in South Indian males. Indian Heart J 2001; 53: 44-7. 14. Snehalatha C, Ramachandran A, Satyavani K, Sivasankari S, Sathyamurthy I, Viswanathan V. Plasma homocysteine concentration and coronary artery disease in Asian Indians. J Assoc Physicians India 2002; 50: 1229-31. 15. Misra A, Reddy RB, Reddy KS, Mohan A, Bajaj JS. Clustering of impaired glucose tolerance, hyperinsulinemia and dyslipidemia in young North Indian patients with coronary heart disease : A preliminary case – control study. Indian Heart J 1999; 51 : 275-89. 16. Reaven GM, Chen YD. Insulin resistance, its consequences and coronary heart disease. Must we choose one culprit ? Circulation 1996; 93 : 1780-3. 17. Misra A, Shukla P, Reddy KS, Lall SB, Peshin SS, Pandey RM. Serum insulin levels in non-obese, non-diabetic Asian Indians with acute coronary and non-coronary events. Indian Heart J 2000; 52:280-4. 18. Montalescot G, Philippe F, Ankri A, et al. Early increase of von Willebrand factor predicts adverse outcome in unstable coronary artery disease: Beneficial effects of Enoxaparin. Circulation 1998; 98 : 294-9. 19. Thompson SG, Kienast J, Pyke SDM, Haverkate F, Jurgen CW van de Loo. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332:635-41.
Scanlon PJ, Faxon DP, Audet A, et al. ACC/AHA guidelines for coronary angiography: Executive summary & recommendations. Circulation 1999; 99: 2345-57.
20. Mehta JL, Saldeen TGP, Rand K. Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary heart disease. J Am Coll Cardiol 1998; 31:1217-25.
6. Siwach SB, Singh H, Sharma D, Katyal VK. Profile of young acute myocardial infarction in Haryana. J Assoc Physicians India 1998; 46: 474-9.
21. Stein JH, Rosenson RS. Lipoprotein(a) excess and coronary heart disease. Arch Intern Med 1997; 157:1170-6.
5.
7. Goel PK, Bharati BB, Pandey CM, et al. A tertiary care hospitalbased study of conventional risk factors including lipid profile in proven coronary artery disease. Indian Heart J 2003; 55: 234-40.
22. Isser HS, Puri VK, Narain VS, Saran RK, Dwivedi SK, Singh S. Lipoprotein(a) and lipid levels in young patients with myocardial infarction and their first degree relatives. Indian Heart J 2001; 53:463-6.
8. Chacko KA. Plasma homocysteine levels in patients with coronary heart disease. Indian Heart J 1998; 50:295-9.
23. Vasisht S, Wasir HS, Srivastava LM. Association between incidence of lipoprotein (a) and coronary heart disease. Indian Heart J 1992; 44: 223-6.
9. Gheye S, Lakshmi AV, Krishna TP, Krishnaswamy K. Fibrinogen and homocysteine levels in coronary artery disease. Indian Heart J 1999; 51: 499-502.
24. Jose J, Selvakumar D, Selvakumar R, Kanagasapabathy AS, Jeyaseelan L. Plasma fibrinogen – An independent risk factor for ischaemic heart disease. Indian Heart J 1998; 50 : 45-8.
10. Chambers JC, Oheid OA, Refsum H, et al. Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian Asian and European men. Lancet 2000; 385:523-7.
25. Ornish D, Scherwitz LW, Billings JH, et al. Intensive life style changes for reversal of coronary heart disease. JAMA 1998; 280: 2001-7.
MJAFI, Vol. 64, No. 4, 2008
Risk Factors for Coronary Artery Disease in Indians Col DS Jaswal*, Col TK Saha+, Col N Aggarwal# Abstract Background: A case control study was carried out to study the emerging risk factors for coronary artery disease in Indians. Methods: The diagnosis of coronary artery disease was based on correlation of clinical, biochemical, electrocardiography, echocardiography, treadmill testing and coronary arteriography findings. The study comprised 100 cases of coronary artery disease (acute coronary syndrome and chronic coronary artery disease) and 100 controls in two tertiary care service hospitals. The subjects were evaluated for total plasma homocysteine, insulin, C-reactive protein (CRP), lipoprotein fibrinogen and antichlamydial anti-bodies. Result: Male to female ratio was 10:1 in study group with similar predominance of males in controls. Mean age of the cases was 47 years (range 25-59 years) and that of controls was 43 years (range 23-56 years). 64% cases had acute coronary syndrome and 34% had chronic coronary artery disease. In the coronary artery disease population, 76% cases had hyperhomocyteinemia, 9% hyperinsulinaemia, 11% abnormal CRP values, 23% abnormal lipoprotein (a) levels, 40% IgG anti-chlamydial anti-bodies and only 11% had Ig M anti-chlamydial antibodies. In the control population, 72% had hyperhomocystinaemia and 6% hyperinsulinaemia while 23 % and 9% controls had IgG and IgM anti chlamydial antibodies respectively. In control group 19% cases had abnormal lipoprotein(a) levels and only 2% had abnormal C reactive protein values. Significant correlation of CAD was seen with CRP values and Ig G anti-chlamydial antibodies. Both the study group and controls had higher homocysteine levels than that observed in some Indian and Western studies. Conclusion: High C reactive protein levels and Ig G anti-chlamydial antibodies are associated with coronary artery disease in Indians. Insulin, lipoprotein A, fibrinogen, lgM anti-chlamydial antibodies and higher levels of total plasma homocysteine have no significant association with coronary artery disease. MJAFI 2008; 64 : 317-319 Key Words: Emerging risk factors; Coronary artery disease
Introduction oronary artery disease (CAD) is the largest killer in developed countries and is rapidly becoming one in developing countries [1-4]. Conventional risk factors do not explain all cases of CAD in the Indian population. The increasing frequency of CAD in the young (CADY) suggests the possible role of non-conventional risk factors. The new risk factors implicated in CAD include thrombogenic factors, insulin resistance, lipid disorders, infection, inflammation and psycho-social factors. There is paucity of data on emerging risk factors for CAD in Indians. The present study was undertaken to evaluate the same in the two subsets of CAD patients viz acute coronary syndrome (ACS) and chronic CAD.
C
Material and Methods The study was carried out in two tertiary care hospitals over a period of two years, involving a total of 100 cases (both ACS and chronic CAD). Equal number of controls were enrolled from those found normal on evaluation for CAD or admitted for management of unrelated disabilities. An informed consent was taken from all the subjects for study.
History, physical examination, electrocardiography (ECG), chest radiograph, haemogram and metabolic profile were done in all cases. Echocardiography and treadmill test (TMT) were done as indicated. Coronary arteriography (CART) was done in suspected cases of acute coronary syndromes. The grading of CAD was based on standard criteria of American Heart Association [5]. Patients with renal disease, liver disease, diabetes mellitus, respiratory or heart failure, and those on drugs influencing glucose or lipid metabolism were excluded. Plasma total homocysteine (tHcy), lipoprotein (a) [Lp (a)], C reactive protein (CRP) and insulin levels were measured. Antichlamydial antibodies were determined by enzyme-linked immunosorbent assay (ELISA) technique. Fibrinogen was estimated by clot assay method (Spin React SA kit). Student’s ‘t’ test was used to compare continuous variables. One way analysis of variance (ANOVA) was used for comparison between the subgroups. Categorical variables were compared using Chi square test. Results The mean age of the patients was 47 years ( range 25-59) and that of controls 43 years (range 23-56) . Male: female ratio
*Senior Advisor (Medicine), Military Hospital, Meerut. +Senior Advisor (Pathology & Biochemistry),Base Hospital, Delhi Cantt. #Senior Advisor (Medicine & Cardiology), INHS Asvini, Mumbai. Received : 24.10.2005; Accepted : 18.10.2007
E-mail : [email protected]
318
Jaswal, Saha and Aggarwal
was 10:1 in study group with similar predominance in controls. The subjects were a mix of middle and upper middle socioeconomic strata. 64% cases had ACS and the rest chronic CAD. 60%, 20% and 12% cases had single, double and triplevessel disease respectively. In 8% cases CART was noncontributory. The results of total plasma homocysteine (tHcy), insulin, CRP, Lp (a), fibrinogen and anti-chlamydial antibodies are shown in Fig.1. Mean tHcy values were significantly higher in study group than controls (34.14μ mol/L vs 24.85μmol/L) though the proportions having abnormal tHcy did not differ significantly 76% vs 72% (p>0.05). The insulin levels did not differ significantly in study group and controls (p> 0.05). Abnormal CRP values were seen in 11% cases and 2% controls (p< 0.05). The CRP levels did not correlate with the extent of disease. Lp (a) values were abnormal in 23% cases and 19% controls (p> 0.05). Higher levels of Lp (a) were associated with multiple vessel disease. 21% cases and 12% controls had abnormal fibrinogen values (p> 0.05). Their levels did not correlate with extent of disease. The Ig G anti- chlamydial antibodies levels were significantly higher in study group whereas no difference was seen for Ig M anti- chlamydial antibodies (Table 1).
Discussion The incidence of CAD in younger age group has been rising in India [6]. Majority of CAD cases lack conventional risk factors while those with conventional risk factors do not develop significant CAD. A strong graded association has been found between plasma total homocysteine (tHcy) levels and overall Table 1 Prevalence of emerging risk factors for CAD Variables tHcy(>15μmol/L) Insulin (>25mU/L) CRP (>8 μg/mL) Lp(a) (>30mg/dL) Fibrinogen (>350mg/dL) Anti-chlamydial IgG + Anti-chlamydial IgM +
ACS (% of cases)
Chronic CAD (% of cases)
‘p’ value
51 9 5 18 14 28 5
24 0 6 7 7 12 6
>0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
Fig. 1 : Prevalence of emerging risk factors for CAD
mortality in patients with angiographically confirmed CAD but a causal relationship has not been proven between tHcy and mortality [7]. Conflicting reports exist about association of tHcy with CAD [8-14]. The present study found no correlation of CAD with tHcy, though it shows higher levels of tHcy in Indian population. This may be due to genetic differences and/or nutritional deficiencies of Vit B12, folic acid and Vit B6. Similar findings have been reported by other Indian workers [8,9,13]. In young patients from North India manifesting with CAD, a high prevalence of metabolic syndrome (hypertension, obesity, impaired glucose tolerance (IGT), hyperinsulinaemia and dyslipidaemia) has been reported [15]. Insulin resistance is also reported in the middleaged or elderly CAD cases [16]. The present study showed no significant difference in fasting insulin levels in CAD cases and controls in contrast to the findings of Misra et al [17]. Our study documented raised levels of CRP which have been directly correlated with incidence of coronary events, suggesting the presence of an inflammatory process in unstable CAD [18,19]. Persistent inflammation in atherosclerotic coronary artery related probably to infection, oxidised lipid, free radicals or products of reninangiotensin system (RAS) is considered an important factor for CAD. Some viruses [cytomegalovirus (CMV), herpes simplex virus (HSV)] and Chlamydia have been reported in atherosclerotic region though the issue is not yet settled [20]. We found IgG anti-chlamydial antibody in a significant number of patients of CAD suggesting a link between the two. Lp (a) has been implicated in pathogenesis of CAD as it increases the risk of thrombosis and atherosclerosis by competing with plasminogen for cell surface binding, thereby reducing the formation of endogenous tissue plasminogen activator [21,22]. In contrast to the study by Vasisht et al [23], this study found no association between Lp(a) and CAD. Some workers [18,19,24] have documented increased incidence of acute coronary syndromes associated with higher baseline concentrations of fibrinogen, however we could not show such association. Psycho-social factors such as
Fig. 2 : Prevalence of some new emerging risk factors in acute coronary syndrome and chronic CAD MJAFI, Vol. 64, No. 4, 2008
Emerging Risk Factors for Coronary Artery Disease
stress, type A personality, depression and hostility have emerged as significant risk factors for CAD. They probably act via neuro - endocrine mechanisms, vasospasm and non-compliance with therapy [25]. To conclude we found an association between coronary artery disease and raised levels of serum CRP and Ig G anti-chlamydial antibodies. Acknowledgements The authors are grateful to Col AT Kalghatgi, Senior Advisor (Pathology), Col DK Mishra, Senior Advisor (Pathology & Haematology) and Mr DR Basannar (Scientist D) for their assistance. Conflicts of Interest This study has been funded by research grants from the O/o DGAFMS. Intellectual Contribution of Author Study Conceptt : Col DS Jaswal, Col N Aggarwal, Col TK Saha Drafting & Manuscript Revision : Col DS Jaswal, Col N Aggarwal, Col TK Saha Study Supervision : Col DS Jaswal, Col N Aggarwal
References 1. Gupta R, Prakash H, Majumdar S, Sharma S, Gupta VP. Prevalence of coronary heart disease and coronary risk factors in an urban population of Rajasthan. Indian Heart J 1995; 47: 331-8. 2. World Health Report 2002.Reducing Risk Promoting Healthy Life. Geneva WHO 2002. 3. AHA Statistical Fact Sheet. International Cardiovascular Disease Statistics. American Heart Association, 2003. 4. Gupta R, Gupta VP. Meta-analysis of coronary heart disease prevalence in India. Indian Heart J 1996; 48: 241-5.
319 11. Majumdar S, Kumar S, Banerjee S, et al. Serum homocysteine level as a risk factor for premature CAD amongst Indians.(Abstract) Indian Heart J 2001; 53 : 565. 12. Puri A, Gupta OK, Dwivedi RN, et al. Plasma homocysteine as a coronary risk factor in young hyperlipidemic patients. (Abstract) Indian Heart J 2001; 53: 568. 13. Deepa R, Velmurugan K, Saravanan G, Karkuzhali K, Dwarakanath V, Mohan V. Absence of association between serum homocysteine levels and coronary artery disease in South Indian males. Indian Heart J 2001; 53: 44-7. 14. Snehalatha C, Ramachandran A, Satyavani K, Sivasankari S, Sathyamurthy I, Viswanathan V. Plasma homocysteine concentration and coronary artery disease in Asian Indians. J Assoc Physicians India 2002; 50: 1229-31. 15. Misra A, Reddy RB, Reddy KS, Mohan A, Bajaj JS. Clustering of impaired glucose tolerance, hyperinsulinemia and dyslipidemia in young North Indian patients with coronary heart disease : A preliminary case – control study. Indian Heart J 1999; 51 : 275-89. 16. Reaven GM, Chen YD. Insulin resistance, its consequences and coronary heart disease. Must we choose one culprit ? Circulation 1996; 93 : 1780-3. 17. Misra A, Shukla P, Reddy KS, Lall SB, Peshin SS, Pandey RM. Serum insulin levels in non-obese, non-diabetic Asian Indians with acute coronary and non-coronary events. Indian Heart J 2000; 52:280-4. 18. Montalescot G, Philippe F, Ankri A, et al. Early increase of von Willebrand factor predicts adverse outcome in unstable coronary artery disease: Beneficial effects of Enoxaparin. Circulation 1998; 98 : 294-9. 19. Thompson SG, Kienast J, Pyke SDM, Haverkate F, Jurgen CW van de Loo. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332:635-41.
Scanlon PJ, Faxon DP, Audet A, et al. ACC/AHA guidelines for coronary angiography: Executive summary & recommendations. Circulation 1999; 99: 2345-57.
20. Mehta JL, Saldeen TGP, Rand K. Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary heart disease. J Am Coll Cardiol 1998; 31:1217-25.
6. Siwach SB, Singh H, Sharma D, Katyal VK. Profile of young acute myocardial infarction in Haryana. J Assoc Physicians India 1998; 46: 474-9.
21. Stein JH, Rosenson RS. Lipoprotein(a) excess and coronary heart disease. Arch Intern Med 1997; 157:1170-6.
5.
7. Goel PK, Bharati BB, Pandey CM, et al. A tertiary care hospitalbased study of conventional risk factors including lipid profile in proven coronary artery disease. Indian Heart J 2003; 55: 234-40.
22. Isser HS, Puri VK, Narain VS, Saran RK, Dwivedi SK, Singh S. Lipoprotein(a) and lipid levels in young patients with myocardial infarction and their first degree relatives. Indian Heart J 2001; 53:463-6.
8. Chacko KA. Plasma homocysteine levels in patients with coronary heart disease. Indian Heart J 1998; 50:295-9.
23. Vasisht S, Wasir HS, Srivastava LM. Association between incidence of lipoprotein (a) and coronary heart disease. Indian Heart J 1992; 44: 223-6.
9. Gheye S, Lakshmi AV, Krishna TP, Krishnaswamy K. Fibrinogen and homocysteine levels in coronary artery disease. Indian Heart J 1999; 51: 499-502.
24. Jose J, Selvakumar D, Selvakumar R, Kanagasapabathy AS, Jeyaseelan L. Plasma fibrinogen – An independent risk factor for ischaemic heart disease. Indian Heart J 1998; 50 : 45-8.
10. Chambers JC, Oheid OA, Refsum H, et al. Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian Asian and European men. Lancet 2000; 385:523-7.
25. Ornish D, Scherwitz LW, Billings JH, et al. Intensive life style changes for reversal of coronary heart disease. JAMA 1998; 280: 2001-7.
MJAFI, Vol. 64, No. 4, 2008