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Background The merits and demerits of classical risk factors in coronary artery disease (CAD) are widely debated. We analyzed the role of conventional (age, gender, diabetes, hypertension, smoking) and non-conventional risk factors (anthropometrics, fasting blood sugar, atherogenic index of plasma — AIP, family history) in Asian Indians with CAD. Methods Out of 11,164 subjects (4855 affected, 6309 unaffected) enrolled in the Indian Atherosclerosis Research Study (IARS), 269 unaffected individuals with abnormal electrocardiogram and seven underage were excluded. Around 10,888 subjects along with two subsets, including 9888 individuals having family history information and 1616 individuals with intermediate Framingham risk score (FRS), were statistically analyzed using SPSS version 17.0 and R software. Results A combination of classical risk factors showed good discrimination between affected and unaffected individuals (C > 0.85). Hypertension (OR 3.79) or male gender (OR 5.31) showed significant association with CAD when lipids were included or excluded from the predictive model, followed by age, diabetes and smoking. Hypertension and diabetes frequencies were higher in older patients (> 55 years) while smoking was more prevalent in younger patients (< 55 years). Family history and AIP provided a modest increase in C index over the classical factors (0.864 to 0.873), with 7.1% net reclassification in the intermediate FRS group. In CAD patients, 4% were classified as high risk by FRS, 52% were classified as having metabolic syndrome with revised criteria and over 90% had a high AIP score. Conclusion Addition of AIP and family history to conventional risk factors improved risk discrimination in Asian Indians with CAD. [ABSTRACT FROM AUTHOR]

Objectives: This study assessed the relationship between diabetic retinopathy (DR) and coronary artery diseases (CAD) in Asian Indians, who are known to be at high risk of CAD and diabetes but have lower prevalence of DR. Subjects and Methods: Type 2 diabetes subjects ( n=1,736) were selected from the urban component of the population-based Chennai Urban Rural Epidemiology Study Eye Study. Four-field stereo retinal color photography was done, and DR when present was classified according to the Early Treatment Diabetic Retinopathy Study grading system. Among the 1,723 subjects with gradable fundus photographs, 12-lead electrocardiogram (ECG) was performed in 1,602 individuals, and analysis was restricted to this group. CAD was diagnosed based on documented medical history of CAD or Minnesota coding of ECGs. Results: The prevalence of CAD was significantly higher among subjects with DR compared with those without (11.3% vs. 6.7%; P=0.007). A significant association was observed between DR and CAD in subjects with glycated hemoglobin (HbA1c) levels >7% ( P=0.002). After controlling for age and gender, only hard exudates were associated with CAD ( P=0.032). Logistic regression analysis revealed that even after adjusting for age, gender, HbA1c, mean arterial blood pressure, smoking, serum cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, DR was significantly associated with CAD among the study subjects (odds ratio [OR]=1.58; 95% confidence interval [CI], 1.00-2.49; P=0.049) and those subjects with duration of diabetes >10 years (OR=4.06; 95% CI, 1.55-10.60; P=0.004). Conclusions: This cross-sectional study shows a significant association between DR and CAD in South Indian subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Leukotrienes are potent inflammatory and lipid mediators that participate in atherosclerosis. We analyzed the association of Leukotriene gene (ALOX5, ALOX5AP, LTA4H, and LTC4S) polymorphisms and plasma Leukotriene B4 (LTB4) levels with coronary artery disease (CAD) in a representative cohort of Asian Indians. In all, 136 functional single nucleotide polymorphisms (SNPs) were selected using in silico tools. Forty-five polymorphic SNPs were ranked for predicted functional effect using FastSNP. Finally, 14 functional SNPs along with 10 SNPs identified from the literature were genotyped in 340 CAD patients and 340 controls. Plasma LTB4 levels were measured in 150 cases and 150 controls. None of the 24 SNPs showed significant association with CAD. Plasma LTB4 levels were higher in cases than in controls (76.42 ± 4.46pg/mL versus 60.89 ± 2.61 pg/mL) (P = 0.003), with greater risk being associated with the top quartile as compared to the bottom quartile after adjusting for potential confounders (OR 8.94, 95% CI 2.56-31.95; P = 0.001). Four SNPs in the LTA4H gene showed significant association with LTB4 levels (P < 0.05)of which rs1978331 (P = 0.035) remained significant after correction for multiple testing. LTB4 showed strong correlation with lipids (r = 0.24-34) only in cases. Our pilot study suggests that the association between Leukotrienes gene polymorphisms and CAD risk may be modulated through plasma LTB4 levels. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: In view of the reported association of SNPs in the paraoxonase (PON1) gene with coronary artery disease (CAD), and the absence of conclusive data from India, we investigated the relationship of three SNPs at different loci (‐108C/T, L55M and Q192R) of the PON1 gene and their haplotypes with CAD among people residing in the northern plains of India. Materials and methods: One hundred and seventy-eight healthy controls and two hundred and four angiographically-proven CAD patients were genotyped using PCR-RFLP. Results: Of the three SNPs, only the R allele of Q192R polymorphism was associated with CAD (p<0.05). Two locus haplotypes QT (OR 0.55, p=0.0004, 95% CI 0.39–0.77, significant) and LQ (odds ratio 0.73, p=0.03, 95% CI 0.55–0.97, trend) showed protective effects, while haplotypes MR (OR=5.36, p=0.0001, 95% CI 2.045–14.049) and MC (OR=2.71, p=0.011, 95% CI 1.221–6.046) were associated with increased risk of CAD. MRT, a minor three-locus haplotype also displayed significant association (OR 4.93, 95% CI 1.7–13.5) with the disease. Significance was assessed after applying Bonferroni''s correction. Conclusions: Our study revealed that only one SNP at a single locus but several haplotype combinations of PON1 coding and promoter-region polymorphisms were associated with the risk of or protection against CAD. Thus, haplotype analysis brought better insights into the association of PON1 gene polymorphisms with CAD in Asian Indians. [Copyright &y& Elsevier]

Abstract: Objectives: Coronary artery disease (CAD) has emerged as the major cause of morbidity and mortality among Asian Indians in the recent past. The following study was undertaken to assess the predictive value of novel biomarkers of dyslipidemia for risk assessment for CAD in the Indian population. Design and methods: The study group comprised of 100 clinically assessed patients of myocardial infarction and 100 age and sex matched healthy controls. Apolipoprotein-A (Apo-AI) and Apolipoprotein-B (Apo-B) were estimated and small dense LDL was derived mathematically. Results: The cases showed significantly high levels of total serum cholesterol, triglycerides, LDL cholesterol, Apo-B, sdLDL, and non-HDL cholesterol. On carrying out multivariate regression analysis, Lp(a)/HDL ratio emerged as the best determinant of CAD risk Conclusion: The above data clearly underlines the role of these novel biomarkers in the risk assessment for CAD in the Indian context. [Copyright &y& Elsevier]

Abstract: Background: In present day atherosclerosis is perceived as a chronic inflammatory vascular condition and infectious diseases are believed to contribute to its pathophysiology. In this context, the microorganisms which are believed to play a role in the pathophysiology include Chlamydia pneumoniae, cytomegalovirus (CMV), and Helicobacter pylori. Method: A case control study (retrospective) was conducted over a two-year period. The study population was divided into two groups with 200 individuals in each group. The first group comprised cases of coronary artery disease (CAD) and the second comprised healthy controls selected from the general population after matching for age and sex. Enzyme-linked immunosorbent assay (ELISA) was done for immunoglobulin (IgG) antibodies to H. pylori, C. pneumonia, and CMV. They were also evaluated for conventional risk factors including hypertension, diabetes, obesity, and dyslipidaemia. Epi Info™ version 6 six software was used for analysis of data. Odds ratio, χ2 for trend and multiple logistic regression analysis were used to find out statistically significant results. Results: Seropositivity for H. pylori was present in 119 patients of CAD (59.5%) but it was present in only 76 controls (38%) (P = 0.001). There was a statistically significant association between seropositivity for H. pylori and CAD. There was no statistically significant association between C. pneumoniae and CMV seropositivity with CAD. Multiple logistic regression analysis was done with CAD as the outcome (dependent variable). The predictor covariates (independent) variables were seropositivity to H. pylori, C. pneumoniae, and CMV, hypertension, obesity, diabetes, and dyslipidaemia. It was found that seropositivity to H. pylori, hypertension, obesity, and dyslipidaemia were significant risk factors for CAD. Conclusion: Our study shows an association between IgG antibody response to H. pylori and CAD. Multiple logistic regression analysis showed that this association was retained even on comparison with the other risk factors. [Copyright &y& Elsevier]

Common single-nucleotide polymorphisms (SNPs) in genes of lipid metabolism modestly influence plasma low-density lipoprotein cholesterol (LDL-C) and risk of coronary artery disease (CAD). We evaluated a panel of LDL-C–modulating SNPs for potential association with risk of CAD in Asian Indians. Fifteen SNPs of CETP, ABCB1, APOAI, CYP7A1, and HMGCR genes were genotyped in 265 CAD patients and 150 controls of North Indian origin. A proatherogenic genotype score was formulated based on number of alleles associated with LDL-C and was evaluated for association with risk of CAD. We observed 12 SNPs from CETP, APOAI, ABCB1, CYP7A1, and HMGCR genes to be associated with baseline LDL-C and high-density lipoprotein cholesterol levels and increased risk of CAD ( p < 0.05). Co-occurrence of three or more risk alleles (proartherogenic genotype score ≥3) was associated with increased risk of CAD and myocardial infarction. Analysis of epistatic interactions revealed CETPTaqIB1B1/405II/APOAI-75GA to be best model of CAD risk prediction in our population. Our study highlights synergistic association of multiple SNPs of lipid pathway with LDL-C levels and risk of CAD, and indicates that co-occurrence of proatherogenic risk alleles may provide incremental information about CAD risk beyond lipid concentrations. [ABSTRACT FROM AUTHOR]

Background:The relationship between plasma leptin and insulin resistance among coronary artery disease (CAD) subjects remains poorly understood. We determined plasma leptin levels in insulin-resistant and insulin-nonresistant CAD patients. We also examined the association of plasma leptin with several cardiometabolic risk factors in all of the study group subjects from an Asian Indian population.Methods:We evaluated 130 subjects among the Asian Indian population. Out of these, 65 were CAD subjects and 65 were age- and sex-matched, healthy, non-CAD controls. Fasting plasma levels of leptin, insulin, glucose, homocysteine, fibrinogen, and lipid parameters were estimated for all the subjects. Body mass index (BMI) and waist circumference (WC) were also determined.Results:We observed raised levels of leptin as well as homocysteine, BMI, and WC among the insulin-resistant CAD subjects compared to the insulin-nonresistant CAD subjects. Similarly, a significant elevation in plasma leptin, homocysteine, BMI, and WC was observed among the insulin-resistant controls compared to the insulin-nonresistant controls. Plasma leptin in CAD patients was correlated significantly with overall and abdominal obesity, insulin resistance, and insulin levels. However, it was nonsignificantly correlated with plasma homocysteine, fibrinogen, mean arterial pressure, and dyslipidemia in CAD subjects. On multiple regression analysis, we observed that raised plasma leptin in CAD was significantly associated with insulin resistance independent of obesity.Conclusions:Our data showed a signifcant association of plasma leptin levels with insulin resistance in CAD that was independent of obesity. [ABSTRACT FROM AUTHOR]

Background: The APOA1-C3-A5 gene cluster plays an important role in the regulation of lipids. Asian Indians have an increased tendency for abnormal lipid levels and high risk of Coronary Artery Disease (CAD). Therefore, the present study aimed to elucidate the relationship of four single nucleotide polymorphisms (SNPs) in the Apo11q cluster, namely the -75G>A, +83C>T SNPs in the APOA1 gene, the Sac1 SNP in the APOC3 gene and the S19W variant in the APOA5 gene to plasma lipids and CAD in 190 affected sibling pairs (ASPs) belonging to Asian Indian families with a strong CAD history. Methods & results: Genotyping and lipid assays were carried out using standard protocols. Plasma lipids showed a strong heritability (h² 48% - 70%; P < 0.0001). A subset of 77 ASPs with positive sign of Logarithm of Odds (LOD) score showed significant linkage to CAD trait by multipoint analysis (LOD score 7.42, P < 0.001) and to Sac1 (LOD score 4.49) and -75G>A (LOD score 2.77) SNPs by single-point analysis (P < 0.001). There was significant proportion of mean allele sharing (pi) for the Sac1 (pi 0.59), -75G>A (pi 0.56) and +83C>T (pi 0.52) (P < 0.001) SNPs, respectively. QTL analysis showed suggestive evidence of linkage of the Sac1 SNP to Total Cholesterol (TC), High Density Lipoprotein-cholesterol (HDL-C) and Apolipoprotein B (ApoB) with LOD scores of 1.42, 1.72 and 1.19, respectively (P < 0.01). The Sac1 and -75G>A SNPs along with hypertension showed maximized correlations with TC, TG and Apo B by association analysis. Conclusion: The APOC3-Sac1 SNP is an important genetic variant that is associated with CAD through its interaction with plasma lipids and other standard risk factors among Asian Indians. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the study was to assess the relation of adiponectin levels with the metabolic syndrome in Asian Indians, a high-risk group for diabetes and premature coronary artery disease. The study was conducted on 100 (50 men and 50 women) type 2 diabetic subjects and 100 age and sex matched subjects with normal glucose tolerance selected from the Chennai Urban Rural Epidemiology Study, an ongoing population study in Chennai in southern India. Metabolic syndrome was defined using modified Adult Treatment Panel III (ATPIII) guidelines. Adiponectin values were significantly lower in diabetic subjects (men: 5.2 vs 8.3 μg/mL, P = .00l; women: 7.6 vs 11.1 μg/mL, P < .00l) and those with the metabolic syndrome (men: 5.0 vs 6.8 μg/mL, P = .01; women: 6.5 vs 9.9 μg/mL, P = .001) compared with those without. Linear regression analysis revealed adiponectin to be associated with body mass index (P < .05), waist circumference (P < .01), fasting plasma glucose (P = .001), glycated hemoglobin (P < .001), triglycerides (P < .00l), high-density lipoprotein (HDL) cholesterol (P < .001), cholesterol/HDL ratio (P < .00l), and insulin resistance measured by homeostasis assessment model (P < .00l). Factor analysis identified 2 factors: factor 1, negatively loaded with adiponectin and HDL cholesterol and positively loaded with triglycerides, waist circumference, and insulin resistance measured by homeostasis assessment model; and factor 2, with a positive loading of waist circumference and systolic and diastolic blood pressure. Logistic regression analysis revealed adiponectin to be negatively associated with metabolic syndrome (odds ratio [OR], 0.365; P < .001) even after adjusting for age (OR, 0.344; P < .00l), sex (OR, 0.293; P < .001), and body mass index (OR, 0.292; P < .00l). Lower adiponectin levels are associated with the metabolic syndrome per se and several of its components, particularly, diabetes, insulin resistance, and dyslipidemia in this urban south Indian population. [Copyright &y& Elsevier]

Abstract: Coronary heart disease (CHD) is the major cause of sudden death amongst adults throughout the globe. Though the prevalence of CHD is increasing steadily all over, CHD amongst Indians is peculiar in the sense that it is more prevalent, more severe and appears at younger age. Development of CHD depends upon the status of various coronary risk factors in one''s body. It has been observed that to measure the impact of risk factors for the cardiac health of a person, collective impact of all the known risk factors taken together should be calculated rather than individual risk factors. DEBEL (Defence Bio-Engineering and Electro-Medical Laboratory) is developing a cardiac risk analyser to calculate the absolute coronary risk of an individual in next 2.5 or 10 years and help in managing his coronary risk status. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Asian Indians have unusually high rates of coronary artery disease. Small low-density lipoprotein (LDL) particle predominance (phenotype B) is associated with a fourfold atherogenic risk. This study examined the accuracy of a triglyceride/high-density lipoprotein cholesterol (HDL) ratio of ≥3.8 (determined from the Adult Treatment Panel III guidelines, normal triglycerides <150 mg/dl and HDL >40 mg/dl) for predicting phenotype B in Asian Indians. Fasting blood samples were collected from 150 healthy Asian Indians. LDL size analysis was performed by nuclear magnetic resonance spectroscopy. The triglyceride/HDL cholesterol ratio correlated inversely with the LDL size and positively with the particle concentration. A triglyceride/HDL cholesterol ratio of ≥3.8 had 76% sensitivity, 93% specificity, and 83% positive and 89% negative predictive values for predicting phenotype B. [Copyright &y& Elsevier]

Abstract: We evaluated the impact of three polymorphisms in the lipoprotein lipase gene (LPL) on coronary artery disease (CAD) susceptibility in Chinese and Asian Indian males residing in Singapore. A total of 1201 CAD patients and 841 healthy controls were recruited. The HindIII/H- and 447X alleles are associated with decreased CAD risk in both Chinese (p=0.025, 0.001, respectively) and Indians (p=0.0014, 0.008, respectively). The same effect of PvuII/P- allele was observed only in Indians (p=0.049). The most common haplotype, P+H+S, was significantly increased CAD risk in both ethnic groups (p=0.0096, 0.0011, respectively). [ABSTRACT FROM AUTHOR]

Introduction: A close association exists between oral health and cardiovascular disease. Periodontal disease induces early vascular changes while oral pathogens have been detected in sub gingival and atheromatous plaques. We examined the interrelationship between Periodontal disease, oral bacteria, surrogate sub-clinical markers and coronary artery disease (CAD) in a representative Asian Indian cohort. Materials and Methods: 532 Gingivitis cases and 282 Periodontitis cases were assessed for early peripheral vascular changes, namely pulse wave velocity (PWV), arterial stiffness index (ASI) and ankle brachial index (ABI) using computerized oscillometry method. Relative quantitation (RQ) of Porphyromonas gingivalis (Pg) was estimated in saliva samples of 54 Periodontitis, 25 Gingivitis and 51 CAD cases (38 also had oral disease) by Taqman assay by amplifying pathogen-specific gene targets, 16srRNA and IktA, respectively, and 16s universal bacterial rRNA as endogenous control. Results: PWV and ASI were elevated in Periodontitis compared to Gingivitis cases (p<0.0001) and in those with diabetes and hypertension. Cases with Periodontitis showed higher mean expression of Pg than Gingivitis (0.37±0.05 versus 0.15±0.04, p<0.0001), while CAD patients with oral disease (N=38) showed lower mean Pg expression than those without oral disease (N=13) (0.712±0.119 versus 1.526±0.257, p=0.008). Higher Pg expression was recorded in subjects with diabetes and hypertension. Conclusion: Oral disease induces early changes in the peripheral blood vessels. Further, common presence of Pg in subjects with oral disease, in those with established cardiovascular risk factors and in patients with symptomatic CAD reflects the importance of oral hygiene in the development of Coronary Artery Disease in Asian Indians. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Thrombospondin 1 and 2 are multidomain calcium-binding extracellular glycoproteins and they play a role in platelet aggregation, inflammatory response and assembly of connective tissue extracellular matrix. The association of thrombospondins (TSP) in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI) is well established. The association of the TSP-1 (Asn700Ser, 2210A→G, rs2228262) and TSP-2 un-translated region (UTR) (3949T→G, rs8089) gene variations among South Indian CAD and MI patients has been examined in the present study. Materials and Methods: We analyzed the thrombospondin polymorphisms in unrelated CAD patients (n=511) and a subgroup with an event of MI (n=173) compared with controls (n=522). The polymorphisms were assessed using polymerase chain reaction, restriction fragment length analysis and the circulating TSP concentration were measured using enzyme linked immune-sorbent assay. Results: The prevalence of TSP-1 and TSP-2 alleles did not show any significant difference statistically, when compared controls against CAD/MI patients. The rare GG genotype of the N700S polymorphism was not observed among the studied population. Further, multiple regression analysis revealed that there was no significant risk for CAD (OR=1.68; 95% CI 0.927 - 3.055; p=0.087) or MI (OR=1.84; 95% CI 0.846 - 4.007; p=0.124) for the GA genotype. The GA genotype showed no impact on clinical characteristics of the CAD patients and their circulating TSP-1 levels. A similar non-association was observed for the TSP-2 in 3949T→G polymorphism (GG genotype) for CAD (OR=0.64; 95% CI 0.278 - 1.455; p=0.636) and MI (OR=0.53; 95% CI 0.166 - 1.675; p=0.278). Conclusions: Our data suggests that the presence of thrombospondin-1 (rs2228262) and thrombospondin-2 (rs8089) variants need not be considered a risk for coronary artery disease or myocardial infarction among South Indians. [Copyright &y& Elsevier]

Background and Aims: Peroxisome proliferator activated receptor-γ (PPARγ) and lipoprotein lipase (LPL) genes are important in pathways of triglyceride metabolism, insulin resistance and adipogenesis. We hypothesized that polymorphisms of PPARγ Pro12Ala, LPL HindIII and LPL Ser447X influence severity of coronary artery disease (CAD) in an Indian population. Methods: PPARγ Pro12Ala, LPL HindIII and LPL Ser447X polymorphisms were genotyped in 414 patients with CAD and matched with 424 controls. The study subjects were inducted after standard diagnostic procedures and analyzed statistically for the association of polymorphisms with clinical characteristics. Results: We found that PPARγ alleles were not associated with CAD among Indians although proline carriers had significantly higher levels of HDL-cholesterol (p = 0.03) among CAD patients. The LPL HindIII also had no significant correlations for CAD or for any clinical characteristics. The Ser447X polymorphism (p = 0.015) influenced lower triglyceride levels among CAD patients with significant associations (OR = 0.66, 95% CI 0.483–0.915, p = 0.012). This protective effect of the 447X allele was more pronounced among the CAD patients without the risk factor of diabetes (OR = 0.60, 95% CI 0.403–0.907, p = 0.014) along with less progression of a severe atherosclerotic disease. Conclusions: PPARγ and LPL have intractable roles in pathways that lead to CAD, but their gene polymorphisms associate differently. Our results imply a significant correlation of Ser447X polymorphism and its protective effect on Indians against severity of CAD modified by the risk of diabetes, than LPL HindIII and PPARγ Pro12Ala. [Copyright &y& Elsevier]