Association of coronary artery disease with polymorphisms of angiotensin-converting enzyme and methylenetetrahydrofolate reductase gene.

OBJECTIVE: Angiotensin-converting enzyme plays an important role in maintaining blood pressure, while methylenetetrahydrofolate reductase is involved in homocysteine metabolism. As hypertension and elevated homocysteine levels are among the various risk factors for coronary artery disease, the two polypeptides might need to be considered while determining the risk. Our study aimed to assess the association between common polymorphisms in these genes and susceptibility to coronary artery disease. METHODS: We studied 268 north Indian individuals with coronary artery disease and 90 age-matched controls. The distribution of the genotypes and allele frequencies of both genes were analyzed using polymerase chain reaction amplification and restriction fragment length polymorphism analysis. RESULTS: The frequency of the D allele was significantly higher among the patients (62%) than the controls (44%) (p=0.001, odds ratio=2.06). The same goes for the DD genotype (37% vs 21%) (p=0.004). The combined frequency of the D allele carriers was significantly higher among patients of coronary heart disease, with a difference of 20% (85% vs 65%) (p=0.003, odds ratio=3.1; CI: 1.3-7.29). However, the frequency of the T and C alleles, as well as that of the CC, CT and TT genotypes of the methylenetetrahydrofolate reductase gene, did not differ significantly between the two groups. CONCLUSION: We conclude that coronary artery disease in north Indian patients is strongly associated with the carrier state of the angiotensin-converting enzyme D allele, but not with the C677T transition in the methylenetetrahydrofolate reductase gene.

Prevention of atherosclerosis progression using atorvastatin in normolipidemic coronary artery disease patients--a controlled randomized trial.

BACKGROUND: Statins have been known to reduce progression of atherosclerosis when used in high dosage in patients with elevated cholesterol. A large majority of Indian patients, however, develop coronary artery disease with average or below average cholesterol level. There is insufficient data on effect of low-dose statins on progression of atherosclerosis in such patients with normal/average lipid levels. METHODS AND RESULTS: In this prospective study, 150 patients with angiographically proven coronary artery disease and baseline total cholesterol <200 mg/dl and low-density lipoprotein cholesterol <130 mg/dl were randomized to treatment with low-dose atorvastatin (10 mg) or placebo. Both groups were comparable in demographic characteristics. Progression of atherosclerosis was assessed using carotid intima media thickness as surrogate marker using standard protocol on B-mode ultrasound including common carotid artery, common carotid bifurcation and internal carotid artery measurements. Follow-up study for carotid intima media thickness was done at end of one year. A decrease in mean maximum carotid intima media thickness was recorded for all the three carotid segments individually from basal to end of one year in atorvastatin group [common carotid artery -0.008 mm (p = 0.01), common carotid bifurcation-0.022 mm (p = 0.001), internal carotid artery -0.009 mm (p = 0.01)] while the same showed an increase in placebo group [common carotid artery +0.011 mm (p = NS), common carotid bifurcation +0.013 mm (p=NS), internal carotid artery +0.007 mm (p=NS)]. The average mean carotid intima media thickness (all three segments included) decreased from 0.739 +/- 0.114 mm to 0.726 +/- 0.115 mm (difference -0.013 mm) in statin group and increased from 0.733 +/- 0.124 mm to 0.742 +/- 0.117 mm (difference + 0.009 mm) in placebo group (p < 0.001). Along side, there was a reduction in the total cholesterol from 144 +/- 26 mg/dl to 130 +/- 18 mg/dl (decreased arrow 9.7%, p = 0.05) and in low-density lipoprotein cholesterol from 86 +/- 24 mg/dl to 74 +/- 19 mg (decreased arrow 13.9%, p = 0.05) in study group and an increase in total cholesterol from 148 +/- 32 mg/dl to 154 +/- 8 mg/dl (increased arrow 4.05%, p=NS) and in low-density lipoprotein cholesterol from 84 +/- 19 mg/dl to 87 +/- 16 mg/dl (increased arrow 3.57%, p=NS) in placebo group at end of one year (p=NS). No adverse effects of statins were reported in the treatment arm. CONCLUSIONS: We conclude that low-dose statins reduce progression of atherosclerosis as observed by carotid intima media thickness in Indian patients with known coronary heart disease and normal lipid values independent of lipid lowering. The study favors use of this therapy in patients with normal/below average cholesterol levels.