Genetic Factors Of Coronary Heart Disease And Its Prevention

PartⅠAssociation between ALDH2 genetic polymorphism and coronary artery diseaseBackground:a homozygous mutant (ALDH2 A/A) of the gene for mitochondrial aldehyde dehydrogenase 2 (ALDH2) at codon 487 was reported to be associated with coronary artery disease among Japanese and Korean population. However, such an association has never been studied in a Chinese population.Methods:Taqman 5'nuclease polymerase chain reaction assay was performed to screen the ALDH2 gene 487G/A polymorphism.490 patients with coronary artery disease (CAD) which was identified by coronary angioplasty (coronary narrow≥50%) and 433 patients without CAD were recruited from Zhongshan Hospital.Results:The frequencies of G and A allele in the whole population were 0.738 and 0.262, respectively. No significant difference was found in the frequencies of the two ALDH2 allele (P=0.142) and in the genotype distribution (P=0.224) between CAD group and control group. multiple logistic regression analysis revealed that ALDH2 genotype AA, together with male, smoking and abnormal high density lipoprotein cholesterol, was an independent risk factor for CAD in Chinese Han populatopn (OR 2.249, P=0.031).Conclusion:ALDH2 polymorphisms may play an important role in the pathogenesis of CAD in Chinese Han population.PartⅡ(1) Aspirin for primary prevention of cardiovascular events in patients with diabetes:a meta-analysisBackground:To systematically review trials concerning the benefit and risk of aspirin therapy for primary prevention of cardiovascular events in patients with diabetes mellitus.Methods:We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Eligible studies were prospective, randomized controlled trials of aspirin therapy for primary cardiovascular prevention in patients with diabetes with follow-up duration at least 12 months.Results:7 trials included 11,618 individuals with diabetes. Aspirin therapy was not associated with a statistically significant reduction in major cardiovascular events (relative risk [RR] 0.92,95% confidence interval [CI] 0.83-1.02, p=0.11). Aspirin use also did not significantly reduce all-cause mortality (0.95,95% CI 0.85-1.06; p= 0.33), cardiovascular mortality (0.95,95% CI 0.71-1.27; p=0.71), stroke (0.83,95% CI 0.63-1.10; p=0.20), or myocardial infarction (MI) (0.85,95% CI 0.65-1.11; p=0.24). There was no significant increased risk of major bleeding in aspirin group (2.46,95% CI 0.70-8.61; p=0.16). Subgroup analysis suggested that aspirin agent could reduce the risk of stroke in women and MI in men.Conclusions:In patients with diabetes, aspirin therapy did not significantly reduce the risk of cardiovascular events without an increased risk of major bleeding, and showed sex-specific effects on MI and stroke.(2) Effects of intensive glucose control on incidence of cardiovascular events in patients with type 2 diabetes:a meta-analysisBackground The benefits of intensive glucose control over conventional glucose control on cardiovascular outcomes of patients with type 2 diabetes remains uncertain.Methods We searched MEDLINE, EMBASE and Cochrane database to identify randomized controlled trials that compared the effects of intensive glucose control and conventional glucose control on cardiovascular events in patients with type 2 diabetes.Results Seven trials involving 34,144 participants with type 2 diabetes were included. Intensive glucose control significantly reduced major cardiovascular events by 10%(relative risk [RR] 0.90,95% CI 0.85-0.96, p=0.0006) and nonfatal myocardial infarction by 16% (0.84,95% CI 0.76-0.93, p=0.0006) at the expense of increased incidence of severe hypoglycemia (2.30,95% CI 1.74-3.03, p<0.00001), while all-cause mortality, cardiovascular death, nonfatal stroke and heart failure were similar between the two strategies. Subgroup analyses showed that patients with longer follow-up duration, shorter diabetic disease duration, less HbAlc reduction, higher HbAlc concentration at follow-up and lower baseline HbAlc benefited more from intensive glucose control. Conclusion Intensive glucose control strategy can effectively reduce the risk of major cardiovascular events but at the expense of a significant increased risk of severe hypoglycemia in patients with type 2 diabetes.