Lack of an association between a polymorphism of the aldosterone synthase gene and left ventricular structure.

Background—Cardiac growth and function may be modulated in part by trophic effects of neurohormones. Specifically, aldosterone has been shown to stimulate the growth of cardiac myocytes and the accumulation of cardiac extracellular matrix proteins. Moreover, a variant of the aldosterone synthase gene (a cytosine/thymidine exchange at position −344 in the transcriptional regulatory region) has been associated with enlargement and disturbed filling of the left ventricle (LV) in a small sample of young white adults. The aim of the present study was to reinvestigate the implications of aldosterone synthase −344C/T allele status for serum aldosterone levels, blood pressure, and LV structure and function in large population-based samples. Methods and Results—Individuals who participated in the echocardiographic substudy of the third MONICA (MONitoring trends and determinants in CArdiovascular disease) survey (n=1445) or in the second follow-up of the first MONICA survey (n=562) were studied by standardized anthropometric, echocardiographic, and biochemical measurements as well as genotyping for aldosterone synthase −344C/T allele status. In both surveys, the distribution of sex, age, arterial blood pressure, and body mass index was homogeneous in the aldosterone synthase genotype groups. Echocardiographic LV wall thicknesses, dimensions, and mass indexes were not significantly associated with a specific aldosterone synthase genotype. Likewise, no association was detectable with echocardiographic measures of LV systolic or diastolic function. Data were consistent in both samples and not materially different in subgroups defined by age, sex, or intake of antihypertensive medication. Finally, no significant association was observed for aldosterone synthase allele status and serum aldosterone levels in the group of 562 individuals. Conclusions—The data are not in favor of a significant contribution of the C/T exchange at position −344 in the aldosterone synthase transcriptional regulatory region to the variability of serum aldosterone levels, blood pressure, or cardiac size or function as found in 2 white population-based samples

Association of Polymorphisms of the Apolipoprotein(a) Gene with Lipoprotein(a) Levels and Myocardial Infarction.

Background— Serum lipoprotein(a) [Lp(a)] concentration is largely determined by variability at the apolipoprotein(a) gene locus. Most prominent effects relate to polymorphisms in the promoter (a pentanucleotide [PN] repeat) and coding regions (a kringle IV [K4] repeat), the latter of which also affects Lp(a) particle size. The impact of these polymorphisms on cardiovascular risk is poorly understood. Methods and Results— We studied both polymorphisms and Lp(a) levels in 834 registry-based myocardial infarction (MI) patients (38% women) and 1548 population-based controls. Lp(a) concentrations were inversely related with the numbers of K4 and PN repeats. However, the effect of the PN polymorphism was restricted to subjects producing small Lp(a) particles (≤8 PN 66.1 mg/dL versus >8 PN 8.7 mg/dL; P<0.0001). The odds to present with MI were elevated in individuals producing small Lp(a) particles (≤22 K4 repeats; OR 1.47 for men and 1.69 for women; P<0.002) and in women with ≤8 PN repeats (OR 1.46, P=0.009). Interestingly, in women, the frequent haplotype with ≤8 PN and ≤22 K4 repeats, which is related to high levels of small Lp(a) particles, resulted in an elevated OR for MI (1.79; P=0.01) independently of Lp(a) serum concentration. Conclusions— The K4 and PN repeat polymorphisms largely explain the high variability of serum Lp(a) levels. A haplotype with ≤8 PN and ≤22 K4 repeats is characterized by high concentrations of small Lp(a) particles. Our observation that this haplotype was associated with MI independently of Lp(a) serum levels may suggest that Lp(a) particle size in addition to its concentration may modulate MI risk in women