Cystatin C levels are decreased in acute myocardial infarction: effect of cystatin C G73A gene polymorphism on plasma levels.

BACKGROUND: Cystatin C is the most abundant protease inhibitor in the plasma. Low plasma levels have been found in patients with aortic aneurysms and they seem correlated with the extension of the aortic lesions in early aneurysms detected by ultrasonography. METHODS: In this study, plasma levels of cystatin C have been investigated in patients with acute myocardial infarction (AMI), unstable angina and controls. The effect on plasma levels of the G73A polymorphism of the CST3 gene has been also evaluated. RESULTS: Patients with acute myocardial infarction showed significantly lower levels of cystatin C compared to unstable angina and controls, but levels were nearly normal in a week after the acute event. The genotype distribution of the G73A polymorphism was not different among the groups. Nevertheless, cystatin C levels decreased proportionally with the number of A alleles. Cystatin C levels were positively correlated with age, triglyceride/HDL cholesterol ratio and creatinine, and negatively with HDL cholesterol and the number of A alleles. All variables, but not HDL cholesterol, were independently correlated in a multivariate analysis. CONCLUSIONS: Cystatin C is decreased in acute myocardial infarction. It is still not clear whether lower cystatin C levels are causally linked to the acute event or just represent a negative acute phase response. The CST3 gene G73A polymorphism functionally affects cystatin C plasma levels.

Differential apolipoprotein(a) isoform expression in heterozygosity is an independent contributor to lipoprotein(a) levels variability.

BACKGROUND AND METHODS: Lipoprotein(a) [Lp(a)] levels represent an independent risk factor for cardio- and cerebrovascular diseases. Since lipoprotein(a) levels show a wide variability even in subjects with similar apolipoprotein(a) isoforms, we investigated the contribution of apolipoprotein(a) heterozygosity to lipoprotein(a) variance. Lipoprotein(a) levels, apolipoprotein(a) isoforms identification and expression, and the correlation with other lipo-apolipoprotein parameters have been investigated in 628 subjects >18 years of age. RESULTS: In our study, 246 subjects were found heterozygous for apolipoprotein(a) isoforms. Lipoprotein(a) levels were higher in females. About 40% of the subjects expressed the larger isoform more intensely than the dominant isoform. Lipoprotein(a) was correlated with apolipoprotein(a) dominant isoform size, HDL-cholesterol and smaller apolipoprotein(a) isoform expression rate. Lipoprotein(a) was independently correlated with the smaller apolipoprotein(a) isoform, with its expression rate and with LDL-cholesterol. The inclusion of the smaller apolipoprotein(a) expression rate in a multiple regression model explained at least an additional 4% of the lipoprotein(a) variance after correction for apolipoprotein(a) size. CONCLUSIONS: The smaller isoforms are not always effectively dominant in heterozygosis since 40% of the subjects expressed more the larger isoform. The individual variability of apolipoprotein(a) isoform expression in heterozygosis could explain part of the lipoprotein(a) levels variability.

Family history, diabetes and extension of coronary atherosclerosis are strong predictors of adverse events after PTCA: A one-year follow-up study.

BACKGROUND AND AIM: In this study we addressed some open questions in patients with coronary artery disease (CAD). First, we analysed which of the traditional risk factors was associated with the spreading of coronary stenosis and second, we aimed to identify if any variable was predictive of post-percutaneous transluminal coronary angioplasty (PTCA) clinical events. METHODS AND RESULTS: We collected a consecutive series of patients with CAD (n=301) and in the subgroup of patients undergoing PTCA (n=135) we performed a prospective one-year follow-up study recording cardiovascular morbidity and total mortality. According to the extension of coronary atherosclerosis, we found a significant relationship with the prevalence of diabetes in men and with plasma HDL-cholesterol concentrations in women. The follow-up was completed in 95% of patients; we did not document any death whereas clinical events were registered in 16% of patients. At univariate analysis, we found that patients with clinical events had a higher prevalence of family history of CAD (43% vs 14%, p<0.005), diabetes (52% vs 21%, p<0.005) and multivessel disease (52% vs 35%, p<0.05). Multivariate analysis (logistic regression) confirmed that family history of CAD (OR 4.6, 95% CI 1.7-12.8, p<0.005), diabetes (OR 4.0, 95% CI 1.5-10.6, p<0.01) and multivessel disease (OR 2.8, 95% CI 1.1-7.4, p<0.05) were the only variables predictive of clinical events. CONCLUSIONS: In this study, factors associated with the spreading of coronary stenosis were different according to the gender. Moreover, the presence of diabetes and multivessel disease had a negative impact on the long-term prognosis of patients undergoing PTCA. In addition, the family history of CAD represented in our study a strong predictor of clinical events. We suggest that in the management of post-PTCA patients, the role of individual baseline clinical characteristics must be taken into account and that subjects with a family history of premature CAD, diabetes and a wide extension of coronary disease represent those with the highest risk.