Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary artery disease.

Recent genetic studies have revealed an association between polymorphisms at the ADAMTS7 gene locus and coronary artery disease (CAD) risk. Functional studies have shown that a CAD-associated polymorphism (rs3825807) affects ADAMTS7 maturation and vascular smooth muscular cell (VSMC) migration. Here, we tested whether ADAMTS7 (A/G) SNP is associated with cardiovascular (CV) survival in patients with established CAD. A cohort of 1,128 patients with angiographic proven CAD, who were followed up prospectively for a mean follow-up period of 63 (range 6-182) mo, were genotyped for rs3825807 A/G. Survival statistics (Cox regression) compared heterozygous (AG) and wild-type (AA) with the reference homozygous GG. Kaplan-Meier (K-M) survival curves were performed according to ADAMTS7 genotypes for CV mortality. Results showed that 47.3% of patients were heterozygous (AG), 36.5% were homozygous for the wild-type allele (AA) and only 16.2% were homozygous for the GG genotype. During the follow-up period, 109 (9.7%) patients died, 77 (6.8%) of CV causes. Survival analysis showed that AA genotype was an independent risk factor for CV mortality compared with reference genotype GG (HR = 2.7, P = 0.025). At the end of follow-up, the estimated survival probability (K-M) was 89.8% for GG genotype, 82.2% for AG and 72.3% for AA genotype (P = 0.039). Carriage of the mutant G allele of the ADAMTS7 gene was associated with improved CV survival in patients with documented CAD. The native overfunctional ADAMTS7 allele (A) may accelerate VSMC migration and lead to neointimal thickening, atherosclerosis progression and acute plaque events. ADAMTS7 gene should be further explored in CAD for risk prediction, mechanistic and therapeutic goals.

Pulse wave velocity and coronary risk stratification.

BACKGROUND: Arterial compliance or stiffness is an important determinant of cardiovascular disease and there is considerable interest in its noninvasive measurement. Pulse wave velocity (PWV) is widely used as an index of arterial stiffness. AIM: To determine whether PWV is useful for risk stratification in both healthy individuals and coronary patients. METHODS: Control subjects, n=510, aged 46.1 +/- 11 years, with no history of coronary disease, were selected from electoral rolls, and coronary patients, n=301, aged 53.7 +/- 10 years, were selected from hospital patients with a history of coronary artery disease (CAD) confirmed by coronary angiogram (at least 75% obstruction of one of the main coronary vessels). The asymptomatic subjects without CAD formed Group A, and were subdivided into A1 (without hypertension, dyslipidemia and/or diabetes) and A2 (with hypertension, dyslipidemia and/or diabetes). The coronary patients formed Group B, who were also subdivided into B1, without these classic risk factors, and B2 with hypertension, dyslipidemia and/or diabetes. We used the Student's t test to compare continuous variables and the chi-square test to compare categorical data. The strength of correlation between continuous variables was tested by Pearson's linear correlation. Independent variables predictive of CAD were determined by backward logistic regression analysis. The statistical analysis was performed using SPSS for Windows version 11.0 and data were expressed as means +/- SD; a p value of 0.05 was considered significant. RESULTS: Comparing the two groups A1 and A2, mean PWV was significantly lower in group A1. Comparing B1 and B2, mean PWV was also significantly lower in group B1. In group A1, PWV was significantly and positively correlated with age, body mass index, waist-to-hip ratio, alcohol consumption, total/HDL cholesterol ratio, systolic, diastolic and mean blood pressure (BP), blood glucose, apo B, triglycerides, and high-sensitivity C-reactive protein, unlike HDL which was inversely correlated (Pearson's coefficient). In group A2, PWV was significantly and positively correlated with age, alcohol consumption, total/HDL cholesterol ratio, systolic, diastolic and mean BP, blood glucose and pulse pressure (PP), but not HDL, which was inversely correlated with PWV. In group B1, PWV was only significantly and positively correlated with age, systolic, mean, and diastolic BP and PP, and presented a significant inverse correlation with ejection fraction. However, in the high-risk coronary population (group B2), there was a positive correlation with age, waist-to-hip ratio, systolic and mean BP, PP and homocysteine. After stepwise logistic regression, PWV remained in the model and proved to be a significant and independent risk factor for CAD. CONCLUSION: The results of our study show that PWV is higher in high-risk groups and significantly correlated with many classic and new CAD risk markers, suggesting that there is a cumulative influence of risk factors in the development of arterial stiffness. We believe that PWV is a useful index of vascular status and hence cardiovascular risk and that it may be useful for risk stratification in both asymptomatic and coronary patients.

[Risk and follow-up after myocardial infarct at a peripheral hospital]. / Risco e seguimento pós-enfarte do miocárdio num hospital periférico.

AIM: Analysing the influence of clinical and paraclinical "markers" in long term prognosis (LTP) of Acute Myocardial Infarction (AMI), in terms of mortality, post AMI Angina, post AMI Heart Failure and non fatal recurrent AMI in patients of a Post AMI Consultation of a peripherical hospital. DESIGN: A) Retrospective study (series A and B) of the average incidence of 17 "markers" of bad post AMI TLP so as to identify those that had a discriminating value with regards to death after hospital discharge. B) Prospective study so as to determine its influence in those patients followed in a post AMI Consultation (series C), with regards to mortality, post AMI Angina, post AMI Heart Failure and non fatal recurrent AMI. PARTICIPANTS: Series A - 97 survivors of AMI treated on the CCU of Madeira's Hospital Center in its 1st year. Series B - 91 survivors of AMI treated of AMI treated on the CCU of Madeira's Hospital Center in its 2nd year. Series C - 88 survivors of AMI treated on the CCU of Madeira's Hospital Center after this period and followed up since then at the post AMI consultation. RESULTS: A) Significant statistical differences were observed in the series A and B, with regards to late mortality, in 5 of those "markers" (aged greater than or equal to 70 years, Auricular Fibrillation and Killip III class during the acute phase of the AMI, frequent ectopic ventricular beats before discharge and a survival probability of less than or equal to 60% at 5 years after AMI). B) It was observed that bearers of greater than or equal to 1 of these 5 clinical "markers" of the series C had significant statistical differences in relation to non bearers with regards to mortality, post AMI Angina, post AMI Heart Failure and non fatal recurrent AMI. CONCLUSIONS: It is considered that those 5 post AMI clinical "markers" allows identification of the very bad cases of post AMI LTP in peripherical hospitals. This identification can lower the ratio cost benefit of the indispensable diagnostic techniques for stratification of post AMI risk, through the rationalization of its use. A Study of its accessibility with regards to peripherical hospitals and a AMI national register became important to evaluate the problem of the Portuguese AMI survivors in terms of Public Health.