Low plasma vitamin B-6 concentrations and modulation of coronary artery disease risk.

BACKGROUND: Low concentrations of pyridoxal-5'-phosphate (PLP), the active metabolite of vitamin B-6, are associated with high C-reactive protein (CRP) concentrations. Both low PLP and elevated inflammatory markers, such as high-sensitivity CRP (hs-CRP) and fibrinogen, are related to higher risk of coronary artery disease (CAD). OBJECTIVES: The objectives were to evaluate the relation between PLP and acute-phase reactants in affecting CAD risk and to estimate the risk of CAD related to low plasma PLP, either alone or in combination with high concentrations of acute-phase reactants and other classic risk factors for CAD. DESIGN: A case-control study was conducted with 742 participants: 475 with severe multivessel CAD and 267 free from coronary atherosclerosis (CAD-free). We measured plasma PLP, fibrinogen, hs-CRP, and serum lipid concentrations and all major biochemical CAD risk factors, including total homocysteine. RESULTS: A significant, inverse, graded relation was observed between PLP and both hs-CRP and fibrinogen (P < 0.001). The prevalence of PLP concentrations in the lower half of the population (<50th percentile: 36.3 nmol/L) was significantly higher among CAD patients than among CAD-free subjects (P < 0.001). The odds ratio for CAD risk related to low PLP concentrations after adjustments for the major classic CAD risk factors, including hs-CRP and fibrinogen, was 1.89 (95% CI: 1.18, 3.03; P = 0.008). The CAD risk as a result of low PLP was additive when considered in combination with elevated hs-CRP concentrations or with an increased ratio of LDL to HDL. CONCLUSION: Low plasma PLP concentrations are inversely related to major markers of inflammation and independently associated with increased CAD risk.

Different impact of deletion polymorphism of gene on the risk of renal and coronary artery disease.

OBJECTIVE: An increased frequency of the angiotensin converting enzyme (ACE) D variant has recently been reported in patients with atheromatous renal artery disease (RAD), whereas controversy exists on the risk of coronary artery disease (CAD) associated with this polymorphism. In spite of the frequent coexistence of RAD and CAD, no studies have specifically compared ACE insertion/deletion (I/D) polymorphism in patients with coronary versus renal artery disease or defined the risk of each disease associated with the D variant. DESIGN: We designed a large case-control study of subjects for whom objective renal or coronary angiographic documentation was available. METHODS AND RESULTS: We analysed ACE I/D genotype and clinical-biochemical data of a total of 942 subjects (123 patients with and 137 without angiographic evidence of RAD, 420 patients with and 262 without angiographic evidence of CAD). Renal (with and without RAD) and coronary patients were similar for most conventional risk factors. There was no difference in DD frequency between CAD and CAD-free patients (38.1 versus 33.6%, NS) and DD homozygosity was not associated with CAD risk (OR = 1.27, 95% CI = 0.82-1.98). In contrast, the DD genotype was more frequent in RAD than in RAD-free patients (54.5 versus 39.4, P < 0.05) and was associated with a 2.25-fold increased risk of RAD in both the univariate and multivariate logistic regression models. Additional predictors of RAD were age and creatinine. In RAD/RAD-free patients with angiographically documented CAD, DD homozygosity was confirmed to be preferentially associated with RAD (P < 0.05). CONCLUSIONS: ACE D variant is preferentially associated with atherosclerotic renal rather than with coronary disease, despite similar exposure to atherogenic noxae. DD homozygosity confers a 2.25-fold increased risk of RAD.

Influence of polymorphisms in the factor VII gene promoter on activated factor VII levels and on the risk of myocardial infarction in advanced coronary atherosclerosis.

In this study, we investigate the influence of three factor VII (FVII) gene polymorphisms on activated FVII levels (FVIIa), and also on the risk of myocardial infarction (MI) in patients with advanced coronary atherosclerotic disease (CAD). The -323A2 allele in the promoter is known to be associated with low FVII levels, and has been suggested to protect against MI in some studies. The -402GA promoter polymorphism, that in vitro has been associated with having opposite effect, is less well studied clinically. For this study, plasma FVIIa levels and three FVII gene polymorphisms were assessed in 934 subjects of both sexes, all with an angiographic documentation of coronary vessels. Our results show that two promoter polymorphisms, plasma cholesterol, and gender, were significant predictors of FVIIa levels. The -402A allele was associated to a significant increase of FVIIa levels in males (by 19.2%). In a selected clinical model including the patients with severe CAD, with or without a thrombotic complication (MI), male carriers of the -402A had an increased risk of MI (OR=1.79; 95% CI 1.15-2.80). The -323A2 allele was associated to a significant decrease in FVIIa (by 36.02% in males, and 39.7% in females). Male carriers of the -323A2 were protected from MI (OR=0.6; 95% CI 0.39-0.94), but only after correction for the confounding effect of combined heterozygosity for the promoter polymorphisms. We can conclude that FVII gene polymorphisms with an opposite effect on FVIIa levels may modulate the risk of MI in males with advanced CAD. This study highlights a "within-gene" interaction, and the need to explore polymorphisms in candidate gene(s) in detail.

Myocardial contrast echocardiography and quantitative videointensity analysis after myocardial infarction: correlation between residual myocardial perfusion, contractile reserve and long-term remodeling.

BACKGROUND: Previous studies have shown the important role played by intracoronary myocardial contrast echocardiography (MCE) in predicting the long-term remodeling and function after myocardial infarction. The left ventricular volume is an important determinant of the clinical outcome following an acute event. No data, however, are available on the role of intravenous MCE in this regard. METHODS: Ten consecutive patients with an anterior myocardial infarction were studied using low-dose dobutamine stress echocardiography (Dob) and intravenous MCE 8 +/- 4 days after the acute event. In all patients the left anterior descending coronary artery (LAD) was identified as the infarct-related vessel. A LAD score was generated using the percent residual stenosis and its location (proximal, mid, distal portion). Quantitative myocardial videointensity plots were then generated for each of the 12 ventricular segments analyzed, while the volumes were assessed during Dob and after 8 +/- 4 months. A higher peak intensity in the dysfunctioning muscle, during intravenous MCE infusion, was assumed to reflect a greater myocardial blood volume. RESULTS: Despite no change in the wall motion score index (WMSI), the percentage changes in systolic volumes during inotropic stimulation showed a linear relation with the LAD score. Furthermore, a normalized myocardial gray level in the asynergic region, taken as the plateau value of the videointensity time curve, showed an inverse relationship with the percentage changes in systolic volumes at follow-up. CONCLUSIONS: The residual microcirculation in the dysfunctioning muscle, quantitatively assessed at intravenous MCE 8 +/- 4 days after the acute event, has the potential of predicting chronic remodeling following an anterior myocardial infarction, irrespective of changes in the WMSI. The product of the degree of the residual infarct-related artery stenosis and its proximity predicts the ventricular volume response during low-dose Dob.

Intravenous contrast echocardiography after myocardial infarction: relationship among residual myocardial perfusion, contractile reserve and long-term remodelling.

OBJECTIVE: Previous studies have shown the potential role played by intracoronary myocardial contrast echocardiography (MCE) in predicting long-term remodelling and function after myocardial infarction (MI). Scanty data, however, are available on the role of intravenous MCE in this regard. The aim of this study was to assess the role of residual myocardial blood volume in the asynergic region in modulating ventricular volume changes over time post-MI. METHODS: Thirty-two consecutive patients with anterior MI were studied predischarge using low-dose dobutamine echocardiography (Dob) and intravenous triggered MCE. Videointensity plots were generated from the apical approach and fitted exponentially. Volumes were assessed at baseline, during Dob and at 8 months. RESULTS: Baseline volumes, which appeared related to the extent of the asynergic region (P < 0.01) but showed no relation with videointensity in that area, did not change at follow-up, although Dob had elicited significant contractile reserve. However, videointensity in the asynergic region showed a significant interaction (P = 0.044) with the change in diastolic volume over time, with patients with the highest videointensity reverting remodelling (n = 11, from 69 +/- 16 to 65 +/- 16 ml/m) as compared with the remaining population (n = 21, from 68 +/- 16 to 73 +/- 21 ml/m). This was not seen when Dob-derived parameters were used. Multivariate analysis ranked videointensity second (P = 0.066), after baseline stroke volume (P = 0.005), in predicting changes in volumes over time. CONCLUSIONS: Unlike inotropic reserve, residual myocardial blood volume in the dysfunctioning muscle, as assessed by predischarge quantitative intravenous MCE, has the potential to modulate remodelling in patients who suffered an anterior MI.