Increased homocysteine and lipoprotein(a) levels highlight systemic atherosclerotic burden in patients with a history of acute coronary syndromes.

BACKGROUND: Strong evidence supports an association between high levels of homocysteine (Hcy) and lipoprotein(a) [Lp(a)] and an increased rate of ischemic vascular events. METHODS: The study population comprised 162 patients (50 women [30.9%]; age, 66.71 ± 12.76 years) having a history of acute coronary syndrome within 1 year who underwent fasting blood sampling, measurement of intima-media thickness and pulse wave velocity at the common carotid and femoral arteries by Doppler ultrasound, and ankle-brachial index measurement. Cutoff values were considered 0.9 mm and 1.2 mm for carotid and femoral intima-media thickness, respectively; 12 m/s for pulse wave velocity; and <0.9 for ankle-brachial index. We included hypertension, dyslipidemia, diabetes, overweight/obesity, smoking, and family history of cardiovascular disease in the count of traditional risk factors (CRFs). Adding Hcy ≥15 µmol/L and Lp(a) ≥500 mg/L to CRFs, we obtained a new score, named TOTAL. RESULTS: On univariate analysis, Hcy and Lp(a) were significantly associated with presence of atherosclerotic extracoronary lesions (for Hcy: ß = .934; standard error = 0.178; P < .0001; for Lp(a): ß = .961; standard error = 0.177; P < .0001) and compliance alterations (for Hcy: odds ratio, 13.3; 95% confidence interval, 3.9-45.3; P < .0001; for Lp(a): odds ratio, 14.6; 95% confidence interval, 5.69-37.62; P < .0001). On multivariate analysis, Lp(a) and Hcy were significantly associated with extracoronary atherosclerosis, even after correction for CRFs. The area under the curve of the TOTAL score for both atherosclerosis and vascular compliance alterations was significantly higher than the area under the curve of traditional CRFs plus only Hcy ≥15 µmol/L or plus Lp(a) ≥500 mg/L, separately added. CONCLUSIONS: The addition of evaluation of Hcy ≥15 µmol/L and Lp(a) ≥500 mg/L to the traditional CRF count does improve detection of systemic atherosclerotic burden of patients with acute coronary syndrome and can offer a new opportunity to optimize secondary prevention.

Peripheral-arterial tonometry for assessing endothelial function in relation to dietary habits.

BACKGROUND: Peripheral-arterial tonometry (PAT) provides, with good reproducibility, measures of nitric oxide-mediated endothelial response, which correlate with flow-mediated dilation (FMD) findings obtained by brachial artery ultrasound. Few data about the ability of exploring endothelial function by PAT in relation to dietary habits are available. The aim of this study was to evaluate natural logarithm of reactive hyperemia index (lnRHI) in subjects referred for primary prevention, in relation to classic risk factors, in particular to adherence to Mediterranean diet and red wine consumption. METHODS: The study population was composed of 95 consecutive clinically stable subjects in primary prevention for cardiovascular diseases. All subjects underwent medical questionnaire, clinical examination, and PAT for endothelial function evaluation. RESULTS: A significant inverse correlation between lnRHI values and body mass index (r = -0.284; P = 0.022) was found. We described a gradual reduction in lnRHI values, corresponding to the increase in the number of risk factors (0.75 [0.31-1.26], 0.66 [0.25-0.97], 0.63 [0.37-1.19], 0.48 [0.32-0.71], 0.43 [0.31-0.91], respectively, for none, 1, 2, 3, and 4 cardiovascular risk factors; P = 0.004). A significant positive correlation between score of adherence to Mediterranean diet and lnRHI values was found (r = 0.307; P = 0.002). Higher adherence to Mediterranean diet was found in subjects with lnRHI values greater than 0.40 in comparison to others (39 [27-50] vs 33 [28-45], respectively; P = 0.064). The lnRHI values were significantly higher in regular drinkers in comparison to nonregular drinkers (0.46 [0.25-0.83] vs 0.70 [0.32-1.26], respectively; P < 0.0001).Relationship between reactive hyperemia index and red wine consumption remained statistically significant even after adjustment for age, sex, body mass index, smoking habit, hypertension, and adherence to Mediterranean diet. CONCLUSIONS: Our findings strengthen the ability of PAT to evaluate alterations of endothelium response to ischemia, in relation to physiological and clinical conditions, so indicating possible usefulness to optimize and personalize risk stratification.

Antiplatelets in acute coronary syndrome: personal perspectives.

High platelet reactivity (HPR) during dual-antiplatelet therapy is a marker of vascular risk, in particular stent thrombosis, in patients with acute coronary syndromes. Genetic determinants (CYP2C19*2 polymorphism), advanced age, female gender, diabetes and reduced ventricular function are related to a higher risk to develop HPR. In addition, inflammation and increased platelet turnover, as revealed by the elevated percentage of reticulate platelets in patients' blood, that characterize the acute phase of acute coronary syndrome are associated with HPR. To overcome the limitation of clopidogrel, new antiplatelet agents (prasugrel and ticagrelor) were developed and the demonstration of their superiority over clopidogrel was obtained in the two randomized trials, TRITON TIMI 38 and PLATO. Due to the current possibility not a choice between multiple antiplatelet strategies, the future prospect is to include, in addition to clinical data and classical risk factors, the definition of platelet function during treatment in order to set a tailored therapy.

Relationship among endothelial response to hyperemia, bone marrow-derived progenitor cells, and parathyroid hormone in renal transplantation.

BACKGROUND: Endothelial dysfunction may contribute to modulate cardiovascular complications in renal transplant recipients (RTRs), and a relationship between endothelial dysfunction and parathyroid hormone (PTH) levels in RTRs has been demonstrated. We evaluated the relationship between endothelial response to hyperemia and circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) PTH, and genetic parameters in RTRs. METHODS: In 120 RTRs and in healthy subjects without (n=107, group A) and with cardiovascular risk factors (n=109, group B), we evaluated endothelial response to hyperemia through digital tonometry (peripheral arterial tonometry) detected by reactive hyperemia index (RHI) and EPCs and CPCs by flow cytometry. RESULTS: In RTRs, RHI median value was lower than in group A (P=0.05). EPC number was significantly lower in RTRs than in groups A and B (P<0.0001), whereas PTH median value was significantly higher (P<0.0001). In RTRs, RHI values were significantly lower according to the presence of three or more risk factors (P=0.04) and positively correlated with EPCs (P=0.04) but not with PTH (P=0.2). In patients who underwent dialysis for more than 5 years, lower RHI values (P=0.08), EPC number (P=0.5), and higher PTH concentrations (P=0.09) than in patients with less than 1 year dialysis time were observed. No relationship between eNOS gene -786T>C, 894G>T, and 4a/4b polymorphisms and RHI, EPC, and CPC number was found. CONCLUSIONS: This study shows an altered endothelial response, associated with reduced EPCs, and increased PTH in RTRs; the evaluation of endothelial status in RTRs may contribute to better assess the risk profile of these patients.