Impact of Valve Morphology on the Prevalence of Coronary Artery Disease : A Systematic Review and Meta-Analysis

Background-Literature studies suggested a lower prevalence of coronary artery disease (CAD) in bicuspid aortic valve (BAV) than in tricuspid aortic valve (TAV) patients. However, this finding has been challenged. We performed a meta-analysis to assess whether aortic valve morphology has a different association with CAD, concomitant coronary artery bypass grafting (CABG), and postoperative mortality. Methods and Results-Detailed search was conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guideline to identify all patients with BAV or TAV and presence of CAD, concomitant myocardial surgical revascularization, and the postoperative mortality. Thirty-one studies on 3017 BAV and 4586 TAV patients undergoing aortic valve surgery were included. BAV patients showed a lower prevalence of CAD (odds ratio [OR]: 0.33; 95% CI: 0.17, 0.65), concomitant CABG (OR, 0.45; 95% CI: 0.35, 0.59), and postoperative mortality (OR, 0.62; 95% CI: 0.40, 0.97) than TAV. However, BAV subjects were significantly younger than TAV (mean difference: -7.29; 95% CI: -11.17, -3.41) were more frequently males (OR, 1.61; 95% CI: 1.33, 1.94) and exhibited a lower prevalence of hypertension (OR, 0.58; 95% CI: 0.39, 0.87) and diabetes (OR, 0.71; 95% CI: 0.54, 0.93). Interestingly, a metaregression analysis showed that younger age and lower prevalence of diabetes were associated with lower prevalence of CAD (Z value: -3.03; P=0.002 and Z value: -3.10; P=0.002, respectively) and CABG (Z value: -2.69; P=0.007 and Z value: -3.36; P=0.001, respectively) documented in BAV patients. Conclusions-Analysis of raw data suggested an association of aortic valve morphology with prevalence of CAD, concomitant CABG, and postoperative mortality. Interestingly, the differences in age and diabetes have a profound impact on prevalence of CAD between BAV and TAV. In conclusion, our meta-analysis suggests that the presence of CAD is independent of aortic valve morphology

Markers of subclinical atherosclerosis in patients with aortic valve sclerosis : A meta-analysis of literature studies

Objective: Growing evidence suggested an association between aortic valve sclerosis (AVSc) and cardiovascular (CV) events. However, little is known about the association of AVSc with major markers of subclinical atherosclerosis. We performed a meta-analysis of literature studies to address this issue. Approach and Results: Studies on the relationship between AVSc and common carotid artery intima-media thickness (IMT), prevalence of carotid plaques (CPs), flow-mediated dilation (FMD), aortic pulse wave velocity (PWV) and augmentation index (AIx) were systematically searched in electronic databases. Thirteen studies enrolling 1086 AVSc patients and 2124 controls were included. Compared to controls, AVSc patients showed higher IMT (MD: 0.32 mm; 95%CI: 0.07, 0.58; p=0.014), and higher prevalence of CPs (OR: 4.06; 95%CI: 2.38, 6.93; p<0.001). Moreover, lower FMD (MD: -4.48%; 95%CI: -7.23, -1.74; p=0.001) and higher PWV (MD: 0.96%; 95%CI: 0.11, 1.81; p=0.027) were found in AVSc subjects than in controls, with no differences in AIx (MD: 0.76%; 95%CI: -0.97, 2.49; p=0.389). In Meta-regression analyses body mass index and triglycerides levels have an impact on the difference in IMT between cases and controls, while male gender and smoking habit were associated with the difference in the prevalence of CPs between the two groups. Conclusion: AVSc is significantly associated with altered markers of subclinical atherosclerosis, thus supporting the concept that AVSc and atherosclerosis share common etiopathological mechanism and/or risk factors. On this basis, an echocardiogram carried out to assess the state of the aortic valve would be desirable whenever an altered subclinical marker of atherosclerosis is found

Homocysteine and arterial thrombosis : Challenge and opportunity

The correlation between homocysteine and vascular disease has been assessed in several clinical studies that demonstrated that elevation of plasma total homocysteine (tHcy) was an independent risk factor for atheriosclerotic disease. Major advances of homocysteine metabolism disorders have been made during the last few years, encompassing the rare homozygous enzyme deficiencies, as well as more common milder abnormalities. In experimental and clinical studies, a homocysteine-mediated oxidant stress has been shown to trigger platelet activation, in turn leading to a tendency to thrombosis, in patients with severe hyperhomocysteinaemia. Likewise, the hypomethylation hypothesis on acquired hyperhomocysteinaemia (chronic renal disease) and the interrelationship between hyperhomocysteinaemia and impaired fibrinolysis, have added further biological plausibility to the role for hyperhomocysteinaemia in vascular medicine. However, whether hyperhomocysteinaemia is causal or a marker of vascular disease, and whether plasma tHcy is only an indicator of the metabolic status remains to be clarified. The role of the intake of some vitamins (folic acid, vit.B12, vit.B6) on cardiovascular disease (CVD) is poorly understood: in spite of the lowering of homocysteine (Hcy) levels, vitamin supplementation failed to exert significant effects on cardiovascular risk. On the other hand, although some lipid-modifying treatments increase Hcy levels in diabetics, there is no evidence that this attenuates the beneficial effects of such treatments on the cardiovascular risk. Because of these uncertainties in the area, the data available do not provide support for routine screening and treatment for elevated Hcy to prevent CV

Exploring newer cardioprotective strategies: \u3c9-3 fatty acids in perspective

In the 1980s, observational retrospective studies showed an inverse relation between coronary heart disease (CHD) and consumption of fish containing fatty acids that belong to the omega (\u3c9)-3 family. Large case-control studies and prospective intervention trials consistently showed that \u3c9-3 fatty acids supplementation lowers fatal myocardial infarction (MI) and sudden cardiac death. By analysing the strengths of the results of individual studies and how the meta-analyses agree with them, putting together relevant backgrounds, and identifying open questions, the following findings/directions emerge. (i) Dietary and non-dietary intake of \u3c9-3 fatty acids reduces overall mortality, mortality due to MI, and sudden death in patients with CHD; (ii) Fish oil consumption directly or indirectly affects cardiac electrophysiology. Fish oil reduces heart rate, a major risk factor for sudden death; (iii) Among patients with implantable cardioverter defibrillators, \u3c9-3 fatty acids do not reduce the risk of ventricular tachycardia/ventricular fibrillation and may actually be pro-arrhythmic; (iv) The consumption of \u3c9-3 fatty acids leads to a 10\u201333% net decrease of triglyceride levels. The effect is dose-dependent, larger in studies with higher mean baseline triglyceride levels, and consistent in different populations (healthy people, people with dyslipidaemia, diabetes, or known cardiovascular risk factors); (v) Outcomes for which a small beneficial effect \u3c9-3 fatty acids is found include blood pressure (about 2 mmHg reduction), re-stenosis rates after coronary angioplasty (14% reduction), and exercise tolerance testing. Major experimental data provide strength (biological plausibility) for these findings, and define directions for newer clinical trials with \u3c9-3 fatty acids

Cardiovascular risk markers in patients with psoriatic arthritis: a meta-analysis of literature studies

Introduction. Several studies reported an increased cardiovascular (CV) morbidity and mortality in patients with psoriatic arthritis (PsA). We performed a meta-analysis on the impact of PsA on major markers of CV risk. Methods. Studies on the relationship between PsA and common carotid artery intima-media thickness (CCA-IMT), prevalence of carotid plaques, flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), pulse wave velocity (PWV), augmentation index (AIx), and ankle-brachial index (ABI) were systematically searched in the PubMed, Web of Science, Scopus, and EMBASE databases. Results. Sixteen case-control studies (898 cases, 1,140 controls) were included. Compared to controls, PsA patients showed a higher CCA-IMT (MD 0.07 mm; 95% CI 0.04, 0.11; P < 0.0001), and a higher frequency of carotid plaques (OR 3.12; 95% CI 1.03, 9.39; P = 0.04). Moreover, a lower FMD was found in PsA subjects than in controls (MD \u20132.56%; 95% CI \u20134.17, \u20130.94; P = 0.002), with no differences in NMD (MD \u20130.40%; 95% CI \u20131.19, 0.39; P = 0.32). Because of the low number of studies, no meta- analytical evaluation was performed for PWV, AIx, and ABI. Despite heterogeneity among studies, PsA appears significantly associated with markers of subclinical atherosclerosis and CV risk. Discussion. These findings could help to establish more specific CV prevention strategies in this clinical setting

New anti-thrombotic drugs for stroke prevention

Ischemic stroke is the third most common cause of death and of long-term disability and exhibits a high recurrence rate. Therefore, appropriate primary and secondary prevention is mandatory. In non-cardioembolic stroke, in addition to lifestyle changes and to targeted treatments, current guidelines recommend antiplatelet treatment. In cardioembolic stroke, Vitamin K antagonists (VKAs) are recommended. Although a favorable risk/benefit ratio of both treatments has also been demonstrated in elderly patients, registry data emphasize that such interventions are often under-used, especially in patients with atrial fibrillation (AF). Furthermore, variability in the inter-individual response to drugs has been recognized as a leading cause of event recurrence. Thus, in addition to poor adherence, efficacy and safety issues appear to be involved in the recurrence rate of stroke. In this review, we report main Registries data on adherence to stroke prevention treatment schedule. We also discuss the major limitations of "traditional" antithrombotic drugs and report Phase III study results on safety and efficacy of new antiplatelet and anticoagulant drugs, with emphasis on stroke prevention

Increased platelet reactivity in Klinefelter men: Something new to consider

Patients with Klinefelter syndrome (KS) exhibit an increased cardiovascular risk, but underlying mechanisms are largely unknown. The present cross-sectional study has been conducted to evaluate platelet reactivity and the expression of platelet activation markers (8-iso-prostaglandin F2α[8-iso-PGF2α] and 11-dehydro-thromboxane-B₂[11-dehydro-TXB2]) in KS patients and healthy controls. Twenty-three consecutive KS patients under testosterone replacement therapy have been included as case group and 46 age-matched healthy males recruited among hospital staff served as controls. Light transmission aggregometry was performed in both cases and controls and maximal platelet aggregation (max-A%) was defined as maximal light transmittance reached within 5 min after the addition of 0.2 or 0.4 mm arachidonic acid (AA). A ≥ 50% irreversible light transmittance (LT-50%) following platelet stimulation defined an adequate platelet aggregation and AC-50% was defined as the minimal agonist concentration needed to achieve LT-50%. The AC-50% was 0.26 mm AA for KS and 0.36 mm for controls (p < 0.001). Whereas AA (0.2 mm) induced LT-50% in 69.6% of KS and in 15.2% of controls (p < 0.001), the stimulation with AA (0.4 mm) determined LT-50% in all cases and controls. However, max-A% was higher in KS than in controls both after AA (0.2 mm) (65.61% vs. 46.30%, p = 0.002,) and after AA (0.4 mm) (96.43% vs. 81.04%, p < 0.001). 8-iso-PGF2α and 11-dehydro-TXB2 were higher in KS than in controls (446.54 pg/mg creatinine vs. 230.00 pg/mg creatinine, p < 0.001 and 1278.36 pg/mg creatinine vs. 595.08 pg/mg creatinine, p = 0.001, respectively) and AC-50% inversely correlated with 8-iso-PGF2α (ρ = -0.548, p < 0.001) and with 11-dehydro-TXB2 (ρ = -0.523, p < 0.001). In a linear regression model, KS independently predicted a lower AC-50% (β = -0.597, p < 0.001) and higher levels of 8-iso-PGF2α (β = 0.709, p < 0.001) and 11-dehydro-TXB2 (β = 0.605, p < 0.001). In contrast, no correlation has been found between max-A%, testosterone and estradiol levels in KS. We observed increased platelet reactivity in KS. This might, at least in part, explain the increased thrombotic risk associated with this disease