C-reactive protein levels in patients at cardiovascular risk: EURIKA study

Background: Elevated C-reactive protein (CRP) levels are associated with high cardiovascular risk, and might identify patients who could benefit from more carefully adapted risk factor management. We have assessed the prevalence of elevated CRP levels in patients with one or more traditional cardiovascular risk factors. Methods: Data were analysed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov Identifier: NCT00882336), which included patients (aged ≥50 years) from 12 European countries with at least one traditional cardiovascular risk factor but no history of cardiovascular disease. Analysis was also carried out on the subset of patients without diabetes mellitus who were not receiving statin therapy. Results: In the overall population, CRP levels were positively correlated with body mass index and glycated haemoglobin levels, and were negatively correlated with high-density lipoprotein cholesterol levels. CRP levels were also higher in women, those at higher traditionally estimated cardiovascular risk and those with greater numbers of metabolic syndrome markers. Among patients without diabetes mellitus who were not receiving statin therapy, approximately 30% had CRP levels ≥3 mg/L, and approximately 50% had CRP levels ≥2 mg/L, including those at intermediate levels of traditionally estimated cardiovascular risk. Conclusions: CRP levels are elevated in a large proportion of patients with at least one cardiovascular risk factor, without diabetes mellitus who are not receiving statin therapy, suggesting a higher level of cardiovascular risk than predicted according to conventional risk estimation systems

The GPIIIA PlA2 polymorphism is associated with an increased risk of cardiovascular adverse events

<p>Abstract</p> <p>Background</p> <p>The clinical impact of PlA2 polymorphism has been investigated in several diseases, but the definition of its specific role on thrombotic cardiovascular complications has been challenging. We aimed to explore the effect of PlA2 polymorphism on outcome in patients with atherosclerosis.</p> <p>Methods</p> <p>We studied 400 consecutive patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention. A replication study was conducted in 74 hypertensive patients with cerebrovascular events while a group of 100 healthy subjects was included as control population. PlA genotype was determined by PCR-RFLP on genomic DNA from peripheral blood cells. Major adverse cardiac events (MACE), were considered as end points, and recorded at a mean follow up of 24 ± 4.3 months.</p> <p>Results</p> <p>The frequencies of PlA2 polymorphism was similar between groups and genotype distribution was in Hardy-Weinberg equilibrium. In patients with CAD, the presence of PlA2 allele was associated with higher incidence of cardiac death (13.1% vs. 1.5%, p = 0.0001), myocardial infarction (10.7% vs. 2.6%, p = 0.004) and needs of new revascularization (34.8% vs. 17.7%, p = 0.010). Accordingly, the Kaplan-Meier analysis for event free survival in patients harboring the PlA2 allele showed worse long-term outcome for these patients (p = 0.015). Cox regression analysis identified the presence of PlA2 as an independent predictor of cardiac death (OR: 9.594, 95% CI: 2.6 to 35.3, p = 0.002) and overall MACE (OR: 1.829, 95% CI: 1.054 to 3.176, p = 0.032). In the replication study, the PlA2 polymorphism increased the risk of stroke (OR: 4.1, 95% CI: 1.63-12.4, p = 0.02) over TIA and was identified as an independent risk factor for stroke (B:-1.39; Wald: 7.15; p = 0.001).</p> <p>Conclusions</p> <p>Our study demonstrates that in patients with severe atherosclerosis the presence of PlA2 allele is associated with thrombotic cardiovascular complications.</p

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Cardiovascular disease and the role of oral bacteria

In terms of the pathogenesis of cardiovascular disease (CVD) the focus has traditionally been on dyslipidemia. Over the decades our understanding of the pathogenesis of CVD has increased, and infections, including those caused by oral bacteria, are more likely involved in CVD progression than previously thought. While many studies have now shown an association between periodontal disease and CVD, the mechanisms underpinning this relationship remain unclear. This review gives a brief overview of the host-bacterial interactions in periodontal disease and virulence factors of oral bacteria before discussing the proposed mechanisms by which oral bacterial may facilitate the progression of CVD

Mesenchymal stromal cells inhibit NLRP3 inflammasome activation in a model of Coxsackievirus B3-induced inflammatory cardiomyopathy

Inflammation in myocarditis induces cardiac injury and triggers disease progression to heart failure. NLRP3 inflammasome activation is a newly identified amplifying step in the pathogenesis of myocarditis. We previously have demonstrated that mesenchymal stromal cells (MSC) are cardioprotective in Coxsackievirus B3 (CVB3)-induced myocarditis. In this study, MSC markedly inhibited left ventricular (LV) NOD2, NLRP3, ASC, caspase-1, IL-1β, and IL-18 mRNA expression in CVB3-infected mice. ASC protein expression, essential for NLRP3 inflammasome assembly, increased upon CVB3 infection and was abrogated in MSC-treated mice. Concomitantly, CVB3 infection in vitro induced NOD2 expression, NLRP3 inflammasome activation and IL-1β secretion in HL-1 cells, which was abolished after MSC supplementation. The inhibitory effect of MSC on NLRP3 inflammasome activity in HL-1 cells was partly mediated via secretion of the anti-oxidative protein stanniocalcin-1. Furthermore, MSC application in CVB3-infected mice reduced the percentage of NOD2-, ASC-, p10- and/or IL-1β- positive splenic macrophages, natural killer cells, and dendritic cells. The suppressive effect of MSC on inflammasome activation was associated with normalized expression of prominent regulators of myocardial contractility and fibrosis to levels comparable to control mice. In conclusion, MSC treatment in myocarditis could be a promising strategy limiting the adverse consequences of cardiac and systemic NLRP3 inflammasome activation

Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

<p>Abstract</p> <p>Background</p> <p>Endothelin-1 and angiotensin II are strong vasoconstrictors. Patients with ischemic heart disease have elevated plasma levels of endothelin-1 and angiotensin II and show increased vascular tone. The aim of the present study was to examine the endothelin and angiotensin II receptor expression in subcutaneous arteries from patients with different degrees of ischemic heart disease.</p> <p>Methods</p> <p>Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A (ET_A) and type B (ET_B), and angiotensin type 1 (AT₁) and type 2 (AT₂) receptors expression and function were examined using immunohistochemistry, Western blot and <it>in vitro </it>pharmacology.</p> <p>Results</p> <p>ET_Aand, to a lesser extent, ET_Breceptor staining was observed in the healthy vascular smooth muscle cells. The level of ET_Breceptor expression was higher in patients undergoing CABG surgery (250% ± 23%; P < 0.05) and in the patients with angina pectoris (199% ± 6%; P < 0.05), than in the healthy controls (100% ± 28%). The data was confirmed by Western blotting. Arteries from CABG patients showed increased vasoconstriction upon administration of the selective ET_Breceptor agonist sarafotoxin S6c, compared to healthy controls (P < 0.05). No such difference was found for the ET_Areceptors. AT₁and, to a lesser extent, AT₂receptor immunostaining was seen in the vascular smooth muscle cells. The level of AT₁receptor expression was higher in both the angina pectoris (128% ± 25%; P < 0.05) and in the CABG patients (203% ± 41%; P < 0.05), as compared to the healthy controls (100% ± 25%). The increased AT₁receptor expression was confirmed by Western blotting. Myograph experiment did however not show any change in vasoconstriction to angiotensin II in CABG patients compared to healthy controls (P = n.s).</p> <p>Conclusion</p> <p>The results demonstrate, for the first time, upregulation of ET_Band AT₁receptors in vascular smooth muscle cells in ischemic heart disease. These receptors may play a role in the pathophysiology of ischemic heart disease and could provide important targets for pharmaceutical interventions.</p

The contribution of a 9p21.3 variant, a KIF6 variant, and C-reactive protein to predicting risk of myocardial infarction in a prospective study

<p>Abstract</p> <p>Background</p> <p>Genetic risk factors might improve prediction of coronary events. Several variants at chromosome 9p21.3 have been widely reported to be associated with coronary heart disease (CHD) in prospective and case-control studies. A variant of <it>KIF6 </it>(719Arg) has also been reported to be associated with increased risk of CHD in large prospective studies, but not in case-control studies. We asked whether the addition of genetic information (the 9p21.3 or <it>KIF6 </it>variants) or a well-established non-genetic risk factor (C-reactive protein [CRP]) can improve risk prediction by the Framingham Risk Score (FRS) in the Cardiovascular Health Study (CHS)--a prospective observational study of risk factors for cardiovascular disease among > 5,000 participants aged 65 or older.</p> <p>Methods</p> <p>Improvement of risk prediction was assessed by change in the area under the receiver-operator characteristic curve (AUC) and by net reclassification improvement (NRI).</p> <p>Results</p> <p>Among white participants the FRS was improved by addition of <it>KIF6 </it>719Arg carrier status among men as assessed by the AUC (from 0.581 to 0.596, P = 0.03) but not by NRI (NRI = 0.027, P = 0.32). Adding both CRP and 719Arg carrier status to the FRS improved risk prediction by the AUC (0.608, P = 0.02) and NRI (0.093, P = 0.008) in men, but not women (P ≥ 0.24).</p> <p>Conclusions</p> <p>While none of these risk markers individually or in combination improved risk prediction among women, a combination of <it>KIF6 </it>719Arg carrier status and CRP levels modestly improved risk prediction among white men; although this improvement is not significant after multiple-testing correction. These observations should be investigated in other prospective studies.</p

Associations between statins and COPD: a systematic review

<p>Abstract</p> <p>Background</p> <p>Statins have anti-inflammatory and immunomodulating properties which could possibly influence inflammatory airways disease. We assessed evidence for disease modifying effects of statin treatment in patients with chronic obstructive pulmonary disease (COPD).</p> <p>Methods</p> <p>A systematic review was conducted of studies which reported effects of statin treatment in COPD. Data sources searched included MEDLINE, EMBASE and reference lists.</p> <p>Results</p> <p>Eight papers reporting nine original studies met the selection criteria. One was a randomized controlled trial (RCT), one a retrospective nested case-control study, five were retrospective cohort studies of which one was linked with a case-control study, and one was a retrospective population-based analysis. Outcomes associated with treatment with statins included decreased all-cause mortality in three out of four studies (OR/HR 0.48–0.67 in three studies, OR 0.99 in one study), decreased COPD-related mortality (OR 0.19–0.29), reduction in incidence of respiratory-related urgent care (OR 0.74), fewer COPD exacerbations (OR 0.43), fewer intubations for COPD exacerbations (OR 0.1) and attenuated decline in pulmonary function. The RCT reported improvement in exercise capacity and dyspnea after exercise associated with decreased levels of C-reactive protein and Interleukin-6 in statin users, but no improvement of lung function.</p> <p>Conclusion</p> <p>There is evidence from observational studies and one RCT that statins may reduce morbidity and/or mortality in COPD patients. Further interventional studies are required to confirm these findings.</p

Carotid Artery Intima-Media Thickness, Carotid Plaque and Coronary Heart Disease and Stroke in Chinese

Background: Our aim was to prospectively investigate the association between carotid artery intima-media thickness (IMT) as well as carotid plaque and incidence of coronary heart disease (CHD) and stroke in Chinese, among whom data are limited. Methods and Findings: We conducted a community-based cohort study composed of 2190 participants free of cardiovascular disease at baseline in one community. During a median 10.5-year follow up, we documented 68 new cases of coronary heart disease and 94 cases of stroke. The multivariate relative risks (RRs) associated with a change of 1 standard deviation of maximal common carotid IMT were 1.38 (95% confidence interval [CI], 1.12–1.70) for CHD and 1.47 (95% CI, 1.28–1.69) for stroke. The corresponding RRs with internal carotid IMT were 1.47 (95% CI, 1.21–1.79) for CHD and 1.52 (95% CI, 1.31–1.76) for stroke. Carotid plaque measured by the degree of diameter stenosis was also significantly associated with increased risk of CHD (p for trend<0.0001) and stroke (p for trend<0.0001). However, these associations were largely attenuated when adjusting for IMT measurements. Conclusions: This prospective study indicates a significant association between carotid IMT and incidence of CHD and stroke in Chinese adults. These measurements may be useful for cardiovascular risk assessment and stratification in Chinese