Association of high-sensitive C-reactive protein with advanced stage beta-cell dysfunction and insulin resistance in patients with type 2 diabetes mellitus

Background: Type 2 diabetes mellitus is associated with increased cardiovascular risk. One laboratory marker for cardiovascular risk assessment is high-sensitivity C-reactive protein (hsCRP). Methods: This cross-sectional study attempted to analyze the association of hsCRP levels with insulin resistance, beta-cell dysfunction and macrovascular disease in 4270 non-insulin-treated patients with type 2 diabetes {[}2146 male, 2124 female; mean age +/- SD, 63.9 +/- 11.1 years; body mass index (BMI) 30.1 +/- 5.5 kg/m(2); disease duration 5.4 +/- 5.6 years; hemoglobin A(1c) (HbA(1c)) 6.8 +/- 1.3% ]. It consisted of a single morning visit with collection of a fasting blood sample. Observational parameters included several clinical scores and laboratory biomarkers. Results: Stratification into cardiovascular risk groups according to hsCRP levels revealed that 934 patients had low risk (hsCRP < 1 mg/L), 1369 patients had intermediate risk (hsCRP 1-3 mg/L), 1352 patients had high risk (hsCRP > 3-10 mg/ L), and 610 patients had unspecific hsCRP elevation ( > 10 mg/ L). Increased hsCRP levels were associated with other indicators of diabetes-related cardiovascular risk (homeostatic model assessment, intact proinsulin, insulin, BMI, beta-cell dysfunction, all p < 0.001), but showed no correlation with disease duration or glucose control. The majority of the patients were treated with diet (34.1%; hsCRP levels 2.85 +/- 2.39 mg/L) or metformin monotherapy (21.1%; 2.95 +/- 2.50 mg/L hsCRP). The highest hsCRP levels were observed in patients treated with sulfonylurea (17.0%; 3.00 +/- 2.43 mg/ L). Conclusions: Our results indicate that hsCRP may be used as a cardiovascular risk marker in patients with type 2 diabetes mellitus and should be evaluated in further prospective studies

New Promises and Challenges on Inflammation and Atherosclerosis: Insights From CANTOS and CIRT Trials

open2siAtherosclerosis is still a great burden on human health and scientific achievements of the past 30 years have definitively proven the inflammatory causes of the disease (1, 2) highlighted by the results of the CANTOS trial (3). Canakinumab inhibition of interleukin-1 (IL1)-beta has been demonstrated to provide protection against cardiovascular (CV) risk irrespective of lipid levels in a cohort of patients with high C–reactive protein (CRP) levels despite achieving blood lipid control, as measured by high sensitivity C-Reactive Protein (hsCRP) (3). The final demonstration of atherosclerosis as an inflammatory-driven pathology is driving research toward new anti-inflammatory approaches that could influence the natural history of the disease and change the clinical paradigms of therapy. Considering the costs of canakinumab and exploiting different avenues of anti-inflammatory therapies, a more affordable approach has been proposed by the authors of the CANTOS study (4).openPalmer, Raymond; Vaccarezza, MauroPalmer, Raymond; Vaccarezza, Maur

Inflammation and Atherothrombosis: Where Have We Been? Where Are We Going? Why Perform the CIRT and CANTOS Trials? From Bench to Bedside to Population and Back: A Story of Clinical Translation

Discussion of clinical and translational science in the context of Dr. Ridker\u27s research on inflammation, atherothrombosis, and cardiovascular disease prevention

Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials

Background: Lowering of LDL cholesterol with standard statin regimens reduces the risk of occlusive vascular events in a wide range of individuals. We aimed to assess the safety and efficacy of more intensive lowering of LDL cholesterol with statin therapy. Methods: We undertook meta-analyses of individual participant data from randomised trials involving at least 1000 participants and at least 2 years' treatment duration of more versus less intensive statin regimens (five trials; 39 612 individuals; median follow-up 5·1 years) and of statin versus control (21 trials; 129 526 individuals; median follow-up 4·8 years). For each type of trial, we calculated not only the average risk reduction, but also the average risk reduction per 1·0 mmol/L LDL cholesterol reduction at 1 year after randomisation. Findings: In the trials of more versus less intensive statin therapy, the weighted mean further reduction in LDL cholesterol at 1 year was 0·51 mmol/L. Compared with less intensive regimens, more intensive regimens produced a highly significant 15% (95% CI 11–18; p<0·0001) further reduction in major vascular events, consisting of separately significant reductions in coronary death or non-fatal myocardial infarction of 13% (95% CI 7–19; p<0·0001), in coronary revascularisation of 19% (95% CI 15–24; p<0·0001), and in ischaemic stroke of 16% (95% CI 5–26; p=0·005). Per 1·0 mmol/L reduction in LDL cholesterol, these further reductions in risk were similar to the proportional reductions in the trials of statin versus control. When both types of trial were combined, similar proportional reductions in major vascular events per 1·0 mmol/L LDL cholesterol reduction were found in all types of patient studied (rate ratio [RR] 0·78, 95% CI 0·76–0·80; p<0·0001), including those with LDL cholesterol lower than 2 mmol/L on the less intensive or control regimen. Across all 26 trials, all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction (RR 0·90, 95% CI 0·87–0·93; p<0·0001), largely reflecting significant reductions in deaths due to coronary heart disease (RR 0·80, 99% CI 0·74–0·87; p<0·0001) and other cardiac causes (RR 0·89, 99% CI 0·81–0·98; p=0·002), with no significant effect on deaths due to stroke (RR 0·96, 95% CI 0·84–1·09; p=0·5) or other vascular causes (RR 0·98, 99% CI 0·81–1·18; p=0·8). No significant effects were observed on deaths due to cancer or other non-vascular causes (RR 0·97, 95% CI 0·92–1·03; p=0·3) or on cancer incidence (RR 1·00, 95% CI 0·96–1·04; p=0·9), even at low LDL cholesterol concentrations. Interpretation: Further reductions in LDL cholesterol safely produce definite further reductions in the incidence of heart attack, of revascularisation, and of ischaemic stroke, with each 1·0 mmol/L reduction reducing the annual rate of these major vascular events by just over a fifth. There was no evidence of any threshold within the cholesterol range studied, suggesting that reduction of LDL cholesterol by 2–3 mmol/L would reduce risk by about 40–50%

Disparate Effects of Atorvastatin Compared With Simvastatin on C-Reactive Protein Concentrations in Patients With Type 2 Diabetes

OBJECTIVE - Reduction in LDL and high sensitivity (hs) C-reactive protein (CRP) are independent indicators of successful cardiovascular risk reduction with statins. This study compared the effect of equivalent LDL-lowering doses of simvastatin and atorvastatin on hsCRP in type 2 diabetic patients. RESEARCH DESIGN AND METHODS - A crossover study of 26 patients with type 2 diabetes taking either 40 mg simvastatin or 10 mg atorvastatin was undertaken. After 3 months on one statin, lipids and hsCRP were measured on 10 occasions over a 5-week period. The same procedure was then followed taking the other statin. RESULTS - LDL was comparable on either treatment: atorvastatin 2.2 +/- 0.2 vs. 2.1 +/- 0.3 mmol/l (mean +/- SD; P = 0.19). CRP of individuals taking atorvastatin was significantly lower than when they were taking simvastatin (median 1.08 vs. 1.47 mg/l, P = 0.0002) and was less variable (median SD of logCRP 0.0036 vs. 0.178, P = 0.0001). CONCLUSIONS - Compared with simvastatin, atorvastatin reduced hsCRP and its variability in type 2 diabetic patients. This enhanced anti-inflammatory effect may prove beneficial if lower CRP is associated with improved cardiovascular risk

Area-Level Socioeconomic Status, Adiposity, Physical Activity, and Inflammation in Young Adults, 2013

INTRODUCTION: We assessed the independent effects of socioeconomic status, sex, adiposity, and physical activity on C-reactive protein in young adults. METHODS: During the fall semester of their first year, college students (n = 177; mean age, 18.1 y; 66.7% female; 65.5% white) were assessed for adiposity via dual x-ray absorptiometry, physical activity via accelerometer, and serum C-reactive protein. Area-level socioeconomic status was based on self-reported home zip code. Hierarchical linear modeling was used to assess the relationship of sex, adiposity, and physical activity on the dependent variable of C-reactive protein, with participants nested within geographic regions of similar socioeconomic characteristics. RESULTS: C-reactive protein was positively associated with adiposity and inversely associated with socioeconomic status (both P < .05). Area-level socioeconomic status explained 28.2% of the variance in C-reactive protein. Adiposity was significantly associated with C-reactive protein in the full model (P = .006); physical activity was not associated with C-reactive protein (P = .48), and area-level socioeconomic status approached significance (P = .05) within the age range of our analysis after accounting for the variance explained by adiposity. CONCLUSION: The significant positive association between adiposity and C-reactive protein suggests that young adults with higher adiposity have higher C-reactive protein levels after accounting for area-level socioeconomic status, sex, and physical activity

Are Statins Anti-Inflammatory?

Large scale clinical trials demonstrate significant reductions in cardiovascular event rates with statin therapy. The observed benefit of statin therapy, however, may be larger in these trials than that expected on the basis of lipid lowering alone. Emerging evidence from both clinical trials and basic science studies suggest that statins have anti-inflammatory properties, which may additionally lead to clinical efficacy. Measurement of markers of inflammation such as high sensitivity C-reactive protein in addition to lipid parameters may help identify those patients who will benefit most from statin therapy