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

Acute-phase proteins and incidence of diabetes: a population-based cohort study

Aims: To examine the relationship between plasma levels of the acute-phase proteins ceruloplasmin, alpha-1-antitrypsin, orosomucoid, haptoglobin and C-reactive protein (CRP), and incidence of diabetes in the population-based Malmö Diet and Cancer Study—Cardiovascular Cohort (MDCS-CC). Methods: The study population consists of 4246 participants (aged 46–67 years, 60.8 % women) with no previous history of diabetes. Participants were followed, and incidence of diabetes was assessed by linkage with national registers and a clinical re-examination of the cohort. Cox proportional hazard regression analysis was used to compare incidence of diabetes in relation to sex-specific quartiles of the acute-phase proteins. Results: During a mean follow-up period of 15.6 ± 3.4 years, a total of 390 participants were diagnosed with diabetes. Orosomucoid, haptoglobin, and CRP showed a significant increased risk of diabetes after adjustment for potential confounders. However, further adjustments for fasting glucose at baseline resulted in significant association only for CRP. The multivariable-adjusted hazard ratios (HR: 4th vs. 1st quartile) were 1.18 (95 % CI: 0.83–1.67; p = 0.51), 1.19 (CI: 0.85–1.62; p = 0.10), and 1.40 (CI: 1.01–1.95; p = 0.046) for orosomucoid, haptoglobin, and CRP respectively. Conclusion: The study demonstrated that there are associations between orosomucoid, haptoglobin and CRP and the risk of incidence of diabetes. However, after additional adjustment for fasting glucose levels at baseline, the association stayed significant only for CRP

Alcohol Consumption and Common Carotid Intima-Media Thickness: The USE-IMT Study

AIMS: Epidemiological evidence indicates a protective effect of light to moderate alcohol consumption compared to non-drinking and heavy drinking. Although several mechanisms have been suggested, the effect of alcohol on atherosclerotic changes in vessel walls is unclear. Therefore, we explored the relationship between alcohol consumption and common carotid intima media thickness, a marker of early atherosclerosis in the general population. METHODS: Individual participant data from eight cohorts, involving 37,494 individuals from the USE-IMT collaboration were used. Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) with alcohol consumption. RESULTS: The mean age was 57.9 years (SD 8.6) and the mean CIMT was 0.75 mm (SD 0.177). About, 40.5% reported no alcohol consumed, and among those who drank, mean consumption was 13.3 g per day (SD 16.4). Those consuming no alcohol or a very small amount (10 g per day, after adjusting for a range of confounding factors. CONCLUSION: In this large CIMT consortium, we did not find evidence to support a protective effect of alcohol on CIMT

Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium

Aims: Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown. Methods and Results: A total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8%) met the diagnostic criteria for OH (systolic/diastolic BP drop ≥20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95% confidence interval: 0.90, 0.85–0.96; P = 0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.75–0.95; P = 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.87–0.98; P= 0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.02–1.24; P = 0.02, rs198358: 1.10, 1.01–1.20; P = 0.04, and rs5068: 1.22, 1.04–1.43; P = 0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P= 0.04). Conclusion: The overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components

Loneliness and social isolation as risk factors for coronary heart disease and stroke: systematic review and meta-analysis of longitudinal observational studies

BACKGROUND: The influence of social relationships on morbidity is widely accepted, but the size of the risk to cardiovascular health is unclear. OBJECTIVE: We undertook a systematic review and meta-analysis to investigate the association between loneliness or social isolation and incident coronary heart disease (CHD) and stroke. METHODS: Sixteen electronic databases were systematically searched for longitudinal studies set in high-income countries and published up until May 2015. Two independent reviewers screened studies for inclusion and extracted data. We assessed quality using a component approach and pooled data for analysis using random effects models. RESULTS: Of the 35 925 records retrieved, 23 papers met inclusion criteria for the narrative review. They reported data from 16 longitudinal datasets, for a total of 4628 CHD and 3002 stroke events recorded over follow-up periods ranging from 3 to 21 years. Reports of 11 CHD studies and 8 stroke studies provided data suitable for meta-analysis. Poor social relationships were associated with a 29% increase in risk of incident CHD (pooled relative risk: 1.29, 95% CI 1.04 to 1.59) and a 32% increase in risk of stroke (pooled relative risk: 1.32, 95% CI 1.04 to 1.68). Subgroup analyses did not identify any differences by gender. CONCLUSIONS: Our findings suggest that deficiencies in social relationships are associated with an increased risk of developing CHD and stroke. Future studies are needed to investigate whether interventions targeting loneliness and social isolation can help to prevent two of the leading causes of death and disability in high-income countries. STUDY REGISTRATION NUMBER: CRD42014010225

C-reactive protein, established risk factors and social inequalities in cardiovascular disease – the significance of absolute versus relative measures of disease

<p>Abstract</p> <p>Background</p> <p>The widespread use of relative scales in socioepidemiological studies has recently been criticized. The criticism is based mainly on the fact that the importance of different risk factors in explaining social inequalities in cardiovascular disease (CVD) varies, depending on which scale is used to measure social inequalities. The present study examines the importance of established risk factors, as opposed to low-grade inflammation, in explaining socioeconomic differences in the incidence of CVD, using both relative and absolute scales.</p> <p>Methods</p> <p>We obtained information on socioeconomic position (SEP), established risk factors (smoking, hypertension, and hyperlipidemia), and low-grade inflammation as measured by high-sensitive (hs) C-reactive protein (CRP) levels, in 4,268 Swedish men and women who participated in the Malmö Diet and Cancer Study (MDCS). Data on first cardiovascular events, i.e., stroke or coronary event (CE), was collected from regional and national registers. Social inequalities were measured in relative terms, i.e., as ratios between incidence rates in groups with lower and higher SEP, and also in absolute terms, i.e., as the absolute difference in incidence rates in groups with lower and higher SEP.</p> <p>Results</p> <p>Those with low SEP had a higher risk of future CVD. Adjustment for risk factors resulted in a rather small reduction in the relative socioeconomic gradient, namely 8% for CRP (≥ 3 mg/L) and 21% for established risk factors taken together. However, there was a reduction of 18% in the absolute socioeconomic gradient when looking at subjects with CRP-levels < 3 mg/L, and of 69% when looking at a low-risk population with no smoking, hypertension, or hyperlipidemia.</p> <p>Conclusion</p> <p>C-reactive protein and established risk factors all contribute to socioeconomic differences in CVD. However, conclusions on the importance of "modern" risk factors (here, CRP), as opposed to established risk factors, in the association between SEP and CVD depend on the scale on which social inequalities are measured. The one-sided use of the relative scale, without including a background of absolute levels of disease, and of what causes disease, can consequently prevent efforts to reduce established risk factors by giving priority to research and preventive programs looking in new directions.</p

Tobacco and myocardial infarction in middle-aged women: a study of factors modifying the risk.

Background. Although myocardial infarction (MI) is strongly related to smoking, few have studied why some smokers are more vulnerable than others. This study explored how the risk of MI in current and former smokers is modified by other cardiovascular risk factors. Methods. Incidence of MI (fatal and nonfatal) amongst 10619 women, 48.3 ± 8.2 years old, were studied in relation to smoking, hypertension, hypercholesterolaemia, diabetes, marital status and occupational level over a mean follow-up of 14 years. Results. Of the 3738 smokers, one-third had at least one major biological risk factor besides smoking; 228 women had MI during follow-up. Smoking and hypertension showed a synergistic effect on incidence of MI. The adjusted relative risks (RR) were 12.2 (95% CI: 7.5-19.8) for smokers with hypertension, 5.3 (CI:3.3-8.1) for smokers with normal blood pressure and 2.4 (CI:1.4-4.3) for never-smokers with hypertension (reference: normotensive never-smokers). The corresponding RRs for diabetic smokers and diabetic never-smokers were 19.0 (CI: 10.2-35.4) and 8.8 (CI: 4.4-17.4), respectively (reference: nondiabetic never-smokers). In terms of attributable risks, hypertension, hypercholesterolaemia and diabetes accounted for 12.9, 11.5 and 7.2%, respectively, of MI in female smokers. Low socio-economic level and being unmarried accounted for 19.6 and 1.6%, respectively. Conclusions. Although smoking is a major risk factor for MI, the risk varies widely between women with similar tobacco consumption. The results illustrate the need of a global risk factor assessment in female smokers and suggest that female smokers should be targets both for intensified risk factor management and programmes to stop smoking

Plasma oxidized LDL: a predictor for acute myocardial infarction?

Objectives. Oxidized LDL has been attributed a key role in the development of atherosclerosis. Previous studies have demonstrated increased plasma levels of oxidized LDL in patients with established coronary artery disease. The aim of the present study was to investigate if plasma oxidized LDL also predicts risk for development of coronary heart disease (CHD). Design. We used a nested case-control design to study the association between plasma levels of oxidized LDL and risk for development of acute myocardial infarction (AMI) and/or death by CHD. Subjects. Oxidized LDL was analysed by ELISA in cases (n = 26), controls (n = 26) and controls with LDL cholesterol >5.0 mmol L-1 (n = 26). Results. Oxidized LDL correlated with total plasma and LDL cholesterol in both cases (r = 0.72, P < 0.01, r = 0.69, P < 0.01, respectively) and controls (r = 0.71, P < 0.01, r = 0.77, P < 0.01, respectively). The oxidized LDL/plasma cholesterol ratio was higher amongst cases (13.5, range 10.7-19.8) than in controls (12.6, range 9.5-15.8, P < 0.05) and hypercholesterolaemic controls (12.2, range 8.0-16.0, P < 0.01). Conclusions. These findings identify high plasma oxidized LDL/total cholesterol ratio as a possible indicator of increased risk for AMI

Multiple anthropometric measures in relation to incidence of diabetes: a Swedish population-based cohort study.

Obesity is the major modifiable risk factor for diabetes. This study investigated the incidence of diabetes in relation to multiple anthropometric measures