Fasting insulin is a stronger cardiovascular risk factor in women than in men

Diabetes is a stronger risk factor for cardiovascular disease (CVD) in women than in men. It is not known whether there is also a sex difference in the association between hyperinsulinaemia, reflecting insulin resistance, and CVD. Fasting insulin was assessed with a specific assay in 6916 fasting, non-diabetic subjects of the PREVEND study without a prior history of CVD. Major Adverse Cardiovascular Events (MACE) (defined as CVD morbidity and CVD mortality) were prospectively recorded after the baseline survey. Cox-regression models were used to investigate the association of fasting insulin with subsequent development of MACE. Fasting insulin was 54 [38-77]pmol/l in women (age 48+/-12yrs) and 57 [40-88] pmol/l in men (age 49+/-13yrs). During follow-up for 7.5 [6.9-7.8]yrs, 98 cardiovascular events were recorded in 3626 women and 242 events in 3290 men. There was a significant (P<0.001) interaction between sex and fasting insulin for MACE, with the strongest association in women. In women, there was a logarithmic association for insulin with MACE, independent of age, alcohol consumption, and smoking (HR=1.50 [95% CI 1.17-1.91] per doubling of insulin, P=0.001). In men, for a similar multivariate model, there was a logarithmic association (HR=1.13 [95% CI [0.97-1.32] per doubling of insulin, P=0.1). Further adjustment for components of the insulin resistance syndrome weakened the association more in men than in women. With HOMA instead of insulin, results were essentially similar. In parallel with diabetes, fasting hyperinsulinaemia reflecting insulin resistance in non-diabetic subjects is associated with an increased risk for cardiovascular disease, which is more pronounced in women than in men.     

Apolipoprotein B, non-HDL cholesterol and LDL cholesterol for identifying individuals at increased cardiovascular risk

Abstract. Holewijn S, den Heijer M, Swinkels DW, Stalenhoef AFH, de Graaf J. (Address: Division of Vascular Medicine, Department of General Internal Medicine; Department of Epidemiology and Biostatistics; Department of Endocrinology; and Department of Laboratory Medicine; Laboratory of Clinical Chemistry, all at the Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands) Apolipoprotein B, non‐HDL cholesterol and LDL cholesterol for identifying individuals at increased cardiovascular risk. J Intern Med 2010; 268 : 567–577. Background. To compare apolipoprotein B (apoB), nonhigh‐density lipoprotein‐cholesterol (non‐HDL‐c) and low‐density lipoprotein‐cholesterol (LDL‐c) for identifying individuals with a deteriorated cardiovascular (CV) risk profile, including a panel of subclinical atherosclerosis measurements and prevalent cardiovascular disease (CVD) in a Dutch population‐based cohort. Methods. Clinical and biochemical measurements and a panel of noninvasive parameters of subclinical atherosclerosis were determined in 1517 individuals, aged 50–70 years. Results. Both men and women with increasing levels of apoB and non‐HDL‐c were more obese, had higher blood pressure and fasting glucose levels, and a more atherogenic lipid profile. Furthermore, compared to the reference group (composed of those with apoB, non‐HDL‐c and LDL‐c levels in the bottom quartiles), participants with high apoB and high non‐HDL‐c levels had a lower ankle–brachial index at rest (?3.5% and ?3.1%, respectively) and after exercise (?6.3% and ?4.7%, respectively), a thicker near wall (+4.8% and +4.2%, respectively), far wall (both +6.2%), and mean intima–media thickness (+5.7% and +5.3%, respectively) and more plaques (+54.2% and +54.3%, respectively). In addition, they also showed increased stiffness parameters (e.g. pulse wave velocity both +3.6%). Less clear differences in CV risk profile and subclinical atherosclerosis parameters were observed when participants were stratified by LDL‐c level. Furthermore, apoB but not LDL‐c detected prevalent CVD, and non‐HDL‐c only detected prevalent CVD in men. The discriminatory power for prevalent CVD expressed as area under the receiver operating characteristic curve was 0.60 (P < 0.001) for apoB, 0.57 (P = 0.001) for non‐HDL‐c and 0.54 (P = 0.108) for LDL‐c. Conclusion. Our data support the use of first apoB and secondly non‐HDL‐c above LDL‐c for identifying individuals from the general population with a compromised CV phenotype.     

Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease

BACKGROUND AND AIMS: The clinical course of inflammatory bowel disease is characterised by a succession of relapses and remissions. The aim of our study was to assess whether the predictive value of faecal calprotectin-a non-invasive marker of intestinal inflammation-for clinical relapse is different in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Seventy nine consecutive patients with a diagnosis of clinically quiescent inflammatory bowel disease (38 CD and 41 UC) were followed for 12 months, undergoing regular clinical evaluations and blood tests. A single stool sample was collected at the beginning of the study from each patient and the calprotectin concentration was assessed by a commercially available enzyme linked immunoassay. RESULTS: In CD, median calprotectin values were 220.1 mug/g (95% confidence interval (CI) 21.7-418.5) in those patients who relapsed during follow up, and 220.5 mug/g (95% CI 53-388) in non-relapsing patients (p=0.395). In UC, median calprotectin values were 220.6 mug/g (95% CI 86-355.2) and 67 microg/g (95% CI 15-119) in relapsing and non-relapsing patients, respectively (p<0.0001). The multivariate Cox (proportional hazard) regression model, after adjustment for possible confounding variables, showed a twofold and 14-fold increase in the relapse risk, respectively, in those patients with CD and UC in clinical remission who had a faecal calprotectin concentration higher than 150 microg/g. CONCLUSIONS: Faecal calprotectin proved to be an even stronger predictor of clinical relapse in UC than in CD, which makes the test a promising non-invasive tool for monitoring and optimising therapy.     

Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study.

BACKGROUND: Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratios are used to predict ischemic heart disease risk. There is, however, no consensus on which of these 2 indices is superior. The objective of the present study was to present evidence that the LDL-C/HDL-C ratio may underestimate ischemic heart disease risk in overweight hyperinsulinemic patients with high triglyceride (TG)-low HDL-C dyslipidemia. METHODS: A total of 2103 middle-aged men in whom measurements of the metabolic profile were performed in the fasting state were recruited from 7 suburbs of the Quebec metropolitan area. RESULTS: The relationship of LDL-C/HDL-C to TC/HDL-C ratios was examined among men in the Quebec Cardiovascular Study classified into tertiles of fasting TG levels. For any given LDL-C/HDL-C ratio, the TC/HDL-C ratio was higher among men in the top TG tertile (>168 mg/dL [>1.9 mmol/L]) than in men in the first and second TG tertiles. Adjustment of the TC/HDL-C ratio for LDL-C/HDL-C by covariance analysis generated significant differences in average TC/HDL-C ratios among TG tertiles (P<.001). Greater differences in features of the insulin resistance syndrome (insulinemia, apolipoprotein B, and LDL size) were noted across tertiles of the TC/HDL-C ratio than tertiles of the LDL-C/HDL-C ratio. CONCLUSION: Variation in the TC/HDL-C ratio may be associated with more substantial alterations in metabolic indices predictive of ischemic heart disease risk and related to the insulin resistance syndrome than variation in the LDL-C/HDL-C ratio.     

A comparison of HDL and LDL cholesterol for prevalent coronary calcification

BACKGROUND: Coronary calcification is a marker for coronary atherosclerosis. It has been postulated that high levels of high density lipoprotein cholesterol (HDL-C) are associated with a reduced amount of atherosclerotic disease while previous reports have found a lack of association between low density lipoprotein cholesterol (LDL-C) and coronary calcification (CAC). The purpose of this study was to compare the correlation and predictive power of HDL-C with LDL-C for prevalent coronary calcification. METHODS: A total of 6093 subjects were studied with respect to coronary calcification, serum cholesterol indices, personal health history and body morphology. Analyses consisted of correlation coefficients, logistic regression and sensitivity analysis to determine the strength of association between HDL-C and coronary calcification after controlling for covariates. RESULTS: The correlation between HDL-C and coronary calcium score (CCS) was three times that of LDL-C. Individuals with an HDL-C level <40 mg/dl had significantly higher calcium scores while increases in HDL-C were associated with a significant reduction in risk for the presence of any calcified plaque. Results of multivariate logistic regression revealed that HDL-C is predictive of calcified plaque development independent of LDL-C. Sensitivities and positive predictive values for both HDL-C and LDL-C were low. CONCLUSIONS: Increasing levels of HDL-C were associated with less coronary calcification and a smaller probability of having any calcified disease supporting the antiatherogenic hypothesis for HDL-C. HDL-C predicts the presence of any calcified atherosclerotic plaque independently of LDL-C. However, neither parameter seems suitable as a screening tool for predicting prevalent calcified atheromatous disease.     

和肽素临床应用的新进展

和肽素是精氨酸加压素的替代物,性质稳定,易于检测。和肽素与TnT联合检测提高冠状动脉综合征的诊断。和肽素是急性非ST段心肌梗死不良事件发生的独立预测因子。联合检测和肽素和脑钠肽预测心力衰竭的预后。     

Apolipoprotein B is a better marker than non-HDL-cholesterol for the metabolic syndrome in Koreans

Apolipoprotein B (apoB) concentration reflects the number of atherogenic particles and is closely associated with atherosclerosis. Non-HDL-cholesterol (non-HDL-C) has been considered a therapeutic target for patients with hypertriglyceridemia. We compared the predictive values of apoB and non-HDL-C for the metabolic syndrome (MetS) in 3335 Korean adults (mean age, 45.2 years) who participated consecutively in a health examination in a university hospital. Anthropometry, blood pressure, fasting glucose, lipid profiles and apoB were measured. MetS, as defined by a modification of the NCEP-ATP III criteria, was present in 22.1% of men and 16.1% of women. Among the components of the MetS, triglycerides showed the strongest correlation with apoB (r=0.393, P<0.001 in men, and r=0.326, P<0.001 in women) and non-HDL-C (r=0.376, P<0.001 in men, and r=0.349, P<0.001 in women). When apoB and non-HDL-C were mutually adjusted, the ORs for the MetS of non-HDL-C were not significant. As a function of the quartile of apoB levels, the ORs for the MetS were 2.04 (1.26-3.30), 3.54 (2.11-5.93), and 5.38 (3.16-9.17) in men (P for trend <0.001) and 3.75 (1.42-9.87), 5.55 (2.09-14.69), and 13.41 (5.02-35.79) in women (P for trend <0.001), respectively. These findings indicate that apoB is a better marker than non-HDL-C for identifying the MetS among Koreans.     

A serum amyloid A and LDL complex as a new prognostic marker in stable coronary artery disease

BACKGROUND: Although some reports have indicated that acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) can predict the prognosis in patients with acute coronary syndrome, the value of these markers in patients with stable coronary artery disease (CAD) still remains obscure. Therefore, our aim was to determine the prognostic value of inflammatory markers in patients with stable coronary artery disease. METHODS AND RESULTS: We conducted a prospective cohort study in 140 consecutive patients with stable coronary artery disease who had at least one coronary stenosis more than 50% in diameter seen on diagnostic coronary angiography (CAG). We determined serum levels of the SAA/LDL complex as a new marker in addition to CRP and SAA. Serum levels of the SAA/LDL complex were measured by a sandwich enzyme-linked immunosorbent assay (ELISA). End-points were defined as cardiac death, myocardial infarction, cerebral infarction, and coronary revascularization. End-point events occurred in 21 patients (2 death from myocardial infarction, 2 cerebral infarction, and 17 revascularization). Age (year) (OR = 1.14, CI: 1.05-1.25), diabetes mellitus (OR = 3.50, CI: 1.08-11.40), triglyceride (10mg/dl) (OR = 1.12, CI: 1.01-1.23) and SAA/LDL complex (10 microg/ml) (OR = 2.32, CI: 1.05-4.70) were independently related to the events. A reconstitution experiment suggested that the SAA/LDL complex is derived by oxidative interaction between SAA and lipoproteins. CONCLUSIONS: The SAA/LDL complex reflects intravascular inflammation directly and can be a new marker more sensitive than CRP or SAA for prediction of prognosis in patients with stable coronary artery disease.     

The associations between visceral fat and calcified atherosclerosis are stronger in women than men

BackgroundPrevious studies have found a significant association between body mass index (BMI) and coronary artery calcium (CAC). Little is known about whether body fatness is linked with atherosclerotic calcium (AC) in the non-coronary vasculature. Accordingly, this study tested the hypothesis that there would be significant associations between CAC and AC in the non-coronary vasculature and BMI, visceral fat (VF), and percent body fat (BF%).MethodsSubjects (n = 1160; mean age 57 years; 55% men) underwent electron beam computed tomography (EBCT) screening for AC in the carotid, coronary, thoracic and abdominal aorta, and iliac arteries. Visceral fat and BF% were measured using EBCT and electrical bioimpedance analysis, respectively.ResultsIn sex-stratified models adjusted for CVD risk factors, there were significant associations among both sexes between 1-SD increments of BMI, BF% and VF and the presence of CAC (p < 0.01) as well as for quartiles of BMI and VF and prevalent CAC. Higher levels (tertiles) of BF% and VF were significantly associated with higher amounts of both abdominal aortic calcium (OR = 1.90, 1.57 with p = 0.02, 0.05 in females and males, respectively) and CAC.ConclusionsMeasures of body morphology are significantly associated with AC in the coronary arteries and abdominal aorta. Of the measures studied, VF appears to be the most relevant by having the most consistent and stronger magnitudes of association, especially in women. These results suggest that VF may be more relevant in women than men with respect to the presence and extent of atherosclerosis in multiple vascular beds.     

Evaluation of the gene-age interactions in HDL cholesterol, LDL cholesterol, and triglyceride levels: the impact of the SORT1 polymorphism on LDL cholesterol levels is age dependent

Several genes that influence HDL-C, LDL-C, and triglyceride levels have been identified. The effects of genetic polymorphisms on lipid levels may be age dependent. We replicated 17 of these previously identified associations and then used cross-sectional and longitudinal analysis to investigate age-SNP interaction effects. The rs646776 SNP at the SORT1 locus showed an age interaction that was significant in cross-sectional analyses of 1350 individuals from Utah (p = 0.0003) and in 2977 individuals from the NHLBI Family Heart Study (p = 0.007) as well as in longitudinal analysis of a subsample of 1099 individuals from the Utah cohort that had been followed for over 20 years (p = 0.0001). The rs646776 genotype-specific difference in LDL-C levels was significantly greater for younger individuals than for older individuals. These findings may help elucidate the mode of action of the SORT1 gene and impact potential therapeutic interventions targeting this pathway.     

Serum cystatin C is associated with other cardiovascular risk markers and cardiovascular disease in elderly men

Renal dysfunction is associated with increased cardiovascular morbidity and mortality. The aim of this cross-sectional study was to investigate the relationship between the glomerular filtration marker cystatin C and other cardiovascular risk markers and morbidity in elderly males. Cystatin C was measured in a group of 77-year-old males (n=792) and compared cystatin C with other known risk markers for cardiovascular disease. Cystatin C values were significantly increased in individuals with diabetes (p=0.05) and cardiovascular diseases (p<0.0001). There were significant correlations between cystatin C values and body mass index, HbA1c, insulin, triglycerides and hsCRP.     

Plasma retinol: a novel marker for cardiovascular disease mortality in Australian adults

Background and aimsVitamin A affects inflammation and immune function and is thus a factor of interest in relation to cardiovascular disease (CVD). As vitamin A circulates in the plasma in the form of retinol, this study aims to describe the relationship between plasma retinol and the 5-year incidence of CVD mortality.Methods and resultsCommunity-dwelling adults (n = 441, 45% with type 2 diabetes) were recruited in Melbourne, assessed at baseline and followed for 5 years. At baseline, CVD risk factors were assessed by clinical evaluation, by personal lifestyle questionnaire and from biochemistry (plasma fasting glucose, lipids, total homocysteine, C-reactive protein, retinol and carotenoids plus the urinary albumin excretion rate over 24 h.). Dietary intake was assessed by a validated food frequency questionnaire. CVD mortality over 5-years was determined by consulting state or national registries. The majority of participants had adequate plasma retinol concentrations (≥30 μg/dL). The final Cox regression model indicated that those in the highest tertile of plasma retinol (mean ± SD) 76 ± 14 μg/dL) had a significantly lower risk of 5-year CVD mortality (hazard ratio 0.27 [95% confidence interval 0.11, 0.68], P = 0.005), an effect that was not readily explained in terms of traditional CVD risk factors or dietary intake.ConclusionIn well-nourished older Australian adults, plasma retinol was inversely associated with CVD mortality via mechanisms apparently unrelated to established CVD risk factors and dietary intake.     

Alcohol consumption and cardiovascular disease mortality in hypertensive men

BACKGROUND: Heavy alcohol drinking is associated with a dose-dependent increase in blood pressure, but data on the relation between alcohol consumption and mortality in hypertensive patients are sparse. OBJECTIVE: To assess the relation between light to moderate alcohol consumption and total mortality from cardiovascular disease (CVD) among men with hypertension. PARTICIPANTS AND DESIGN: From the Physicians' Health Study enrollment cohort of 88,882 men who provided self-reported information on alcohol intake, we identified a group of 14,125 men with a history of current or past treatment for hypertension who were free of myocardial infarction, stroke, cancer, or liver disease at baseline.Main Outcome Measure Comparison of total and CVD mortality among men with hypertension who had reported to be either nondrinkers or rare drinkers, or light to moderate drinkers. RESULTS: During 75,710 person-years of follow-up, there were 1018 deaths, including 579 from CVD. Compared with individuals who rarely or never drank alcoholic beverages, those who reported monthly, weekly, and daily alcohol consumption, respectively, had multivariate adjusted relative risks (RRs) for CVD mortality of 0.83 (95% confidence interval [CI], 0.62-1.13), 0.61 (CI, 0.49-0.77), and 0.56 (CI, 0.44-0.71) (P<.001 for linear trend). In the same groups, RRs for total mortality were respectively 0.86 (CI, 0.67-1.10), 0.72 (CI, 0.60-0.86), and 0.73 (CI, 0.61-0.87) (P<.001 for linear trend). Among men with a systolic blood pressure of 140 mm Hg or higher or a diastolic blood pressure of 90 mm Hg or higher, the RRs for CVD mortality were, respectively, 1.00 (referent), 0.82 (CI, 0.56-1.21), 0.64 (CI, 0.48-0.85), and 0.56 (CI, 0.42-0.75) (P<.001 for linear trend). On the other hand, we found no significant association between moderate alcohol consumption and cancer mortality (P =.8 for linear trend). CONCLUSION: These results, which require confirmation in other large-scale studies, suggest that light to moderate alcohol consumption is associated with a reduction in risk of total and CVD mortality in hypertensive men.     

Intra-individual variability of total cholesterol is associated with cardiovascular disease mortality: A cohort study

Background and aimsThe relationship between serum total cholesterol (TC) and mortality remains inconsistent. Additionally, intra-individual variability of cholesterol has been of increasing interest as a new indicator for health outcomes. We aimed to examine the association between TC and its variability and risk of mortality.Methods and resultsWe performed a retrospective cohort study with 122,645 individuals aged over 40 years in Ningbo, China. The intra-individual variability was calculated using four metrics including standard deviation, coefficient variation, variation independent of mean and average successive variability. Hazard ratios and 95% confidence intervals were estimated for the associations of baseline and variability in TC with risk of mortality by Cox proportional hazards regression models. During 591,585.3 person-years of follow-up, 4563 deaths (including 1365 from cardiovascular disease, 788 from stroke and 1514 from cancer) occurred. A U-shaped association was observed for baseline TC level and risk of total, cardiovascular and cancer mortality, with lowest mortality at 5.46 mmol/L, 5.04 mmol/L and 5.51 mmol/L, respectively. As compared with subjects with TC variability in the lowest quartile, individuals in the highest quartile had 21% higher risk of all-cause mortality (HR = 1.21, 95% CI: 1.05 to 1.40), and 41% higher risk of CVD mortality (HR = 1.41, 95%CI: 1.10 to 1.81).ConclusionBoth too low and too high baseline TC level were associated with higher risk of total, cardiovascular disease and cancer mortality. Variability of TC could be a risk factor of total and CVD mortality, independent of mean TC level. Future studies are needed to confirm these findings.