Fifty-three year follow-up of coronary heart disease versus HDL2 and other lipoproteins in Gofman's Livermore Cohort

To assess the relationships of lipoprotein mass concentrations to all-cause and coronary heart disease (CHD) mortality, we analyzed the prospective 53-year follow-up of 1,905 men measured for lipoprotein mass concentrations by analytic ultracentrifugation between 1954 and 1957. Cause of death was determined from medical records and death certificates before 1979 and from National Death Index death diagnoses thereafter. Of the 1,329 men (69.8%) who died through 2008, CHD was listed as a contributing cause of death for 409 men, including 113 deaths from premature CHD (age ≤ 65 years). When adjusted for age, the risk associated with the lowest HDL2 quartile increased 22% for all-cause (P = 0.001), 63% for total CHD (P < 10(-5)), and 117% for premature CHD mortality (P = 0.0001). When adjusted for standard risk factors (age, total cholesterol, blood pressure, BMI, smoking) and the lowest HDL3 quartile, the corresponding risk increases were 14% (P = 0.05), 38% (P = 0.004), and 62% (P = 0.02), respectively. Men with HDL3 ≤ 25(th) percentile had 28% greater total CHD risk (P = 0.03) and 71% greater premature CHD risk (P = 0.01). Higher LDL-mass concentrations increased total CHD risk by 3.8% (P < 10(-9)) and premature CHD risk by 6.1% (P < 10(-7)) per 10 mg/dl increase in concentration. Thus, low HDL2 is associated with increased CHD risk.     

Erectile Dysfunction and Cardiovascular Events in Diabetic Men: A Meta-analysis of Observational Studies

Background

Several studies have shown that erectile dysfunction (ED) influences the risk of cardiovascular events (CV events). However, a meta-analysis of the overall risk of CV events associated with ED in patients with diabetes has not been performed.

Methodology/Principal Findings

We searched MEDLINE and the Cochrane Library for pertinent articles (including references) published between 1951 and April 22, 2012. English language reports of original observational cohort studies and cross-sectional studies were included. Pooled effect estimates were obtained by random effects meta-analysis.A total of 3,791 CV events were reported in 3 cohort studies and 9 cross-sectional studies (covering 22,586 subjects). Across the cohort studies, the overall odds ratio (OR) of diabetic men with ED versus those without ED was 1.74 (95% confidence interval [CI]: 1.34–2.27; P<0.001) for CV events and 1.72 (95% CI: 1.5–1.98; P<0.001) for coronary heart disease (CHD). The funnel plot, Begg''s test, and Egger''s test did not show evidence of publication bias (all P>0.05). Moreover, meta-regression analysis found no relationship between the method used to assess ED (questionnaire or interview), mean age, mean hemoglobin A_1c, mean body mass index, or mean duration of diabetes and the risk of CV events or CHD. In the cross-sectional studies, the OR of diabetic men with ED versus those without ED was 3.39 (95% CI: 2.58–4.44; P<0.001) for CV events (N = 9), 3.43 (95% CI: 2.46–4.77; P<0.001) for CHD (N = 7), and 2.63 (95% CI: 1.41–4.91; P = 0.002) for peripheral vascular disease (N = 5).

Conclusion/Significance

ED was associated with an increased risk of CV events in diabetic patients. Prevention and early detection of cardiovascular disease are important in the management of diabetes, especially in view of the rapid increase in its prevalence.     

The association of mid-regional pro-adrenomedullin and mid-regional pro-atrial natriuretic peptide with mortality in an incident dialysis cohort

High levels of the plasma peptides mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) are associated with clinical outcomes in the general population. Data in patients with chronic kidney disease are sparse. We therefore investigated the association of MR-proANP and MR-proADM levels with all-cause and cardiovascular (CV) mortality, CV events and peripheral arterial disease in 201 incident dialysis patients of the INVOR-Study prospectively followed for a period of up to more than 7 years. The overall mortality rate was 43%, thereof 43% due to CV events. Both baseline MR-proANP and MR-proADM were associated with higher risk of all-cause (HR = 1.44, p = 0.001 and HR = 1.32, p = 0.002, respectively) and CV mortality (HR = 1.75, p<0.001 and HR = 1.41, p = 0.007, respectively) after adjustment for age, sex, previous CV events, diabetes mellitus and time-dependent type of renal replacement therapy. We then stratified patients in high risk (both peptides in the upper tertile), intermediate risk (only one of the two peptides in the upper tertile) and low risk (none in the upper tertile). Although demographic, clinical and laboratory variables were similar among the intermediate and high risk group, to be with both parameters in the upper tertile was associated with a 3-fold higher risk for all-cause (HR = 2.87, p<0.001) and CV mortality (HR = 3.58, p = 0.001). In summary, among incident dialysis patients MR-proANP and MR-proADM were shown to be associated with all-cause and CV mortality, with the highest risk when both parameters were in the upper tertiles.     

Interleukin-6 as an independent predictor of future cardiovascular events in high-risk Japanese patients: comparison with C-reactive protein

Inflammation is associated with the development of atherosclerotic vascular lesions and some inflammatory parameters are used as cardiovascular (CV) risk markers. The present study was designed to assess the predictive power of interleukin (IL)-6 for future CV events. In 121 Japanese patients with multiple CV risk factors and/or disease, serum concentrations of IL-6 and high sensitive C-reactive protein (hs-CRP) were measured. During follow-up periods (mean, 2.9 years) after the baseline assessment, 50 patients newly experienced CV events such as stroke/transient ischemic attack (n=10), heart failure hospitalization (n=6), acute coronary syndrome (n=7), and revascularization for coronary artery disease (n=15) and peripheral arterial disease (n=12). The serum level of IL-6, but not hs-CRP, was significantly higher in patients who had CV events than in event-free subjects (3.9±2.6 and 3.0±2.2 pg/mL, P=0.04). When the patients were divided into three groups by tertiles of basal levels of IL-6 (<1.85, 1.85-3.77, and ≥3.77 pg/mL), cumulative event-free rates by the Kaplan-Meier method were decreased according to the increase in basal IL-6 levels (65%, 50%, and 19% in the lowest, middle, and highest tertiles of IL-6, respectively; log-rank test, P=0.002). By univariate Cox regression analysis, previous CV disease, creatinine clearance, and serum IL-6 levels were significantly associated with CV events during follow-up. Among these possible predictors, the highest tertile of IL-6 was only an independent determinant for the morbidity in the multivariate analysis (hazard ratio 2.80 vs. lowest tertile, P=0.006). These findings indicate that IL-6 is a powerful independent predictor of future CV events in high-risk Japanese patients, suggesting its predictive value is superior to that of hs-CRP.     

Plasma PAF-acetylhydrolase in patients with coronary artery disease: results of a cross-sectional analysis

Inflammation underlies both onset and perpetuation of atherosclerosis. Plasma lipoproteins transport the platelet-activating factor-acetylhydrolase (PAF-AH) with potentially anti-inflammatory activities. Our aim was to determine whether PAF-AH activity was associated with inflammatory markers and with coronary artery disease (CAD). PAF-AH activity and a panel of inflammatory mediators were measured in plasma of 496 patients with CAD and in 477 controls; 276 patients presented with stable angina pectoris and 220 with acute coronary syndrome (ACS). Individuals within the highest quartile of PAF-AH activity had an 1.8-fold increase in CAD risk [95% confidence interval (CI), 1.01 to 3.2; P = 0.048] compared with those in the first quartile (adjusted for clinical and metabolic factors). When excluding individuals receiving statin and angiotensin-converting enzyme-inhibitor medication, individuals within the highest quartile of PAF-AH activity revealed a 3.9-fold increase in CAD risk (95% CI, 2.0 to 7.7; P < 0.0001). In these subjects, the plasma PAF-AH activity increased gradually in stable angina and in ACS both in men (P < 0.0001) and in women (P < 0.001), as compared with controls.No correlation was found between PAF-AH levels and those of common markers of inflammation. This study and the previous ones raise the important issue of whether PAF-AH is simply a marker of risk or directly promotes atherosclerosis.     

The Association of Serum Leptin with Mortality in Older Adults

Objective

Elevated levels of serum leptin are associated with increased adiposity and production of pro-inflammatory cytokines. Both cytokines and body adiposity have been shown to predict cardiovascular events and mortality. The primary objective of the present study is to explore the associations between serum leptin and all-cause mortality and mortality from cardiovascular disease (CVD) over a span of 10 years, controlling for body adiposity and proinflammatory cytokines.

Methods

The Health, Aging and Body Composition (Health ABC) study is a prospective cohort of 3,075 older adults aged 70 to 79 years. This analysis includes 2,919 men and women with complete serum leptin and vital status data. Data on all-cause mortality and incident cardiovascular events (including Coronary Heart Disease and Congestive Heart Failure) were collected over 10 years of follow-up (mean 8.4 years).

Results

Women with leptin in quartile 2 and 3 were at lower risk of all-cause mortality, and those with leptin in quartile 2 were at lower risk of mortality from CVD as compared to women with lowest leptin values when adjusted for age, race, site, years of education, alcohol use, smoking, and physical activity. When these associations were additionally adjusted for body fat, C-reactive protein and pro-inflammatory cytokines, women with leptin values in quartile 3 were at lower risk of all-cause mortality and women with leptin in quartile 2 and 3 were at lower risk of mortality from CVD than women with lowest leptin values. These associations were not significant among men after adjusting for body fat and cytokines.

Conclusions

The present study suggests that moderately elevated concentrations of serum leptin are independently associated with lower risk of all-cause mortality and CVD-related mortality among older women. Among men, serum leptin is not associated with reduced risk of all-cause and CVD mortality after controlling for body fat and cytokines.     

Lycopene,atherosclerosis, and coronary heart disease

Diets rich in fruits and vegetables containing carotenoids have been of interest because of their potential health benefit against chronic diseases such as cardiovascular diseases (CVD) and cancer. Interest particularly in lycopene is growing rapidly following the recent publication of epidemiological studies that have associated high lycopene levels with reductions in CVD incidence. Two studies were conducted. In the first one, we examined the role of lycopene as a risk-lowering factor with regard to acute coronary events and stroke in the prospective Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study. The subjects were 725 middle-aged men free of coronary heart disease and stroke at the study baseline. In a Cox's proportional hazards' model adjusting for covariates, men in the lowest quartile of serum levels of lycopene had a 3.3-fold (P < 0.001) risk of the acute coronary event or stroke as compared with others. In the second study, we assessed the association between plasma concentration of lycopene and intima-media thickness of the common carotid artery wall (CCA-IMT) in a cross-sectional analysis of the Antioxidant Supplementation in the Atherosclerosis Prevention (ASAP) study data in 520 asymptomatic men and women. In a covariance analysis adjusting for common cardiovascular risk factors, low plasma levels of lycopene were associated with an 18% increase of IMT in men as compared with men in whom plasma levels were higher than median (P = 0.003 for difference). In women, the difference did not remain significant after the adjustments. On the basis of these works, it is evident that the circulating levels of lycopene play some role with regard to cardiovascular health in Finland, at least in men. We conclude that circulating levels of lycopene, a biomarker of tomato-rich food, may play a role in early stages of atherogenesis and may have clinical and public health relevance.     

Aerobic exercise training reduces epicardial fat in obese men

The purpose of this study was to determine the effects of exercise training on ventricular epicardial fat thickness in obese men and to investigate the relationship of the change in epicardial fat thickness to changes in abdominal fat tissue following exercise training. Twenty-four obese middle-aged men [age, 49.4 +/- 9.6 yr; weight, 87.7 +/- 11.2 kg; body mass index (BMI), 30.7 +/- 3.3 kg/m(2); peak oxygen consumption, 28.4 +/- 7.2 ml.kg(-1).min(-1); means +/- SD] participated in this study. Each participant completed a 12-wk supervised exercise training program (60-70% of the maximal heart rate; 60 min/day, 3 days/wk) and underwent a transthoracic echocardiography. The epicardial fat thickness on the free wall of the right ventricle was measured from both parasternal long- and short-axis views. The visceral adipose tissue (VAT) and subcutaneous adipose tissues were measured by computed tomography. Following exercise training, the epicardial fat thickness was significantly decreased (P < 0.001). The percentage change of epicardial fat thickness was twice as high compared with those of waist, BMI, and body weight of original values (P <0.05). There was a significant relationship (r = 0.525, P = 0.008) between changes in the epicardial fat thickness and VAT with exercise training. Stepwise multiple regression analysis revealed that the change in VAT, change in systolic blood pressure, and change in quantitative insulin sensitivity check index were independently related to the change epicardial fat thickness (P < 0.05). The ventricular epicardial fat thickness is reduced significantly after aerobic exercise training and is associated with a decrease in VAT. These results suggest that aerobic exercise training may be an effective nonpharmacological strategy for decreasing the ventricular epicardial fat thickness and visceral fat area in obese middle-aged men.     

Association study of MIA3 rs17465637 polymorphism with cardiovascular disease in rheumatoid arthritis patients

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis. Melanoma inhibitor protein 3 (MIA3) is required for the export of collagen VlI (COL7A1) from the endoplasmic reticulum and it appears to be a tumor suppressor of malignant melanoma. Genome-wide association studies have described an association between MIA3 rs17465637 A/C polymorphisms and coronary artery disease and myocardial infarction. Because of that, we assessed the MIA3 rs17465637 polymorphism in 1505 RA Spanish patients stratified according to the presence/absence of cardiovascular (CV) disease. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using carotid ultrasound to establish carotid intima-media wall thickness and carotid plaques and brachial ultrasonography to determine the presence of endothelial dysfunction by flow-mediated endothelium-dependent and independent vasodilatation. MIA3 rs17465637 allele A showed a trend for association with the presence of carotid plaques (odds ratio 1.56, 95% confidence interval [0.96-2.51]; p=0.07). However, apart from an association of the MIA3 rs17465637 A allele with the risk of CV events in RA patients with dyslipidemia (p=0.018), no other significant associations were found between the presence of MIA3 rs17465637 A allele and the risk of suffering CV events or other surrogate markers of atherosclerosis. In conclusion, our results suggest a potential association of the MIA3 rs17465637 with CV disease in dyslipidemic patients with RA. However, additional studies are required to better establish the role of the MIA3 gene in mechanisms leading to the accelerated atherogenesis observed in RA.     

Strongmen sport is associated with larger absolute heart size and impaired cardiac relaxation

This study was carried out to compare cardiac structure and function and blood lipids among Strongmen, sedentary controls, and marathoners. Echocardiography was performed, and endothelial function, blood lipids and maximal oxygen uptake were measured in 27 Caucasian adult men (8 Strongmen, 10 marathoners, 9 controls). Absolute cardiac size parameters such as left ventricular (LV) diameter and wall thickness of Strongmen were higher (p < 0.05), but relative (body surface area indexed) parameters were not different between controls and Strongmen. In Strongmen, the relative LV diameter (p < 0.05), wall thickness (p < 0.001), and LV mass index (p < 0.01) were lower than in marathoners. The absolute but not relative right ventricular diameter was larger in Strongmen as compared with controls, whereas all of the measured relative cardiac size parameters were higher in marathoners as opposed to in controls. The endothelial function and the ratio of wall thickness to chamber diameter were similar among the groups (p > 0.05). Maximal oxygen uptake of Strongmen was lower than in controls (p < 0.05) and marathoners (p < 0.001). Global diastolic LV function of Strongmen was impaired in comparison to controls (p < 0.05) and marathoners (p < 0.05). Plasma lipids were not different between Strongmen and sedentary controls, but in comparison to runners, Strongmen had higher low-density lipoprotein-cholesterol (p < 0.05) and lower high-density lipoprotein cholesterol (p < 0.01). Participation in Strongmen sport is associated with higher absolute but not relative cardiac size parameters, impaired myocardial relaxation, and low cardiorespiratory fitness. Therefore, Strongmen may demand greater attention as an extreme group of athletes with regard to cardiovascular risk.     

Visceral fat accumulation determines postprandial lipemic response,lipid peroxidation,DNA damage,and endothelial dysfunction in nonobese Korean men

Visceral fat has been associated with multiple cardiovascular disease (CVD) risk factors. The aim of this study was to identify anthropometrical measures most closely associated with some well-known CVD risk factors. Because most Asians at risk have normal body mass index (BMI) according to Western standards, we studied healthy nonobese Korean males (n = 102; age: 36.5 +/- 0.8 years, BMI: 23.8 +/- 0.2 kg/m2). Visceral fat area (VFA) at the fourth lumbar vertebra was associated with increased postprandial triglyceride (TG) response (r = 0.53, P < 0.001) and with plasma malondialdehyde (MDA) (r = 0.36, P < 0.01) and PGF2alpha (r = 0.24, P < 0.05). When matched for BMI and age, men with high VFA (HVFA) (>/=100 cm2; n = 27) had higher blood pressure (P < 0.01), increased consumption of cigarettes (P < 0.01), and lower ratio of energy expenditure to calorie intake (P < 0.01) as compared with low VFA men (<100 cm2; n = 27). Men with HVFA showed higher TG, glucose, and insulin responses following fat and oral glucose tolerance tests respectively higher plasma concentrations of MDA (P < 0.001), urinary PGF2alpha (P < 0.05), and lymphocytes deoxyribonucleic acid tail moments (P < 0.01). Conversely, HVFA was associated with lower testosterone, insulin-like growth factor-1, and brachial artery flow-mediated dilation (P < 0.001). In conclusion, our data indicate that visceral fat accumulation, even in nonobese men, is a major factor contributing to increased CVD risk.     

Plasma adrenomedullin as an independent predictor of future cardiovascular events in high-risk patients: comparison with C-reactive protein and adiponectin

This study investigated the predictive power of plasma adrenomedullin (AM) for future cardiovascular (CV) events. In 121 patients with multiple CV risk factors and/or disease, plasma concentrations of AM, high sensitive C-reactive protein (hs-CRP), and adiponectin were measured. During follow-up periods (mean, 3.5 years) after the baseline assessment, 28 patients newly experienced CV events such as stroke/transient ischemic attack, acute coronary syndrome, and congestive heart failure. The plasma level of AM, but not hs-CRP or adiponectin, was significantly higher in patients who had CV events than in event-free subjects. When the patients were divided into three groups by tertiles of basal levels of AM (<10.1, 10.1-13.1, and > or =13.1 fmol/mL), cumulative event-free rates by the Kaplan-Meier method were decreased according to the increase in basal AM levels (83.2%, 68.6%, and 52.8% in the lowest, middle, and highest tertiles of AM, respectively; log-rank test, P=0.033). By univariate Cox regression analysis, previous coronary artery disease, creatinine clearance, and plasma AM and hs-CRP levels were significantly associated with CV events during follow-up. Among these possible predictors, high plasma AM (P=0.004) and low creatinine clearance (P=0.043) were independent determinants for morbidity in multivariate analysis. These findings indicate that plasma AM is a powerful independent predictor of future CV events in high-risk patients, suggesting its predictive value is superior to that of hs-CRP or adiponectin.     

Threshold values of high-risk echocardiographic epicardial fat thickness

Objective: Echocardiographic epicardial adipose tissue is a new index of cardiac and visceral adiposity with great potential as a diagnostic tool and therapeutic target. In this study, we sought to provide threshold values of echocardiographic epicardial fat thickness associated with metabolic and anthropometric risk factors. Methods and Procedures: Epicardial fat thickness was measured in 246 consecutive white subjects (120 women, 126 men, median age 46 years (30–65), median BMI 32 kg/m² (22–52), median waist circumference 100.5 cm (85–140)), who underwent routine transthoracic echocardiogram for standard clinical indications. Metabolic syndrome (MetS), Insulin resistance, BMI, and waist circumference categories were identified and epicardial fat was calculated. Results: Among 246 subjects, 58% had MetS. These subjects showed median values of epicardial fat thickness of 9.5 and 7.5 mm (in men and women, respectively), significantly higher than those found in subjects without MetS (no MetS) (P < 0.001). Receiver operating characteristics (ROC) analysis showed that epicardial fat thickness of 9.5 and 7.5 mm maximize the sensitivity and specificity to predict MetS, in men and women, respectively. In separate analyses, median epicardial fat thickness values of 9.5 and 7.5 mm were cutoff points associated with high abdominal fat in men and women, respectively. When insulin sensitivity was considered separately, epicardial fat thickness of 9.5 mm was associated with insulin resistance. Discussion: Median values of 9.5 and 7.5 mm should be considered the threshold values for high‐risk echocardiographic epicardial fat thickness in white men and women, respectively. Echocardiographic epicardial fat measurement may be of help for cardiometabolic risk stratification and therapeutic interventions targeting the fat.     

Changes in conduction velocity, median frequency, and root mean square-amplitude of the electromyogram during 25% maximal voluntary contraction of the triceps brachii muscle, to limit of endurance

The objective of the present study was to investigate whether isometric contraction of the right triceps brachii muscle, of maximal duration and at 25% of the maximal voluntary contraction (MVC), would reduce mean fibre conduction velocity (CV) for the active motor units (MU). In addition to the cross-correlation of surface electromyograms (EMG) for CV determination, median frequency (fm) and root-mean-square amplitude (rms-amplitude) were calculated. The initial 5 min of the recovery of the three parameters was also investigated. The MVC were performed before and after the sustained contraction. Seven males-six in their twenties and one aged 43-participated in the investigation. Mean CV for the unfatigued muscle was 4.5 m.s-1, SD 0.38. On average, CV decreased less than 10% during the sustained contraction (P less than 0.05). The fm decreased almost linearly (46%) during the endurance time, while three quarters of the 250% increase in rms-amplitude took place during the last 50% of the contraction (P less than 0.001, both parameters). The MVC was reduced by 39% immediately after exhaustion (P less than 0.05). During the 1st min of recovery the rms-amplitude decreased by 50%, and the fm increased from 54% to 82% of the initial value (both P less than 0.05). No measurable simultaneous CV restitution occurred. A parallel 15% increase in fm and CV took place during the last 4 min of recovery (both P less than 0.001), while the amplitude remained constant. Since mean CV was essentially unchanged during the last 50% of the endurance time where large changes in fm and rms-amplitude occurred, factors supplementary to CV probably caused the striking changes in fatigue EMG, notably-MU recruitment, synchronization of MU activity, and lowering of MU firing frequencies. Nevertheless, during the last 4 min of recovery the entire increase in fm could be accounted for by the simultaneous increase in CV.     

Sex differences in HDL ApoC-III in American Indian youth

ABSTRACT: BACKGROUND: Since American Indians are predisposed to type 2 diabetes (DM2) and associated cardiovascular risk, Cherokee boys and girls (n = 917) were studied to determine whether BMI Z (body mass index Z score) is associated with the apoC-III (apolipoprotein C-III) content of HDL (high density lipoprotein), a previously reported predictor of DM2. METHODS: An ad hoc cross-sectional analysis was conducted on a previously studied cohort. Participants were grouped by gender-specific age groups (5 to 9, 10 to 14 and 15 to 19 years). ApoA-I (apolipoprotein A-I) and HDL apoC-III were assayed by immunoturbidimitry. ApoC-III was measured in whole plasma, and in HDL to determine the molar proportion to apoA-I. General linear models were used to assess association. RESULTS: The HDL apoC-III to apoA-I molar ratio increased by BMI Z quartile in girls aged 10--14 years (p < 0.05 for linear trend, p < 0.05 for difference in BMI Z quartile IV vs. I to III) and aged 15--19 years (p < 0.05 for trend). In boys the increase by BMI Z occurred only at ages 15--19 years (p < 0.01 for trend and for quartile difference). CONCLUSIONS: ApoC-III showed an obesity-related increase relative to apoA-I during adolescence beginning in girls aged 10 to 14 years and in boys aged 15 to 19 years. The earlier changes in girls may alter HDL's protective properties on the beta-cell and contribute to their increased risk for DM2.     

Arterial endothelial dysfunction and idiopathic deep venous thrombosis

Recent epidemiological studies have highlighted higher risk of subsequent development of atherosclerotic disease in patients with deep venous thrombosis (DVT). We evaluated the Flow Mediated Dilation (FMD) looking for arterial endothelial dysfunction, predictive for future ischaemic cardiovascular events, in patients with idiopathic DVT. FMD was measured in the brachial artery in 60 subjects with idiopathic DVT (age 60.1±17.4) and in 60 subjects without idiopathic DVT (age 61.2±15.1), with a similar cardiovascular risk factor profile. DVT patients showed lower FMD (6.78%±5.53% vs 10.88±3.31%, p<0.001). Univariate linear models showed that obesity (p=0.010), dyslipidemia (p=0.004), arterial hypertension (p=0.046), use of platelet anti-aggregating agents (p=0.018) and DVT (p<0.001) were associated to lower levels of FMD. In multivariate linear model, only DVT (p<0.001) remained an independent predictor of lower levels of FMD. Furthermore, an 8.5% cut-off value of FMD was chosen in a ROC curve analysis. Values of FMD ≤ 8.5% were more frequent in DVT patients (71.67% vs 41.67%, p<0.001). Univariate logistic regression models showed that dyslipidemia (p=0.008), use of platelet anti-aggregating agents (p=0.004) and DVT (p<0.001) were associated to a higher risk of having FMD ≤ 8.5%. Multivariate logistic regression model showed that DVT was the unique independent predictor for FMD ≤ 8.5% (p<0.001). In conclusion, DVT patients more frequently have impaired FMD, recognized as an indicator of arterial endothelial dysfunction and a marker for increased cardiovascular risk.     

The longitudinal relationship between body composition and patella cartilage in healthy adults

Background: Although obesity is a risk factor for patellofemoral osteoarthritis (OA), it is unclear whether the components of body composition, such as muscle and fat mass, are major determinants of articular cartilage properties at the patella. Objective: The aim of this study was to determine whether anthropometric and body composition measures, assessed over 10 years, were related to articular patella cartilage volume and defects in healthy adults with no clinical knee OA. Methods and Procedures: Two hundred and ninety‐seven healthy, community‐based adults aged 50–79 years with no clinical history of knee OA were recruited. Anthropometric and body composition (fat‐free mass and fat mass) data were measured at baseline (1990–1994) and follow‐up (2003–2004). Patella cartilage volume and defects were assessed at follow‐up (2003–2004) using magnetic resonance imaging (MRI). Results: After adjustment for potential confounders, increased measures of obesity (weight, BMI, waist circumference, and fat mass) at baseline and follow‐up were associated with an increased risk for the presence of patella cartilage defects at follow‐up for both men and women (all P ≤ 0.03). Increased baseline values for these variables tended to be associated with reduced patella cartilage volume at follow‐up for women (all P ≤ 0.11), but not men (all P ≤ 0.87). Discussion: We have demonstrated that increased anthropometric measures of obesity, as well as fat mass, are associated with an increased risk for the presence of patella cartilage defects in both men and women. Women, but not men, with greater baseline body mass, particularly adipose‐derived mass, appear to have an associated reduction in their patella cartilage volume. Interventions targeting a reduction in adipose tissue may help reduce the risk for the onset and progression of patellofemoral OA, particularly in women.     

Combined Impact of Adiponectin and Retinol‐binding Protein 4 on Metabolic Syndrome in Elderly People: The Korean Longitudinal Study on Health and Aging

The prevalence of metabolic syndrome (MS) increases with progressing and is potentially associated with changes in adipose‐derived cytokines, including adiponectin and retinol‐binding protein 4 (RBP4). We aimed to determine the prevalence of MS, and the relationships between these factors and MS in elderly people. A population‐based cohort study, the Korean Longitudinal Study on Health and Aging (KLoSHA), was performed on subjects aged ≥65 years by random stratified sampling in 2005–2006 (439 men and 561 women). Anthropometrics, biochemical factors including adiponectin and RBP4 levels, body composition, and abdominal fat by computed tomography (CT) were measured. The prevalence of MS was 61.0% in women and 39.9% in men. After adjustment for age, gender, smoking, alcohol, and exercise status and muscle mass, participants with the lowest quartile of adiponectin had a higher risk for having MS than those with the highest quartile (odds ratio (OR) = 4.12, P < 0.01). Similarly, subjects with the highest quartile of RBP4 showed an increased risk for having MS (OR = 1.73, P < 0.01). When both the lowest adiponectin and the highest RBP4 quartiles were combined, the OR increased to 6.22 compared with the opposite quartiles (i.e., highest adiponectin and lowest RBP4 concentrations). Furthermore, circulating levels of adiponectin and RBP4 were significantly correlated with visceral fat and insulin resistance index. In this study, the increased prevalence of MS in elderly but relatively lean population was associated with low adiponectin and high RBP4 levels. The combination of these factors might predict older subjects at high risk for having MS.     

Dyslipidemia and eye diseases in the adult Chinese population: the Beijing eye study

To determine associations between dyslipidemia and ocular diseases, the population-based Beijing Eye Study 2006 examined 3251 subjects (age≥45 years) who underwent a detailed ophthalmic examination and biochemical blood analysis. Dyslipidemia was defined as any of the following: hypercholesterolemia (total cholesterol concentration≥5.72 mmol/L (220 mg/dL)) or hypertriglyceridemia (triglyceride concentration≥1.70 mmol/L (150 mg/dL)) or low high-density lipoprotein-cholesterol (HDL-C concentration≤0.91 mmol/L (35 mg/dL)). Biochemical blood examinations were available for 2945 (90.6%) subjects. After adjustment for age, gender, habitation region, body mass index, self reported income, blood glucose concentration, diastolic blood pressure and smoking, dyslipidemia was significantly associated with higher intraocular pressure (P<0.001) and beta zone of parapapillary atrophy (P = 0.03). Dyslipidemia was not significantly associated with the prevalence of glaucoma (P = 0.99), retinal vein occlusions (P = 0.92), diabetic retinopathy (P = 0.49),presence of retinal vascular abnormalities such as focal or general arteriolar narrowing, age-related macular degeneration(P = 0.27), nuclear cataract (P = 0.14), cortical cataract (P = 0.93), and subcapsular cataract (P = 0.67). The results make one conclude that, controlled for systemic and socioeconomic parameters, dyslipidemia was not associated with common ophthalmic disorders including glaucoma and age-related macular degeneration.     

Statins in cardiometabolic disease: what makes pitavastatin different?

The term cardiometabolic disease encompasses a range of lifestyle-related conditions, including Metabolic syndrome (MetS) and type 2 diabetes (T2D), that are characterized by different combinations of cardiovascular (CV) risk factors, including dyslipidemia, abdominal obesity, hypertension, hyperglycemia/insulin resistance, and vascular inflammation. These risk factors individually and interdependently increase the risk of CV and cerebrovascular events, and represent one of the biggest health challenges worldwide today. CV diseases account for almost 50% of all deaths in Europe and around 30% of all deaths worldwide. Furthermore, the risk of CV death is increased twofold to fourfold in people with T2D. Whilst the clinical management of CV disease has improved in Western Europe, the pandemic of obesity and T2D reduces the impact of these gains. This, together with the growing, aging population, means the number of CV deaths is predicted to increase from 17.1 million worldwide in 2004 to 23.6 million in 2030. The recommended treatment for MetS is lifestyle change followed by treatment for the individual risk factors. Numerous studies have shown that lowering low-density lipoprotein-cholesterol (LDL-C) levels using statins can significantly reduce CV risk in people with and without T2D or MetS. However, the risk of major vascular events in those attaining the maximum levels of LDL-C-reduction is only reduced by around one-third, which leaves substantial residual risk. Recent studies suggest that low high-density lipoprotein-cholesterol (HDL-C) (<1 .0 mmol/l; 40 mg/dl) and high triglyceride levels (≥1.7 mmol/l; 150 mg/dl) are independent risk factors for CV disease and that the relationship between HDL-C and CV risk persists even when on-treatment LDL-C levels are low (<1.7 mmol/l; 70 mg/dl). European guidelines highlight the importance of reducing residual risk by targeting these risk factors in addition to LDL-C. This is particularly important in patients with T2D and MetS because obesity and high levels of glycated hemoglobin are directly related to low levels of HDL-C and high triglyceride. Although most statins have a similar low-density lipoprotein-lowering efficacy, differences in chemical structure and pharmacokinetic profile can lead to variations in pleiotropic effects (for example, high-density lipoprotein-elevating efficacy), adverse event profiles, and drug-drug interactions. The choice of statin should therefore depend on the needs of the individual patient. The following reviews will discuss the potential benefits of pitavastatin versus other statins in the treatment of patients with dyslipidemia and MetS or T2D, focusing on its effects on HDL-C quantity and quality, its potential impact on atherosclerosis and CV risk, and its metabolic characteristics that reduce the risk of drug interactions. Recent controversies surrounding the potentially diabetogenic effects of statins will also be discussed.