Associations of serum alkaline phosphatase with metabolic syndrome and mortality

Background

Recent data suggest that elevated serum alkaline phosphatase levels are associated with increased mortality, but the mechanisms for this association are unknown. As metabolic syndrome is associated with higher serum alkaline phosphatase levels, we examined the joint association of mortality with metabolic syndrome and serum alkaline phosphatase levels in the US general population.

Methods

Retrospective observational study of 15,234 adult participants in the National Health and Nutrition Examination Survey III. Multivariable Cox regression analyses were used to jointly relate mortality risk to serum alkaline phosphatase and indicators of metabolic syndrome.

Results

Prevalence of metabolic syndrome was 14% to 41% among patients in lowest and higher quartiles, respectively, for baseline serum alkaline phosphatase. The mortality hazard ratio for each doubling of serum alkaline phosphatase was 1.52 (95% confidence interval [CI], 1.35–1.72) adjusting only for demographic factors, and 1.37 (95% CI, 1.21–1.56) adjusting for both demographic and metabolic syndrome factors in the full cohort, and was 1.83 (95% CI, 1.36–2.46) adjusting for demographic factors in the subgroup without any of the component conditions of metabolic syndrome.

Conclusions

In the US general population, higher levels of serum alkaline phosphatase is a predictor of mortality independent of the baseline prevalence of metabolic syndrome. Further studies are warranted to unravel the mechanisms of this association.     

Relationship between age and metabolic disorders in the population of Bali

Background/Purpose

The purpose of this study is to examine the association between age and metabolic disorders in the population of Bali.

Method

A cross-sectional study was conducted on metabolic syndrome (MS) as defined on the basis of recommended parameters for diagnosis of the syndrome in the population of seven villages of Bali comprising six villages and one suburban area. At least three of the five parameters must be present for the diagnosis. Three hundred ten elderly people aged 60 years or more, with a male:female ratio of 168:142, of 1840 subjects were recruited in the study. The criteria for obesity were based on the 2000 World Health Organization recommendations for Asia Pacific population, for prediabetes [impaired fasting glycemia (IFG) and impaired glucose tolerance] and diabetes mellitus (DM) by American Diabetes Association (2009), and for MS by a joint statement of International Diabetes Federation, National Heart, Lung, and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, and International Association for the Study of Obesity (2009).

Results

The prevalence of IFG and DM were twofold in the elderly as compared with those in the younger-aged groups (21.4 vs. 11.7; 11.7 vs. 4.8, respectively). Blood pressure and fasting blood sugar levels were higher in the elderly than in the younger-aged group (133/81 mmHg vs. 117/76 mmHg; 102.7 mg/dL vs. 93.0 mg/dL, respectively; p < 0.001). There was no statistically significant difference in triglyceride and high-density lipoprotein cholesterol levels between both groups. Waist circumferences were lower among the elderly than among younger-aged groups (75.8 cm vs. 80.9 cm; p < 0.001). The elderly, with lower waist circumference, revealed significantly higher prevalence of MS as compared with the younger-aged group {22.9% vs. 17.3%; p = 0.026; prevalence risk 1.423 [confidence interval (CI) = 1.043G–1.944]}. The subjects who had 1, 2, 3, 4, and 5 components of MS were 34.6%, 23.8%, 13.0%, 4.3%, and 0.9%, respectively. The prevalence risk of each component of MS for the occurrence of MS were: elevated triglyceride [30.2 (CI = 14.5G–63.1)], elevated fasting blood sugar [8.5 (CI = 4.5G–15.8)], increased waist circumference [8.1 (CI = 4.3G–15.0)], reduced high-density lipoprotein cholesterol [4.4 (CI = 2.4G–7.9)], and elevated blood pressure [3.7 (CI = 1.9G–7.2)].

Conclusions

It could be inferred that in comparison with the younger-age group, the elderly had higher (twice) prevalence of IFG and DM, lower prevalence of central obesity, but higher prevalence of MS. Old age (60 years and more) had 1.4-fold risk for MS as compared with that in the younger-aged group, and elevated triglyceride levels appeared to be the most important risk factor for MS.     

The rs1801278 G>A polymorphism of IRS-1 is associated with metabolic syndrome in healthy nondiabetic men. Modulation by cigarette smoking status

Aims

To explore associations between IRS-1 rs1801278 G > A polymorphism and metabolic syndrome (MS).

Methods

rs1801278 G > A was genotyped in 610 healthy Argentinian men.

Results

GA carriers had lower risk of MS (OR = 0.52, P = 0.045), particularly among smokers (OR = 0.10, P = 0.006).

Conclusions

rs1801278 GA carriers had lower risk of MS, especially among smokers.     

Dietary patterns and the prevalence of metabolic syndrome in Korean women

Background and aims

: The role of dietary patterns in metabolic syndrome has not been adequately investigated in Asian women. We aimed to identify dietary patterns and to evaluate the cross-sectional relationship between dietary patterns and the prevalence of metabolic syndrome in Korean women.

Methods and results

: In a cross-sectional study of 4984 women aged 30–79 years, dietary patterns were derived from 16 food groups using factor analysis. Metabolic syndrome was defined based on the Adult Treatment Panel III of the National Cholesterol Education Program (ATPIII NCEP) criteria as having three or more risk factors using a modified obesity index. Logistic regression was used to estimate the association between dietary pattern and the prevalence of metabolic syndrome. Three dietary patterns (Western, healthy and traditional) were identified. Higher consumption of the healthy pattern was inversely associated with metabolic syndrome (OR [95% CI] for highest vs. lowest quartile: 0.58 [0.50–0.91]; P for trend = 0.012) and most components of metabolic syndrome. In a stratified analysis by menopausal status, the inverse association of the healthy dietary pattern and metabolic syndrome was statistically significant only among postmenopausal women (OR [95% CI] for highest vs. lowest quartile: 0.60 [0.40–0.86]; P for trend = 0.004). The Western and traditional patterns showed no association with metabolic syndrome, but were related to some individual risk factors for metabolic syndrome.

Conclusions

: These results suggest that the healthy dietary pattern is associated with a reduced risk for metabolic syndrome in Korean women, particularly in postmenopausal women.     

Significant variation of traditional markers of liver injury after a half-marathon run

Background

While the promotion of health-related fitness is thereby widespread, less focus is currently being given on the biological influence that physical activity might exert on results of laboratory testing. As such, this study was undertaken to assess the kinetics of liver injury markers following physical exercise.

Design and methods

Total and direct bilirubin as well as the activity of biochemical markers of liver injury including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT) and creatine kinase (CK), were measured before and after a half-marathon.

Results

Significant increases occurred for GGT, AST, LDH, CK, total and direct bilirubin immediately after the run. AST, LDH, CK, total and direct bilirubin were still increased 24 h thereafter, whereas GGT decreased after 6 h. None of the athletes exceed the upper reference limit for ALT, ALP and GGT, whereas significant variations were instead observed for LDH, AST, CK, total and direct bilirubin.

Conclusions

Taken together, the results of our prospective investigation clearly attest that an acute bulk of aerobic physical exercise, such as a half-marathon, might produce significant changes in the activity of traditional biomarkers of liver injury, which should be carefully considered when investigating physically active individuals undergoing laboratory testing.     

Association of Lp-PLA2 activity and LDL size with interleukin-6, an inflammatory cytokine and oxidized LDL, a marker of oxidative stress, in women with metabolic syndrome

Objective

We investigated an association between lipoprotein-associated phospholipase A₂ (Lp-PLA₂) activity, inflammation, and oxidative stress in women with metabolic syndrome (MS).

Methods

We performed a case–control study in MS women (n = 368) and non-MS women (n = 854). Lp-PLA₂ activity LDL particle size; leukocyte number; ox-LDL, LDL-cholesterol, TNF-α, IL-6, and CRP levels were measured.

Results

MS women had smaller LDL particle size; higher plasma ox-LDL levels and Lp-PLA₂ activity; and higher serum TNF-α, IL-6, and CRP, than non-MS women. In controls, Lp-PLA₂ activity weakly but significantly correlated with LDL-cholesterol; in MS women, Lp-PLA₂ activity positively correlated with LDL-cholesterol, ox-LDL, TNF-α, and IL-6 after adjusting for age and BMI. The relationship between Lp-PLA₂ activity and ox-LDL still maintained after further adjustment for LDL-cholesterol. Additionally, Lp-PLA₂ activity together with LDL particle size were significant independent predictors of MS (multivariate analysis), and ox-LDL was a major contributor to the increase in Lp-PLA₂ activity in MS women (multiple stepwise regression). In a subgroup analysis, Lp-PLA₂ activity was negatively associated with IL-6 levels in non-MS postmenopausal women, but positively with IL-6 in both postmenopausal and premenopausal women with MS. Postmenopausal women with MS had significantly higher Lp-PLA₂ activity, ox-LDL and IL-6 than those without MS, and premenopausal women with or without MS, after the adjustment.

Conclusions

Elevated plasma Lp-PLA₂ activity was associated with an increase in inflammatory cytokines, particularly IL-6 and ox-LDL in MS women. This association was also affected by menopause status, suggesting that Lp-PLA₂ may represent a novel marker for oxidation and inflammation in MS.     

Familial concordance of metabolic syndrome in Korean population--Korean National Health and Nutrition Examination Survey 2005

Aims

To investigate the familial concordance of metabolic syndrome and its components in a nationally representative survey in Korean.

Methods

We used data from the Korean National Health and Nutrition Examination Survey (KNHANES), a nationwide survey examining the general health and nutritional status of the Korean people. We enrolled 1641 married couples and 1527 parents–1342 offspring.

Results

Prevalence of the metabolic syndrome was 17.1% for husbands, 11.7% for wives, 14.3% for parents, and 7.2% for offspring. After adjustment for age, there were strong positive correlations between family members for the metabolic variables. Compared with husbands whose wives did not have metabolic syndrome, adjusted odds ratio in husbands whose wives had metabolic syndrome was 1.43 (95% CI: 1.10–1.87) for the risk of having metabolic syndrome. Similarly, wives whose husbands had metabolic syndrome had 1.41 (95% CI: 1.08–1.84) times higher risk of having metabolic syndrome. Compared with children whose parents did not have metabolic syndrome, adjusted odds ratio in children with at least one parent with the metabolic syndrome was 2.56 (95% CI: 1.09–5.98) for the metabolic syndrome.

Conclusions

Our study revealed that there is significant familial concordance for metabolic syndrome and its components in Korean families.     

Serum gamma glutamyl transferase: a novel biomarker for screening of premature coronary artery disease

Background

We aimed to elucidate the association between gamma glutamyl transferase (GGT) activity with prevalence of premature coronary artery disease (CAD) in young Pakistani patients undergoing diagnostic coronary angiography.

Methods

A total of 218 young adults (age≤45 years) underwent diagnostic angiography. Serum samples were taken from all the patients and analyzed for serum GGT activity, cholesterol and triglycerides.

Results

Coronary artery disease patients had significantly increased GGT activity (P=.001) and exhibited a significant positive correlation with blood pressure, cholesterol, blood glucose, and smoking and negative correlation with total antioxidant status (P<.01).

Conclusion

The study revealed good diagnostic accuracy at cutoff of 35 U/L with a sensitivity of 92%, specificity of 81%, and diagnostic odds ratio of 48 in estimation of premature CAD in young Pakistanis.     

Study of adiponectin in chronic liver disease and cholestasis

Purpose

Adiponectin is an adipocytokine suggested to have a hepatoprotective effect. To date, little information is available in the literature regarding changes in serum adiponectin levels in cirrhosis and cholestasis and the associated metabolic disturbances. In order to elucidate the role of adiponectin in chronic liver disease our aim was to determine serum adiponectin in patients with different grades of cirrhosis and cholestasis and to correlate it with markers of liver injury, inflammation and cholestasis. We also aimed to correlate adiponectin with markers of metabolic syndrome such as body mass index and insulin resistance.

Methods

Forty patients with cirrhosis; 30 patients with cirrhosis and cholestasis; and 20 matched controls were studied. They were subjected to clinical assessment, laboratory investigations: serum bilirubin, ALT, AST, alkaline phosphatase, GGT, albumin, C-reactive protein, prothrombin activity, fasting blood sugar, insulin. HOMA index was calculated. Abdominal ultrasonography and upper GI endoscopy were performed.

Results

Adiponectin was elevated in patients with cirrhosis and cirrhosis/cholestasis and was significantly higher in Child A and B. Adiponectin showed correlation with liver cell injury, marker of inflammation, synthetic liver function and markers of cholestasis. Adiponectin did not correlate with complications of cirrhosis as ascites and esophageal varices nor did it correlate with BMI or HOMA.

Conclusions

Adiponectin is elevated in cirrhosis and shows correlation with degree of hepatocellular injury and cholestasis. Finally, adiponectin levels in cirrhosis do not correlate with parameters of body composition or metabolism but exclusively with reduced liver function.     

The Relationship Among Atrium Electromechanical Interval,Insulin Resistance,and Metabolic Syndrome

Background

Metabolic syndrome (MS) is an important risk factor of atrial fibrillation. However, an understanding of the adverse effects of MS on left atrial (LA) functional assessment in terms of electromechanical interval, a convenient parameter that can reflect the process of LA remodelling, has been lacking. The goal of this study was to investigate the association between electromechanical interval and MS.

Methods

In all, 337 patients (91 with MS) with mean age of 51.9 ± 9.0 years were enrolled. Metabolic syndrome was defined by National Cholesterol Education Program–Adult Treatment Panel III score. Insulin resistance was assessed by the homeostasis model assessment–insulin resistance method. The electromechanical interval, defined as the time from initiation of P wave deflection to peak of mitral inflow Doppler A wave (PA-PDI), was measured.

Results

Patients with MS had significantly longer PA-PDI intervals compared with those of patients without MS (131.0 ± 12.4 milliseconds vs 123.2 ± 14.0 milliseconds, P < 0.001). Longer PA-PDI intervals were observed in subjects with higher metabolic scores (P < 0.05). In patients with small LA size, PA-PDI intervals, but not LA dimensions, were significantly different between groups with and without MS (P < 0.05). Additionally, PA-PDI interval was positively correlated with insulin resistance (r = 0.267, P < 0.001).

Conclusions

PA-PDI intervals were longer in patients with MS compared with those of patients without MS and tracked with insulin resistance. PA-PDI may be a useful clinical parameter to represent the degree of atrial remodelling in subjects with metabolic derangements.     

Metabolic syndrome is an independent predictor of cardiovascular events in high-risk patients with occlusive and aneurysmatic peripheral arterial disease

Objective

Metabolic syndrome (MetSyn) is a well-known risk factor for cardiovascular (CV) disease in the general population; however, the additional predictive value for CV events in high-risk patients with peripheral arterial disease (PAD) is unknown. The aims of the current study were to assess and compare: (1) prevalence of MetSyn, and (2) predictive value of MetSyn for CV events, in patients with either occlusive or aneurysmatic PAD.

Methods

We screened 2069 patients scheduled for lower occlusive arterial revascularization (n = 1031) or abdominal aortic aneurysm repair (n = 1038) for the presence of MetSyn. Adult Treatment Panel III report (ATP III) was used for defining MetSyn. Central obesity was defined as body-mass-index >30 kg/m². Main outcomes were the occurrence of CV events and CV mortality during a median follow-up of 6 years (IQR 2–9 years).

Results

Metabolic syndrome was diagnosed in 421 (41%) and 432 (42%) patients with occlusive and aneurysmatic PAD, respectively (p = 0.72). Patients with occlusive or aneurysmatic PAD and MetSyn had an increased risk for the development of CV events, when compared to patients without MetSyn (27% vs. 18% and 27% vs. 19%, p < 0.001, respectively). In occlusive and aneurysmatic PAD, MetSyn was independently associated with an increased risk of CV events (HR = 1.6; 95%CI 1.2–2.1 and HR = 1.4; 95%CI 1.1–1.8). No significant association between the presence of MetSyn and CV mortality was observed.

Conclusions

Metabolic syndrome is highly prevalent in high-risk PAD patients. In occlusive and aneurysmatic PAD patients, MetSyn is an independent predictor of long-term CV events.     

Free fatty acids are associated with insulin resistance but not coronary artery atherosclerosis in rheumatoid arthritis

Background

Free fatty acids (FFAs) affect insulin signaling and are implicated in the pathogenesis of insulin resistance and atherosclerosis. Inflammatory cytokines such as interleukin-6 (IL-6) increase lipolysis and thus levels of FFAs. We hypothesized that increased IL-6 concentrations are associated with increased FFAs resulting in insulin resistance and atherosclerosis in rheumatoid arthritis (RA).

Methods

Clinical variables, serum FFAs and inflammatory cytokines, homeostasis model assessment for insulin resistance (HOMA-IR), and coronary artery calcium were measured in 166 patients with RA and 92 controls. We compared serum FFAs in RA and controls using Wilcoxon rank sum tests and further tested for multivariable association by adjusting for age, race, sex and BMI. Among patients with RA, we assessed the relationship between serum FFAs and inflammatory cytokines, HOMA-IR, and coronary artery calcium scores using Spearman correlation and multivariable regression analyses.

Results

Serum FFAs did not differ significantly in patients with RA and controls (0.56 mmol/L [0.38–0.75] and 0.56 mmol/L [0.45–0.70] respectively, p = 0.75). Presence of metabolic syndrome was associated with significantly increased serum FFAs in both RA and controls (p = 0.035 and p = 0.025). In multivariable regression analysis that adjusted for age, race, sex and BMI, serum FFAs were associated with HOMA-IR (p = 0.011), CRP (p = 0.01), triglycerides (p = 0.005) and Framingham risk score (p = 0.048) in RA, but not with IL-6 (p = 0.48) or coronary artery calcium score (p = 0.62).

Conclusions

Serum FFAs do not differ significantly in patients with RA and controls. FFAs may contribute to insulin resistance, but are not associated with IL-6 and coronary atherosclerosis in RA.     

The relationship of insulin resistance and extracoronary calcification in the multi-ethnic study of atherosclerosis

Objective

We hypothesized that insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA), is independently associated with prevalent and incident extra-coronary calcification (ECC).

Methods

We studied calcium scores of the aortic valve calcification (AVC), mitral valve calcification (MVC), thoracic aorta calcification (TAC) and aortic valve root calcification (AVR) in 6104 MESA participants not on diabetes medication who had baseline cardiac CT scans; 5312 had follow-up scans (mean 2.4 years). Relative-risk regression modeled prevalent and incident ECC adjusted for baseline demographics (model 1), and additionally for CVD risk factors (model 2).

Results

In model 1, prevalence and incidence risk-ratios for the highest versus lowest quartile of HOMA were 20–30% higher in all ECC locations (p-value for trend ≤0.05 for all but incident-AVC). In model 2, all associations were attenuated, primarily by adjustment for metabolic syndrome components.

Conclusions

HOMA has a positive and graded association with ECC, but not independently of cardiovascular risk factors—particularly metabolic syndrome components.     

Pericardial fat inflammation correlates with coronary artery disease

Objectives

Serum gamma-glutamyltransferase (γ-GT) predicts incident cardiovascular disease and mortality. The present study examined whether γ-GT also is associated with prognosis in patients with stable coronary heart disease.

Methods and results

This study included 1152 participants (aged 30–70 years at baseline) of an in-patient rehabilitation programme after acute coronary syndrome, recruited in two rehabilitation clinics in Germany in the years 1999–2000 (KAROLA study). Until year 8 follow-up, 147 participants had experienced a non-fatal or fatal secondary cardiovascular disease event. Confounder-adjusted Cox proportional hazards models revealed an increase in risk for secondary events over ascending γ-GT quartiles, with hazard ratios (95% confidence interval) of 1.21 (0.72–2.03), 1.32 (0.80–2.16) and 1.75 (1.08–2.83) for the 2nd, 3rd and 4th in reference to the lowest quartile (P_trend = 0.024). The association with all-cause mortality examined as a secondary outcome was slightly stronger (hazard ratio of 4th quartile: 1.97 [1.15–3.36]; P_trend = 0.017).

Conclusions

In patients with stable coronary heart disease, serum γ-GT was associated with prognosis independent of a variety of established risk markers. The association appeared similar to that reported for primary cardiovascular disease, which should motivate additional studies of its clinical utility in cardiovascular patient care.     

Progression of glycaemia and cardiovascular risk factors in patients of different age groups with new type 2 diabetes over 5 years of follow-up in a diabetes quality improvement initiative

Aims

To examine progression of glycaemia and cardiovascular risk factors in type 2 diabetes cases participating in a quality improvement initiative.

Methods

1108 new type 2 diabetes cases enrolled on the Otago Diabetes Register had clinical data recorded at baseline and 5 years. Means and standard deviations or percentages were calculated for variables of interest for <40, 40–59, 60–79 and 80–100 year age groups. p-Values for differences over time and among groups were calculated. Ordinal regression, with robust standard errors, was used to examine intensification of diabetes treatment.

Results

For all age groups blood pressure and lipid levels approached recommended targets at 5 years (p < 0.001). Glycated haemoglobin worsened, especially in the youngest age group (from 7.3 ± 1.9% to 7.9 ± 1.7%, p < 0.001) who had the highest odds of more intense diabetes treatment at 5 years: 6.2 (95% CI 3.5–11.2) compared with 3.3 (95% CI 2.7–4.1) for 40–59-year olds, 2.8 (95% CI 2.3–3.3) for 60–79-year olds and 1.4 (95% CI 0.9–2.0) for ≥80-year olds.

Conclusions

Good management of type 2 diabetes patients, principally in primary care, can lead to improved blood pressure and lipid levels. Targets for glycaemic control and weight are less readily achieved especially among young age groups.     

Cardiovascular risk factors in patients with lichen planus

Background

Chronic inflammation was found to play an important role in the development of cardiovascular risk factors. Recently a case-control study found that lichen planus was associated with dyslipidemia in a large series of patients. However, no data were presented about lipid values, glucose levels, or blood pressure.

Objective

The objective of this case-control study was to evaluate cardiovascular risk factors included in Adult Treatment Panel III criteria for metabolic syndrome in men and women with lichen planus and in healthy controls.

Patients and Methods

This case-control study included 200 patients, 100 with lichen planus (50 men and 50 women) and 100 controls consecutively admitted to the outpatient clinic in Dermatology departments in Granada, Spain.

Results

Analysis of metabolic syndrome parameters revealed a higher significant prevalence of dyslipidemia in patients with lichen planus. No significant differences were observed in glucose levels, abdominal obesity, or blood pressure. Elevated levels of C-reactive protein, erythrocyte sedimentation rate, and fibrinogen were noted in patients with lichen planus. Adjusted odds ratio for dyslipidemia in patients with lichen planus was 2.85 (95% confidence interval, 1.33-5.09; P = .001).

Conclusion

Chronic inflammation in patients with lichen planus may explain the association with dyslipidemia. Lipid levels screening in men or women with lichen planus may be useful to detect individuals at risk and start preventive treatment against the development of cardiovascular disease.     

Impact of soluble TWEAK and CD163/TWEAK ratio on long-term cardiovascular mortality in patients with peripheral arterial disease

Aim

Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) has recently been introduced as a potential mediator of cardiovascular disease. We examined the associations between sTWEAK, its scavenger receptor sCD163, sCD163/sTWEAK ratio and risk for long-term all-cause and cardiovascular mortality in patients with lower-extremity peripheral arterial disease (PAD).

Methods

sTWEAK and sCD163 serum levels were measured retrospectively in a cohort of 295 patients with symptomatic PAD followed for 6.1 ± 2.1 years. The endpoints were defined as all-cause or cardiovascular death. The relationship between sTWEAK, sCD163 levels, sCD163/sTWEAK ratio, and times to fatal outcome was examined by Cox proportional hazards analysis.

Results

sTWEAK levels were significantly lower (672 (IQR 515; 872) pg/ml vs. 814 (IQR 673; 957) pg/ml, p < 0.0001), and sCD163/sTWEAK ratio significantly higher (0.91 (IQR 0.63; 1.37) vs. 0.77 (IQR 0.55; 1.12), p = 0.008) in patients with critical limb ischemia (CLI) on admission as compared with those with intermittent claudication (IC). During follow-up, 80 (27%) patients died, hereof 33 (11.5%) of cardiovascular causes. Cox regression analysis revealed that an increase of 100 pg/ml of baseline sTWEAK were associated with a decreased risk for all cause [adjusted hazard ratio (HR) 0.89 (95%CI (0.80–0.99)), p = 0.043] and cardiovascular mortality [adjusted HR 0.83 (95% CI (0.69–0.99)), p = 0.038]. The patients with lower sTWEAK concentrations had a higher risk for cardiovascular death being more than two times as great as patients in the two upper tertiles (adjusted HR 2.2, 95% CI (1.06–4.87), p = 0.035). Similarly, the risk of cardiovascular death was 3-fold increased for patients in the upper tertile of sCD163/sTWEAK ratio as comparing with the patients in two lower tertiles (adjusted HR 3.04, 95% CI (1.44–6.43), p = 0.004). The model including sCD163/sTWEAK ratio have shown a significant improvement in accuracy of cardiovascular death prediction (the area under ROC curve 0.79 (0.72–0.86) vs. 0.84 (0.78–0.90), p = 0.019).

Conclusions

Decreased sTWEAK concentration, and increased sCD163/sTWEAK ratio were significantly and independently associated with long-term cardiovascular mortality in patients with lower-extremity PAD.     

Lipoprotein particle distribution and size, insulin resistance, and metabolic syndrome in Alaska Eskimos: the GOCADAN study

Background

Metabolic syndrome (MS) is associated with dyslipidemia, and insulin resistance (IR) may be a main determinant of this dyslipidemia.

Objective

To determine how lipoprotein particle concentration and size are related to MS and IR in a population-based sample of Alaska Eskimos.

Design

Participants underwent a physical exam, personal interview, collection of biological specimens, and diagnostic tests.

Setting

This study was conducted in the Norton Sound region of Alaska.

Participants

One thousand one hundred fifty-eight Inupiat Eskimo adults (women = 653, men = 505).

Main outcome measures

Lipoprotein particle profile was evaluated by nuclear magnetic resonance (NMR) and related to presence of MS and level of IR.

Results

Participants with MS had (a) significantly higher concentrations of all VLDLs and a larger VLDL size (women, p = 0.007; men, p = 0.0001); (b) higher concentrations of small LDL (women, p < 0.0001; men, p = 0.09) and lower concentrations of large LDL (women, p < 0.0001), leading to a smaller overall LDL size (women, p < 0.0001; men, p < 0.05); (c) significantly lower concentrations of large HDL (both genders, p < 0.0001) and an increase in intermediate (women, p < 0.05) and small HDL (women, p < 0.0001; men, p < 0.004). Lipoprotein profile with increasing HOMA-IR resembled that of individuals with MS.

Conclusions

In this population MS is characterized by lipoprotein distribution and size abnormalities independent of obesity, age, and other cardiovascular risk factors, including lipid concentration. IR seems the major determinant.     

The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells

Objective

Obesity and cardiovascular disease recognize a common metabolic soil and may therefore share part of their genetic background. Genome-wide association studies have identified variability at the SH2B1 locus as a predictor of obesity. We investigated whether SNP rs4788102, which captures the entire SH2B1 variability, is associated with coronary artery disease (CAD) and/or myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM).

Design and setting

SNP rs4788102 was typed in 2015 White subjects with T2DM from three CAD case–control studies [n = 740 from the Gargano Hearth Study (GHS, Italy); n = 818 from the Joslin Hearth Study (JHS, Boston); n = 457 from the University of Catanzaro (CZ, Italy)].

Results

SNP rs4788102 (G/A) was not associated with CAD (overall allelic OR = 1.06, 95% CI = 0.93–1.21; p = 0.37). On the contrary, it was associated with MI in GHS (1.42, 1.12–1.81; p = 0.004) and in the three samples analyzed together (1.21, 1.04–1.41; p = 0.016). Insulin stimulated nitric oxide synthase (NOS) activity in human vein endothelial cells from G/G (n = 4, p = 0.03) but not the G/A (n = 5, p = 0.83) genotype. Of the SNPs in perfect LD with rs4788102, one (rs7498665) affects amino acid polarity (Ala484Thr) and falls into a highly conserved protein segment of SH2B1 containing a class II SH3 domain binding site.

Conclusions

Variability at the SH2B1 obesity locus is associated with MI in diabetic patients and with reduced insulin-stimulated NOS activity in human endothelial cells. Further studies are needed to replicate this association and dissect the biology underlying this finding.     

The influence of sex and age on the relationship between sleep duration and metabolic syndrome in Korean adults

Aims

To investigate the influence of sex and age on the relationship between sleep duration and metabolic syndrome in a nationally representative population.

Methods

We used data from the Korea National Health and Nutrition Examination Survey (2001–2010) and enrolled 24,511 participants aged 20–79 years. Sleep duration was categorized into five groups: ≤5, 6, 7 (referent), 8, and ≥9 h/day. Age was categorized into three groups: younger (20–39 y), middle-aged (40–59 y), and older (60–79 y). The association between sleep duration and metabolic syndrome was assessed in the total, separately in men and women, then in six groups based on sex and age.

Results

The prevalence of metabolic syndrome by sleep category demonstrated a U-shaped pattern in the total population. However, after adjusting for age, education, occupation, exercise, smoking, alcohol, and body mass index, the prevalence of metabolic syndrome increased in long sleepers (OR 1.31; 95% CI 1.14–1.51) but not in short sleepers (OR 1.00; 95% CI 0.89–1.11). The relationship between sleep duration and metabolic syndrome varied by sex and age–long sleep (≥9 h/day) was positively associated with metabolic syndrome only in younger (OR 2.13; 95% CI 1.38–3.28) and middle-aged (OR 1.63; 95% CI 1.21–2.21) women. Short sleep (≤5 h/day) was not associated with metabolic syndrome in any sex and age groups. However, extremely short sleep (≤4 h/day) was associated with metabolic syndrome in middle-aged men (OR 1.76, 95% CI 1.05–2.96).

Conclusion

These data suggest that sex and age significantly modify the relationship between sleep duration and metabolic syndrome.