A polymorphism in the resistin gene promoter and the risk of coronary artery disease in a Chinese population

Objective Resistin, a novel adipocyte‐derived peptide, has been linked to the pathogenesis of atherosclerosis. Recently, –420C>G, a variant located in the promoter region of the resistin gene (RETN) was identified. The aim of this study was to investigate the association between this RETN–420C>G polymorphism and the risk of coronary artery disease (CAD). Design A hospital‐based case–control study. Patients A total of 225 CAD patients and 225 age‐ and sex‐matched control subjects. Measurements Genotyping was performed by polymerase chain reaction (PCR) and restriction enzyme analysis to detect the presence of the RETN–420C>G polymorphism. Results The frequencies of RETN–420C>G genotypes in the CAD group were significantly different from those in the control group (P = 0·024). Subjects with the variant genotypes (CG and GG) had a 62% increased risk of CAD compared to CC carriers [adjusted odds ratio (OR) = 1·62, 95% confidence interval (CI) = 1·09–2·41, P = 0·016]. However, there were no significant differences between the genotypes with respect to weight, body mass index (BMI) and lipid profiles in CAD patients, and no significant association was found between the RETN–420C>G polymorphism and the severity of CAD. Conclusions Our data suggest that the RETN–420C>G polymorphism might be associated with an increased risk of CAD in a Chinese population.     

抵抗素基因-420C>G位点多态性对脑出血患者血浆抵抗素水平的影响

目的探讨抵抗素基因-420C>G位点单核苷酸多态性对脑出血患者血浆抵抗素水平的影响。方法选取344例高血压性基底核出血患者,入院时抽取外周血提取DNA,采用聚合酶反应-限制性片断多态性分析基因型,同时采用ELISA法检测血浆抵抗素浓度,进行统计分析。结果酶切后可见抵抗素基因-420C>G位点有CC、CG和GG三种基因型,等位基因C和G的频率分别为71.08%和28.92%,基因型CC、CG和GG的频率依次为50.29%、41.57%和8.14%。经Hardy-Weinberg遗传平衡定律检验,各基因型频率符合遗传平衡。CC、CG和GG基因型患者血浆抵抗素浓度依次为(23.83±7.09)ng/mL、(26.54±7.32)ng/mL和(27.18±9.97)ng/mL。CC基因型患者血浆抵抗素均显著低于CG和GG基因型患者(P<0.01,P<0.05)。结论抵抗素基因-420C>G位点单核苷酸多态性显著影响脑出血患者血浆抵抗素水平,可能参与脑出血炎症反应。     

Resistin gene variation is associated with systemic inflammation but not plasma adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic Caucasians

Objective Resistin causes insulin resistance and diabetes in mice whereas in humans it is linked to inflammation and atherosclerosis. Few human genetic studies of resistin in inflammation and atherosclerosis have been performed. We hypothesized that the –420C>G putative gain‐of‐function resistin variant would be associated with inflammatory markers and atherosclerosis but not with metabolic syndrome or adipokines in humans. Design and methods We examined the association of three resistin polymorphisms, –852A>G, –420C>G and +157C>T, and related haplotypes with plasma resistin, cytokines, C‐reactive protein (CRP), adipokines, plasma lipoproteins, metabolic syndrome and coronary artery calcification (CAC) in nondiabetic Caucasians (n = 851). Results Resistin levels were higher, dose‐dependently, with the –420G allele (CC 5·9 ± 2·7 ng/ml, GC 6·5 ± 4·0 ng/ml and GG 7·2 ± 4·8 ng/ml, trend P = 0·04) after age and gender adjustment [fold higher for GC + GG vs. CC; 1·07 (1·00–1·15), P < 0·05)]. The –852A>G single nucleotide polymorphism (SNP) was associated with higher soluble tumour necrosis factor‐receptor 2 (sol‐TNFR2) levels in fully adjusted models [1·06 (95% CI 1·01–1·11), P = 0·01)]. The estimated resistin haplotype (GGT) was associated with sol‐TNFR2 (P = 0·04) and the AGT haplotype was related to CRP (P = 0·04) in the fully adjusted models. Resistin SNPs and haplotypes were not associated with body mass index (BMI), fasting glucose, insulin resistance, metabolic syndrome, adipokines or CAC scores. Conclusions Despite modest associations with plasma resistin and inflammatory biomarkers, resistin 5′ variants were not associated with metabolic parameters or coronary calcification. This suggests that resistin is an inflammatory cytokine in humans but has little influence on adiposity, metabolic syndrome or atherosclerosis.     

Effect of the -420C/G variant of the resistin gene promoter on metabolic syndrome, obesity, myocardial infarction and kidney dysfunction

OBJECTIVE: Resistin is an adipokine that has been suggested to be correlated with markers of inflammation and to be predictive of coronary atherosclerosis and type II diabetes in humans. A common single nucleotide polymorphism (SNP) (-420C/G) in the promoter of resistin is associated with increased resistin plasma levels and susceptibility to type II diabetes. The aim of this study was to investigate the association of the -420C/G polymorphism with metabolic syndrome, obesity, myocardial infarction and kidney disease. DESIGN AND RESULTS: First we studied 1542 subjects from the PLIC study (a population based cohort). GG carriers showed an higher prevalence of obesity and metabolic syndrome as well as increased plasma triglycerides levels, BMI, systolic and diastolic blood pressure and cardiovascular risk according to Framingham algorithm (P < 0.05 for all). Next we investigated the presence of the -420C/G resistin polymorphism in a case-control study that included 300 subject with myocardial infarction and 300 age and sex matched controls and then we studied the role of the -420C/G SNP in 88 patients with mild to moderate renal dysfunction. No statistically significant differences in allele frequencies between the PLIC study, the myocardial infarction (MI) cases and the subjects with renal dysfunction were observed. Pro-inflammatory gene expression profiling of peripheral blood mononuclear cells failed to detect any difference between wild type subjects and carriers of the rare allele. CONCLUSION: Our data suggest that the presence of the -420C/G SNP of the resistin gene is associated with increased obesity and metabolic syndrome, although it is not different in subjects at high cardiovascular risk such as patients with myocardial infarction or patients with renal dysfunction compared with controls.     

Association of tumor necrosis factor-α gene promoter polymorphism at sites -308 and -238 with non-alcoholic fatty liver disease: a meta-analysis

Background and Aim: Environmental and genetic factors play a role in the pathogenesis and natural history of non‐alcoholic fatty liver disease (NAFLD). The objective of this study was to quantitatively evaluate the association between tumor necrosis factor (TNF)‐α gene promoter polymorphism at sites ‐308 and ‐238 and NAFLD susceptibility. Methods: We performed an extensive search of relevant studies and made a meta‐analysis, including eight studies with 837 NAFLD cases and 990 controls in the association between TNF‐α ‐308 polymorphism and NAFLD; and seven studies with 771 cases and 787 controls in TNF‐α ‐238 polymorphism. Results: The combined results showed that there was a significant difference in TNF‐α‐238 genotype distribution between NAFLD and control based on all studies (GA/AA vs GG [odds ratio = 2.06, 95% confidence interval = 1.58–2.69, P < 0.000 01]). However, the combined results based on all studies showed there was no evidence of association of TNF‐α‐308 genotype distribution between NAFLD cases and controls (GA/AA vs GG [odds ratio = 1.08, 95% confidence interval = 0.82–1.42, P = 0.60]). When stratifying for race, the significant results did not change materially compared with whole populations. Conclusion: This meta‐analysis suggested that TNF‐α gene promoter polymorphism at position ‐238 but not ‐308 might be a risk factor for NAFLD.     

Association of plasma resistin with glomerular filtration rate and albuminuria in hypertensive adults

Resistin, a recently discovered proinflammatory cytokine, has been variably associated with insulin resistance, inflammation, and renal dysfunction. We investigated the association of plasma resistin with estimated glomerular filtration rate and albuminuria in 1575 hypertensive adults without known coronary heart disease or stroke (857 blacks and 718 non-Hispanic whites). Resistin was measured by a solid phase sandwich immunoassay, estimated glomerular filtration rate was estimated from serum creatinine, and albuminuria was expressed as urine albumin:creatinine ratio. After adjustment for coronary heart disease risk factors (age, sex, body mass index, smoking history, systolic blood pressure, diabetes, and total and high-density lipoprotein cholesterol) and use of renin-angiotensin blockers and statins, higher plasma resistin levels were associated with lower estimated glomerular filtration rate in both ethnic groups (each P<0.0001); the association remained significant after further adjustment for a marker of insulin resistance (homeostasis model assessment for insulin resistance) and a marker of inflammation (plasma C-reactive protein) and was seen in subjects with and without diabetes (each P<0.0001) in both ethnic groups. Higher plasma resistin levels were associated with a higher urine albumin:creatinine ratio in black subjects with diabetes (P<0.0001) and non-Hispanic white subjects with diabetes (P=0.032), independent of coronary heart disease risk factors, hypertension medication use, and statin use; the association remained significant after additional adjustment for homeostasis model assessment for insulin resistance and C-reactive protein. In adults with hypertension, higher circulating resistin levels were associated with a lower estimated glomerular filtration rate and with increased urine albumin:creatinine ratio in the presence of concomitant diabetes. This association was independent of coronary heart disease risk factors and markers of insulin resistance and inflammation.     

Plasma resistin concentration determined by common variants in the resistin gene and associated with metabolic traits in an aged Japanese population

Aims/hypothesis

Resistin is a cytokine derived from adipose tissue and is implicated in obesity-related insulin resistance and type 2 diabetes mellitus. Polymorphisms of the resistin gene (RETN) have been shown to affect the plasma resistin concentration. The aims of this study were to identify polymorphisms of RETN that influence plasma resistin concentration and to clarify the relation between plasma resistin level and metabolic disorders in an aged Japanese cohort.

Methods

The study participants comprised 3133 individuals recruited to a population-based prospective cohort study (KING study). Plasma resistin concentration, BMI, abdominal circumference, blood pressure, fasting plasma glucose and serum insulin concentrations, HbA_1c content and serum lipid profile were measured in all participants. The HOMA index of insulin resistance (HOMA-IR) was also calculated. Eleven polymorphisms of RETN were genotyped.

Results

A combination of ANOVA and multiple linear regression analysis in screening and large-scale subsets of the study population revealed that plasma resistin concentration was significantly associated with rs34861192 and rs3745368 polymorphisms of RETN. Multiple linear regression analysis with adjustment for age and sex also showed that the plasma resistin level was significantly associated with serum concentrations of HDL-cholesterol, triacylglycerol and insulin, as well as with BMI.

Conclusions/interpretation

Our results implicate the rs34861192 and rs3745368 polymorphisms of RETN as robust and independent determinants of plasma resistin concentration in the study population. In addition, plasma resistin level was associated with dyslipidaemia, serum insulin concentration and obesity. Trial registration: ClinicalTrials.gov NCT00262691 Funding: This study was supported by Grants-in-Aids for Scientific Research from the Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science, and Technology of Japan.     

Association of resistin gene 3'-untranslated region +62G-->A polymorphism with type 2 diabetes and hypertension in a Chinese population

Resistin, a recently discovered polypeptide, antagonizes insulin action and may play a part in the pathogenesis of insulin resistance. This study investigates whether resistin gene polymorphism can be associated with type 2 diabetes. We studied 1102 Chinese type 2 diabetes patients and 743 subjects without diabetes. The resistin 3'-untranslated region (UTR) +62G-->A polymorphism was determined by PCR. Type 2 diabetes subjects had a lower frequency of resistin gene 3'UTR +62A allele (GG:GA/AA, 83.5%:16.5%) than the controls (GG:GA/AA, 75.1%:24.9%; odds ratio, 1.524; 95% confidence interval, 1.268-1.831; P < 0.001). Unexpectedly, diabetic patients with the GG genotype had a higher prevalence of hypertension (GG:GA/AA, 49.8%:36.2%; odds ratio, 1.375; 95% confidence interval, 1.116-1.693; P = 0.001). Logistic regression analysis confirmed that the resistin gene 3'UTR +62G-->A polymorphism acts as an independent contributing factor to type 2 diabetes and hypertension. The mean systolic and diastolic blood pressure levels in diabetic subjects with the GG genotype (144 +/- 21/87 +/- 13 mm Hg) were significantly higher than those in subjects with GA/AA variants (139 +/- 21/84 +/- 14 mm Hg; P = 0.004 and P = 0.002, respectively). Multiple linear regression analysis showed resistin gene polymorphism to be an independent factor associated with systolic and diastolic blood pressures in type 2 diabetes patients. These findings suggest that resistin may play a role in the pathogenesis of type 2 diabetes and insulin resistance-related hypertension.     

Serum resistin is reduced by glucose and meal loading in healthy human subjects

Resistin is an adipokine that induces insulin resistance in mice; serum concentrations are decreased by fasting and increased by feeding. Adiponectin, another adipokine, improves insulin sensitivity. The aims of this study were to determine the effects of glucose and meal loading on serum resistin and total and high-molecular weight (HMW) adiponectin in humans and to explore potential determinants of fasting serum resistin and of changes in resistin. Serum resistin and total and HMW adiponectin were measured by enzyme-linked immunosorbent assay in young, lean, nondiabetic subjects during 75-g oral glucose tolerance test (OGTT) and meal tolerance test (MTT). Resistin single nucleotide polymorphism (SNP) -420 was typed. Serum resistin was decreased at 60 and 120 minutes during OGTT compared with baseline (n = 36, 1-way repeated-measures analysis of variance, P < .0001; Scheffe, P = .0457 and P < .0001, respectively). Serum resistin was also reduced at 240 minutes during MTT (n = 33, 1-way repeated measures analysis of variance, P < .0001; Scheffe, P = .0002). Multiple regression analysis adjusted for age, sex, and body mass index revealed that the reductions in serum resistin were dependent on baseline resistin levels. Subjects with greater baseline concentrations of resistin experienced more pronounced declines in resistin (OGTT, unstandardized regression coefficient (beta) = -0.19, P = .0005; MTT, beta = -0.63, P < .0001). Serum total and HMW adiponectin was unchanged. Fasting serum resistin was positively correlated with the G allele number of SNP -420 (beta = 7.70, P = .01) and white blood cell count (beta = 0.007, P = .0001) adjusted for age, sex, and body mass index. Therefore, in young, lean, nondiabetic humans, serum resistin was reduced by glucose and meal loading; the reduction in resistin was greater in subjects with higher fasting resistin. Fasting resistin was correlated with SNP -420 and white blood cell count.     

Relationship of resistin levels with endometrial cancer risk

Cancer of endometrium (CAE) is the most common gynecologic malignancy in industrialized nations. Increased resistin levels, an adipocytokine produced by adipose tissue and macrophages, have been considered as a risk factor in gastric, colon and breast cancer, recently. No studies associating resistin levels with endometrial cancer have been done so far. The purpose of this case-control study was to determine the relationship between serum circulating resistin levels and resistin gene -420C>G (rs3219175) variant in endometrial cancer patients. 37 Caucasian female patients and 39 healthy controls were enrolled in this study. Difference in resistin levels between age and BMI matched patients group (mean 24.2 ng/ml) and control subjects (mean 10.1 ng/ml) were statistically significant (p <001). We also determined single nucleotide polymorphism -420C>G (rs3219175) within resistin gene and no significant association between resistin levels and investigated polymorphism was found. Furthermore, no significant association between higher resistin levels and diabetes mellitus 2, body mass index, smoking or age have been observed within studied groups. To our knowledge, this is the first study examining the relationship between serum resistin levels and endometrial cancer and our results show, that patients with endometrial cancer have significantly increased circulating levels of resistin compared to control subjects.     

血清抵抗素水平与动脉粥样硬化的相关性研究

目的探讨血清抵抗素与动脉粥样硬化的关系及其可能在糖尿病大血管并发症中所起的作用。方法病例选自2004年9月至2005年3月北京军区总医院的行冠状动脉造影的患者共88例,分为单纯冠心病组、糖尿病合并冠心病组、单纯糖尿病组以及正常对照组。受试者空腹采血,行生化检查及血清抵抗素、高敏C反应蛋白(hs-CRP)、可溶性肿瘤坏死因子受体2(sTNF-R2)的测定。结果各组患者血清抵抗素以及hs-CRP、sTNF-R2均高于正常对照组(P<0·05);抵抗素与sTNF-R2呈正相关(r=0·24,P=0·025),而与hs-CRP无显著相关性(P=0·613);多元回归分析显示,性别(b=0·194,P=0·029)及冠状动脉病变支数(b=0·155,P=0·001)是影响血清抵抗素水平的因素;随着冠脉病变支数的增加,血清抵抗素呈增高的趋势(P=0·004)。结论冠心病患者,特别是糖尿病合并冠心病患者,血清抵抗素水平增高;冠脉病变支数是影响血清抵抗素的重要因素;血清抵抗素水平与炎症标志呈正相关,提示抵抗素可能作为炎症因子在动脉粥样硬化以及糖尿病大血管并发症的发病机制中发挥作用。     

Serum uric acid level as an independent risk factor for all‐cause,cardiovascular, and ischemic stroke mortality: A chinese cohort study

Objective

The association between hyperuricemia and cardiovascular events has been documented in high‐risk groups, but is still undetermined in general populations, especially Chinese. This study assessed the temporal association between serum uric acid level, hyperuricemia, and cardiovascular mortality.

Methods

A prospective cohort study of 41,879 men and 48,514 women ages ≥35 years was conducted using data from the MJ Health Screening Centers in Taiwan. Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease were compared according to increasing serum uric acid levels.

Results

A total of 1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup 8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7 mg/dl) were estimated with Cox regression model after adjusting for age, sex, body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy cigarette smoking, and frequent alcohol consumption. In all patients, HRs were 1.16 (P < 0.001) for all‐cause mortality, 1.39 (P < 0.001) for total CVD, and 1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for cardiovascular risk remained significant in patients with hypertension (1.44, P < 0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low metabolic risk subgroup, the HRs for all‐cause mortality and total cardiovascular morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively.

Conclusion

Hyperuricemia was an independent risk factor of mortality from all causes, total CVD, and ischemic stroke in the Taiwanese general population, in high‐risk groups, and potentially in low‐risk groups.     

Increased serum resistin levels in patients with type 2 diabetes are not linked with markers of insulin resistance and adiposity

Abstract The role of resistin in human biology remains uncertain. We measured serum resistin levels in Japanese patients with (n=111) and without (n=98) type 2 diabetes mellitus and investigated the significance of this hormone in the pathophysiology of diabetes. The levels of serum adiponectin and leptin were also measured. Resistin levels were increased significantly in patients with type 2 diabetes compared with non-diabetic subjects (24.7±2.6 vs. 15.0±1.2 ng/ml, p=0.0013). However, there was no correlation in either patient group between serum resistin levels and markers of insulin resistance, obesity or hyperlipidaemia. These results were in direct contrast to the data of leptin or adiponectin, both of which were closely related to these clinical markers of diabetes. Multivariate regression analysis on the combined data of the two groups demonstrated that the presence of diabetes and HDL cholesterol levels were significant predictors of serum resistin levels (diabetes: =0.159, p=0.035; HDL: =-0.172, p=0.039). No correlation was observed between C-reactive protein and resistin adjusted for BMI. Taken together, these findings demonstrate that serum resistin levels are increased in patients with type 2 diabetes, but this increase is not linked to markers of insulin resistance or adiposity. Further studies are necessary to elucidate the significance of serum resistin concentration in human pathophysiology.     

Serum resistin is positively correlated with the accumulation of metabolic syndrome factors in type 2 diabetes

Objective Resistin, secreted from adipocytes, causes insulin resistance in rodents. We reported that the G/G genotype of a resistin gene promoter single nucleotide polymorphism (SNP) at ?420 increases type 2 diabetes (T2DM) susceptibility by enhancing promoter activity. We also showed that serum resistin was positively correlated with G at SNP‐420, the duration of T2DM, and HbA1c in T2DM. The aim of this study was to determine the relation between serum resistin and factors related to the metabolic syndrome (MetS) in T2DM. Design, patients and measurements We analysed 238 Japanese T2DM subjects (124 males and 114 females, age 60·2 ± 11·3 years, body mass index (BMI) 24·1 ± 3·9) whose overnight fasting sera were available. Serum resistin was measured using ELISA. Results Serum resistin was higher in subjects with either obesity (P = 0·041), low HDL (P = 0·004), high triglycerides (TG) (P = 0·019), hypertension (HT) (P = 0·001) or atherosclerosis (P = 0·012). Simple regression analysis revealed that serum resistin was correlated with lower HDL, TG and high‐sensitivity C‐reactive protein (hsCRP). Multiple regression analysis (or logistic regression analysis for HT), adjusted for age, gender, BMI and the duration of T2DM, revealed that serum resistin was correlated with lower HDL (P = 0·008), TG (P = 0·041), HT (P = 0·031) and hsCRP (P = 0·004). Serum resistin was positively correlated with the number of MetS factors, independent of age, gender and the duration of T2DM (P < 0·001). Adjustment by either thiazolidinedione (TZD) treatment or hsCRP had no effects on these findings. Conclusions Serum resistin was positively correlated with the accumulation of MetS factors in T2DM.     

Resistin is not an appropriate biochemical marker to predict severity of acute pancreatitis: A case-controlled study

AIM: To assess levels of serum resistin upon hospital admission as a predictor of acute pancreatitis (AP) severity.METHODS: AP is both a common and serious disease, with severe cases resulting in a high mortality rate. Several predictive inflammatory markers have been used clinically to assess severity. This prospective study collected data from 102 patients who were diagnosed with an initial acute biliary pancreatitis between March 2010 and February 2013. Measurements of body mass index (BMI) and waist circumference (WC) were obtained and serum resistin levels were analyzed at the time of hospital admission using enzyme-linked immunosorbent assay. Additionally, resistin levels were measured from a control group after matching gender, BMI and age.RESULTS: A total of 102 patients (60 females and 42 males) were diagnosed with acute gallstone-induced pancreatitis. The mean age was 45 years, and mean BMI value was 30.5 kg/m² (Obese, class I). Twenty-two patients (21.6%) had severe AP, while eighty-eight patients had mild pancreatitis (78.4%). Our results showed that BMI significantly correlated with pancreatitis severity (P = 0.007). Serum resistin did not correlate with BMI, weight or WC. Furthermore, serum resistin was significantly higher in patients with AP compared to control subjects (P < 0.0001). The mean resistin values upon admission were 17.5 ng/mL in the severe acute biliary pancreatitis group and 16.82 ng/mL in the mild AP group (P = 0.188), indicating that resistin is not an appropriate predictive marker of clinical severity.CONCLUSION: We demonstrate that obesity is a risk factor for developing severe AP. Further, although there is a correlation between serum resistin levels and AP at the time of hospital admission, resistin does not adequately serve as a predictive marker of clinical severity.     

Eicosapentaenoic Acid and Prevalence of Cardiovascular Disease in Hemodialysis Patients

Eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio showed inverse associations with cardiovascular disease (CVD) in general population. However, this has not been examined enough in dialysis patients. We cross‐sectionally investigated the relationship between EPA/AA ratio and prevalence of CVD in 321 chronic hemodialysis patients (64 ± 11 years old; 110 women; dialysis vintage 10 ± 8 years) in an urban area of Tokyo. CVD was defined as a composite of ischemic heart disease, ischemic stroke and hemorrhagic stroke. The frequency of dietary fish intake was also examined. Logistic regression was used to quantify the association of EPA/AA ratio with CVD. EPA/AA ratio was 0.31 ± 0.19 and 154 patients (48%) consumed fish once or less weekly. One hundred and thirty patients (41%) had CVD, including 65 with ischemic heart disease, 70 with ischemic stroke, and 20 with hemorrhagic stroke. Age (odds ratio [OR], 1.04; P = 0.01), hypertension (OR, 2.25; P = 0.002), and dialysis vintage (OR, 1.04; P = 0.02) were associated with CVD; however, EPA/AA was not after adjustment for other risk factors. A similar relationship was observed between fish intake and CVD prevalence. We did not find any significant association between EPA/AA ratio and prevalence of CVD, although traditional risk factors such as age, hypertension and dialysis vintage were associated with CVD. These results might have been influenced by the fact that only a small proportion of our patients showed a high EPA/AA ratio.     

Absolute and attributable risks of cardiovascular disease incidence in relation to optimal and borderline risk factors: comparison of African American with white subjects--Atherosclerosis Risk in Communities Study

BACKGROUND: Among white Americans, a large proportion of cardiovascular disease (CVD) events is explained by borderline or any elevated CVD risk factor levels. The degree to which this is true among African American subjects is unclear. METHODS: The Atherosclerosis Risk in Communities Study included 14 162 middle-aged adults who were free of recognized stroke or coronary heart disease and had baseline information on risk factors. Based on national guidelines, we categorized risk factors (blood pressure, cholesterol levels, diabetes, and smoking) into 3 categories, ie, optimal, borderline, and elevated. Incidence of CVD (composite of stroke and coronary heart disease) (n = 1492) and CVD mortality (n = 612) were identified for a 13-year period. RESULTS: The proportion of subjects with all optimal risk factor levels was lower in African American (3.8%) than in white (7.5%) subjects. Conversely, the proportion of subjects with at least 1 elevated risk factor was higher in African American (approximately 80%) than in white (approximately 60%) subjects. After adjustment for these risk factor differences and education level, African American and white subjects had virtually identical rates of CVD (relative hazard for African American subjects, 1.01; 95% confidence interval, 0.90-1.14). The proportion of CVD events explained by elevated risk factors was high in African American subjects (approximately 90%) compared with approximately 65% in white subjects. CONCLUSIONS: The higher CVD incidence rate in African American than in white subjects seems largely attributable to a high frequency of elevated CVD risk factors in African American subjects. Primary prevention of elevated CVD risk factors in African American subjects might greatly reduce CVD occurrence as much as it has for white subjects.     

Free fatty acids are associated with pulse pressure in women, but not men, with type 1 diabetes mellitus

Cardiovascular disease (CVD) is the leading cause of death in type 1 diabetes mellitus (T1D). Pulse pressure, a measure of arterial stiffness, is elevated in T1D and associated with CVD. Free fatty acids (FFAs), elevated in women and abdominal adiposity, are also elevated in T1D and CVD. We thus examined the association of fasting FFAs with pulse pressure and coronary artery calcification (CAC, a marker of coronary atherosclerotic burden) in an adult population (n = 150) of childhood-onset T1D and whether any such associations varied by abdominal adiposity and sex. Mean age and diabetes duration were 42 and 33 years, respectively, when CAC, visceral abdominal adiposity (VAT), and subcutaneous abdominal adiposity (SAT) were determined by electron beam tomography. Free fatty acids were determined by in vitro colorimetry. Pulse pressure was calculated as systolic blood pressure minus diastolic blood pressure. Free fatty acids were log transformed before analyses, and all analyses were controlled for serum albumin. Free fatty acids were associated with pulse pressure in women (r = 0.24, P = .04), but not in men (r = 0.07, P = .55). An interaction for the prediction of pulse pressure was noted between FFAs and both VAT (P = .03) and SAT (P = .008) in women, but only a marginal interaction with SAT (P = .09) and no interaction for VAT (P = .40) with FFAs were observed in men. In multivariable linear regression analysis allowing for serum albumin, age, height, heart rate, albumin excretion rate, hemoglobin A_1c, high-density lipoprotein cholesterol, hypertension medication use, FFAs, SAT, and the interaction between FFAs and SAT, the interaction between FFAs and SAT remained associated with pulse pressure in women (FFAs, P = .04; interaction term, P = .03), but not men (FFAs, P = .32; interaction term, P = .32). FFAs showed no association with log-transformed CAC. Although FFAs were not associated with CAC in either sex, they were associated with pulse pressure in women and their effect appeared to vary by abdominal adiposity, particularly SAT. This finding might help explain the loss of the sex difference in CVD in T1D.     

Plasma resistin levels and risk of myocardial infarction and ischemic stroke

CONTEXT: Resistin is a hormone that has been linked to insulin resistance, inflammatory processes, and coronary heart disease in case-control studies; however, prospective data on the association between plasma resistin levels and future risk of cardiovascular disease are lacking. OBJECTIVE: The objective of the study was to investigate the association between plasma resistin levels and risk of future myocardial infarction (MI) and ischemic stroke (IS) in a large prospective cohort. METHODS: We investigated the association between plasma resistin levels and risk of MI and IS in a case-cohort design among 26,490 middle-aged subjects from the European Investigation into Cancer and Nutrition-Potsdam Study without history of MI or stroke at time of blood draw. Plasma resistin levels were measured in baseline blood samples of 139 individuals who developed MI, 97 who developed IS, and 817 individuals who remained free of cardiovascular events during a mean follow-up of 6 yr. RESULTS: After multivariable adjustment for established cardiovascular risk factors including C-reactive protein, individuals in the highest compared with the lowest quartile of plasma resistin levels had a significantly increased risk of MI (relative risk 2.09; 95% confidence interval 1.01-4.31; P for trend = 0.01). In contrast, plasma resistin levels were not significantly associated with risk of IS (relative risk 0.94; 95% confidence interval 0.51-1.73; P for trend = 0.88). CONCLUSION: Our data suggest that high plasma resistin levels are associated with an increased risk of MI but not with risk of IS. Further studies are needed to evaluate the predictive value of plasma resistin levels for cardiovascular disease.