The impact of radiofrequency ablation on quality of life/symptoms (VEINES-QOL/Sym questionnaire score) in patients with chronic venous insufficiency.

Purpose: Chronic venous insufficiency is defined as a progressive disease that impairs the quality of life. Symptomatic patients can be treated with a 97% success rate through endovenous radiofrequency ablation (RFA) procedures. The aim of this study is to evaluate the effect and impact of RFA therapy on both the Venous Insufficiency Epidemiological and Economic Study Quality of Life/Symptom Questionnaire (VEINES-QOL/Sym) scale and the VEINES-QOL/Sym severity score in patients with isolated vena saphena magna insufficiency. Methods: Between March and June 2018, a retrospective analysis was conducted on 45 patients with a healthy vena saphena parva. They were divided into two groups based on the diameter of the great saphenous vein (GSV). Patients with GSV < 6 mm were assigned to group I (n = 22, 15 males, 7 females, mean age 52.45 ± 13.98 years), while patients with GSV ≥ 6 mm were assigned to group II (n = 23, 14 males, 9 females, mean age 55.04 ± 10.18 years). The pre-procedural Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification and post-procedural quality of life and symptom assessment at 12-24 months were evaluated using the VEINES-QOL/Sym questionnaire scale. Results: When all patients were assessed in terms of the VEINES-QOL/Sym questionnaire scale, compared to the previous year, it was found that 57.8% of patients (n = 26) still experienced complaints, and 24.4% of patients (n = 14) reported slightly worse symptoms than the previous year. In group II, 56.5% of patients (n = 13) reported experiencing similar complaints as the previous year, while 30.4% (n = 7) noted slightly worse symptoms. Conclusions: Our study findings revealed that the increase in vessel diameter does not significantly impact the severity of symptoms and quality of life outcomes after RFA therapy; however, it does have a notable impact on the improvement of symptom characteristics. As a result, early intervention for symptomatic patients is crucial in order to address their symptoms and improve their quality of life.

Evaluating renin and aldosterone levels in children with organic acidemia-therapeutic experience with fludrocortisone.

Hyporeninemic hypoaldosteronism has been reported in only a few cases with methylmalonic acidemia (MMA) and has been attributed to the renal involvement. This study aims to investigate renin-aldosterone levels along with the renal functions of the patients with organic acidemia. This is a cross-sectional study conducted in patients with MMA, propionic acidemia (PA), and isovaleric acidemia (IVA). Serum renin, aldosterone, sodium, and potassium levels were measured, and glomerular filtration rates (GFR) were calculated. Comparisons were made between the MMA and non-MMA (PA+IVA) groups. Thirty-two patients (MMA:PA:IVA = 14:13:5) were included. The median GFR was significantly lower in the MMA group than in the non-MMA group (p < 0.001). MMA patients had the highest incidence of kidney damage (71.4%), followed by PA patients (23%), while none of the IVA patients had reduced GFR. GFR positively correlated with renin levels (p = 0.015, r = 0.433). Although renin levels were significantly lower in the MMA group than the non-MMA group (p = 0.026), no significant difference in aldosterone levels was found between the two groups. Hyporeninemic hypoaldosteronism was found in 3 patients with MMA who had different stages of kidney damage, and fludrocortisone was initiated, which normalized serum sodium and potassium levels.  Conclusions: This study, which has the largest number of patients among the studies investigating the renin-angiotensin system in organic acidemias to date, has demonstrated that hyporeninemic hypoaldosteronism is not a rare entity in the etiology of hyperkalemia in patients with MMA, and the use of fludrocortisone is an effective treatment of choice in selected cases. What is Known: • Hyperkalemia may be observed in cases of methylmalonic acidemia due to renal involvement and can be particularly prominent during metabolic decompensation. • Hyporeninemic hypoaldosteronism has been reported to be associated with hyperkalemia in only a few cases of methylmalonic acidemia. What is New: • Hyporeninemic hypoaldosteronism was found in one-fifth of cases with methylmalonic acidemia. • Fludrocortisone therapy leads to the normalization of serum sodium and potassium levels.

Association of Intelectin 1 Gene rs2274907 A > T Polymorphism with Obesity, Type 2 Diabetes, Serum Intelectin-1 Levels and Lipid Profiles in Turkish Adults.

The anti-inflammatory adipokine intelectin-1, which is encoded by the ITLN1 gene, is hypothesized to be linked to the pathogenesis of type 2 diabetes (T2DM) and obesity. The purpose of this study was to examine the effect of the ITLN1 gene polymorphism rs2274907 on obesity and T2DM in Turkish adults. The impact of genotype on lipid profiles and serum intelectin levels in the obese and diabetes groups was also investigated. Randomly selected 2266 adults (mean age, 55.0 ± 11.7 years; 51.2% women) participating in the population-based Turkish adult risk factor study were cross-sectionally analyzed. The genotyping of rs2274907 A > T polymorphism was performed by using the hybridization probe based LightSNiP assay in real-time PCR. T2DM were defined using the criteria of the American Diabetes Association. Obesity was described as Body mass index ≥ 30 kg/m2. Statistical analyses were used to investigate the association of genotypes with clinical and biochemical measurements. According to findings, there was no vital connection between the rs2274907 polymorphism and obesity, T2DM, or serum intelectin-1 level. The TA+AA carriers had significantly higher triglyceride levels (p = 0.007) compared with the TT carriers in both obese and T2DM women when adjusted for relevant covariates. ITLN1 rs2274907 polymorphism is not correlated with the risk of obesity and T2DM and not affect serum ITLN1 levels in Turkish adults. However, this polymorphism appears to be important in regulating triglyceride levels in obese and diabetic women.

Association of polymorphisms in the sex hormone genes with the presence and severity of coronary artery disease.

OBJECTIVE: Coronary artery disease (CAD) is an important public health problem worldwide. Therefore, it is important to identify the molecular mechanisms and the candidate gene polymorphisms involved in the development of CAD. In this study, we focused on 2 polymorphisms of the atherosclerosis-related genes, ESR1 and CYP19A1. METHODS: Unselected 339 individuals who underwent coronary angiography were divided into 2 groups: those with normal coronary arteries (≤30% stenosis) and those with critical disease (≥50% stenosis). Individuals were genotyped for CYP19A1 rs10046 C/T and ESR1 rs2175898 A/G polymorphisms using hybridization probes in real-time PCR. In addition, Gensini and SYNTAX scores were assessed. RESULTS: ESR1 polymorphism was significantly associated with CAD in men (p=0.036) via G allele carriage. Multiple logistic regression analyses showed that ESR1 rare allele carriage was associated with CAD presence (Odds ratio=2.12, 95% confidence interval 1.01-4.1, p=0.025), adjusted for age, HDL-C, LDL-C and smoking status in the male group. CYP19A1 rs10046 T allele carriers had a 2.84-fold increased risk for complex CAD in multiple logistic regression analysis (p=0.016). Furthermore, the univariate analysis of variance indicated that T allele carriage of rs10046 polymorphism was associated with increased SYNTAX and Gensini scores (p<0.05). Female patients who were ESR1 G allele carriers with CAD had higher adiponectin levels (p=0.005), whereas HbA1c levels were associated with T allele of CYP19A1 in the CAD group (p=0.004) and male CAD group (p=0.018). CONCLUSION: The CYP19A1 and ESR1 polymorphisms were associated with the presence and severity of CAD. These gene polymorphisms warrant further studies for the elucidation of their contribution to CAD development.

Inflammation Markers in Infants of Mothers with Gestational Diabetes.

AimPentraxin-3, high sensitive CRP (HsCRP) and adropin were investigated in cord blood of infants of mothers with gestational diabetes mellitus (IDM) to evaluate the exposure of fetus to inflammation and whether there is any correlation with clinical findings.MethodsForty IDM and forty three infants whose mother did not have diabetes were included in this prospective study. Adropin, pentraxin-3 and HsCRP levels were measured in the cord blood samples. Echocardiographic measurements were performed in the first three days of life.ResultsAdropin and pentraxine-3 levels were significantly lower and HsCRP levels were significantly higher in IDM group. Echocardiographic measurements of myocardial hypertrophy were negatively correlated with adropin.ConclusionAlterations in these markers in IDM supports the hypothesis of in utero fetal exposure to inflammation caused by gestational diabetes mellitus. Potentially, cord blood adropin might be used as a predictor for complications of diabetes.

Differences Between Morbid Obesity With Metabolic Syndrome and Overweight Turkish Adult Participants in Multiple Atherosclerotic Cardiovascular Disease Risk Factors.

Obesity and metabolic syndrome (MetS) are public health problems and are increasing globally. We assessed the differences in lipid profiles through lipid testing, thrombotic and inflammatory parameters, and oxidative stress indexes between overweight and obese patients with MetS in a Turkish adult population. We included 100 obese (body mass index [BMI] >30 kg/m2) patients with MetS (66 women, 34 men, mean age 54.0 ± 10.1 years) and 15 overweight (BMI 25-30 kg/m2) individuals (11 women, 4 men, mean age 50.2 ± 14.5 years) as controls. The group with MetS had significantly higher levels of glycaemia, uric acid, high-sensitivity C-reactive protein, homocysteine, fibrinogen, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, small dense LDL, oxidized LDL, apolipoprotein B (Apo B), lipoprotein (a), small and intermediate high-density lipoprotein (HDL) particles, oxidative stress index, and significantly lower levels of HDL-cholesterol (HDL-C), Apo A, and large HDL particles. In conclusion, obesity with MetS increase atherogenic dyslipidemia and thrombotic, inflammatory and oxidative stress biomarkers. Furthermore, obesity with MetS decreases protective mechanisms of atherosclerosis. We should at least try to prevent overweight individuals from becoming obese with MetS.

Changes in pentraxin 3 and oxidative parameters during coronary bypass grafting and factors affecting postoperative atrial fibrillation.

OBJECTIVE: The performance of coronary bypass grafting (CBG) induces a type of subclinical systemic inflammatory response syndrome. The present study was performed to examine the changes in pentraxin 3 (PTX3) and oxidative parameters during cross-clamping in patients undergoing CBG. We also examined factors affecting the development of postoperative atrial fibrillation (POAF). METHOD: This study involved 40 patients who underwent elective on-pump CBG (33 men, 7 women; mean age, 60.8 ± 8.0 years). Blood specimens were drawn before anaesthesia and after aortic cross-clamping. POAF was detected by analysing the rhythm records of telemetry units for 96 hours postoperatively. RESULTS: The mean PTX3 concentration prior to surgery was 176.3 ± 148.4 pg/mL. After cross-clamping, it increased to 947.7 ± 377.2 pg/mL. The increase was statistically significant. Twelve patients had POAF. The leucocyte count and change in the oxidative stress index were significantly higher in patients without than with POAF. Although the increase in PTX3 was higher in patients without POAF, the difference was not statistically significant. CONCLUSION: The PTX3 concentration significantly increases during CBG. A significant change in the oxidative stress index and a more intense increase in the PTX3 concentration were seen in patients without POAF.

The Association between Oxidative Stress and Cardiac Functions in Infants Born to Preeclamptic Mothers.

OBJECTIVE: The present study aimed to assess the global oxidant and antioxidant status in infants born to preeclamptic mothers and their correlation with cardiac functions. STUDY DESIGN: We compared 40 infants born to preeclamptic mothers with 40 premature infants born to normotensive mothers. We assessed the relationship between echocardiographic measurements and total antioxidant capacity (TAC) and total oxidant status (TOS) values. RESULTS: In the study group, TAC, TOS, and oxidative stress index (OSI) levels were significantly higher in the cord blood (p = 0.03, 0.04, and 0.039, respectively) than in the control group. We did not observe any correlation between echocardiographic measurements and TAC, TOS, and OSI levels in infants born to preeclamptic mothers. CONCLUSION: Compared with the control group, despite higher TAC levels in infants born to preeclamptic mothers, concurrent elevated OSI levels reveal that the oxidant-antioxidant balance is disturbed in favor of oxidants. Furthermore, the findings of this study suggest that echocardiographic parameters are unaffected by the oxidant status.

Pulmonary hypertension experience in an expert university hospital.

OBJECTIVE: Pulmonary artery hypertension (PAH) is characterized by remodeling of the small pulmonary arteries, leading to a progressive increase in pulmonary vascular resistance and right ventricular failure. In this study, we aimed to share our 10 years of experience dealing with pulmonary hypertension (PH) and provide information in real-life settings in terms of demographics, clinical course, PH subgroup distribution, and treatment patterns in patients with PAH in a tertiary center. METHODS: In this retrospective, single-center, observational study, we screened the patients who applied to PH outpatient clinic of Istanbul University Institute of Cardiology due to the suspicion of PAH between 2008 and 2017. While group 1, 4, and 5 PH patients were included, group 2 and 3 PH patients were excluded from the study. RESULTS: Our study group comprised 162 patients (115 females, 71%). The female:male ratio was 2.4. The mean age was 52±16 years. Most (86.4%) of the patients were in group 1 PH (PAH). The rest (13.6%, n=22) of the patients were in group 4 PH (chronic thromboembolic PH). In group 1 PH, 45.7% of patients (n=64) were classified as having idiopathic PAH (IPAH) after excluding the alternative diagnosis using PH diagnostic algorithm. The remaining 54.3% of group 1 PH patients (n=76) had various diseases that caused PAH, which is called associated PAH (APAH); APAH group included PAH associated with congenital heart diseases (n=70), connective tissue disorders (scleroderma, n=4) and portal hypertension (n=2). CONCLUSION: Our data provides important information in real-life settings in terms of demographics, clinical course, PH subgroup distribution, and treatment patterns in patients with PAH in a reference tertiary center in Turkey.

Population-based serum omentin-1 levels: paradoxical association with cardiometabolic disorders primarily in men.

AIM: The conflicting relationships of serum omentin with inflammation markers and cardiometabolic disorders were investigated. Results & methods: Unselected 864 population-based middle-aged adults were cross-sectionally studied by sex-specific omentin tertiles. Men in the lowest omentin tertile (T1) had lower systolic blood pressure, HbA1c and glucose values and tended in T3 to higher lipoprotein(a) levels. Logistic regression analysis, adjusted for four covariates, revealed significant independent associations with the presence of hypertension and diabetes only in men. Sex- and age-adjusted odds ratio in gender combined for T2 & T3 versus T1 was 1.34 (95% CI: 1.00-1.79) for metabolic syndrome. DISCUSSION & CONCLUSION: The elicited adverse relationships of omentin-1 support the notion of oxidative stress-induced proinflammatory conversion of omentin, rendering loss of anti-inflammatory properties.

Modified risk associations of lipoproteins and apolipoproteins by chronic low-grade inflammation.

INTRODUCTION: Lipoproteins and the apolipoproteins (apo) that they carry are major determinants of cardiovascular diseases (CVD) as well as metabolic, renal and inflammatory chronic disorders either directly or through mediation of risk factors. The notion that elevated low-density lipoprotein cholesterol (LDL-C) and apoB levels are related to the acquisition of CVD and, high-density lipoprotein cholesterol (HDL-C) and apoA-I indicate protection against CVD has been challenged in the past decade. Advanced age, adiposity, ethnicity or impaired glucose intolerance rendered autoimmune activation in an environment of pro-inflammatory state/oxidative stress and may disrupt the linear risk association between lipoproteins. Areas covered: This review summarizes the modified risk associations of lipoproteins and apolipoprotein by an environment of chronic systemic low-grade inflammation with special emphasis on the non-linear relationship of lipoprotein(a) [Lp(a)], a biomarker of renewed interest in cardiometabolic risk. Expert commentary: It seems that autoimmune activation in an environment of pro-inflammatory state/oxidative stress not only disrupts the linear risk association between lipoproteins, but also may cause interference in immunoassays. Hence, methodological improvement in immunoassays and much further research focusing on population segments susceptible to a pro-inflammatory state is necessary for further advances in knowledge.

Lower circulating migration inhibitory factor protein is associated with metabolic syndrome and diabetes.

AIM: The controversial relationship between macrophage migration inhibitory factor (MIF) and the likelihood of cardiometabolic diseases was investigated. Results/methodology: Assayed MIF protein from 1225 adults was cross-sectionally analyzed. MIF was independently inversely associated with age, total testosterone and positively with high-density lipoprotein-cholesterol. In men MIF correlation with age, testosterone and waist circumference converted from inverse in the upper to positive in the bottom MIF third. Both metabolic syndrome and diabetes were significantly associated, in combined gender, with the intermediate (vs the highest) MIF tertile at an odds ratio 1.6. Coronary heart disease was not significantly related with MIF in either gender. DISCUSSION/CONCLUSION: Findings are consistent with oxidative damage to MIF protein and its involvement in autoimmune activation, likely more extensive in women.

Lipoprotein(a)-activated immunity, insulin resistance and new-onset diabetes.

OBJECTIVES: Some evidence suggests that serum lipoprotein[Lp](a) may be inversely linked to type-2 diabetes. We aimed to determine in nondiabetic people the relationship of serum [Lp](a) with insulin resistance and new-onset diabetes (NOD). MATERIALS AND METHODS: Population-based middle-aged adults (n = 1685) were categorized by fasting glucose and stratified to gender, having excluded prevalent diabetic subjects. NOD (n = 90) occurred over a median 5 years' follow-up. RESULTS: Subjects that subsequently developed NOD, derived both from the normoglycemia and impaired fasting glucose (IFG) groups,were distinguished, among others, primarily by significantly elevated serum gamma glutamyltransferase, reduced Lp(a) (by 31%) and, compared to IFG, by low total cholesterol levels. Partial correlation of Lp(a) with homeostatic model assessment (HOMA) was inverse in normoglycemic men; such correlation, neutral in normoglycemic women, proved inverse in IFG (r = -0.17). Circulating Lp(a) in individuals with paired measures increased significantly (1.55-fold) in the period from baseline up to NOD. Multivariable-adjusted logistic regression analysis for NOD in combined sexes indicated independent and additive prediction by serum Lp(a), albeit inverse in direction (RR 0.84, [95%CI 0.72; 0.97]). CONCLUSION: Lp(a) is significantly reduced in the period preceding NOD and is inversely associated with HOMA index, observations consistent with underlying autoimmune activation.

Algorithm for predicting CHD death risk in Turkish adults: conventional factors contribute only moderately in women.

OBJECTIVE: To assist the management strategy of individuals, we determined an algorithm for predicting the risk of coronary heart disease (CHD) death in Turkish adults with a high prevalence of metabolic syndrome (MetS). METHODS: The risk of CHD death was estimated in 3054 middle-aged adults, followed over 9.08±4.2 years. Cox proportional hazard regression was used to predict risk. Discrimination was assessed using C-statistics. RESULTS: CHD death was identified in 233 subjects. In multivariable analysis, the serum high-density lipoprotein-cholesterol (HDL-C) level was not predictive in men and the non-HDL-C level was not predictive in women. Age, presence of diabetes, systolic blood pressure ≥160 mm Hg, smoking habit, and low physical activity were predictors in both sexes. The exclusion of coronary disease at baseline did not change the risk estimates materially. Using an algorithm of the 7 stated variables, individuals in the highest category of risk score showed a 19- to 50-fold higher spread in the absolute risk of death from CHD than those in the second lowest category. C-index of the model using age alone was as high as 0.774 in men and 0.836 in women (p<0.001 each), while the incorporation of 6 conventional risk factors contributed to a C-index of 0.058 in males and 0.042 in females. CONCLUSION: In a middle-aged population with prevalent MetS, men disclosed anticipated risk parameters (except for high HDL-C levels) as determinants of the risk of CHD death. On the other hand, serum non-HDL-C levels and moderate systolic hypertension were not relevant in women. The moderate contribution of conventional risk factors (beyond age) to the estimation of the risk of CHD death in women is consistent with the operation of autoimmune activation.

Fasting glycemia and glycated hemoglobin categories: Relationship to serum lipoprotein(a) level and disparity in 2 geographic regional groups of Turkey.

OBJECTIVE: The goal of the present study was to determine covariates of serum lipoprotein (Lp) (a) within fasting glucose and glycated hemoglobin (HbA1c) categories, and to detect features that were different among covariates based on residence in Marmara and Central Anatolia (Marm-CA) regions or remaining 5 geographic regions of Turkey. METHODS: Data of randomly-selected group of 1167 men and women (mean age 61 years) who participated in biennial surveys of 2013 and 2015 were cross-sectionally analyzed in 6 categories. RESULTS: In multiple linear regression analysis of nondiabetic women, homeostatic model assessment (HOMA) index score was inversely associated with Lp(a) (ß coefficient 0.49; p=0.001); this was not true for men. In the whole sample, Lp(a) was significantly positively associated with female sex and with serum creatinine, and inversely in each sex with HOMA index (ß coefficient 0.63; p<0.001). Linear models within separate categories showed significant associations of Lp(a) only in individuals with no evidence of diabetes other than HbA1c >6.5%: in women, positive association with total cholesterol and inverse relationship with creatinine were found, and in men, positive association with apolipoprotein (apo) B was determined. Similar age, diastolic blood pressure, fasting glucose, triglyceride, uric acid, and C-reactive protein values were obtained from participants of 2 regional groups. Residents of the Marm-CA region who were nondiabetic exhibited significantly (by 23%) lower serum Lp(a) among individuals with HbA1c ≥5.7%, significantly higher HOMA index score, concentrations of apoB, and low-density lipoprotein cholesterol. CONCLUSION: Hallmark of prediabetic and diabetic glycemia/HbA1c categories seems to be an independent inverse association between Lp(a) protein (yet not of apoB) and HOMA score, this being primarily so in residents of Marm-CA region.

Oxidant Status following Cardiac Surgery with Phosphorylcholine-Coated Extracorporeal Circulation Systems.

Introduction. Extracorporeal circulation (ECC) related systemic oxidative stress is a well-known entity but the underlying mechanisms are not clearly described. Our aim was to investigate the relation between the oxidative stress indices, inflammatory markers, and phosphorylcholine-coated (PCC) ECC systems. Patients and Methods. Thirty-two consecutive coronary artery bypass grafting (CABG) cases were randomly assigned to Group I (PCC, n = 18) and Group II (noncoated, n = 14) ECC circuits. Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Tumor Necrosis Factor-α (TNF-α), Interleukin-1ß (IL-ß), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), and Procalcitonin (PCT) levels were measured at 5 different time points. The association between the oxidative indices levels and PCC system used was analyzed. Results. In Group I TOS and TAS statuses were increased at T1, T2, T3, and T4, while IL-10 and TNF-α levels accompanied those raises only at T2 (Group I-Group II, 4.73 ± 2.04 versus 2.79 ± 0.63, p = 0.002, and 30.56 ± 8.11 versus 23.97 ± 7.8, p = 0.031, resp.). In contrast, mean TAS and TOS levels were similar to baseline at all time points in Group II but IL-6 and IL-8 levels were increased at T2 (Group I-Group II, 16.84 ± 5.63 versus 44.81 ± 17.0, p = 0.001, and 38.88 ± 9.8 versus 46.14 ± 9.25, p = 0.038, resp.). Conclusion. Even coated ECC systems are still incapable of attenuating the inflammatory response to cardiopulmonary bypass (CPB).

Gender-modulated risk of coronary heart disease, diabetes and coronary mortality among Turks for three major risk factors, and residual adiposity risk.

BACKGROUND: We determined the proportion of the effects of body mass index (BMI) or its categories on cardiometabolic outcomes mediated through systolic blood pressure (SBP), total cholesterol and fasting glucose. METHODS: Cox regression analyses were performed for incident outcomes among Turkish Adult Risk Factor study participants in whom the three mediators had been determined (n = 2158, age 48.5 ± 11 years). Over a mean 10.2-years' follow-up, new coronary heart disease (CHD) developed in 406, diabetes in 284 individuals, and 149 CHD deaths occurred. RESULTS: Hazard ratios (HR) of BMI for incident diabetes were no more than marginally attenuated by the 3 mediators including glucose, irrespective of gender. Compared to "normal-weight", sex- and age-adjusted RRs for incident CHD of overweight and obesity were 1.40 and 2.24 (95 % CI 1.68; 2.99), respectively, in gender combined. Only three-tenths of the excess risk was retained by BMI in men, six-tenths in women. No mediation of glycemia was discerned in males, in contrast to greatest mediation in females. HR of age-adjusted continuous BMI was a significant but modest contributor to CHD mortality in each gender. While the BMI risk of CHD death was abolished by mediation of SBP in men, HR strengthened to over two-fold in women through mediation of fasting glucose. CONCLUSIONS: Mediation of adiposity by 3 traditional factors exhibited among Turkish adults strong gender dependence regarding its magnitude for CHD risk and the mediation by individual risk factors. Retention of the large part of risk for diabetes in each sex and for CHD in women likely reflects underlying autoimmune activation.

Advances in understanding gender difference in cardiometabolic disease risk.

Gender differences exist in cardiovascular or metabolic disease risk, beyond the protective effect of estrogens, mostly burdening the postmenopausal female. We aimed to review herein sex differences in pro-inflammatory states, the independence of inflammation from insulin resistance, differences in high-density lipoprotein dysfunction, in gene-environment interactions, and in the influence of current and former smoking on cardiometabolic risk. Sex differences in absorption of long-chain fatty acids are highlighted. Differences exist in the first manifestation of cardiovascular disease, men being more likely to develop coronary heart disease as a first event, compared to women who have cerebrovascular disease or heart failure as a first event. Autoimmune activation resulting from pro-inflammatory states, a fundamental mechanism for numerous chronic diseases in people prone to metabolic syndrome, is much more common in women, and these constitute major determinants. Therapeutic approaches to aspects related to sex difference are briefly reviewed.