Coronary Heart Disease In Men Research Articles

Gender-related impact of vitamin D status on severity of coronary artery disease

Abstract Funding Acknowledgements None. Background Vitamin D has cardioprotective properties. A status of hypovitaminosis D, defined as vitamin D ≤ 20 ng/ml, was found to have a comparable effect to diabetes mellitus (DM) in terms of adverse outcomes in patients with acute myocardial infarction (AMI). To date, it is known that hypovitaminosis D is more frequent in women than men but there is still a paucity of data on how gender differences in vitamin D levels are associated with the extent of coronary heart disease (CAD). Purpose To evaluate the relationship between vitamin D status on CAD incidence and severity in patients with AMI. Methods Blood samples were obtained from 1484 patients with AMI on hospital admission. Levels of vitamin D ≤ 10 ng/ml were considered as severe hypovitaminosis D. CAD was defined as the presence of at least one coronary vessel stenosis greater than 50%, while severe CAD was defined as left main disease and/or three-vessel disease. The endpoint was all-cause mortality. Results The cohort's mean age was 66.25 (11.47) years, the majority were male (71.8%) and 24.3% of patients had DM. Overall, 86.2% of patients had CAD and 32.9% severe CAD. The median vitamin D concentration was 17.25 [10.3 - 24.7] ng/ml, and 23.6% of patients had severe hypovitaminosis D. In female patients, hypovitaminosis D was significantly more common in whom with severe CAD (74.1% vs 58.1%, p=0.002), but not in men (61.3% vs 57.1%, p=0.193). On the other hand, severe hypovitaminosis D was significantly more frequent in patients with severe CAD in both genders (male and female respectively 26.6% vs 17.9%, p=0.005; 40.5% vs 26.4%, p=0.001). In female patients, severe CAD was predicted by hypovitaminosis D (OR: 1.85 [1.14 – 3.03], p=0.013) along with DM and older age after correction for confounders as GFR<60 mL/min/1.73 m2, higher cholesterol levels and body mass index. However, hypovitaminosis D was not an independent predictor of severe CAD in men. Moreover, a composite of hypovitaminosis D and DM was identified as a predictor of severe CAD when compared to patients with neither hypovitaminosis D nor DM (OR: 3.56 [1.8 – 7.03], p=0.021) only in female patients. Conclusions The identification of an association between hypovitaminosis D and severe CAD in women but not in men is a novelty in this field. Furthermore, we found that the presence of both hypovitaminosis D and DM has a greater contribution to severe CAD in female patients with AMI.

INDUCTION OF CARDIAC ARRHYTHMIAS DURING BICYCLE ERGOMETRY IN THE DIAGNOSIS OF CORONARY HEART DISEASE

HighlightsThe frequency of arrhythmias during bicycle ergometry was compared in patients with and without coronary heart disease. Their diagnostic significance in diagnosing this disease was analyzed separately for men and women. AbstractAim. To determine the diagnostic significance of exercise-induced cardiac arrhythmias (CAs) during bicycle ergometry (BEM) in patients with suspected coronary heart disease (CHD).Methods. For the retrospective study, 384 case histories of patients discharged from the cardiology department between 2011 and 2020 were selected according to the inclusion and exclusion criteria. The data of BEM and coronary angiography were studied. The correlation between the occurrence of induction of different types of CAs during BEM and the presence of coronary artery blood flow abnormalities was investigated. Indicators of the diagnostic significance of CAs in the diagnosis of coronary artery disease, such as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) results, were determined separately for men and women. The statistical significance of the results was assessed.Results. Statistically significant specificity and PPV for the induction of ventricular arrhythmias (VAs) without taking into account rare single monomorphic ventricular extrasystoles (VEs) in the diagnosis of CHD in men were 83.5% and 73.1%, respectively. The same indicators for VAs, excluding all single VEs, were 95.3% and 82.6% in men.Conclusion. The induction of VAs in men on BEM, with the exception of rare single monomorphic VEs, is diagnostically significant in the detection of CHD and allows us to qualify the result of BEM as “positive”. The induction of other CAs on BEM has not shown diagnostic significance in the detection of CHD.

Birth Weight, Childhood and Young Adult Overweight, and the Risk of Coronary Heart Disease in Men.

Low birth weight is a known risk factor for adult coronary heart disease (CHD), but the additional effect of weight development during childhood and early adult life has not been studied. We included 35 659 men born 1945 to 1961 from the population-based BMI Epidemiology Study Gothenburg, with data available on birthweight, BMI in childhood (8 years), and BMI in young adulthood (20 years). Information on CHD diagnoses was retrieved from national registers. We used Cox proportional hazards regression to estimate hazard ratios and 95% CIs for the risk of early and late CHD (before and after 58.4 years of age, respectively). During follow-up, a total of 3380 cases of CHD (fatal and nonfatal) were registered. Birth weight was inversely associated with the risk of both early (hazard ratio, 0.88 per SD increase [95% CI, 0.84-0.92]) and late (hazard ratio, 0.94 per SD increase [95% CI, 0.90-0.98]) CHD, independently of BMI at 8 years and BMI change during puberty. In a model including birth weight (below or above the median) together with overweight at 8 and 20 years, only birth weight and young adult overweight, but not overweight in childhood, were significantly associated with the risk of CHD. A birth weight below the median, followed by overweight at 20 years of age was associated with a more than doubled risk of early CHD (hazard ratio, 2.29 [95% CI, 1.86-2.81]), compared with the reference (birth weight above the median and normal weight at 20 years of age). This excess risk was even more pronounced for a birthweight below 2.5 kg. We demonstrate that low birth weight and young adult overweight are important developmental markers of risk for adult CHD. These findings motivate a life course perspective for prevention and risk assessment of adult CHD.

Social Networks and Cardiovascular Disease Events in the Jackson Heart Study.

Background Cardiovascular disease (CVD) disproportionately affects Black adults. Greater social networks (SNs), or social connectedness, may lower the risk of CVD events. This study determined the association of SNs and incident CVD and tested mediation by depressive symptoms, hypertension control, and diabetes control. Methods and Results We used the Social Network Index at exam 1 (2000-2004) to develop a continuous standardized SN score and binary categories (high versus low) among participants in the Jackson Heart Study (n=4686; mean age, 54.8 years). Surveillance of coronary heart disease, stroke, and heart failure events occurred after exam 1 (2005 for HF) until 2016. Using Cox proportional hazards regression, we estimated the association of SNs and CVD events by sex and tested the mediation of depressive symptoms, hypertension control, and diabetes control. Models adjusted for age, education, health behaviors, CVD comorbidities, and depressive symptoms. Among women, the SN score was associated with a lower hazard of stroke, coronary heart disease, and heart failure after full adjustment (hazard ratio [HR], 0.78 [95% CI, 0.64-0.95]; HR, 0.79 [95% CI, 0.71-0.88]; and HR, 0.78 [95% CI, 0.66-0.92], respectively). SN scores were also associated with a lower hazard of coronary heart disease in men (HR, 0.84 [95% CI, 0.75-0.94]) after full adjustment. High versus low SNs were associated with a lower hazard of coronary heart disease and heart failure among women after full adjustment. There was no evidence of mediation by depressive symptoms, diabetes control, and hypertension control. Conclusions Higher SNs may lower the risk of CVD events, especially in women.

Sex-specific associations of the difference between 2-hour post-load and fasting plasma glucose with cardiovascular risk in a normoglycemic population

Abstract Background Elevated levels of fasting plasma glucose (FPG) and 2-hour post-load glucose (2hPG) have been established as individual risk factors for cardiovascular disease (CVD), coronary heart disease (CHD), and stroke. However, it is unclear whether the difference between 2hPG and FPG (2hPG-FPG) within normoglycemic influences the cardiovascular risk in women and men. Purpose To investigate the association between 2hPG-FPG and the incidence of CVD, CHD, and stroke among normoglycemic women and men in a large population-based cohort. Methods In this prospective cohort study, a total of 7224 participants with the normoglycemic state (mean age 37±11; women, 57.4%) that had baseline measurements of both FPG and 2hPG values and did not have prior CVD, CHD, or stroke were included and were followed for incidence of outcomes annually until March 2018. The normoglycemic range was defined as FPG< 5.55 and 2 h-PG< 7.77 mmol/L and not taking anti-diabetic medications. CHD was defined as either positive ECG findings and biomarkers, cardiac symptoms accompanied by either positive ECG or biomarker, or angiographic-proven CHD. Stroke was defined based on the WHO criteria. Also, CVD was defined as a composite of CHD and stroke. A Multivariable Cox­-regression model adjusted for age, body mass index, hypertension, hyperlipidemia, FPG, education level, and smoking status was used to assess the association between 2hPG-FPG and incident CVD, CHD, and stroke in women and men. We also used a cumulative incidence curve to illustrate the cumulative sex-specific incidence of CVD, CHD, and stroke during the follow-up time (Figure 1). Results During a median follow-up of 17.9 years (IQR: 13.75-18.46), 487 CVD (174 women), 427 CHD (140 women), and 76 stroke (37 women) events occurred. Among men, 2hPG-FPG was associated with an increased risk of CVD (hazard ratio [HR]:1.11, 95% confidence interval [CI]:1.01-1.22, p=0.03) and CHD (HR:1.11, 95% CI:1.00-1.22, p=0.04 ), but not stroke (HR:1.14, 95% CI:0.88-1.50, p= 0.33). No significant associations among women were found between 2hPG-FPG and the incidence of outcomes, with adjusted HRs of 1.02 (95% CI, 0.88-1.18, p=0.82), 1.00 (0.85-1.17, p=0.99), and 1.10 (0.80-1.52, p=0.54) for incident CVD, CHD, and stroke, respectively (Table 1). Conclusion A greater difference between 2hPG and FPG (2hPG-FPG) within the normoglycemic range was associated with an increased risk for incidence of CVD and CHD in men but not women. Further studies are warranted to explore the potential use of 2hPG-FPG for cardiovascular risk stratification, particularly among those with normal glucose parameters.Association of 2hPG-FPG with CV riskCumulative incidence of CVD, CHD, stroke

Ratio of visceral fat area to body fat mass (VBR) is a superior predictor of coronary heart disease.

Ratio of visceral fat area to body fat mass (VBR) is a superior predictor of coronary heart disease.

Abstract P387: FOXO3 Longevity Genotype Mitigates The Risk Of Coronary Heart Disease In Men With Hypertension

Background: We have shown that the FOXO3 longevity genotype moderates the mortality risk in men with hypertension. This study aimed to test whether the FOXO3 longevity genotype moderates the risk of incident coronary heart disease (CHD) in men with hypertension. Methods: The study included 6,312 Japanese American men who were free of CHD at the baseline examination of the Kuakini Honolulu Heart Program (1965-1968, age 53.9±5.4, range 45-68 years), and had been genotyped for the FOXO3 SNP rs2802292 ( FOXO3-292 ). The minor G allele, i.e., TG or GG (TG / GG) genotype is associated with longevity vs. the common TT genotype, which is not . Hypertension was defined as systolic/diastolic BP ≥ 140/90 mmHg or taking antihypertensive medication. Incident CHD was diagnosed from hospital records and follow up examinations to 12/31/2000 (35 years of follow-up). The date of the first coronary event was defined as onset date of CHD, including myocardial infarction, coronary insufficiency, angina, coronary bypass, coronary angioplasty, silent myocardial ischemia, and CHD death. Cox proportional hazard models were used to assess the association of FOXO3-292 genotype and hypertension with incident CHD. Results: During follow-up, 1,629 men developed incident CHD. The age-adjusted incidence rate of CHD was 8.99, 8.31, and 8.62 per 1,000 person-years ( p =0.62) for FOXO3-292 genotypes TT, TG, and GG , respectively. The Cox model, adjusting for age and CVD risk factors, showed hazard ratio (95%CI) for CHD with FOXO3-292 genotypes TG / GG compared to genotype TT was 0.91 (0.82-1.00; p =0.058). The full Cox model, adjusting for age and CVD risk factors, showed a significant interaction effect of FOXO3-292 genotypes TG / GG with hypertension on incident CHD (β= -0.22, p =0.03). After stratifying for hypertension, FOXO3-292 genotypes TG / GG had no effect on incident CHD in those without hypertension HR=1.01 (0.88-1.17; p =0.84) but had a protective effect on incident CHD HR=0.82 (0.74-0.95; p = 0.0064) in those with hypertension. Conclusion: We found the longevity associated FOXO3 genotype may not independently affect the risk of CHD in all men but was associated with protection against incident CHD in men with hypertension.

Sex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women.

The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women. We investigated the association between SHBG and the risk of incident CHD in 128 322 men and 135 103 women free of CHD at baseline in the prospective United Kingdom Biobank (UKB) cohort. The unconfounded associations were estimated using Mendelian randomization (MR) analysis. We further conducted a meta-analysis to integrate currently available prospective evidence. CHD events included nonfatal and fatal myocardial infarction and coronary revascularization. In the UKB, during a median of 11.7 follow-up years, 10 405 men and 4512 women developed CHD. Serum levels of SHBG were monotonically associated with a decreased risk of CHD in both men (adjusted hazard ratio [HR] per log nmol/L increase in SHBG: 0.88 [0.83-0.94]) and women (HR: 0.89 [0.83-0.96]). MR-based analyses suggested causality and a dose-response relationship of SHBG with CHD risk. A cumulative meta-analysis including 216 417 men and 138 282 women from 11 studies showed that higher levels of SHBG were prospectively associated with decreased CHD risk in men comparing the highest with the lowest quartile: pooled relative risk (RR) 0.81 (0.74-0.89) and women (pooled RR: 0.86 [0.78-0.94]). Higher circulating SHBG levels were directly and independently predictive of lower CHD risk in both men and women. The utility of SHBG for CHD risk stratification and prediction warrants further study.

Effect of Coffee Consumption on Risk of Coronary Heart Disease in a Systematic Review and Meta-Analysis of Prospective Cohort Studies

Previous prospective studies have reported inconsistent findings on the association between coffee consumption and the risk of coronary heart disease (CHD). This study aimed to investigate their association using a meta-analysis of prospective studies. We searched PubMed and EMBASE for prospective cohort studies of the association between coffee consumption and the risk of CHD in the general population. We conducted a random-effects meta-analysis and also subgroup meta-analyses by various factors. Of 870 studies searched from databases, 32 prospective cohort studies were included in the final analysis. In the main meta-analysis of all studies, no significant association between coffee consumption and the risk of CHD was observed (relative risk [RR] 1.05, 95% confidence interval [CI] 0.97 to 1.14, I2=64.9%). In the subgroup meta-analyses by gender, coffee consumption significantly increased the risk of CHD in men (RR 1.19, 95% CI 1.05 to 1.35, n=17), whereas a nonsignificantly decreased risk of CHD was observed in women (RR 0.91, 95% CI 0.77 to 1.08, n=11). Also, in the subgroup meta-analyses by follow-up period, coffee consumption significantly increased the risk of CHD in the follow-up of 20years or longer (RR 1.16, 95% CI 1.06 to 1.27, n=4) regardless of gender. In conclusion, in the current meta-analysis of prospective studies, we found that, overall, no significant association between coffee consumption and the risk of CHD was observed. However, coffee consumption showed a differential effect by gender, with an increased risk of CHD in men and a potentially decreased risk in women.

Low Serum Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate Are Associated With Coronary Heart Disease in Men With Type 2 Diabetes Mellitus.

AimsSex hormones play an important role in the pathogenesis of cardiovascular disease (CVD). This cross-sectional study aimed to explore the associations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with coronary heart disease (CHD) and stroke in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM).Materials and MethodsA total of 995 patients with T2DM were included in the study analysis. Serum levels of DHEA and DHEAS were quantified using liquid chromatography–tandem mass spectrometry. Binary logistic regression analyses were performed to assess the associations of DHEA and DHEAS with CHD and stroke. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal DHEA and DHEAS cutoff values for the detection of CHD in men with T2DM.ResultsIn men with T2DM, after adjustment for potential confounders in model 3, the risk of CHD decreased with an increasing serum DHEA level [odds ratio (OR) = 0.38, quartile 4 vs. quartile 1; 95% confidence interval (CI) = 0.16–0.90; p = 0.037 for trend). Consistently, when considered as a continuous variable, this association remained significant in the fully adjusted model (OR = 0.59, 95% CI = 0.40–0.87, p < 0.05). When taken as a continuous variable in model 3, serum DHEAS level was also inversely related to the risk of CHD among men (OR = 0.56, 95% CI = 0.38–0.82, p < 0.05). Similarly, this relationship remained statistically significant when DHEAS was categorized into quartiles (OR = 0.27, quartile 4 vs. quartile 1; 95% CI = 0.11–0.67; p = 0.018 for trend). ROC curve analyses revealed that the optimal cutoff values to detect CHD in men with T2DM were 6.43 nmol/L for DHEA and 3.54 μmol/L for DHEAS. In contrast, no significant associations were found between DHEA and DHEAS on the one hand and stroke on the other in men and women with T2DM (all p > 0.05).ConclusionsSerum DHEA and DHEAS were significantly and negatively associated with CHD in middle-aged and elderly men with T2DM. This study suggests potential roles of DHEA and DHEAS in CHD pathogenesis.

Mathematical Analysis of the Healthcare Treatment of 215 Patients with Coronary Heart Disease

The main risk factors for CHD and the comorbidity include hyperlipidemia (HL), hypertension, smoking, dietary factors, and genetic factors. In this work, 215 patients with coronary heart disease, including 128 males and 87 females, were analyzed for a better understanding of the related clinical pharmacology. Nonparametric test, analysis of variance, chi-square test, correlation analysis, and other methods were used to sort out the data. From the analysis, there are significant differences in age among different gender samples. The incidence of coronary heart disease in men is five years younger than that in women. The sample pairs from different regions showed differences in the presence of family history of diabetes, indicating that a series of patients in some regions concentrated on the disease status of family history of diabetes. Age has a significant positive effect on cardiac functional classification. The older you are, the larger the cardiac functional classification is and the worse the cardiac function is. Age was negatively correlated with VTE score, diastolic blood pressure, CAR, TG, neutrophil, and TC. The older you are, the lower these six values are. Samples of different types of CHD showed significant differences in the presence of comorbidity and family history of CHD. The most significant are unstable angina pectoris and ischemic cardiomyopathy. Samples of different CHD types showed significant effects on VTE score, creatine kinase, low-density lipoprotein cholesterol (LDL⁃C), and lactate dehydrogenase. The highest lactate dehydrogenase is ischemic cardiomyopathy. The highest LDL cholesterol is ST-segment elevation angina. The highest creatine kinase is ischemic cardiomyopathy. The VTE score was the highest for ischemic cardiomyopathy, followed by non-ST-segment elevation angina. Samples taken with or without lipid-lowering drugs showed significant differences in lactate dehydrogenase, creatinine, and TC. There was a significant positive correlation between VTE scores and lactate dehydrogenase, myoglobin, and creatine kinase. High VTE score indicates high lactate dehydrogenase, myoglobin, and creatine kinase. TC has a significant positive correlation with HDL⁃C and TG, respectively. Higher TC values indicate higher HDL⁃C and TG values.

Some indicators of the attitude to their health and medical care in the presence of coronary heart disease in men and women of the open population of Western Siberia

Some indicators of the attitude to their health and medical care in the presence of coronary heart disease in men and women of the open population of Western Siberia

Association of long-term inhalation of caffeine-sodium benzoate with coronary heart disease in men.

A possible correlation between caffeine and coronary heart disease (CHD) is controversial. The objective of this study was to explore the effect of long-term inhalation of caffeine-sodium benzoate (CSB) on the development of CHD in men, the severity of coronary artery lesions and the possible contributing effects of smoking. A retrospective analysis was performed on 2,001 consecutive men who underwent selective coronary angiography. These men were assigned to a CSB inhalation group (CSB; 1-6 times/d, 274-1,644mg/d, >10years; n=326) or a non-inhalation group (non-CSB; n=1,675). The two groups were compared for the prevalence, onset age, and risk factors of CHD. The men were also stratified as CSB-only, smoking-only, combined CSB+ smoking, and the control (non-CSB+non-smoking). The prevalence, onset age, risk factors of CHD, and severity of coronary artery lesions and major adverse cardiovascular events (MACE) were compared among these groups. The prevalence of CHD in the CSB group was higher compared with the non-CSB group (91.72 vs. 86.09%, p<0.01). In the CSB+smoking group, the percentages of men with CHD (93.11%) or >70% stenosis of the coronary artery lesion (64.92%) were significantly higher than that of the smoking-only group (88.19 and 54.29%, respectively) or control (83.20 and 52.90%), while the percentage with stenosis involving the anterior descending branch was lower (62.30 vs. 72.29% and 74.17%, p<0.01). Men who inhaled CSB long-term had a higher rate of CHD compared with those who did not take CSB. The combination of CSB inhalation and smoking appears to increase synergistically the risk and severity of CHD.

Weight change during middle age and risk of stroke and coronary heart disease: The Japan Public Health Center–based Prospective Study

Background and aimsThe impact of weight changes in middle age on the incidence of cardiovascular disease has not been well elucidated. We investigated whether a 5-year weight change was associated with risk of stroke and coronary heart disease (CHD) in middle-aged individuals. MethodsWe analyzed data of 74,928 participants aged 40–69 years who provided responses to the baseline and 5-year follow-up questionnaires in the Japan Public Health Center–based Prospective Study. Weight change was calculated by subtracting self-reported weight at baseline from that at 5-year follow-up. Stroke and CHD events were confirmed by reviewing hospital records. ResultsDuring 997,406 person-years of follow-up, we documented 3,975 stroke and 914 CHD events. The multivariable HRs of stroke for losing ≥5 kg compared to stable weight (change ≤2 kg) was 1.17 (95% CI, 1.01–1.37) in men versus 1.33 (1.13–1.57) for losing ≥5 kg and 1.61 (1.36–1.92) for gaining ≥5 kg in women (U-shaped association). These associations did not change after the exclusion of early events. The multivariable HR of CHD for gaining ≥5 kg was 1.22 (0.95–1.58) in men. After exclusion of early events within another 5 years, that positive association became stronger [multivariable HR 1.34 (1.00–1.82)]. ConclusionsWeight gain during middle age was associated with an increased risk of stroke in women and an increased risk of CHD in men. Weight loss was associated with an increased risk of stroke in both men and women.

Abstract 15749: Sex-differences in Coronary Heart Disease Between Individuals With Familial Hypercholesterolemia and Controls in Norway During 1992-2017

Introduction: During the last 30 years, treatment of familial hypercholesterolemia (FH) has been revolutionized, but it is not known if both sexes equally benefit in these advances, and whether this could have affected the sex difference in risk of coronary heart disease (CHD). We aimed to study sex difference in the risk of CHD between men and women with FH compared to non-FH men and women. Methods: We obtained data on CHD hospitalization and death from Norwegian health registries in 4,525 individuals diagnosed with FH between 1992 and 2014 and an age and sex matched control population of 88,892. The sex distribution was about 50/50 between women and men, and the mean age at start of follow-up was 36 years. Results: The cumulative incidence of CHD (FH vs. non-FH controls) in women and men are shown in Figure 1 with a clear increased risk in FH compared to controls. The cumulative incidence starts to increase at a younger age in men compared with women, both in FH and non-FH controls. This corresponds to an age adjusted 2.6-fold higher risk of CHD in men compared with women in both the FH and control population. In the FH population, men aged 20-39 years had a hazard ratio (HR) of 5.3 (95% CI: 2.6-10.9) compared with women, whereas the corresponding HR between women and men in non-FH controls was 3.7 (95% CI: 2.6-5.3). There was no significant interaction between sex and FH status, indicating that the excess risk in men was similar in FH and non-FH controls. Stratified by sex and adjusted for age, we found that both men and women with FH had a 2-fold higher risk of CHD than controls. The highest excess risk was observed in ages 20-30 years with a of HR= 4.5 (95% CI: 2.2-9.2) and a HR of= 5.5 (95%CI: 4.60-9.34) in women and men, respectively. Conclusions: The risk of CHD among individuals with FH was higher in men than in women in all age groups presented, with no differences between the FH sample and the non-FH controls. However, the relative risk in FH compared with controls was similar for both sexes.

Periodontitis and risk of prevalent and incident coronary heart disease events.

To investigate periodontitis as a risk factor for prevalent and incident coronary heart disease (CHD) in a group of middle-aged men from Northern Ireland. A representative sample of 1400 dentate men had a comprehensive periodontal examination between 2001 and 2003. Prevalent and incident CHD events were validated by independent cardiologists. Logistic regression was used to assess the cross-sectional relationship between periodontitis and prevalent CHD and Cox's proportional hazards analysis to assess the longitudinal relationship between periodontitis and incident CHD. The mean age of the men at baseline was 63.7 (SD 3.0)years. Of the 1400 men examined, 126 (9%) had prevalent CHD. After adjusting for confounding variables, men with highest mean CAL (Q4) had an odds ratio of 2.15 (95% CI 1.15-4.02), p=0.02 for prevalent CHD in comparison to men with the lowest CAL (Q1). During a median follow-up of 12.7years, 137 (10.8%) of the 1274 men free of CHD at baseline had an incident CHD event. After adjusting for confounding variables, the hazard ratio for incident CHD in men in Q4 versus Q1 CAL categories was 1.36 (95% CI 0.81-2.29), p=0.24. In this group of dentate men, periodontitis was associated with prevalent CHD. However, there was no association with incident CHD.

Abstract 23: Sexual Dimorphism In Genetic Associations Of Testosterone And Sex-hormone Binding Globulin With Coronary Heart Disease

Introduction: Men have higher prevalence and mortality of coronary heart disease (CHD) than women. Sex differences in associations of testosterone (T) and sex-hormone binding globulin (SHBG) with CHD risk have been recognized. But mechanisms underlying sex differences in CHD are unknown. Hypothesis: Genetic regulations of T and SHBG may differ by sex; such genetic heterogeneity may contribute to sex differences in CHD. Methods: We carried out a sex-stratified genome-wide association study for T, SHBG, and CHD in 187,888 men and 221,014 women from the UK Biobank, to identify sex-specific ( P &lt;5х10 -8 in one sex and P ≥5х10 -8 in the other) and sex-differed ( P &lt;5х10 -8 in both sexes but effects differed significantly by sex) loci for each trait. Plasma T and SHBG were measured by immunoassay. Genetic correlations were estimated using linkage disequilibrium score regressions. We used cross-traits meta-analyses to identify loci that coregulate a biomarker (T or SHBG) and CHD. Results: The median T levels in men were 10-12 times higher than that in women across all age groups. Women had higher SHBG levels. We identified 344 sex-specific/sex-differed loci for T and 89 for SHBG ( Fig. A ). Genetic correlations between sexes were 0.02 for T, suggesting mostly sex-specific genetic regulation, and were 0.86 for SHBG and 0.94 for CHD, suggesting partially sex-differed genetic regulation. We observed a significant inverse genetic correlation between T and CHD in men ( r g =-0.15; P =1.4х10 -5 ) but not in women. The inverse genetic correlation between SHBG and CHD was stronger in women ( r g =-0.33; P =5.2х10 -11 ) than men ( r g =-0.18; P =2.8х10 -7 ). We identified 31 sex-specific loci coregulating T and CHD (26 for men and 5 for women), and 48 sex-specific loci coregulating SHBG and CHD (35 for men and 13 for women) ( Fig. B ). Tissue-specific gene expression regulations at some loci (e.g. LPA ) were also differed by sex ( Fig. C ). Conclusions: The between-sex heterogeneity in genetic coregulations of T and SHBG with CHD may contribute to the sex-differences in CHD etiology.

Polymorphisms of Intracellular Cholesterol Transporters Genes: Relationship to Blood Lipid Levels, Carotid Intima-Media Thickness, and the Development of Coronary Heart Disease

The influence of single nucleotide polymorphism (SNP) of genes encoding intracellular cholesterol transporters, such as rs1883025 of ABCA1, rs217406 of NPC1L1, and rs881844 of STARD3, on blood lipid levels, carotid intima-media thickness (CIMT), and the risk of coronary heart disease (CHD) has been studied. SNP genotyping was performed using the MassARRAY 4 system. The effects of polymorphic genes on transformed values of blood lipids and CIMT were evaluated by linear regression analysis separately in men and women and adjusted for age and body mass index. SNP rs881844 of the STARD3 gene was associated with decreased risk of CHD in men (OR = 0.67, 95% CI 0.46–0.96, P = 0.02). In women, SNP rs1883025 of ABCA1 showed an association with decreased risk of CHD (OR = 0.65, 95% CI 0.44–0.95, P = 0.02). In men, SNP rs1883025 of the ABCA1 gene was associated with the levels of low density lipoprotein cholesterol (P = 0.05), whereas SNP rs217406 was associated with triglyceride levels (P = 0.02). Polymorphisms such as rs217406 of NPC1L1 and rs881844 of STARD3 in women and rs1883025 of ABCA1 in men were associated with CIMT. The present study has identified for the first time that rs1883025 of ABCA1 and rs881844 of STARD3 are associated with susceptibility to coronary heart disease and showed clear sex-specific differences in the associations between the genes and the studied phenotypes. Thus, polymorphic variants of genes encoding intracellular cholesterol transporters are potentially involved in the formation of the atherosclerotic process through the mechanisms that seem to be not directly related to the metabolism of cholesterol and cholesterol of low density lipoproteins.

Sex-specific associations of TCF7L2 variants with fasting glucose, type 2 diabetes and coronary heart disease among Turkish adults.

Objective:TCF7L2 is a repressor and transactivator of genes, and its variants are strongly associated with diabetes. This study aimed to evaluate the sex-specific relationship between the most common TCF7L2 gene variants (-98368G>T, rs12255372 and -47833C>T, rs7903146) with diabetes and coronary heart disease in Turkish Adult Risk Factor (TARF) Study.Methods:Single nucleotide variants (SNVs) have been genotyped using the TaqMan allelic discrimination assays in 2,024 (51.3% in women, age: 55±11.8) Turkish adults participating in the TARF study. Statistical analyses were used to investigate the association of genotypes with clinical and biochemical measurements.Results:Among the TARF study participants, 11.7%, 24.3%, 14.1%, and 38.3% had diabetes, hypertension, coronary heart disease (CHD), and obesity, respectively. The frequencies of T allele for -47833C>T and -98368G>T in Turkish adults were determined to be 0.35 and 0.33, respectively. -47833C>T was significantly associated with higher fasting glucose concentrations in all participants, especially in men. Both SNVs were significantly associated with diabetes and CHD in all participants (p<0.05). When study population was stratified according to sex, -98368G>T was associated with diabetes in women (p=0.041) and -47833C>T was associated with diabetes and CHD in men (p=0.018 and p=0.032, respectively). Also, both SNVs and the diplotypes of common haplotype (H1) remained strongly associated with type 2 diabetes after risk factors were adjusted (p<0.05).Conclusion:T allele homozygosity of two SNVs as well as the diplotype H1-/H1- reflects risk of diabetes primarily in men. Enhanced CHD risk is determined by the presence of diplotype H1-/H1- among nondiabetic participants.

P6293Assessment of testosterone/estradiol ratio, DHEA-S level and correlation with coronary inflammatory markers IL-1 &amp; 6, TNF-1 and hsCRP predict 5 years risk of cardiovascular disease in men

Abstract Background Previous data showed the adrenal sex hormone dehydroepiandrosterone (DHEA) which is present in serum mainly as the sulfate DHEA-S is the most abundant steroid hormone and another hormones like testosterone, estradiol are related to cardiovascular risk in men. Literatures revealed vascular and metabolic actions of DHEA/-S, evidence for an association between DHEA/-S levels and cardiovascular events is controversy. Objectives Our aim is to review and clear the contradictory point regarding cardiovascular risk and correlation of testeosterone/ estradiol ratio, DHEA-S level with coronary inflammatory markers in men. Methods Large population based cohort study done at multi centre of cardiology from 2013- 2018 in India. We enrolled total 23631 normal healthy male population age between 40 to 60 years and divided into two groups based on testosterone/estradiol ratio (Group A (n=2450) lower value of T/E ratio and Group B (n=21181) normal or higher T/E ratio. We did cohort analysis for 5 years and evaluated DHEA-S level and correlated it with coronary inflammatory markers and cardiovascular risk. Results In group A (low T/E ratio) we found low level of DHEA-S (98% of individual) and higher value of interleukins IL-1 (68%),IL-6 (74%) and tumor necrosis factor TNF-1 (71%) and high sensitive C-reactive protein (hsCRP) (73% of individual). Data revealed two fold increase of high blood pressure and LDL cholesterol level as compared to group B (normal or high T/E ratio and normal or high value of DHEA-S). 2.5 fold higher rate of coronary heart disease (CHD) found in group A versus in group B. We did not found as much significant difference in stroke, carotid and peripheral artery disease. T/E ratio and DHEA-S levels were inversely associated with the age-adjusted risk of a CHD event; the hazard ratios and 95% confidence intervals per standard deviation (SD) increase were 0.76 (0.66 to 0.91) and 0.82 (0.72 to 0.93), respectively. Conclusions Decrease ratio of testosterone/estradiol levels correlate decreased levels of DHEA-S which may increase the risk of CHD in men. For future aspect, correction of T/E ratio, DHEA-S and increase its awareness should be at mass level for prevention of CHD.