Differences In Coronary Heart Disease Research Articles

Cardiovascular Health, Lifestyle Factors, and Social Determinants in Asian Subpopulations in the United States

Asian Americans are often aggregated in national public health surveillance efforts, which may conceal important differences in the health status of subgroups that are included in this highly diverse population. Little is known about how cardiovascular health varies across Asian subpopulations and the extent to which lifestyle and social risk factors contribute to any observed differences. This national study used data from the National Health Interview Survey to evaluate the burden of cardiovascular risk factors (hypertension, hyperlipidemia, diabetes mellitus) and cardiovascular diseases (heart attack, coronary heart disease, angina, stroke) across Asian groups (Chinese, Asian Indian, Filipino, Other Asian), and determine whether differences are related to lifestyle factors and/or social determinants of health. The weighted study population included 13,592,178 Asian adults. Filipino adults were more likely to have hypertension than Chinese adults (29.4% vs 15.4%; adjusted odds ratio [OR] 2.40, 95% confidence interval [1.91 to 3.02]), as were Asian Indians (15.7%; OR 1.59 [1.25 to 2.02]). These patterns were similar for hyperlipidemia and diabetes mellitus. For cardiovascular diseases, Filipino adults were significantly more likely to have coronary heart disease (4.2% vs 1.9%; OR 2.19 [1.32 to 3.56]), heart attack (2.6% vs 0.9%; OR 2.79 [1.44 to 5.41]), angina (1.8% vs 0.9%; OR 2.15 [1.06 to 4.32]), and stroke (2.1% vs 0.8%; OR 2.54 [1.42 to 4.55]) compared with Chinese adults, whereas there were no differences compared with Asian Indian adults. Adjustments for lifestyle factors and social determinants completely attenuated differences in coronary heart disease, heart attack, and angina among subpopulations. In conclusion, these findings demonstrate that cardiovascular risk factors and diseases vary significantly across Asian subpopulations, with Filipino adults experiencing the highest burden and Chinese adults the lowest, and that differences in cardiovascular disease are largely attenuated after adjustment for lifestyle and social determinants.

Sex-specific association between microvascular health and coagulation parameters: the Netherlands Epidemiology of Obesity study

BackgroundMicrovascular dysfunction is a growing determinant of sex differences in coronary heart disease (CHD). Dysregulation of the coagulation system is involved in CHD pathogenesis and can be induced by endothelial glycocalyx (EG) perturbation. However, little is known about the link between EG function and coagulation parameters in population-based studies on sex specificity. ObjectivesWe sought to examine the sex differences in the relationship between EG function and coagulation parameters in a middle-aged Dutch population. MethodsUsing baseline measurements of 771 participants from the Netherlands Epidemiology of Obesity study (age, 56 years [IQR, 51-61 years]; 53% women; body mass index, 27.9 kg/m2 [IQR, 25.1-30.9 kg/m2]), associations between glycocalyx-related perfused boundary region (PBR) derived using sidestream dark-field imaging and coagulation parameters (factor [F]VIII/IX/XI; thrombin generation parameters; and fibrinogen) were investigated using linear regression analyses, adjusting for possible confounders (including C-reactive protein, leptin, and glycoprotein acetyls), followed by sex-stratified analyses. ResultsThere was a sex difference in the associations between PBR and coagulation parameters. Particularly in women, 1-SD PBR (both total and feed vessel, indicating poorer glycocalyx status) was associated with higher FIX activity ([1.8%; 95% CI, 0.3%-3.3%] and [2.0%; 95% CI, 0.5%-3.4%], respectively) and plasma fibrinogen levels ([5.1 mg/dL; 95% CI, 0.4-9.9 mg/dL] and [5.8 mg/dL; 95% CI, 1.1-10.6 mg/dL], respectively). Furthermore, 1-SD PBRcapillary was associated with higher FVIII activity (3.5%; 95% CI, 0.4%-6.5%) and plasma fibrinogen levels (5.3 mg/dL; 95% CI, 0.6-10.0 mg/dL). ConclusionWe revealed a sex-specific association between microcirculatory health and procoagulant status, which suggests that microvascular health be considered during early development of CHD in women.

Abstract 106: Single Cell High Dimensional Analysis of Human Peripheral Blood Mononuclear Cells Reveals Unique Intermediate Monocyte Subsets Associated with Sex Differences in Coronary Heart Disease

Monocytes are innate immune cells that are defined by three subsets: classical (cMo), intermediate (iMo) and non-classical (nMo). How these subsets become more heterogeneous in phenotype and function in CVD progression remains elusive. We employed single-cell transcriptome and protein analysis to define how human monocytes differ in subjects with moderate to severe CVD. Peripheral blood mononuclear cells (PBMC) were obtained from 61 human subjects, undergoing coronary angiography as part of the Coronary Assessment of Virginia (CAVA) Cohort. Coronary atherosclerosis severity was quantified using Gensini Score (GS). We analyzed 487 immune-related genes and 49 surface proteins at the single cell level in PBMC from each subject using the BD-Rhapsody platform. WNN Seurat 4.0 was used for high dimensional analysis. Data was normalized using GLMM to control for covariates (age, sex, diabetes, and statin use). We identified cMo, iMo, nMo, plasmacytoid DC, and classical DC. We found a significant increase only in the frequencies of intermediate (iMo) monocytes in subjects with high CVD (GS>30) compared to subjects with low CVD (GS<6) ( p =0.004). Spearman correlation analysis with GS from each subject revealed a positive correlation with iMo frequencies (r=0.314, p =0.014) and further showed sex-dependent positive correlation in female patients (r=0.663, p =0.0037). Interestingly, cMo, thought to be potently atherogenic, did not correlate with CVD severity. Further analysis identified 3 iMo subsets, distinguished by expression of HLA-DR, CD86, CXCR3, and PD-L1. We found that frequencies of two of them, iMo_CXCR3 + PDL1 lo ( p =0.0003) and iMo_HLA-DR + CD86 int ( p =0.019), were associated with CVD severity. The iMo_CXCR3 + PDL1 lo immunoregulatory subset was positively correlated with GS in both females (r=0.66, p =0.004) and males (r=0.315, p =0.037). However, the iMo_HLA-DR + CD86 int subset was positively correlated only in females (r=0.55, p =0.022), illustrating substantial heterogeneity among monocyte subsets in a sex-dependent manner. In sum, we identified novel sex- and CVD-dependent iMo subsets in subjects with CVD. Future functional analysis of iMo populations should provide a deeper understanding of long-known sex-differences in CVD progression.

Abstract 10446: Sex-Specific Genetic Loci Shared Between Sex Hormone Biomarkers and Coronary Heart Disease Are Associated with Sex- and Tissue-Specific Gene Expression

Introduction: Sex differences in coronary heart disease (CHD) have been well-recognized, but the underlying mechanisms are poorly understood. To examine sex differences in the shared genetics between sex hormone biomarkers and CHD, we have previously performed a sex-stratified genome-wide association study for testosterone (T), sex-hormone binding globulin (SHBG), and CHD using data from the UK Biobank (187,888 men and 221,014 women). We then performed sex-stratified genome-wide cross-traits meta-analyses and identified 13 loci coregulating T or SHBG and CHD, with the coregulation effects specific to one sex ( P meta <5х10 -8 in one sex and P meta ≥1х10 -5 in the other). Hypothesis: The identified sex-specific coregulatory loci are associated with gene expression in a sex-dependent manner, which could help elucidate sex-specific biological functions of shared genetics between sex hormones and CHD. Methods: Based on gene expression data in 49 different human tissues for >900 post-mortem donors of both sexes (the Genotype-Tissue Expression project; V8 release), we estimated genetic effects on sex- and tissue-specific expression for the 13 identified sex-specific coregulatory loci. False discovery rate (FDR) was used to account for multiple testing. Results: We observed 149 significant locus-gene associations in men (FDR men <0.05) and 72 in women (FDR women <0.05) in various tissues. Moreover, 19 locus-gene pairs showed sex-differed associations in various tissues (FDR for sex-locus interactions <0.05), 13 of which were in brain tissues (5 in cortex, 3 in cerebellum, 3 in hypothalamus, and 2 in basal ganglia); all of these loci were associated with expressions of genes whose transcription start sites are located at over 1 million bases away or on a different chromosome. We also observed 11 locus-gene pairs in male-specific tissues (9 in testis and 2 in prostate) and another 9 pairs in female-specific tissues (5 in vagina, 3 in ovary, and 1 in uterus). Conclusions: Sex-specific genetic loci shared between T or SHBG and CHD are associated with gene expressions in various tissues, predominantly in brain tissues, and such associations significantly differ by sex. Our findings may help advance the understanding of mechanisms underlying sex differences in CHD.

Characteristics of Blood Metabolic Profile in Coronary Heart Disease, Dilated Cardiomyopathy and Valvular Heart Disease Induced Heart Failure.

Purpose: Metabolic impairment is one key contributor to heart failure (HF) pathogenesis and progression. The major causes of HF, coronary heart disease (CHD), dilated cardiomyopathy (DCM), and valvular heart disease (VHD) remains poorly characterized in patients with HF from the view of metabolic profile. We sought to determine metabolic differences in CHD-, VHD-, and DCM-induced HF patients and identify significantly altered metabolites and their correlations.Procedure: In this study, a total of 96 HF cases and 97 controls were enrolled. The contents of 23 amino acids and 26 carnitines in fasting plasma were measured by a targeted liquid chromatography and mass spectrometry (LC-MS) approach.Results: Nine metabolites (Histidine, Arginine, Citrulline, Glutamine, Valine, hydroxyhexadecenyl-carnitine, acylcarnitine C22, hydroxytetradecanoyl-carnitine, and carnitine) were found to be related with the occurrence of HF. Arginine, Glutamine and hydroxytetradecanoyl-carnitine could effectively distinguish CHD and DCM patients, and hydroxytetradecanoyl-carnitine and aspartic acid were able to classify CHD and VHD cohorts.Conclusion: This study indicated that circulating amino acids and long-chain acylcarnitine levels were closely associated with progression of heart failure. Monitoring these metabolic alterations by LC-MS may help the differentiation of CHD, VHD, and DCM in the early stage, and provide new diagnostics targets or therapeutic interventions.

Study on the Risk Factors for Hyperuricaemia and Related Vascular Complications in Patients with Type 2 Diabetes Mellitus.

PurposeThe study aimed to identify diseases that exhibit significant differences between hyperuricaemia (HUA) and non-hyperuricaemia (NHUA) groups and analyse the risk factors for HUA based on the related diseases in type 2 diabetes mellitus (T2DM).MethodsA total of 3264 T2DM patients were investigated from 2013 to 2017 in the Jinyang and Sanlin communities by obtaining basic data from the electronic medical record system (EMRS). From September 2018 to July 2019, 3000 patients (264 patients were missing during follow-up) were investigated with questionnaires, physical examinations and biochemical index tests. After removing missing values, 2899 patients were divided into HUA and NHUA groups. The chi-square test was used to identify diseases with differences. Using Lasso analysis and logistic regression analysis, risk factors for HUA based on the related diseases were obtained. The C-index, receiver operating characteristic (ROC) curve and calibration plot were used to validate the discrimination and accuracy of the factors.ResultsThe chi-square test showed that there were significant differences in coronary heart disease (CHD) and diabetic nephropathy (DN) between the HUA group and the NHUA group. Through Lasso regression, glycosylated haemoglobin A1c (HbA1c), triglyceride (TG), blood urea nitrogen (BUN) and serum creatinine (SCR) were screened in the CHD group. Body mass index (BMI), HbA1c, total cholesterol (TC), TG, BUN, SCR and urine microalbumin (UMA) were screened in the DN group. The P-value of all the variables was less than 0.05. Through the C-index, calibration, and ROC curve analyses, these risk factors had medium accuracy.ConclusionHUA was significantly related to CHD and DN. The level of UA was correlated with HbA1c, TG, BUN, and SCR based on CHD. The level of UA was associated with BMI, HbA1c, TC, TG, BUN, SCR, and UMA based on DN.

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 <5х10 -8 in one sex and P ≥5х10 -8 in the other) and sex-differed ( P <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.

Abstract MP20: Ethnic Differences in Coronary Heart Disease and Stroke Diagnosis Among Blacks in the United States

Introduction: African-Americans bear a disproportionate burden of atherosclerotic cardiovascular disease than other racial/ethnic groups in the U.S. With current globalization trends, Black immigrants from Africa and Caribbean Islands contribute to the ethnic diversity of Blacks in the U.S. Despite the diversity in socioeconomic status, culture and genetic admixture, Black immigrants are traditionally combined with African Americans, therefore limiting opportunities to understand the health of Black immigrants. Hypothesis: Ethnic differences in coronary heart disease (CHD) and stroke prevalence exist among African-Americans (AAs), African-immigrants (AIs) and Afro-Caribbean (ACs). Methods: We conducted a cross-sectional study of the 2010-2016 National Health Interview Survey. CHD and stroke diagnoses were self-reported. We performed a descriptive and multivariable logistic regression analyses adjusting for demographic and health characteristics and stratified by sex. Results: We included 34,513 participants who were AAs (N=30,516), AIs (N=1,371) and ACs (N=2,626). Significant differences in sociodemographic characteristics were observed. AIs were the youngest (39 years) with the highest proportion of college graduates (51%). AAs (42%) were more likely to report hypertension diagnosis than AIs (19%) and ACs (36%) (p<0.05)Also, AAs (44%) were more likely to be overweight/obese than AIs (24%) and ACs (31%) (p<0.05). Diabetes prevalence was similar for AAs (13.7%) and ACs (12.8%), and lower for AIs (6.3%). Adjusted models showed that AAs were more likely to report CHD or stroke diagnoses than AIs and ACs (p<0.05). Sex-stratified models showed AA (4.2%) and AI (3.2%) women reporting similar rates of CHD diagnosis. (Table) Conclusion: Ethnic differences were noted in the prevalence of CHD and stroke diagnosis and risk among Blacks. Future studies should examine the health advantage of AIs and ACs to inform interventions and policy to improve the health of AAs and maintain the health of foreign-born Blacks.

Sex differences in coronary heart disease and stroke mortality: a global assessment of the effect of ageing between 1980 and 2010

BackgroundCardiovascular disease mortality rates are well known to be lower in women than men and to increase with age. Whether these sex and age effects have changed over recent decades,...

Beta-blockers for hypertension.

BackgroundBeta‐blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long‐term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta‐blockers were thought to have similar beneficial effects when used as first‐line therapy for hypertension. However, the benefit of beta‐blockers as first‐line therapy for hypertension without compelling indications is controversial. This review is an update of a Cochrane Review initially published in 2007 and updated in 2012.ObjectivesTo assess the effects of beta‐blockers on morbidity and mortality endpoints in adults with hypertension.Search methodsThe Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to June 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE (from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference lists of relevant reviews, and reference lists of studies potentially eligible for inclusion in this review, and also searched the the World Health Organization International Clinical Trials Registry Platform on 06 July 2015.Selection criteriaRandomised controlled trials (RCTs) of at least one year of duration, which assessed the effects of beta‐blockers compared to placebo or other drugs, as first‐line therapy for hypertension, on mortality and morbidity in adults.Data collection and analysisWe selected studies and extracted data in duplicate, resolving discrepancies by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed‐effect or random‐effects meta‐analyses, as appropriate. We also used GRADE to assess the certainty of the evidence. GRADE classifies the certainty of evidence as high (if we are confident that the true effect lies close to that of the estimate of effect), moderate (if the true effect is likely to be close to the estimate of effect), low (if the true effect may be substantially different from the estimate of effect), and very low (if we are very uncertain about the estimate of effect).Main resultsThirteen RCTs met inclusion criteria. They compared beta‐blockers to placebo (4 RCTs, 23,613 participants), diuretics (5 RCTs, 18,241 participants), calcium‐channel blockers (CCBs: 4 RCTs, 44,825 participants), and renin‐angiotensin system (RAS) inhibitors (3 RCTs, 10,828 participants). These RCTs were conducted between the 1970s and 2000s and most of them had a high risk of bias resulting from limitations in study design, conduct, and data analysis. There were 40,245 participants taking beta‐blockers, three‐quarters of them taking atenolol. We found no outcome trials involving the newer vasodilating beta‐blockers (e.g. nebivolol).There was no difference in all‐cause mortality between beta‐blockers and placebo (RR 0.99, 95% CI 0.88 to 1.11), diuretics or RAS inhibitors, but it was higher for beta‐blockers compared to CCBs (RR 1.07, 95% CI 1.00 to 1.14). The evidence on mortality was of moderate‐certainty for all comparisons.Total CVD was lower for beta‐blockers compared to placebo (RR 0.88, 95% CI 0.79 to 0.97; low‐certainty evidence), a reflection of the decrease in stroke (RR 0.80, 95% CI 0.66 to 0.96; low‐certainty evidence) since there was no difference in coronary heart disease (CHD: RR 0.93, 95% CI 0.81 to 1.07; moderate‐certainty evidence). The effect of beta‐blockers on CVD was worse than that of CCBs (RR 1.18, 95% CI 1.08 to 1.29; moderate‐certainty evidence), but was not different from that of diuretics (moderate‐certainty) or RAS inhibitors (low‐certainty). In addition, there was an increase in stroke in beta‐blockers compared to CCBs (RR 1.24, 95% CI 1.11 to 1.40; moderate‐certainty evidence) and RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; moderate‐certainty evidence). However, there was little or no difference in CHD between beta‐blockers and diuretics (low‐certainty evidence), CCBs (moderate‐certainty evidence) or RAS inhibitors (low‐certainty evidence). In the single trial involving participants aged 65 years and older, atenolol was associated with an increased CHD incidence compared to diuretics (RR 1.63, 95% CI 1.15 to 2.32). Participants taking beta‐blockers were more likely to discontinue treatment due to adverse events than participants taking RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; moderate‐certainty evidence), but there was little or no difference with placebo, diuretics or CCBs (low‐certainty evidence).Authors' conclusionsMost outcome RCTs on beta‐blockers as initial therapy for hypertension have high risk of bias. Atenolol was the beta‐blocker most used. Current evidence suggests that initiating treatment of hypertension with beta‐blockers leads to modest CVD reductions and little or no effects on mortality. These beta‐blocker effects are inferior to those of other antihypertensive drugs. Further research should be of high quality and should explore whether there are differences between different subtypes of beta‐blockers or whether beta‐blockers have differential effects on younger and older people.

Evidence from randomised controlled trials does not support current dietary fat guidelines: a systematic review and meta-analysis

ObjectivesNational dietary guidelines were introduced in 1977 and 1983, by the USA and UK governments, respectively, with the ambition of reducing coronary heart disease (CHD) mortality by reducing dietary fat...

Coronary heart disease differences in Eastern versus Western Europe: A demanding situation

Coronary heart disease differences in Eastern versus Western Europe: A demanding situation

Gender differences in coronary heart disease

### Learning objectives The importance of coronary heart disease (CHD) as a disease of both genders tends to be underappreciated, although in 2014 CHD claimed almost three times more lives...

Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis.

Atrial fibrillation (AF) is the most common sustained arrhythmia in women and men worldwide. During the past century, a range of risk factors has been associated with AF, severe complications from the arrhythmia have been identified, and its prevalence has been increasing steadily. Whereas evidence has accumulated regarding sex-specific differences in coronary heart disease and stroke, the differences between women and men with AF has received less attention. We review the current literature on sex-specific differences in the epidemiology of AF, including incidence, prevalence, risk factors, and genetics, and in the pathophysiology and the clinical presentation and prognosis of patients with this arrhythmia. We highlight current knowledge gaps and areas that warrant future research, which might advance understanding of variation in the risk factors and complications of AF, and ultimately aid more-tailored management of the arrhythmia.

Unique Coronary Artery Disease Differences in Women as Related to Revascularization.

There are significant differences in coronary heart disease (CHD) in women whenever a comparison is made to men and these carry over to revascularization procedures including percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery. The coronary arteries of women are smaller, which presents additional challenges for PCI and CABG procedures. Unique atypical symptomatology in response to acute coronary syndrome (ACS) in women can confound diagnosis, women notoriously delay seeking medical help for ACS, and physicians and other caregivers have had a tendency to minimize the significance of these symptoms, contributing further to a delay in necessary care. There also appears to be an increased association of inflammation and CHD in women. The younger the female patient with CHD, the higher the mortality and that mortality clearly exceeds that of comparable male patients. For cardiovascular (CV) risk prevention in women, statins have had controversy associated with their use but overall, the proof of beneficial outcomes results from statins is also valid in women. An increased rate of adverse outcomes has been reported in women after PCI and CABG surgery. These worse clinical outcomes have persisted in contemporary years but lessened due to advancement in invasive techniques. Nevertheless, PCI that could improve clinical outcomes in women who have high-risk ACS is, unfortunately, performed on a less frequent basis and, in addition, there are greater delays involving women as compared to men. With increased clinical comorbidity associated with complex CHD in women, a lower anatomical SYNTAX score (from: SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery [SYNTAX] trial) appears necessary in order for women to achieve a similar long-term mortality benefit from CABG surgery as compared to PCI.

Evidence from randomised controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis

ObjectivesNational dietary guidelines were introduced in 1977 and 1983, by the US and UK governments, respectively, with the ambition of reducing coronary heart disease (CHD) by reducing fat intake. To...

A blunted diurnal cortisol response in the lower educated does not explain educational differences in coronary heart disease: Findings from the AGES-Reykjavik Study

Lower educational attainment generally is a strong predictor of coronary heart disease (CHD). The underlying mechanisms of this effect are, however, less clear. One hypothesis is that stress related to limitations imposed by lower socioeconomic status elicits changes in hypothalamic-pituitary-adrenal axis functioning, which, in turn, increases risk of CHD. In a large cohort study, we examined whether educational attainment was related to risk of fatal and non-fatal CHD and the extent to which salivary cortisol mediated this relation independent of potential confounders, including lifestyles. Data came from 3723 participants aged 66 through 96 from the Age, Gene/Environment Susceptibility (AGES) – Reykjavik Study. Between 2002 and 2006, data were collected using questionnaires and examinations including morning and evening salivary samples. Hospital admission records and cause of death registries (ICD-9 and ICD-10 codes) were available until December 2009. Linear regression and Cox proportional hazards analyses were performed. Even after adjustment for potential confounders, including lifestyle, persons with lower educational attainment showed a blunted cortisol response and also greater risk of incident CHD. However, our data did not support the role of cortisol as a mediator in the association between education and CHD in an older sample (192).

Secular changes in rates of coronary heart disease, fatal coronary heart disease, and out-of-hospital fatal coronary heart disease

Secular changes in rates of coronary heart disease, fatal coronary heart disease, and out-of-hospital fatal coronary heart disease

The number of X chromosomes influences protection from cardiac ischaemia/reperfusion injury in mice: one X is better than two

Sex differences in coronary heart disease have been attributed to sex hormones, whereas the potential role of the sex chromosomes has been ignored so far. Here, we investigated the role of the sex chromosomes in causing sex differences in myocardial ischaemia/reperfusion (I/R) injury. We used two unique mouse models, the 'four core genotypes' [XX mice with ovaries (XXF) or testes (XXM) and XY mice with ovaries (XYF) or testes (XYM)] and XY* (gonadal male or female mice with one or two X chromosomes). All mice were gonadectomized (GDX). In vivo or isolated Langendorff-perfused hearts were subjected to I/R injury. The in vivo infarct size in XY mice was significantly smaller than XX mice regardless of their gonadal type (24.5 ± 4.1% in XYF and 21.8 ± 3.3% in XYM vs. 37.0 ± 3.2% in XXF and 35.5 ± 2.1% in XXM, P < 0.01). Consistent with the results in vivo, the infarct size was markedly smaller and cardiac functional recovery was significantly better in XY mice compared with XX ex vivo. The mitochondrial calcium retention capacity was significantly higher in XY compared with XX mice (nmol/mg protein: XXF = 126 ± 9 and XXM = 192 ± 45 vs. XYF = 250 ± 56 and XYM = 286 ± 51, P < 0.05). In XY* mice, mice with 2X chromosomes had larger infarct size (2X females = 41.4 ± 8.9% and 2X males = 46.3 ± 9.5% vs. 1X females = 23.7 ± 3.9% and 1X males = 26.6 ± 6.9%, P < 0.05) and lower heart functional recovery, compared with those with 1X chromosome. Several X genes that escape X inactivation (Eif2s3x, Kdm6a, and Kdm5c) showed higher expression in XX than in XY hearts. XX mice have higher vulnerability to I/R injury compared with XY mice, which is due to the number of X chromosomes rather than the absence of the Y chromosome.

Coronary heart disease differences across Europe

In the Seven Countries Study of Cardiovascular Diseases, 16 cohorts of middle-aged men were enrolled in eight nations of seven countries in three continents in the late 1950s and early 1960s for a total of 12 763 individuals. Thirteen cohorts were located in Europe, two in Finland, one in the Netherlands, three in Italy, two in Croatia - former Yugoslavia, three in Serbia - former Yugoslavia, and two in Greece. Another cohort was enrolled in the USA and two cohorts in Japan. Baseline prevalence of coronary heart disease (CHD) was largely different across areas, as well as 10-year incidence of major CHD events and CHD mortality for periods ranging from 25 to 40 years of follow-up. Higher rates were found in Northern Europe, lower rates in Southern Europe and intermediate rates in Eastern Europe, represented by Serbia. Differences across countries were partly explained by different entry mean levels of serum cholesterol, blood pressure, consumption of saturated fatty acids and adherence to traditional dietary patterns. Forty-year trends of CHD mortality were largely explained by early changes in serum cholesterol and blood pressure levels, with large risk increases in Serbia and Greece, and the tendency to declines in Finland and the Netherlands. These trends in Seven Countries' experience are in line with those manifests in official mortality data. An attempt of interpretation is presented pointing to socio-economic evolution in the involved countries, which heavily modifies health and dietary habits and contributes to explaining these differences at population level.