Human articular chondrocytes express 15-lipoxygenase-1 and -2: potential role in osteoarthritis

Introduction

Although cardiovascular morbidity and mortality are increased in rheumatoid arthritis, little is known about the burden of subclinical coronary atherosclerosis in these patients.

Methods

Using computed tomography, coronary artery calcification was measured in 195 men and women with rheumatoid arthritis aged 45 to 84 years without clinical cardiovascular disease and compared with 1,073 controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis.

Results

The prevalence of coronary calcification (Agatston score > 0) was significantly higher in men, but not women, with rheumatoid arthritis after adjusting for sociodemographic and cardiovascular risk factors (prevalence ratio = 1.19; P = 0.012). Among participants with prevalent calcification, those with rheumatoid arthritis had adjusted mean Agatston scores 53 units higher than controls (P = 0.002); a difference greater for men than women (P for interaction = 0.017). In all analyses, serum IL-6 attenuated the association between rheumatoid arthritis and coronary calcification, suggesting its role as a potential mediator of enhanced atherosclerosis. Notably, increasing severity of rheumatoid arthritis was associated with a higher prevalence and extent of coronary calcification among both men and women with rheumatoid arthritis, and for all age categories. The largest percentage difference in coronary arterial calcification between rheumatoid arthritis patients and their nonrheumatoid arthritis counterparts was observed in the youngest age category.

Conclusions

Increasing rheumatoid arthritis disease severity was associated with a higher prevalence and greater extent of coronary artery calcification, potentially mediated through an atherogenic effect of chronic systemic inflammation. Gender and age differences in association with coronary calcification suggest that preventive measures should be emphasized in men with rheumatoid arthritis, and considered even in younger rheumatoid arthritis patients with low levels of traditional cardiovascular risk factors.     

Confounding by Indication Probably Distorts the Relationship between Steroid Use and Cardiovascular Disease in Rheumatoid Arthritis: Results from a Prospective Cohort Study

Objective

To evaluate the risk of cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids.

Methods

Retrospective analysis of exposure to glucocorticoids in a prospective cohort of 353 patients with rheumatoid arthritis followed from June 2001 up to November 2011 for incident cardiovascular disease in a hospital-based outpatient cohort in the Netherlands. Hazard ratios with 95%-confidence intervals were calculated for the association between different types of exposure to glucocorticoids and incident cardiovascular disease. Associations were adjusted for demographics, cardiovascular risk factors and disease related parameters.

Results

Recent and current exposure to glucocorticoids were associated with incident cardiovascular disease, as was a longer duration of exposure and cumulative exposure to glucocorticoids. Adjustment for disease activity and severity negated the association.

Conclusion

In observational studies the finding of incident cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids is strongly confounded by indication due to high disease activity. The adverse cardiovascular effects of glucocorticoids might be balanced by positive effects working through inflammation control.     

Total calcium-sensing receptor expression in circulating monocytes is increased in rheumatoid arthritis patients with severe coronary artery calcification

Introduction

Human circulating monocytes express the calcium-sensing receptor (CaSR) and are involved in atherosclerosis. This study investigated the potential association between vascular calcification in rheumatoid arthritis (RA) and CaSR expression in circulating monocytes.

Methods

In this cross-sectional study, 50 RA patients were compared to 25 control subjects matched for age and gender. Isolation of peripheral blood mononuclear cells and flow cytometry analysis were performed to study the surface and total CaSR expression in circulating monocytes. Coronary artery calcium (CAC) and abdominal aortic calcification (AAC) scores were evaluated by computed tomography and an association between these scores and the surface and/or total CaSR expression in circulating monocytes in RA patients was investigated.

Results

The two groups were similar in terms of age (RA: 60.9 ± 8.3 years, versus controls: 59.6 ± 5.3 years) and gender (RA: 74.0% females versus 72.0% females). We did not find a higher prevalence and greater burden of CAC or AAC in RA patients versus age- and gender-matched controls. When compared with control subjects, RA patients did not exhibit greater total CaSR (101.6% ± 28.8 vs. 99.9% ± 22.0) or surface CaSR (104.6% ± 20.4 vs. 99.9% ± 13.7) expression, but total CaSR expression in circulating monocytes was significantly higher in RA patients with severe CAC (Agatston score ≥200, n = 11) than in patients with mild-to-moderate CAC (1 to 199, n = 21) (P = 0.01).

Conclusions

This study demonstrates for the first time that total CaSR expression in human circulating monocytes is increased in RA patients with severe coronary artery calcification.     

Osteoprotegerin CGA Haplotype Protection against Cerebrovascular Complications in Anti-CCP Negative Patients with Rheumatoid Arthritis

Introduction

Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG) has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis.

Methods

Three OPG gene variants (rs3134063, rs2073618 and rs3134069) were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression.

Results

No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31–0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04–0.78; p = 0.022, respectively).

Conclusion

Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.     

Association of Serum Uric Acid and Coronary Artery Disease in Premenopausal Women

Objective

To date, no study in the published literature has investigated the role of various serum uric acid (SUA) concentrations in the development of angiographically-proven coronary artery disease (CAD) in premenopausal women. Therefore, the aim of this study was to investigate the role SUA levels may play in the prevalence, severity, and prognosis of CAD in premenopausal women.

Methods

This cross-sectional retrospective study included 607 premenopausal women who had undergone coronary angiography. The CAD diagnosis was based upon stenosis affecting ≥50% of the luminal diameter. Association of the SUA levels with CAD prevalence, severity, and clinical outcomes were assessed by statistical analysis.

Results

In total, 369 (60.8%) of the patients were diagnosed with CAD. The CAD patients had significantly higher SUA levels than those without CAD (5.3±1.9 vs. 4.8±1.7 mg/dL, P = 0.001). The SUA levels were found to be significantly associated with CAD prevalence (P = 0.013). Patients with higher levels of SUA also showed increased rates of multivessel disease and composite end-points, such as major adverse cardiac events. Furthermore, multivariate analysis identified abnormally high levels of uric acid (hyperuricemia) as an independent risk factor for CAD (OR 1.51 (1.11–2.53), P<0.05).

Conclusions

The SUA levels are significantly associated with the prevalence of CAD. The SUA levels may be a predictor for incidence of major cardiovascular events in premenopausal women.     

Impact of Age and Gender on the Prevalence and Prognostic Importance of the Metabolic Syndrome and Its Components in Europeans. The MORGAM Prospective Cohort Project

Objective

To investigate the influence of age and gender on the prevalence and cardiovascular disease (CVD) risk in Europeans presenting with the Metabolic Syndrome (MetS).

Methods

Using 36 cohorts from the MORGAM-Project with baseline between 1982–1997, 69094 men and women aged 19–78 years, without known CVD, were included. During 12.2 years of follow-up, 3.7%/2.1% of men/women died due to CVD. The corresponding percentages for fatal and nonfatal coronary heart disease (CHD) and stroke were 8.3/3.8 and 3.1/2.5.

Results

The prevalence of MetS, according to modified definitions of the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII), increased across age groups for both genders (P<0.0001); with a 5-fold increase in women from ages 19–39 years to 60–78 years (7.4%/7.6% to 35.4%/37.6% for IDF/NCEP-ATPIII) and a 2-fold increase in men (5.3%/10.5% to 11.5%/21.8%). Using multivariate-adjusted Cox regressions, the associations between MetS and all three CVD events were significant (P<0.0001). For IDF/NCEP-ATPIII in men and women, hazard ratio (HR) for CHD was 1.60/1.62 and 1.93/2.03, for CVD mortality 1.73/1.65 and 1.77/2.06, and for stroke 1.51/1.53 and 1.58/1.77. Whereas in men the HRs for CVD events were independent of age (MetS*age, P>0.05), in women the HRs for CHD declined with age (HRs 3.23/3.98 to 1.55/1.56; MetS*age, P = 0.01/P = 0.001 for IDF/NCEP-ATPIII) while the HRs for stroke tended to increase (HRs 1.31/1.25 to 1.55/1.83; MetS*age, P>0.05).

Conclusion

In Europeans, both age and gender influenced the prevalence of MetS and its prognostic significance. The present results emphasise the importance of being critical of MetS in its current form as a marker of CVD especially in women, and advocate for a redefinition of MetS taking into account age especially in women.     

Likelihood of Treatment in a Coronary Care Unit for a First-Time Myocardial Infarction in Relation to Sex,Country of Birth and Socioeconomic Position in Sweden

Objective

To examine the relationship between sex, country of birth, level of education as an indicator of socioeconomic position, and the likelihood of treatment in a coronary care unit (CCU) for a first-time myocardial infarction.

Design

Nationwide register based study.

Setting

Sweden.

Patients

199 906 patients (114 387 men and 85,519 women) of all ages who were admitted to hospital for first-time myocardial infarction between 2001 and 2009.

Main outcome measures

Admission to a coronary care unit due to myocardial infarction.

Results

Despite the observed increasing access to coronary care units over time, the proportion of women treated in a coronary care unit was 13% less than for men. As compared with men, the multivariable adjusted odds ratio among women was 0.80 (95% confidence interval 0.77 to 0.82). This lower proportion of women treated in a CCU varied by age and year of diagnosis and country of birth. Overall, there was no evidence of a difference in likelihood of treatment in a coronary care unit between Sweden-born and foreign-born patients. As compared with patients with high education, the adjusted odds ratio among patients with a low level of education was 0.93 (95% confidence interval 0.89 to 0.96).

Conclusions

Foreign-born and Sweden-born first-time myocardial infarction patients had equal opportunity of being treated in a coronary care unit in Sweden; this is in contrast to the situation in many other countries with large immigrant populations. However, the apparent lower rate of coronary care unit admission after first-time myocardial infarction among women and patients with low socioeconomic position warrants further investigation.     

The Association between the History of Cardiovascular Diseases and Chronic Low Back Pain in South Koreans: A Cross-Sectional Study

Background

Cardiovascular disease and related risk factors have been suggested as a mechanism leading to atherosclerosis of the lumbar vessels and consequent lumbar pain or sciatica. But there is continued controversy concerning its generalization. This study examined whether cardiovascular disease or its risk factors were associated with chronic low back pain (cLBP) in Koreans.

Methods

Health surveys and examinations were conducted on a nationally representative sample (n = 23,632) of Koreans. A total of 13,841 eligible participants (aged 20 to 89 years) were examined to determine the association between cardiovascular disease, the Framingham risk score, major cardiovascular risk factors (blood pressure, diabetes, cholesterol, and smoking habits) and chronic LBP.

Results

The total prevalence of cLBP was 16.6% (men: 10.8%, women: 21.1%) and that in patients with a history of cardiovascular diseases was 36.6% (men: 26.5%, women: 47.1%). The results showed that patients’ medical history of cardiovascular disease was significantly associated with cLBP in both men and women when adjusted for covariates (men: OR 2.16; 95%CI 1.34∼3.49; women: OR 2.26; 95%CI 1.51∼3.38). No association was observed between cLBP and the Framingham risk score, medication for hyperlipemia, hypertension, diabetes, and major cardiovascular risk factors (systolic blood pressure, total cholesterol, high density lipoprotein cholesterol, triglycerides, glucose and smoking habits) in either men or women.

Conclusions

The prevalence of cLBP is correlated to a history of cardiovascular disease, but not to the major cardiovascular risk factors from the Framingham study. Further studies on whether these results were affected by psychological factors in patients with a history of cardiovascular diseases or whether new potential risk factors from the artery atherosclerosis hypothesis applying to Koreans exist are needed.     

Cardiovascular Risk Factors Have Larger Impact on Endothelial Function in Self-Reported Healthy Women than Men in the HUNT3 Fitness Study

Background

Several studies suggest that cardiovascular risk factors comprising the metabolic syndrome have larger effects on the development of cardiovascular disease in women than in men. A recent study in self-reported healthy subjects demonstrated a marked gender difference in endothelial dysfunction that may be an important precursor of manifest cardiovascular disease. The aim of the present study was to determine whether the association between endothelial function and cardiovascular risk factors is different in self-reported healthy women compared to self-reported healthy men.

Methods and Results

Associations between endothelial function (flow mediated dilation, FMD, of the brachial artery measured by ultrasound), anthropometric variables, peak oxygen uptake (VO_2peak), blood pressure, serum lipids, blood glucose and a questionnaire on general health and lifestyle including smoking status were studied by logistic and linear regression in 2 528 women and 2 211 men aged 20–89 years, free from self-reported cardiovascular disease. In women with hyperglycemia, endothelial dysfunction (FMD ≤0%) occurred twice as frequently as in male counterparts. The presence of the metabolic syndrome, high blood pressure and low VO_2peak increased the prevalence of endothelial dysfunction more in women than in men.

Conclusion

Endothelial dysfunction is more strongly associated with cardiovascular risk factors in self-reported healthy women than in self-reported healthy men. This finding could explain why the metabolic syndrome, and especially hyperglycemia, is associated with higher cardiovascular risk and a worse prognosis in women.     

Socioeconomic Status and Subclinical Coronary Disease in the Whitehall II Epidemiological Study

Background

There are pronounced socioeconomic disparities in coronary heart disease, but the extent to which these primarily reflect gradients in underlying coronary artery disease severity or in the clinical manifestation of advanced disease is uncertain. We measured the relationship between socioeconomic status (SES) as indexed by grade of employment and coronary artery calcification (CAC) in the Whitehall II epidemiological cohort, and tested the contribution of lifestyle, biological and psychosocial factors in accounting for this association.

Methods and Findings

CAC was assessed in 528 asymptomatic men and women aged 53–76 years, stratified into higher, intermediate and lower by grade of employment groups. Lifestyle (smoking, body mass index, alcohol consumption, physical activity), biological (blood pressure, lipids, fasting glucose, inflammatory markers) and psychosocial factors (work stress, financial strain, social support, depression, hostility, optimism) were also measured. Detectable CAC was present in 293 participants (55.5%). The presence of calcification was related to lifestyle and biological risk factors, but not to grade of employment. But among individuals with detectable calcification, the severity of CAC was inversely associated with grade of employment (p = 0.010), and this relationship remained after controlling for demographic, lifestyle, biological and psychosocial factors. Compared with the higher grade group, there was a mean increase in log Agatston scores of 0.783 (95% C.I. 0.265–1.302, p = 0.003) in the intermediate and 0.941 (C.I. 0.226–1.657, p = 0.010) in the lower grade of employment groups, after adjustment for demographic, lifestyle, biological and psychosocial factors.

Conclusions

Low grade of employment did not predict the presence of calcification in this cohort, but was related to the severity of CAC. These findings suggest that lower SES may be particularly relevant at advanced stages of subclinical coronary artery disease, when calcification has developed.     

Aortic Unfolding Determined Using Non-Contrast Cardiac Computed Tomography: Correlations with Age and Coronary Artery Calcium Score

Objective

Aortic unfolding occurs with aging and reflects proximal aortic dilation, aortic arch widening, and decreased curvature. This study 1) evaluated the relationship between aortic unfolding measured using non-contrast cardiac-gated computed tomography (CT) and age, 2) assessed factors influencing aortic unfolding, and 3) determined the association of this measurement with coronary artery calcium (CAC) score.

Methods

We reviewed the charts of 219 subjects (142 men, 77 women; mean age 54.2±9.3 years) who underwent coronary artery calcium scanning during routine health screening from December 2010 to May 2011. Multivariate regression analysis according to cardiovascular risk factors was performed. We also analyzed the relationship between aortic unfolding measurements and CAC score using stepwise multiple linear regression.

Results

Mean aortic unfolding was 103.7±13.9 mm (men, 106.5±13.5 mm; women, 98.4±12.9 mm). Age, body surface area, and hypertension were exclusively associated with aortic unfolding. The association between aortic unfolding and CAC score was significant after adjustment for age and gender (β = 1.89, p = 0.017) and for Framingham risk score (β = 2.83, p<0.001).

Conclusions

Aortic unfolding defined by measuring aortic width was a reproducible and practical method with non-contrast cardiac CT and associated with age, body surface area, and hypertension. CAC score, a well-established surrogate marker of cardiovascular disease, is positively associated with aortic unfolding. Further study to evaluate aortic unfolding as a potential predictor of cardiovascular risk is warranted.     

Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study

Introduction

A candidate gene approach, in a large case–control association study in the Dutch population, has shown that a 480 kb block on chromosome 4q27 encompassing KIAA1109/Tenr/IL2/IL21 genes is associated with rheumatoid arthritis. Compared with case–control association studies, family-based studies have the added advantage of controlling potential differences in population structure. Therefore, our aim was to test this association in populations of European origin by using a family-based approach.

Methods

A total of 1,302 West European white individuals from 434 trio families were genotyped for the rs4505848, rs11732095, rs6822844, rs4492018 and rs1398553 polymorphisms using the TaqMan Allelic discrimination assay (Applied Biosystems). The genetic association analyses for each SNP and haplotype were performed using the Transmission Disequilibrium Test and the genotype relative risk.

Results

We observed evidence for association of the heterozygous rs4505848-AG genotype with rheumatoid arthritis (P = 0.04); however, no significance was found after Bonferroni correction. In concordance with previous findings in the Dutch population, we observed a trend of undertransmission for the rs6822844-T allele and rs6822844-GT genotype to rheumatoid arthritis patients. We further investigated the five SNP haplotypes of the KIAA1109/Tenr/IL2/IL21 gene region. We observed, as described in the Dutch population, a nonsignificant undertransmission of the AATGG haplotype to rheumatoid arthritis patients.

Conclusions

Using a family-based study, we have provided a trend for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in populations of European descent. Nevertheless, we failed to replicate a significant association of this region in our rheumatoid arthritis family sample. Further investigation of this region, including detection and testing of all variants, is required to confirm rheumatoid arthritis association.     

Shared epitope alleles remain a risk factor for anti-citrullinated proteins antibody (ACPA)--positive rheumatoid arthritis in three Asian ethnic groups

Background

To investigate the associations between HLA-DRB1 shared epitope (SE) alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia.

Methods

1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA) and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping.

Results

The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups.

Conclusion

The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.     

Relationship between Insulin Resistance and Coronary Artery Calcium in Young Men and Women

Background

The gender disparity in cardiovascular disease (CVD) risk is greatest between young men and women. However, the causes of that are not fully understood. The objective of this study was to evaluate the relationship between insulin resistance and the presence of coronary artery calcium (CAC) to identify risk factors that may predispose young men and women to CVD.

Methodology/Principal Findings

Insulin resistance and CVD risk factors were examined in 8682 Korean men and 1829 women aged 30–45 years old. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), and CAC was measured using computed tomography. Women were less likely to be insulin resistant (upper quartile of HOMA-IR, 18% vs. 27%, p<0.001) and had a lower prevalence of CAC (1.6% vs. 6.4%, p<0.001). Even when equally insulin resistant men and women were compared, women continued to have lower prevalence of CAC (3.1% vs. 7.2%, p = 0.004) and a more favorable CVD risk profile. Finally, after adjustment for traditional CVD risk factors, insulin resistance remained an independent predictor of CAC only in men (p = 0.03).

Conclusions/Significance

Young women have a lower risk for CVD and a lower CAC prevalence compared with men. This favorable CVD risk profile in women appears to occur regardless of insulin sensitivity. Unlike men, insulin resistance was not a predictor of CAC in women in this cohort. Therefore, insulin resistance has less impact on CVD risk and CAC in young women compared with men, and insulin resistance alone does not explain the gender disparity in CVD risk that is observed at an early age.     

Calcifications of the Thoracic Aorta on Extended Non-Contrast-Enhanced Cardiac CT

Background

The presence of calcified atherosclerosis in different vascular beds has been associated with a higher risk of mortality. Thoracic aorta calcium (TAC) can be assessed from computed tomography (CT) scans, originally aimed at coronary artery calcium (CAC) assessment. CAC screening improves cardiovascular risk prediction, beyond standard risk assessment, whereas TAC performance remains controversial. However, the curvilinear portion of the thoracic aorta (TA), that includes the aortic arch, is systematically excluded from TAC analysis. We investigated the prevalence and spatial distribution of TAC all along the TA, to see how those segments that remain invisible in standard TA evaluation were affected.

Methods and Results

A total of 970 patients (77% men) underwent extended non-contrast cardiac CT scans including the aortic arch. An automated algorithm was designed to extract the vessel centerline and to estimate the vessel diameter in perpendicular planes. Then, calcifications were quantified using the Agatston score and associated with the corresponding thoracic aorta segment. The aortic arch and the proximal descending aorta, “invisible” in routine CAC screening, appeared as two vulnerable sites concentrating 60% of almost 11000 calcifications. The aortic arch was the most affected segment per cm length. Using the extended measurement method, TAC prevalence doubled from 31% to 64%, meaning that 52% of patients would escape detection with a standard scan. In a stratified analysis for CAC and/or TAC assessment, 111 subjects (46% women) were exclusively identified with the enlarged scan.

Conclusions

Calcium screening in the TA revealed that the aortic arch and the proximal descending aorta, hidden in standard TA evaluations, concentrated most of the calcifications. Middle-aged women were more prone to have calcifications in those hidden portions and became candidates for reclassification.     

Aromatase gene polymorphisms are associated with survival among patients with cardiovascular disease in a sex-specific manner

Introduction

CYP19A1 encodes aromatase, the enzyme responsible for the conversion of androgens to estrogens, and may play a role in variation in outcomes among men and women with cardiovascular disease. We sought to examine genetic variation in CYP19A1 for its potential role in sex differences in cardiovascular disease outcomes.

Methods

Caucasian individuals from two independent populations were assessed: 1) a prospective cohort of patients with acute coronary syndromes with 3-year mortality follow-up (n = 568) and 2) a nested case-control study from a randomized, controlled trial of hypertension patients with stable coronary disease in which the primary outcome was death, nonfatal myocardial infarction (MI) or nonfatal stroke (n = 619). Six CYP19A1 SNPs were genotyped (-81371 C>T, -45965 G>C, M201T, R264C, 80 A>G, and +32226 G>A). The sex*genotype interaction term was assessed for the primary outcome and compared by genotype in men and women when a significant interaction term was identified.

Results

We identified a significant interaction between -81371 C>T and sex (p = 0.025) in the ACS population. The variant allele was associated with a 78% increase in mortality in men (HR 1.78, 95% confidence interval [CI] 1.08-2.94) and a nonsignificant 42% decrease in mortality among women (HR 0.58, 95% CI 0.22-1.54). We identified a similar association in the hypertensive CAD group, the -81371 C>T*sex interaction term was p<0.0001, with an associated 65% increase in death, MI, or stroke (HR 1.65, 95% CI 1.00-2.73) in men and a 69% decrease (HR 0.31, 95% CI 0.16-0.6) in women.

Conclusions

Using two independent populations, this study is the first to document a significant interaction between CYP19A1 genotype and sex on cardiovascular outcomes. These findings could illuminate potential mechanisms of sex differences in cardiovascular disease outcomes.     

Effect of gender difference on platelet reactivity

Background

Previous studies have suggested that women do not accrue equal therapeutic benefit from antiplatelet medication as compared with men. The physiological mechanism and clinical implications behind this gender disparity have yet to be established.

Methods

On-treatment platelet reactivity was determined in 717 men and 234 women on dual antiplatelet therapy, undergoing elective coronary stent implantation. Platelet function testing was performed using arachidonic acid and adenosine diphosphate-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12 and Aspirin assays. Also the incidence of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and ischaemic stroke was evaluated.

Results

Women had higher baseline platelet counts than men. Women exhibited a higher magnitude of on-aspirin platelet reactivity using LTA, but not using the VerifyNow Aspirin assay. The magnitude of on-clopidogrel platelet reactivity was significantly higher in women as compared with men with both tests used. The cut-off value to identify patients at risk as well as the incidence of clinical endpoints was similar between women and men (16/234[6.8%] vs. 62/717[8.6%], p = 0.38).

Conclusion

Although the magnitude of platelet reactivity was higher in women, the absolute difference between genders was small and both the cut-off value to identify patients at risk and the incidence of the composite endpoint were similar between genders. Thus, it is unlikely that the difference in platelet reactivity accounts for a worse prognosis in women.     

Secular Trends in Prevalence of Overweight and Obesity among Adults in Rural Tianjin,China from 1991 to 2011: A Population-Based Study

Objectives

Obesity is associated with cardiovascular diseases and has become the main public health issue in western countries and urban China. However, the prevalence and secular trends of obesity in rural China are currently unknown. The aim of this study was to investigate secular trends in the prevalence of overweight and obesity among rural adults in northern China between 1991 and 2011.

Method

The prevalence of overweight and obesity was assessed in adults aged 35–74 years living in a rural area in northern China by comparing two surveys that were conducted in 1991 and 2011, respectively.

Result

The age-adjusted prevalence of overweight increased from 24.5% in 1991 to 42.0% in 2011, and the prevalence of obesity increased from 5.7% in 1991 to 19.6% in 2011. Over the 21-year period, there were significant increases in the prevalence of overweight and obesity for both men and women in all age groups; however, the greatest increase was observed in men aged 35–44 years, with an 10.3-fold increase in obesity prevalence. The prevalence of obesity increased significantly in all risk factors categories, including education levels, blood pressure categories, diabetes previous history, current smoking situation and alcohol drinking situation over the past 21 years overall (p<0.05). The greatest increase in obesity prevalence appeared among those who consumed alcohol (increased by 8.0-fold). Next, there was a 5.3-fold increase in the prevalence of obesity in illiterate residents.

Conclusion

The prevalence of overweight and obesity has increased rapidly among rural adults in Tianjin over the past 21 years, with the most dramatic increase observed in young men. Therefore, the burden of obesity should serve as a call for action.     

Sex-related differences in access to care among patients with premature acute coronary syndrome

Background:

Access to care may be implicated in disparities between men and women in death after acute coronary syndrome, especially among younger adults. We aimed to assess sex-related differences in access to care among patients with premature acute coronary syndrome and to identify clinical and gender-related determinants of access to care.

Methods:

We studied 1123 patients (18–55 yr) admitted to hospital for acute coronary syndrome and enrolled in the GENESIS-PRAXY cohort study. Outcome measures were door-to-electrocardiography, door-to-needle and door-to-balloon times, as well as proportions of patients undergoing cardiac catheterization, reperfusion or nonprimary percutaneous coronary intervention. We performed univariable and multivariable logistic regression analyses to identify clinical and gender-related determinants of timely procedures and use of invasive procedures.

Results:

Women were less likely than men to receive care within benchmark times for electrocardiography (≤ 10 min: 29% v. 38%, p = 0.02) or fibrinolysis (≤ 30 min: 32% v. 57%, p = 0.01). Women with ST-segment elevation myocardial infarction (MI) were less likely than men to undergo reperfusion therapy (primary percutaneous coronary intervention or fibrinolysis) (83% v. 91%, p = 0.01), and women with non–ST-segment elevation MI or unstable angina were less likely to undergo nonprimary percutaneous coronary intervention (48% v. 66%, p < 0.001). Clinical determinants of poorer access to care included anxiety, increased number of risk factors and absence of chest pain. Gender-related determinants included feminine traits of personality and responsibility for housework.

Interpretation:

Among younger adults with acute coronary syndrome, women and men had different access to care. Moreover, fewer than half of men and women with ST-segment elevation MI received timely primary coronary intervention. Our results also highlight that men and women with no chest pain and those with anxiety, several traditional risk factors and feminine personality traits were at particularly increased risk of poorer access to care.Despite improvements in the management of acute coronary syndrome over the past few decades, differences in mortality between men and women persist, especially among younger adults.¹ The reasons for poorer outcomes among women are thought to be multifactorial and may include higher baseline prevalence of risk factors for cardiovascular disease^2–4 and poorer access to care.^2–6 However, in the cited studies, patients were relatively old, and only one study⁴ considered clinical factors as potential confounders in the relationship. Moreover, determinants of access to care in men and women with premature acute coronary syndrome remain unknown.The effect of gender-related factors on access to care has not been investigated. Unlike sex, which is a biological characteristic, gender has a wider scope, incorporating the effects of social norms and expectations for men and women. Gender-related variables include gender identity, social roles, socioeconomic status and interpersonal relationships. There has been a considerable reduction in the gender gap in North America in the past decades.⁷ As a result, more women are gaining access to education and employment, and sharing of household and workplace responsibilities is becoming more common. Therefore, assessing sex alone cannot adequately account for differences in access to care among young adults with premature acute coronary syndrome. To better understand differences in access to care between men and women, a detailed examination of both sex- and gender-related factors is required.Our primary objective in this study was to assess sex-related differences in access to care among adults with premature acute coronary syndrome. Our secondary objective was to identify clinical and gender-related determinants of access to care among men and women.     

Socio-Demographic Inequalities in the Prevalence,Diagnosis and Management of Hypertension in India: Analysis of Nationally-Representative Survey Data

Background

Hypertension is a major contributing factor to the current epidemic of cardiovascular disease in India. Small studies suggest high, and increasing, prevalence especially in urban areas, with poor detection and management, but national data has been lacking. The aim of the current study was to use nationally-representative survey data to examine socio-demographic inequalities in the prevalence, diagnosis and management of hypertension in Indian adults.

Methods

Using data on self-reported diagnosis and treatment, and blood pressure measurement, collected from 12,198 respondents aged 18+ in the 2007 WHO Study on Global Ageing and Adult Health in India, factors associated with prevalence, diagnosis and treatment of hypertension were investigated.

Results

22% men and 26% women had hypertension; prevalence increased steeply with body mass index (<18.5 kg/m²: 18% men, 21% women; 25-29.9 kg/m²: 35% men, 35% women), was higher in the least poor vs. poorest (men: odds ratio (95%CI) 1.82 (1.20 to 2.76); women: 1.40 (1.08 to 1.81)), urban vs. rural men (1.64 (1.19 to 2.25)), and men recently vs. never using alcohol (1.96 (1.40 to 2.76)). Over half the hypertension in women, and 70% in men, was undetected with particularly poor detection rates in young urban men, and in poorer households. Two-thirds of men and women with detected hypertension were treated. Two-thirds of women treated had their hypertension controlled, irrespective of urban/rural setting or wealth. Adequate blood pressure control was sub-optimal in urban men.

Conclusion

Hypertension is very common in India, even among underweight adults and those of lower socioeconomic position. Improved detection is needed to reduce the burden of disease attributable to hypertension. Levels of treatment and control are relatively good, particularly in women, although urban men require more careful attention.