Ratio For Coronary Heart Disease Research Articles

Atherogenic index of plasma as a predictor of coronary artery disease: a cohort study in south of Iran

BackgroundCoronary artery disease (CAD) is an atherosclerotic disease of an inflammatory nature. Previous studies examining the relationship between triglycerides and high-density lipoprotein cholesterol have highlighted the importance of plasma atherogenic index (AIP) as an important predictor of coronary heart disease. However, due to the lack of adequate information on this topic, this study aimed to investigate the relationship between AIP and coronary heart disease risk.ResultsThis study included 2,226 women and 1,690 men aged 35–70 years who participated in the Bandar Kong Cohort study and met the eligibility criteria. The data was collected using a checklist and questionnaires, which were designed by experienced individuals. After participants completed a registration form and gave informed consent, face-to-face interviews were conducted by trained experts. The validity and reliability of the questionnaire had been verified by the national cohort team prior to its use. The Ethics Committee of Hormozgan University of Medical Sciences (IR.HUMS.REC.1400.171) approved the study. Data from the initial cohort survey using SPSS software version 25, were analyzed to include several factors, including age, sex, smoking status, body mass index (BMI), physical activity level, socioeconomic status, AIP, systolic blood pressure, and diastolic blood pressure. The prevalence of coronary heart disease was found to be 7.5% higher in people with a BMI of 25 or higher. Also, Individuals with low physical activity had a higher prevalence. Individuals with CAD had significantly higher mean values for the AIP, age, systolic blood pressure, and diastolic blood pressure (0.46, 57.50, 128.43, and 81.10, respectively) compared to those without CAD. Furthermore, patients with CAD had lower years of education (2649.45 and 3.59) than individuals without CAD (P < 0.05). Importantly, our findings showed that AIP increased the odds ratio of coronary heart disease by 1.86 as an independent risk factor.ConclusionsBased on our investigation, the AIP is a valuable and independent predictive risk factor for coronary artery disease. This index can be utilized effectively due to its accessibility and affordability, making it a promising tool for risk assessment in clinical settings.

Hemoglobin Levels, Sex, Race and Coronary Heart Disease Risk in the Reasons for Geographic and Racial Differences in Stroke Study

Background: Prior studies demonstrated both low and high hemoglobin concentrations are associated with increased mortality. It is unknown whether hemoglobin concentration has a similar U-shaped pattern for coronary heart disease (CHD) risk, or if the relationship differs by age, sex or race.Objective: We determined the association between hemoglobin concentration and risk of CHD in the national REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, and addressed whether this association was affected by age, sex, or race.Methods: REGARDS participants were black and white adults age 45 years and older, enrolled in their homes across the contiguous United States in 2003-7 and followed every 6 months for health outcomes. Baseline risk factors levels were measured using standardized methods, including complete blood counts at a central laboratory, which was initiated after 8608 participants had been recruited. We included REGARDS participants free of CHD at baseline. Incident CHD outcomes were adjudicated by a committee based on medical records review. Cox proportional hazard models were used to examine the association of hemoglobin with incident CHD (both fatal and non-fatal events). Models were adjusted for demographic variables (age, sex, race, and region of residence) and CHD risk factors (hypertension, diabetes, smoking status (current, former, never), total cholesterol (mg/dL), HDL cholesterol (mg/dL), and use of lipid lowering medications). Penalized regression splines were used to graphically represent associations using the adjusted model. Analyses were also stratified by age (≤ 63 vs. > 63), sex (male vs. female), and race (black vs. white).Results: Of 30,239 REGARDS participants, 15,764 had hemoglobin measures, were CHD-free at baseline, and had all baseline variables. The mean age was 63 (IQR 56, 70), 34% were male, and 42% were black. The mean baseline hemoglobin was 13.6 g/dL (SD 1.4). During 118,529 person-years of follow up (median 7.4 years) there were 637 incident CHD events. A significant non-linear association of hemoglobin with CHD was identified after multivariate adjustment (p <0.001). The penalized regression spline graph demonstrated a U-shaped relationship with increasing risk for CHD with lower and higher hemoglobin concentrations, although the confidence intervals were wide (Figure 1). The appearance of age, sex, and race specific regression splines were similar. When hemoglobin was divided into age, sex, and race-specific quintiles, participants in the lowest (HR 1.77; 95% CI 1.38, 2.28) and highest (HR 1.32; 95% CI 1.00, 1.73) quintiles had increased risk of CHD compared to the 4th quintile. The 2nd (HR 1.14; 95% CI 0.86, 1.50) and 3rd quintile (HR 1.22; 95% CI 0.92, 1.60) were not associated with CHD risk.Conclusion: Hemoglobin concentration was an independent risk factor for CHD, with lower and higher concentrations associated with increased CHD risk. The effect of hemoglobin concentration on CHD risk was a similar shape regardless of age, sex, or race. Further research is needed to explore possible mechanisms mediating the increased CHD risk, but these data point to “optimal” hemoglobin concentrations associated with the lowest CHD risk. Whether hemoglobin concentration is causative or reflects underlying comorbid conditions not accounted for in our analysis requires further work.Figure 1: Penalized Regression Spline - Hemoglobin Concentration and Hazard Ratio for Coronary Heart Disease [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Association of Body Mass Index With Coronary Artery Calcium and Subsequent Cardiovascular Mortality: The Coronary Artery Calcium Consortium.

Obesity is associated with higher risk for coronary artery calcium (CAC), but the relationship between body mass index (BMI) and mortality is complex and frequently paradoxical. We analyzed BMI, CAC, and subsequent mortality using data from the CAC Consortium, a multi-centered cohort of individuals free of established cardiovascular disease (CVD) who underwent CAC testing. Mortality was assessed through linkage to the Social Security Death Index and cause of death from the National Death Index. Multivariable logistic regression was used to determine odds ratios for the association of clinically relevant BMI categories and prevalent CAC. Cox proportional hazards regression modeling was used to determine hazard ratios for coronary heart disease, CVD, and all-cause mortality according to categories of BMI and CAC. Our sample included 36 509 individuals, mean age 54.1 (10.3) years, 34.4% female, median BMI 26.6 (interquartile range, 24.1-30.1), 46.6% had zero CAC, and 10.5% had CAC ≥400. Compared with individuals with normal BMI, the multivariable adjusted odds of CAC >0 were increased in those overweight (odds ratio, 1.13 [95% CI, 1.1-1.2]) and obese (odds ratio, 1.5 [95% CI, 1.4-1.6]). Over a median follow-up of 11.4 years, there were 1550 deaths (4.3%). Compared with normal BMI, obese individuals had a higher risk of coronary heart disease, CVD, and all-cause mortality while overweight individuals, despite a higher odds of CAC, showed no significant increase in mortality. In a sex-stratified analysis, the increase in coronary heart disease, CVD, and all-cause mortality in obese individuals appeared largely limited to men, and there was a lower risk of all-cause mortality in overweight women (hazard ratio, 0.79 [95% CI, 0.63-0.98]). In a large sample undergoing CAC scoring, obesity was associated with a higher risk of CAC and subsequent coronary heart disease, CVD, and all-cause mortality. However, overweight individuals did not have a higher risk of mortality despite a higher risk for CAC.

A sialoadenectomy is associated with an increased risk of coronary heart disease: A three-year follow-up study.

Little is known regarding the long-term adverse effects of a sialoadenectomy. The purpose of this study was to estimate the risk of coronary heart disease (CHD) among patients receiving a sialoadenectomy procedure by utilizing a cohort study based on a population-based database in Taiwan. This study retrieved data of the study sample from the Longitudinal Health Insurance Database 2005. This retrospective cohort study included 608 patients who underwent a sialoadenectomy and 1824 propensity score-matched comparison patients. We individually tracked each sampled patient for a 3-year period from their index date to discriminate those who subsequently received a diagnosis of CHD during the follow-up period. We found that respective incidence rates of CHD during the 3-year follow-up period were 3.87 (95% confidence interval (CI): 3.01–4.91) and 1.79 (95% CI: 1.45–2.18) per 100 person-years for patients who did and those who did not undergo a sialoadenectomy. The stratified Cox proportional analysis revealed that the hazard ratio of CHD during the 3-year follow-up period was 2.43 (95% CI: 1.77–3.33) than comparison patients. This study demonstrates an association between sialoadenectomy and CHD.

Sex difference in the effect of the fasting serum glucose level on the risk of coronary heart disease

ObjectiveDiabetic women have a greater relative risk of coronary heart disease than diabetic men. However, the sex difference in the effect of fasting serum glucose levels below the diabetic range on the risk of coronary heart disease is unclear. We investigated whether the association between nondiabetic blood glucose levels and the incident risk of coronary heart disease is different between men and women. MethodsThe fasting serum glucose levels and other cardiovascular risk factors at baseline were measured in 159,702 subjects (100,144 men and 59,558 women). Primary outcomes were hospital admission and death due to coronary heart disease during the 11-year follow-up. ResultsThe risk for coronary heart disease in women significantly increased with impaired fasting glucose levels (≥110mg/dL) compared to normal glucose levels (<100mg/dL), whereas the risk for coronary heart disease in men was significantly increased at a diabetic glucose range (≥126mg/dL). Women had a higher hazard ratio of coronary heart disease associated with the fasting serum glucose level than men (p for interaction with sex=0.021). ConclusionsThe stronger effect of the fasting serum glucose levels on the risk of coronary heart disease in women than in men was significant from a prediabetic range (≥110mg/dL).

PCSK9 Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke: Data From 9 Studies of Blacks and Whites.

PCSK9 loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of PCSK9 LOF variants with LDL-C and incident coronary heart disease and stroke through a meta-analysis of data from 8 observational cohorts and 1 randomized trial of statin therapy. These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between PCSK9 LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel-Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32-39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11-16) lower LDL-C in whites. PCSK9 LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28-0.92) in blacks and 0.82 (95% CI, 0.63-1.06) in whites. PCSK9 LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48-1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80-1.41 in whites). PCSK9 LOF variants were associated with lower LDL-C and coronary heart disease incidence. PCSK9 LOF variants were not associated with stroke risk.

Lipoprotein(a) Management: Pharmacological and Apheretic Treatment.

Lipoprotein (a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle with an additional apolipoprotein, apolipoprotein (a), [apo(a)] attached to apolipoprotein B. Recent epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) is causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). The risk association between Lp(a) concentrations and CVD is still controversial but seems to be continuous and without an obvious threshold Lp(a) level. Circulating concentrations of Lp(a) are genetically determined; desirable levels are < 50 mg/dl. A plasma concentration of 60 mg/dl is associated with an odds ratio for coronary heart disease of about 1.5 after adjustment for other cardiovascular risk factors. Extended-release niacin is an option for decreasing elevated Lp(a) levels (by ~20-30%) but it is often poorly tolerated. Dietary measures, exercise and lipid-lowering drugs such as statins and ezetimibe are without significant effect. In patients with severe progressive CVD and very high Lp(a) levels, lipoprotein apheresis can decrease Lp(a) concentrations. The method is expensive and impractical for most patients and its feasibility depends mainly on the healthcare reimbursement system. Since no established treatment reduces Lp(a) without influencing other lipoproteins, there has been no trial that evaluated whether decreasing Lp(a) concentrations translates to clinical benefits. Recently, an antisense oligonucleotide against apo(a), IONIS-APO(a)Rx, has been shown to selectively decrease Lp(a) by almost 80%. A phase 2 study with this drug has been completed in late 2015 and results are expected to be published soon.

Apolipoprotein(a) Antisense Oligonucleotides: A New Treatment Option for Lowering Elevated Lipoprotein(a)?

Lipoprotein(a) [Lp(a)] is a particle similar to LDL that contains an additional protein called apolipoprotein(a) [apo(a)]. Recent epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) may be causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). While the risk association between Lp(a) concentrations and CVD is weak it seems to be continuous in shape and without an obvious threshold for Lp(a) levels. Circulating concentrations of Lp(a) are genetically determined and desirable levels are < 50 mg/dl. A plasma concentration of 60 mg/dl is associated with an odds ratio for coronary heart disease of about 1.5 after adjustment for other cardiovascular risk factors. Extended-release niacin is the pharmacologic means of choice for decreasing elevated Lp(a) levels by ~20-30% but it is often poorly tolerated due to adverse reactions. Diet, exercise and lipid-lowering drugs such as statins, fibrates and ezetimibe are without effect. In patients with severe progressive CVD and very high Lp(a) levels, lipoprotein apheresis may be used to decrease Lp(a) concentrations. However, it is an expensive and impractical treatment for most patients and its feasibility depends on the healthcare reimbursement system of the respective country. Since no established treatment reduces Lp(a) without influencing other lipoproteins, there has been no trial examining whether decreasing Lp(a) concentrations translates to clinical benefits. Recently, an antisense oligonucleotide against apo(a), IONIS-APO(a)Rx, has been shown to selectively decrease Lp(a) by ~80%. A phase 2 study with this drug has been completed in late 2015 and results are expected to be published soon.

Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study

Objective To examine the association of long term intake of gluten with the development of incident coronary heart disease.Design Prospective cohort study.Setting and participants 64 714 women in the Nurses’...

Genetic invalidation of Lp-PLA2 as a therapeutic target: Large-scale study of five functional Lp-PLA2-lowering alleles.

AimsDarapladib, a potent inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2), has not reduced risk of cardiovascular disease outcomes in recent randomized trials. We aimed to test whether Lp-PLA2 enzyme activity is causally relevant to coronary heart disease.MethodsIn 72,657 patients with coronary heart disease and 110,218 controls in 23 epidemiological studies, we genotyped five functional variants: four rare loss-of-function mutations (c.109+2T > C (rs142974898), Arg82His (rs144983904), Val279Phe (rs76863441), Gln287Ter (rs140020965)) and one common modest-impact variant (Val379Ala (rs1051931)) in PLA2G7, the gene encoding Lp-PLA2. We supplemented de-novo genotyping with information on a further 45,823 coronary heart disease patients and 88,680 controls in publicly available databases and other previous studies. We conducted a systematic review of randomized trials to compare effects of darapladib treatment on soluble Lp-PLA2 activity, conventional cardiovascular risk factors, and coronary heart disease risk with corresponding effects of Lp-PLA2-lowering alleles.ResultsLp-PLA2 activity was decreased by 64% (p = 2.4 × 10–25) with carriage of any of the four loss-of-function variants, by 45% (p < 10–300) for every allele inherited at Val279Phe, and by 2.7% (p = 1.9 × 10–12) for every allele inherited at Val379Ala. Darapladib 160 mg once-daily reduced Lp-PLA2 activity by 65% (p < 10–300). Causal risk ratios for coronary heart disease per 65% lower Lp-PLA2 activity were: 0.95 (0.88–1.03) with Val279Phe; 0.92 (0.74–1.16) with carriage of any loss-of-function variant; 1.01 (0.68–1.51) with Val379Ala; and 0.95 (0.89–1.02) with darapladib treatment.ConclusionsIn a large-scale human genetic study, none of a series of Lp-PLA2-lowering alleles was related to coronary heart disease risk, suggesting that Lp-PLA2 is unlikely to be a causal risk factor.

The association between blood group and the risk of vascular disease in Quebec blood donors.

The association between antigens A and B and arterial thrombosis, such as coronary heart disease, cerebrovascular disease or peripheral vascular disease, is still unclear. We evaluated the association between blood groups and thrombotic events in a cohort of blood donors from the province of Quebec, Canada. Among all whole blood donors aged ≥18 years in Quebec between June 1990 and March 2009, a study sample with known blood groups was linked with the provincial hospitalisation and death records to count vascular events. All hospital admissions and deaths with codes for primary and relevant secondary diagnoses of coronary, cerebrovascular or peripheral diseases, including coronary heart disease interventions, were included. Cox regression was used to evaluate the hazard ratio associated between blood groups and these events adjusted for other baseline characteristics. Among the blood donors, 64,686 had a known blood group and were linked with the provincial health databases. The mean age of these donors was 38 years. The Cox multivariate adjusted hazard ratio for coronary, cerebrovascular or peripheral diseases was 1.19 (95% confidence interval: 1.01-1.40) for subjects with blood group AB compared to those with blood group O. There were no statistically significant associations with other blood groups. Only among women aged ≥40 years did those with blood group A have a higher hazard ratio for coronary heart disease (1.40 [1.01-1.92]) than those with blood group O, after adjusting for other characteristics. When compared to blood group O, only blood group AB was associated with a higher risk of hospitalisation or death because of thrombotic events such as coronary, cerebrovascular or peripheral diseases. However, the associations differed according to age and sex because only females aged ≥40 years with blood group A had a higher risk of coronary heart disease.

Ethnic Differences in Risk of Coronary Heart Disease in a Large Contemporary Population.

Racial/ethnic differences in diabetes and cardiovascular disease are well documented, but disease estimates are often confounded by differences in access to quality health care. The objective of this study was to evaluate the ethnic differences in risk of future coronary heart disease in patient populations stratified by status of diabetes mellitus and prior coronary heart disease among those with uniform access to care in an integrated healthcare delivery system in Northern California. A cohort was constructed consisting of 1,344,899 members with self-reported race/ethnicity, aged 30-90 years, and followed from 2002 through 2012. Cox proportional hazard regression models were specified to estimate race/ethnicity-specific hazard ratios for coronary heart disease (with whites as the reference category) separately in four clinical risk categories: (1) no diabetes with no prior coronary heart disease; (2) no diabetes with prior coronary heart disease; (3) diabetes with no prior coronary heart disease; and (4) diabetes with prior coronary heart disease. Analyses were performed in 2015. The median follow-up was 10 years (10,980,800 person-years). Compared with whites, blacks, Latinos, and Asians generally had lower risk of coronary heart disease across all clinical risk categories, with the exception of blacks with prior coronary heart disease and no diabetes having higher risk than whites. Findings were not substantively altered after multivariate adjustments. Identification of health outcomes in a system with uniform access to care reveals residual racial/ethnic differences and point to opportunities to improve health in specific subgroups and to improve health equity.

Ideal cardiovascular health and risk of cardiovascular events in the EPIC-Norfolk prospective population study.

The American Heart Association has prioritised seven cardiovascular health metrics to reduce the cardiovascular burden, including: body mass index, healthy diet, physical activity, smoking status, blood pressure, glycated haemoglobin A1c and total cholesterol. The aim of the current study was to assess the association between the American Heart Association-defined health metrics and the risk of cardiovascular events in the EPIC-Norfolk prospective study. Prospective cohort study. An overall cardiovascular health score was calculated based on the number of health metrics including ideal, intermediate or poor. Cox proportional hazards models were used to describe the association of the seven metrics separately and the overall health score with risk of coronary heart disease, stroke and cardiovascular disease. A total of 10,043 participants was included in the analysis (follow-up 1993-2008). For all individual health metrics a more ideal status was associated with a lower risk of cardiovascular events. As for the overall cardiovascular health score, those in the highest (i.e. healthiest) category (score 12-14) had an adjusted hazard ratio for coronary heart disease of 0.07 (95% confidence interval (CI) 0.02-0.29, P < 0.001), for stroke of 0.16 (95% CI 0.02-1.37, P = 0.09) and for cardiovascular disease of 0.07 (95% CI 0.02-0.23, P < 0.001), compared to people in the lowest (i.e. unhealthiest) category (score 0-2). The overall cardiovascular health score was strongly and inversely associated with risk of coronary heart disease, stroke and cardiovascular disease. Our data suggest that even small improvements in modifiable risk factors may lead to substantial reductions in the risks of cardiovascular events.

Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials

Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, p<0·0001) and that for the high genetic risk category was 1·72 (1·55-1·92, p<0·0001). In terms of the benefit of statin therapy in the four randomised trials, we noted a significant gradient (p=0·0277) of increasing relative risk reductions across the low (13%), intermediate (29%), and high (48%) genetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high genetic risk in JUPITER, and 57, 47, and 20, respectively, in ASCOT. A genetic risk score identified individuals at increased risk for both incident and recurrent coronary heart disease events. People with the highest burden of genetic risk derived the largest relative and absolute clinical benefit from statin therapy. National Institutes of Health.

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis

SummaryBackgroundTo investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation.MethodsWe created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1α and IL-1β); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants).FindingsFor each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0·22 SD (95% CI 0·18–0·25; 12·5%; p=9·3 × 10−33), concentrations of interleukin 6 decreased by 0·02 SD (−0·04 to −0·01; −1·7%; p=3·5 × 10−3), and concentrations of C-reactive protein decreased by 0·03 SD (−0·04 to −0·02; −3·4%; p=7·7 × 10−14). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1·15 (1·08–1·22; p=1·8 × 10−6) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1·03 (1·02–1·04; p=3·9 × 10−10). Per-allele odds ratios were 0·97 (0·95–0·99; p=9·9 × 10−4) for rheumatoid arthritis, 0·99 (0·97–1·01; p=0·47) for type 2 diabetes, 1·00 (0·98–1·02; p=0·92) for ischaemic stroke, and 1·08 (1·04–1·12; p=1·8 × 10−5) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk.InterpretationHuman genetic data suggest that long-term dual IL-1α/β inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations.FundingUK Medical Research Council, British Heart Foundation, UK National Institute for Health Research, National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council, and European Commission Framework Programme 7.

Occupational class differences in later life hospital use by women who survived to age 80: the Renfrew and Paisley prospective cohort study.

population ageing challenges the sustainability of healthcare provision. to investigate occupational class differences in hospital use in women aged 80+ years. a total of 8,353 female residents, aged 45-64, took part in the Renfrew and Paisley prospective cohort study in 1972-76. Information on general and mental health hospital discharges was provided from computerised linkage with the Scottish Morbidity Records data to 31 December 2012. Numbers of admissions and bed-days after the 80th birthday were calculated for all and specific causes. Rate ratios by occupational class were calculated using negative binomial regression analysis, adjusting for age and a range of risk factors. four thousand and four hundred and seven (56%) women survived to age 80 and had 17,563 general admissions thereafter, with a mean stay of 19.4 days. There were no apparent relationships with occupational class for all general admissions, but lower occupational class was associated with higher rate ratios for coronary heart disease and stroke and lower rate ratios for cancer. Adjustment for risk factors could not fully explain the raised rate ratios. Bed-day use was higher in lower occupational classes, especially for stroke. There were strong associations with mental health admissions, especially dementia. Compared with the highest occupational class, admission rate ratios for dementia were higher for the lowest occupational class (adjusted rate ratio = 2.60, 95% confidence interval 1.79-3.77). in this population, there were no socio-economic gradients seen in hospital utilisation for general admissions in old age. However, occupational class was associated with mental health admissions, coronary heart disease, stroke and cancer.

Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data

Objective To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Design Mendelian randomisation meta-analysis...

Genetic determination of lipoprotein(a) and its association with cardiovascular disease: convenient does not always mean better

Genetic determination of lipoprotein(a) and its association with cardiovascular disease: convenient does not always mean better

Abstract P326: Apparent Treatment Resistant Hypertension and Risk for Stroke, Coronary Heart Disease and All-cause Mortality

Apparent treatment resistant hypertension (aTRH) is characterized as uncontrolled hypertension (HTN) with the use of 3 or more antihypertensive medication classes or controlled HTN while treated with 4 or more antihypertensive medication classes. Few data are available on the association of aTRH with cardiovascular disease outcomes in comparison to more easily controlled HTN. We evaluated the risk for stroke, coronary heart disease (CHD) and all-cause mortality among 2,043 participants with aTRH and 9,519 participants with controlled HTN (systolic blood pressure &lt; 140 mm Hg and diastolic blood pressure &lt; 90 mm Hg) treated with &lt; 4 antihypertensive medication classes from the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study. aTRH was further categorized as controlled aTRH (≥ 4 antihypertensive medication classes and controlled HTN) and uncontrolled aTRH (≥ 3 antihypertensive medication classes and uncontrolled HTN). Participants with and without aTRH, respectively, were 68±9 and 66±9 years of age, 60.5% (1236 0f 2043) and 46.8% (4455 of 9519) black, and 49.2% (1005 of 2043) and 40.8% (3884 of 9519) male. After adjusting for demographic, clinical and comorbid factors, the hazard ratio (HR) for stroke, CHD, and all-cause mortality associated with aTRH (vs. controlled HTN and &lt; 4 medication classes) was 1.29 (95% CI 0.96-1.73), 1.90 (95% CI 1.40-2.58), and 1.36 (95% CI 1.20-1.55), respectively. Compared to those with controlled hypertension, the multivariable-adjusted HR for stroke, CHD and all-cause mortality was increased for those with uncontrolled aTRH but not those with controlled aTRH (Table 1). Compared to those with controlled aTRH, uncontrolled aTRH was associated with CHD (HR 2.33; 95% CI: 1.21 [[Unable to Display Character: &amp;#8211;]] 4.48) but not stroke (HR 1.05; 95% CI: 0.61 [[Unable to Display Character: &amp;#8211;]] 1.81) or all-cause mortality (HR 1.15; 95% CI: 0.91 [[Unable to Display Character: &amp;#8211;]] 1.45). We conclude achieving blood pressure control within aTRH is paramount to decrease risk for events similarly to other patients with more easily controlled HTN. Table 1. Hazard ratios for stroke, coronary heart disease, and all-cause mortality associated with apparent treatment resistant hypertension (aTRH). *&lt; 4 antihypertensive medication classes Models are adjusted for age, race, gender, and geographic region of residence, waist circumference, smoking status, physical activity, alcohol consumption, C - reactive protein, statin use, Morisky score for medication adherence, total cholesterol, HDL-cholesterol, and hypertension duration, estimated glomerular filtration rate &lt; 60 ml/min/1.73m 2 , albuminuria, and diabetes. Hazard ratios for stroke were also adjusted for history of coronary heart disease. Hazard ratios for coronary heart disease were also adjusted for history of stroke. Hazard ratios for all-cause mortality were also adjusted for history of coronary heart disease and stroke.

Hemostatic factors and risk of coronary heart disease in general populations: new prospective study and updated meta-analyses.

BackgroundActivation of blood coagulation and fibrinolysis may be associated with increased risk of coronary heart disease. We aimed to assess associations of circulating tissue plasminogen activator (t-PA) antigen, D-dimer and von Willebrand factor (VWF) with coronary heart disease risk.DesignProspective case-control study, systematic review and meta-analyses.MethodsMeasurements were made in 1925 people who had a first-ever nonfatal myocardial infarction or died of coronary heart disease during follow-up (median 19.4 years) and in 3616 controls nested within the prospective population-based Reykjavik Study.ResultsAge and sex-adjusted odds ratios for coronary heart disease per 1 standard deviation higher baseline level were 1.25 (1.18, 1.33) for t-PA antigen, 1.01 (0.95, 1.07) for D-dimer and 1.11 (1.05, 1.18) for VWF. After additional adjustment for conventional cardiovascular risk factors, corresponding odds ratios were 1.07 (0.99, 1.14) for t-PA antigen, 1.06 (1.00, 1.13) for D-dimer and 1.08 (1.02, 1.15) for VWF. When combined with the results from previous prospective studies in a random-effects meta-analysis, overall adjusted odds ratios were 1.13 (1.06, 1.21) for t-PA antigen (13 studies, 5494 cases), 1.23 (1.16, 1.32) with D-dimer (18 studies, 6799 cases) and 1.16 (1.10, 1.22) with VWF (15 studies, 6556 cases).ConclusionsConcentrations of t-PA antigen, D-dimer and VWF may be more modestly associated with first-ever CHD events than previously reported. More detailed analysis is required to clarify whether these markers are causal risk factors or simply correlates of coronary heart disease.