Nonfatal Coronary Heart Disease Events Research Articles

Combined population genomic screening for three high-risk conditions in Australia: a modelling study

No previous health-economic evaluation has assessed the impact and cost-effectiveness of offering combined adult population genomic screening for mutliple high-risk conditions in a national public healthcare system. This modeling study assessed the impact of offering combined genomic screening for hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia to all young adults in Australia, compared with the current practice of clinical criteria-based testing for each condition separately. The intervention of genomic screening, assumed as an up-front single cost in the first annual model cycle, would detect pathogenic variants in seven high-risk genes. The simulated population was 18-40 year-olds (8,324,242 individuals), modelling per-sample test costs ranging AU$100-$1200 (base-case AU$200) from the year 2023 onwards with testing uptake of 50%. Interventions for identified high-risk variant carriers follow current Australian guidelines, modelling imperfect uptake and adherence. Outcome measures were morbidity and mortality due to cancer (breast, ovarian, colorectal and endometrial) and coronary heart disease (CHD) over a lifetime horizon, from healthcare-system and societal perspectives. Outcomes included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER), discounted 5% annually (with 3% discounting in scenario analysis). Over the population lifetime (to age 80 years), the model estimated that genomic screening per-100,000 individuals would lead to 747 QALYs gained by preventing 63 cancers, 31 CHD cases and 97 deaths. In the total model population, this would translate to 31,094 QALYs gained by preventing 2612 cancers, 542 non-fatal CHD events and 4047 total deaths. At AU$200 per-test, genomic screening would require an investment of AU$832 million for screening of 50% of the population. Our findings suggest that this intervention would be cost-effective from a healthcare-system perspective, yielding an ICER of AU$23,926 (∼£12,050/€14,110/US$15,345) per QALY gained over the status quo. In scenario analysis with 3% discounting, an ICER of AU$4758/QALY was obtained. Sensitivity analysis for the base case indicated that combined genomic screening would be cost-effective under 70% of simulations, cost-saving under 25% and not cost-effective under 5%. Threshold analysis showed that genomic screening would be cost-effective under the AU$50,000/QALY willingness-to-pay threshold at per-test costs up to AU$325 (∼£164/€192/US$208). Our findings suggest that offering combined genomic screening for high-risk conditions to young adults would be cost-effective in the Australian public healthcare system, at currently realistic testing costs. Other matters, including psychosocial impacts, ethical and societal issues, and implementation challenges, also need consideration. Australian Government, Department of Health, Medical Research Future Fund, Genomics Health Futures Mission (APP2009024). National Heart Foundation Future Leader Fellowship (102604).

Obesity, metabolic health and clinical outcomes after incident cardiovascular disease: A nationwide population-based cohort study.

The association between metabolic syndrome and increased cardiovascular disease (CVD) risk is well-established. However, in patients with incident CVD, the relationship between obesity, metabolic health, and subsequent CVD and mortality outcomes are less well-established. This study investigated the association between body mass index (BMI), metabolic health and the risk of subsequent cardiovascular mortality and morbidity outcomes in patients with incident CVD events. This cohort study identified 130685 patients from the nationwide Clinical Practice Research Datalink (CPRD GOLD) and Hospital Episode Statistics (HES) databases in the United Kingdom. Patients were ≥18years with incident CVD [coronary heart disease (CHD), stroke, or peripheral vascular disease (PVD)] between 1 January 1998 and 31 December 2017. BMI (in kg/m2 ) was categorized as underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9) and obese (≥30). Within each BMI category, patients were grouped by increasing count of 1, 2 or 3 metabolic risk factors [RF] (dyslipidaemia, diabetes mellitus and hypertension) and were regarded as metabolically unhealthy while absence of these factors was considered metabolically healthy (MH). Multivariable Cox regression was used to assess the risk (hazard ratio with 95% confidence interval) of subsequent outcomes (non-fatal CHD, stroke, PVD, incident heart failure, CVD-mortality and all-cause mortality) in BMI subgroups with incremental count of metabolic RFs. During a median follow-up of 13.0years, a higher BMI was associated with reduced risk for stroke, PVD, CVD-mortality and all-cause mortality within each metabolic risk category, while increasing metabolic RFs within each BMI subgroup accounted for increasing risks. When compared with patients with normal BMI and no RF, CVD-mortality risk in overweight patients with no RF was 0.76 (0.70-0.84), and in obese patients with no RF was 0.85 (0.76-0.96). The respective risk for all-cause mortality in patients with overweight and no RF was 0.69 (0.65-0.72), and in obese patients with no RF was 0.75 (0.70-0.79). Subsequent outcomes of stroke and PVD showed similar trends. In contrast, the risk of subsequent non-fatal CHD events and incident HF increased with higher BMI and with incremental metabolic risk factors within each BMI category. Underweight was constantly associated with increased risk for all outcomes regardless of the presence of metabolic RFs except for non-fatal CHD events. In patients with incident CVD, overweight and obesity were related to a more favourable prognosis for subsequent stroke, PVD and mortality (CVD-related and all-cause) irrespective of the presence of other metabolic risk factors.

Changing associations of coronary heart disease incidence with current partnership status and marital history over three decades

Married men and women have better health than non-married, but little is known about how cohabitation and marital history are associated with coronary heart disease (CHD) incidence and how these associations have changed over time. We analyzed these associations by fitting Cox regression models to register data covering the whole Finnish population aged 35 years or older (N = 4,415,590), who experienced 530,560 first time non-fatal or fatal CHD events during the years 1990–2018. Further, we used stratified Cox regression models to analyze CHD incidence within same-sex sibling pairs (N = 377,730 pairs). Married men and women without previous divorce had the lowest CHD incidence whereas cohabitation and a history of divorce were associated with higher CHD incidence. The associations were stronger in younger (35–64 years old) than older participants (65 years or older). These associations remained after adjusting for several indicators of social position, and the lower CHD incidence among those married without previous divorce was also observed within sibling pairs with a shared family background. The differences in CHD incidence between the categories generally widened over time; the largest and most systematic widening was observed among women in the younger age category. The long standing negative effect of divorce suggests that selection may partly explain the association between partnership status and CHD incidence. Partnership status is an increasingly important factor contributing to social inequalities in health.

Oral Condition and Incident Coronary Heart Disease: A Clustering Analysis

Poor oral health has been linked to coronary heart disease (CHD). Clustering clinical oral conditions routinely recorded in adults may identify their CHD risk profile. Participants from the Paris Prospective Study 3 received, between 2008 and 2012, a baseline routine full-mouth clinical examination and an extensive physical examination and were thereafter followed up every 2 y until September 2020. Three axes defined oral health conditions: 1) healthy, missing, filled, and decayed teeth; 2) masticatory capacity denoted by functional masticatory units; and 3) gingival inflammation and dental plaque. Hierarchical cluster analysis was performed with multivariate Cox proportional hazards regression models and adjusted for age, sex, smoking, body mass index, education, deprivation (EPICES score; Evaluation of Deprivation and Inequalities in Health Examination Centres), hypertension, type 2 diabetes, LDL and HDL serum cholesterol (low- and high-density lipoprotein), triglycerides, lipid-lowering medications, NT-proBNP and IL-6 serum level. A sample of 5,294 participants (age, 50 to 75 y; 37.10% women) were included in the study. Cluster analysis identified 3,688 (69.66%) participants with optimal oral health and preserved masticatory capacity (cluster 1), 1,356 (25.61%) with moderate oral health and moderately impaired masticatory capacity (cluster 2), and 250 (4.72%) with poor oral health and severely impaired masticatory capacity (cluster 3). After a median follow-up of 8.32 y (interquartile range, 8.00 to 10.05), 128 nonfatal incident CHD events occurred. As compared with cluster 1, the risk of CHD progressively increased from cluster 2 (hazard ratio, 1.45; 95% CI, 0.98 to 2.15) to cluster 3 (hazard ratio, 2.47; 95% CI, 1.34 to 4.57; P < 0.05 for trend). To conclude, middle-aged individuals with poor oral health and severely impaired masticatory capacity have more than twice the risk of incident CHD than those with optimal oral health and preserved masticatory capacity (ClinicalTrials.gov NCT00741728).

Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women

BackgroundGenetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate...

Vitamin D supplementation, cardiac events and stroke: A systematic review and meta-regression analysis

IntroductionObservational data has suggested a link between vitamin D deficiency and coronary heart disease (CHD). However, randomized controlled trials (RCTs) have failed to show benefit. The objective of this study is to analyze the RCTs investigating vitamin D supplementation and the risk of CHD and stroke. MethodsAll RCTs that compared vitamin D supplementation to placebo and evaluated nonfatal myocardial infarction (MI), cardiac mortality, stroke and CHD events (a composite of cardiac mortality, MI, unstable angina and revascularization) were included. Rate ratios (RR) were calculated for each endpoint and to test for heterogeneity of treatment effect (HTE) the Chi2 and I2 tests were used for younger vs. older participants, shorter vs. longer trial duration, vitamin D supplements with vs. without calcium, and daily vs. monthly dosages of vitamin D. A meta-regression was performed with baseline vitamin D concentration as the covariate. Results22 RCTs were identified (n = 83,200). Vitamin D supplementation had no effect on nonfatal MI (RR 0.98, 95% confidence interval (CI) 0.89–1.08), cardiac death (RR 0.94, CI 0.84–1.06), CHD events (RR 1.00, CI 0.91–1.10), or stroke (RR, 0.97, CI 0.9–1.03). When performing the meta-regression with baseline circulating 25-hydroxyvitamin D (25(OH)D) concentrations as the covariate, vitamin D supplementation’s treatment effect on CVD outcomes was not associated with baseline 25(OH)D. ConclusionVitamin D did not reduce CHD and stroke. A linear relationship does not exist between baseline 25(OH)D and vitamin D supplementation’s effect on CVD. Vitamin D levels should be checked and repleted in those with an absolute indication.

Effect of Bariatric Surgery on Cardiovascular Events and Metabolic Outcomes in Obese Patients with Insulin-Treated Type 2 Diabetes: a Retrospective Cohort Study.

To compare non-fatal cardiovascular (CV) events and metabolic outcomes, among obese patients with insulin-treated type 2 diabetes who underwent bariatric surgery compared with a propensity-matched non-bariatric cohort. A retrospective cohort study was conducted among 11,125 active patients with type 2 diabetes from The Health Improvement Network (THIN) database. Propensity score matching (up to 1:6 ratio) was used to identify patients who underwent bariatric surgery (N = 131) with a non-bariatric cohort (N = 579). Follow-up was undertaken for 10years (9686 person-years) to compare differences in metabolic outcomes and CV risk events that included the following: acute myocardial infarction (AMI), stroke, coronary heart disease (CHD), heart failure (HF) and peripheral artery disease (PAD). Cox proportional regression was used to compute the outcomes between groups. The mean age was 52 (SD 13) years (60% female); the baseline weight and BMI were 116 (SD 25) kg and 41 (SD 9) kg/m2, respectively. Significant reductions in weight and BMI were observed in bariatric group during 10years of follow-up. Bariatric surgery had a significant cardioprotective effect by reducing the risk of non-fatal CHD (adjusted hazard ratio [aHR] 0.29, 95% CI 0.16-0.52, p < 0.001) and PAD events (aHR 0.31, 95% CI 0.11-0.89, p = 0.03). However, the surgery had no significant effect on AMI (aHR 0.98, p = 0.95), stroke (HR 0.87, p = 0.76) and HF (HR 0.89, p = 0.73) risks. Bariatric surgery had favourable effects on insulin independence, HbA1c and BP. Among obese insulin-treated patients with type 2 diabetes, bariatric surgery is associated with significant reductions in non-fatal CHD and PAD events, lower body weight, HbA1c, BP and a greater likelihood of insulin independency during 10years of follow-up.

Leukocyte telomere length and risk of coronary heart disease and stroke mortality: prospective evidence from a Russian cohort

Previous studies suggest that reduced leukocyte telomere length (LTL) is related to higher risk of mortality and several chronic conditions, including coronary heart disease (CHD) and stroke. However, the consistency of this association differs across populations. We investigated the relationship of LTL with CHD, stroke and all-cause mortality together with non-fatal CHD and stroke events in a Russian cohort with a mean age of 58 years at baseline. Data from 1,144 individuals in the Russian subset of the Health Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE) cohort study were used. The associations between LTL at baseline and fatal/non-fatal outcomes during 12 years of follow-up were assessed using multivariable Cox regression models, which yielded adjusted hazard ratios (HR). Compared to individuals in the shortest tertile, those in the longest tertile of LTL had a 42% lower risk of death from all-causes (HR 0.58; 95% CI: 0.39–0.88) and 58% lower risk of death from CHD (HR 0.42; 95%CI: 0.19–0.97). Similar patterns of association were identified for non-fatal and combined fatal/non-fatal CHD and stroke events but the associations were weaker. Consistent with results of previous studies in Western populations, this cohort of elderly Russian adults found an inverse association between LTL and CHD and all-cause mortality. These findings reinforce the hypothesis that LTL may play (or be a marker of) an aetiological role in human health across diverse populations.

Serum dietary fatty acids and coronary heart disease risk – A nested case-control-study within the CARLA cohort

Background and AimsDiet is known to play a decisive role in the development of coronary heart disease (CHD). One factor believed to decrease lifetime risk of CHD is the consumption of omega-3 fatty acids. Yet, conclusive evidence regarding the potential cardioprotective effects of fatty acids is far from being reached. The present study aimed to provide further evidence on the association of serum fatty acid profiles with CHD risk. Methods and ResultsThe CARdio-vascular Disease, Living and Ageing in Halle study (CARLA study) is an observational cohort study comprising an older adult's general population with a high level of cardiovascular risk factors. In a matched case–control design the serum fatty acid concentrations of 73 subjects with an incident fatal or nonfatal CHD event were compared to 146 controls matched for sex and age. Our data show that the participants of the CARLA study are underserved in unsaturated fatty acids with respect to current dietary recommendations. In addition, the ratio of omega-6 to omega-3 fatty acids was determined to be 8:1 which underlines the consumption of a Western-style diet enriched in omega-6 fatty acids. There were no significant differences in fatty acid patterns between cases and controls. Thus, no clear association of particular serum fatty acid levels with cardiovascular risk was found. ConclusionOur results support the conclusion that in populations with a homogenous low level of omega-3 polyunsaturated fatty acids consumption, serum fatty acid levels are not associated with CHD risk.

Association of longitudinal alcohol consumption trajectories with coronary heart disease: a meta-analysis of six cohort studies using individual participant data

BackgroundStudies have shown that alcohol intake trajectories differ in their associations with biomarkers of cardiovascular functioning, but it remains unclear if they also differ in their relationship to actual coronary heart disease (CHD) incidence. Using multiple longitudinal cohort studies, we evaluated the association between long-term alcohol consumption trajectories and CHD.MethodsData were drawn from six cohorts (five British and one French). The combined analytic sample comprised 35,132 individuals (62.1% male; individual cohorts ranging from 869 to 14,247 participants) of whom 4.9% experienced an incident (fatal or non-fatal) CHD event. Alcohol intake across three assessment periods of each cohort was used to determine participants’ intake trajectories over approximately 10 years. Time to onset for (i) incident CHD and (ii) fatal CHD was established using surveys and linked medical record data. A meta-analysis of individual participant data was employed to estimate the intake trajectories' association with CHD onset, adjusting for demographic and clinical characteristics.ResultsCompared to consistently moderate drinkers (males: 1–168 g ethanol/week; females: 1–112 g ethanol/week), inconsistently moderate drinkers had a significantly greater risk of incident CHD [hazard ratio (HR) = 1.18, 95% confidence interval (CI) = 1.02–1.37]. An elevated risk of incident CHD was also found for former drinkers (HR = 1.31, 95% CI = 1.13–1.52) and consistent non-drinkers (HR = 1.47, 95% CI = 1.21–1.78), although, after sex stratification, the latter effect was only evident for females. When examining fatal CHD outcomes alone, only former drinkers had a significantly elevated risk, though hazard ratios for consistent non-drinkers were near identical. No evidence of elevated CHD risk was found for consistently heavy drinkers, and a weak association with fatal CHD for inconsistently heavy drinkers was attenuated following adjustment for confounding factors.ConclusionsUsing prospectively recorded alcohol data, this study has shown how instability in drinking behaviours over time is associated with risk of CHD. As well as individuals who abstain from drinking (long term or more recently), those who are inconsistently moderate in their alcohol intake have a higher risk of experiencing CHD. This finding suggests that policies and interventions specifically encouraging consistency in adherence to lower-risk drinking guidelines could have public health benefits in reducing the population burden of CHD. The absence of an effect amongst heavy drinkers should be interpreted with caution given the known wider health risks associated with such intake.Trial registrationClinicalTrials.gov, NCT03133689.

Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study

ObjectiveTo investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke.DesignMulticentre case-cohort study.SettingA study of cardiovascular disease (CVD) determinants...

Abstract MP070: Saturated Fat Intake by Food Source and Risk of Incident Coronary Heart Disease in Men: the Kuopio Ischaemic Heart Disease Risk Factor Study

Introduction: The epidemiological evidence of the role of dietary saturated fatty acids (SFA) in the etiology of coronary heart disease (CHD) is inconsistent. However, the proportions of different SFAs in different foods vary, and food sources of SFA (such as dairy and meat products) have had distinct associations with risk of CHD and its risk factors. Hypothesis: We assessed the hypothesis that SFA from different food sources have distinct associations with CHD risk in men. Methods: A total of 1981 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study from eastern Finland, aged 42-60 years and free of CHD at baseline, were included. The consumption of foods was assessed with instructed 4-day food recording by household measures. Dietary intakes were adjusted for total energy using the residuals method. Multivariable-adjusted Cox regression analyses included age, examination year, body mass index, diabetes, hypertension, family history of CHD, smoking, education, leisure-time physical activity, and intakes of alcohol, energy, fiber, polyunsaturated fatty acids, and fruits, berries and vegetables. Fatal and nonfatal CHD events were ascertained from national registries, with no loss to follow-up. Results: The mean±SD total SFA intake was 49.1±10.4 g/d (18.1 E%). SFA from dairy (16.1±7.7 g/d, excluding butter), butter (16.0±11.1 g/d), plant sources (6.7±5.0 g/d), processed red meat (4.7±4.2 g/d), and unprocessed red meat (3.6±2.7 g/d) contributed most to the total intake. During the mean follow-up of 19.6 years, 458 CHD events occurred. The extreme-quartile hazard ratios (95% CIs) were 1.08 (0.79-1.47, P-trend=0.57) for the highest vs. the lowest quartile of total SFA, 0.99 (0.75-1.32, P-trend=0.93) for total dairy SFA, 1.17 (0.84-1.63, P-trend=0.45) for butter SFA, 0.96 (95% CI 0.70-1.32, P-trend=0.62) for plant SFA, 1.09 (0.82-1.44, P-trend=0.76) for processed red meat SFA, and 1.15 (0.88-1.49, P-trend=0.29) for SFA from unprocessed red meat. Only SFA from fermented dairy (mean±SD intake 4.6±4.6 g/d) was associated with the risk (hazard ratio in the highest vs. the lowest quartile 0.69, 95% CI 0.52-0.91, P-trend=0.02). The associations were not appreciably different with a shorter, 10-y follow-up (199 cases). Conclusions: Our results suggest an overall non-significant role for SFA intake in the CHD risk and little difference in the associations with SFA from various food sources. Because milk is the raw material in all dairy products, the inverse association with fermented dairy likely reflects other constituents in these products than SFA.

Abstract MP049: Fermented vs. Non-fermented Dairy and Risk of Coronary Heart Disease in Men: the Kuopio Ischaemic Heart Disease Risk Factor Study

Introduction: Most of the recent dairy studies, including multiple meta-analyses, show either no relationship or an inverse association between total dairy intake and risk of cardiovascular diseases. Some of these studies have suggested that especially fermented rather than non-fermented dairy might provide benefits on cardiovascular health, but the data is inconclusive. Also, the average dairy intake has been modest in many study populations, which reduces the generalizability of the findings to populations with high dairy intake. Hypothesis: We assessed the hypothesis that fermented and non-fermented dairy products have distinct associations with the risk of coronary heart disease (CHD) in men from eastern Finland, a population with high intake of dairy products. Methods: A total of 1981 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study from eastern Finland, aged 42-60 years, with no CHD at baseline, were included. The consumption of foods was assessed with instructed 4-day food recording by household measures. Dairy products with fat content &lt;3.5% were considered low-fat. Multivariable Cox regression analyses included age, examination year, smoking, leisure-time physical activity, education, family history of CHD, and intakes of alcohol, energy, fiber, polyunsaturated fatty acids, and fruits, berries and vegetables. Fatal and non-fatal CHD events were ascertained from national registries, with no loss to follow-up. Results: The mean±SD intakes were 733±375 g/d for total, 187±218 g/d for fermented and 546±345 g/d for non-fermented dairy. Low-fat products comprised 87% (162±218 g/d) of the fermented and 43% (317±291 g/d) of the non-fermented dairy intake. During the mean follow-up of 20.1 years, 472 CHD events occurred. The multivariable-adjusted hazard ratio (95% CI) in the highest (&gt;280 g) vs. the lowest (&lt;26 g) quartile of total fermented dairy was 0.73 (0.56-0.95, P-trend=0.02) and in the highest (&gt;727 g) vs. the lowest (&lt;258 g) quartile of total non-fermented dairy 1.44 (1.06-1.94, P-trend=0.009). When low-fat and high-fat dairy were evaluated separately, only low-fat products were associated with the risk. The extreme-quartile hazard ratios (95% CIs) were 0.74 (0.57-0.96, P-trend=0.02) for low-fat fermented dairy and 1.47 (1.08-1.99, P-trend=0.02) for low-fat non-fermented dairy. Intakes of total dairy (extreme-quartile HR 1.03, 95% CI 0.74-1.42, P-trend=0.727), high-fat fermented dairy (HR 0.92, 95% CI 0.69-1.22, P-trend=0.32) or high-fat non-fermented dairy (HR 1.09, 95% CI 0.77-1.56, P-trend=0.44) were not associated with the risk of CHD. Conclusions: Our results suggest that low-fat fermented dairy products are associated with a lower risk of CHD, whereas low-fat non-fermented dairy products are associated with a higher risk in a population with high intake of dairy products.

Risk factors measured in middle-aged men predicting coronary events in geriatric age

ObjectivesTo explore the duration of the predictive power of major coronary risk factors measured on a single occasion in middle aged men for the occurrence of coronary heart disease (CHD) incidence and mortality during 50years of follow-up. Material and methodsIn the Italian Rural Areas of the Seven Countries Study 1677 CHD-free men aged 40–59 were enrolled in 1960 and age, cigarette smoking, systolic blood pressure and serum cholesterol were measured. During 50years of follow-up 1641 men died, 451 had a major fatal or non-fatal CHD event (incidence) and 263 died from CHD. Five partitioned Cox proportional hazards models were computed, one for each independent and subsequent 10-year period. Five 10-year partitioned hazard scores, derived from multivariable coefficients, were cumulated for each risk factor and plotted against time. ResultsThe resulting curves showed increasing time trends for CHD incidence and mortality as a function of cigarette smoking, systolic blood pressure and serum cholesterol for the first 30–40years followed by a decline in the association that was more evident for serum cholesterol. The curves fit straight lines with large correlation coefficient ranging 0.82 to 0.99. The loss of predictive power after 30–40years was confirmed in a model covering 50years of follow-up and including the interaction term of risk factors/time. ConclusionA single measurement of major coronary risk factors is associated with CHD incidence and mortality for at least 30–40years of follow-up, entering the gerontologic age.

High-Density Lipoprotein Subclasses and Noncardiovascular, Noncancer Chronic Inflammatory-Related Events Versus Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis.

BackgroundHigh-density lipoprotein (HDL) particles have properties beyond reverse cholesterol transport. We hypothesized that their protection extends to inflammation-related disease. The predictive value of HDL particle subclasses and inflammatory markers was studied for noncardiovascular, noncancer chronic inflammation–related death and hospitalization, and for incident cardiovascular disease (CVD).Methods and ResultsA multiethnic, multicenter, prospective observational study was conducted in 6475 men and women (aged 45 to 84 years) free of known CVD at baseline with median follow-up of 10.1 years. Fasting venous samples were analyzed for baseline lipid profile and lipoprotein particles. We focused on the HDL family of variables (small-, medium-, and large-diameter HDL particles and HDL cholesterol). Analyses identified the sum of small- plus medium-diameter HDL particles as important. Small- plus medium-diameter HDL particles were inversely associated with diagnostic code–based noncardiovascular, noncancer chronic inflammation–related death and hospitalization (n=1054) independent of covariates: relative risk per SD 0.85 (95% CI: 0.79 to 0.91, P<0.0001). Small- plus medium-diameter HDL particles were also associated with adjudicated fatal and nonfatal coronary heart disease events (n=423): relative risk per SD 0.88 (95% CI 0.77 to 0.98, P=0.02).ConclusionsSmall- plus medium-diameter HDL particles are an independent predictor for noncardiovascular, noncancer chronic inflammation–related death and hospitalization and for coronary heart disease events in subjects initially free of overt CVD. These findings support the hypothesis that smaller HDL particles of diameter <9.4 nm have anti-inflammatory properties in the general population.

Thyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts.

Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). To assess the association between differences in thyroid function within the reference range and CHD risk. Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55,412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. Thyroid function as expressed by serum thyrotropin levels at baseline. Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. Among 55,412 individuals, 1813 people (3.3%) died of CHD during 643,183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48,875 individuals (9.5%) experienced a first-time CHD event during 533,408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.

Dietary fatty acids and risk of coronary heart disease in men: the Kuopio Ischemic Heart Disease Risk Factor Study.

The epidemiological evidence of the role of dietary saturated fatty acids (SFA) in the development of coronary heart disease (CHD) is inconsistent. We investigated the associations of dietary fatty acids with the risk of CHD and carotid atherosclerosis in men with high SFA intake and high rates of CHD. In total, 1981 men from the population-based Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), aged 42 to 60 years and free of CHD at baseline in 1984 to 1989, were investigated. Food consumption was assessed with 4-day food recording. Multivariate nutrient-density models were used to analyze isocaloric replacement of nutrients. CHD events were ascertained from national registries. Carotid atherosclerosis was assessed by ultrasonography of the common carotid artery intima-media thickness in 1015 men. During the average follow-up of 21.4 years, 183 fatal and 382 nonfatal CHD events occurred. SFA or trans fat intakes were not associated with CHD risk. In contrast, monounsaturated fat intake was associated with increased risk and polyunsaturated fat intake with decreased risk of fatal CHD, whether replacing SFA, trans fat, or carbohydrates. The associations with carotid atherosclerosis were broadly similar, whereas the associations with nonfatal CHD were weaker. Our results suggest that SFA intake is not an independent risk factor for CHD, even in a population with higher ranges of SFA intake. In contrast, polyunsaturated fat intake was associated with lower risk of fatal CHD, whether replacing SFA, trans fat, or carbohydrates. Further investigation on the effect of monounsaturated fat on the CHD risk is warranted.

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

A longitudinal general population-based study of job strain and risk for coronary heart disease and stroke in Swedish men

ObjectivesThe aim was to investigate whether psychosocial stress based on the job-demand-control (JDC) model increased the risk for coronary heart disease (CHD) and stroke.SettingSwedish men.ParticipantsThe Primary Prevention Study (PPS) comprises...

Homocysteine Levels and Treatment Effect in the Prospective Study of Pravastatin in the Elderly at Risk

ObjectivesTo assess the effect of preventive pravastatin treatment on coronary heart disease (CHD) morbidity and mortality in older persons at risk for cardiovascular disease (CVD), stratified according to plasma levels of homocysteine.DesignA post hoc subanalysis in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), started in 1997, which is a double-blind, randomized, placebo-controlled trial with a mean follow-up of 3.2 years.SettingPrimary care setting in two of the three PROSPER study sites (Netherlands and Scotland).ParticipantsIndividuals (n = 3,522, aged 70–82, 1,765 male) with a history of or risk factors for CVD were ranked in three groups depending on baseline homocysteine level, sex, and study site.InterventionPravastatin (40 mg) versus placebo.MeasurementsFatal and nonfatal CHD and mortality.ResultsIn the placebo group, participants with a high homocysteine level (n = 588) had a 1.8 higher risk (95% confidence interval (CI) = 1.2–2.5, P = .001) of fatal and nonfatal CHD than those with a low homocysteine level (n = 597). The absolute risk reduction in fatal and nonfatal CHD with pravastatin treatment was 1.6% (95% CI = −1.6 to 4.7%) in the low homocysteine group and 6.7% (95% CI = 2.7–10.7%) in the high homocysteine group (difference 5.2%, 95% CI = 0.11–10.3, P = .046). Therefore, the number needed to treat (NNT) with pravastatin for 3.2 years for benefit related to fatal and nonfatal CHD events was 14.8 (95% CI = 9.3–36.6) for high homocysteine and 64.5 (95% CI = 21.4–∞) for low homocysteine.ConclusionIn older persons at risk of CVD, those with high homocysteine are at highest risk for fatal and nonfatal CHD. With pravastatin treatment, this group has the highest absolute risk reduction and the lowest NNT to prevent fatal and nonfatal CHD.