Decreased Risk Of Coronary Heart Disease Research Articles

Abstract 4119941: Identification of individuals who benefit from omega-3 fatty acid supplementation to prevent coronary heart disease: A machine-learning analysis of the VITAL

Backgrounds: Randomized controlled trials (RCTs) have demonstrated benefits of marine omega-3 polyunsaturated fatty acids (omega-3 FA) supplementation for the prevention of coronary heart disease (CHD). However, it has not been clear which individuals would benefit the most from the supplementation. We sought to predict the individual treatment effect of omega-3 FA supplementation on CHD prevention and to develop an omega-3 effect score to stratify individuals according to their expected benefit from the supplementation. Methods: Among the 25,871 randomized participants without history of CVD in the VITamin D and OmegA-3 TriaL (VITAL), we applied machine-learning (ML) approaches to predict individual treatment effect of omega-3 FA supplementation on 5-year CHD risk (a composite of myocardial infarction, coronary revascularization, and CHD death) using 11 covariates pre-specified in the VITAL trial protocol. A 10-fold cross-validation was used and held-out test dataset was used for the evaluation. An omega-3 effect score was developed such that each covariate contributed linearly, and utility of the score was further evaluated by transportability analysis using the National Health and Nutrition Examination Survey (NHANES) data as the target population. Results: Omega-3 FA intervention led to absolute 0.48% [SE: 0.20] reduction in CHD in the total population. ML algorithms effectively stratified participants by their expected benefit according to individual factors; decreased CHD risk was observed in those with quintile 1 and 2 of the expected benefit (absolute CHD risk reduction %: 1.30 % [0.55] and 1.32 % [0.51] in quintile 1 and 2, respectively). Race, diabetes, and fish intake most contributed to the omega-3 effect score. CHD incidence rates per 1000 person-year were 5.5 [0.44] if treated and 8.5 [0.55] if not treated (35.3% reduction) in individuals with the score ≥11 (upper 40th percentile), and 3.9% [0.31] if treated and 3.4% [0.55] if not treated (14.7% increase) in those with the score <11, respectively. The transportability of the utility of the score to baseline NHANES data was confirmed. Conclusion: In VITAL, ML approaches identified individuals who experienced greater CHD reduction from the omega-3 FA intervention, and an omega-3 effect score stratified the expected benefit. Although it warrants testing in a new RCT, the omega-3 effect score holds promise for guiding the indication of omega-3 FA supplementation in US primary prevention population.

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

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

Association between microRNA-146a rs2910164 polymorphism and coronary heart disease: An updated meta-analysis.

Coronary heart disease (CHD) is one of the manifestations of atherosclerosis with a high morbidity rate. MicroRNA (miRNA)-146a rs2910164, a single nucleotide polymorphism, is associated with the progression of CHD risk. However, the results are controversial and uncertain. Therefore, an updated meta-analysis was conducted to evaluate the association between rs2910164 and CHD susceptibility. PubMed, Cochrane Library, EMBASE, Web of Science, China's National Knowledge Infrastructure, VIP, and Wan fang were searched for the eligible articles until April 30, 2022. The odds ratios (ORs) with 95% confidence interval (CIs) were calculated to assess the correlation. Bonferroni correction was utilized between multiple comparisons. Trial sequential analysis was performed to measure the required information size and assess the reliability of the meta-analysis results. A total of 18 eligible studies, including 6859 cases and 8469 controls, were analyzed in our meta-analysis. After Bonferroni correction, we found that the G allele at rs2910164 was associated with significantly decreased CHD risk in the allelic model (OR = 0.86), homozygous model (OR = 0.79), and heterozygous model (OR = 0.89) in total population. In the subgroup analysis, the subjects containing the G allele and GG genotype were associated with a lower risk of CHD in the Chinese population, not the GG + CG and CG genotype. In addition, under the allelic, homozygous, heterozygous, and dominant models, miR-146a rs2910164 was at lower CHD risk in the large size population except in the recessive model. These results show that miR-146a rs2910164 might be associated with lower CHD susceptibility.

Effect of Selective Androgen Receptor Modulator on Cholesterol Efflux Capacity, Size, and Subspecies of HDL Particles.

ContextSelective androgen receptor modulators (SARMs), because of their preferential muscle vs prostate selectivity, are being developed for muscle-wasting conditions. Oral SARMs suppress high-density lipoprotein cholesterol (HDL-C) but their effects on functional capacity and atherogenic potential of HDL particles are unknown.ObjectiveTo determine the effects of an oral SARM (OPK-88004) on cholesterol efflux capacity, HDL particle number and size, apolipoprotein particle number and size and HDL subspeciesMethodsWe measured cholesterol efflux capacity (CEC); HDL particle number and size; APOB; APOA1; and protein-defined HDL subspecies associated with coronary heart disease (CHD) risk in men, who had undergone prostatectomy for low-grade prostate cancer during 12-week treatment with placebo or 1, 5, or 15 mg of an oral SARM (OPK-88004).ResultsSARM significantly suppressed HDL-C (P < .001) but HDL particle size did not change significantly. SARM had minimal effect on CEC of HDL particles (change + 0.016, –0.036, +0.070, and –0.048%/µmol-HDL/L–1 at 0, 1, 5, and 15 mg SARM, P = .045). SARM treatment suppressed APOAI (P < .001) but not APOB (P = .077), and reduced APOA1 in HDL subspecies associated with increased (subspecies containing α2-macroglobulin, complement C3, or plasminogen) as well as decreased (subspecies containing APOC1 or APOE) CHD risk; relative proportions of APOA1 in these HDL subspecies did not change. SARM increased hepatic triacylglycerol lipase (HTGL) (P < .001).ConclusionSARM treatment suppressed HDL-C but had minimal effect on its size or cholesterol efflux function. SARM reduced APOA1 in HDL subspecies associated with increased as well as decreased CHD risk. SARM-induced increase in HTGL could contribute to HDL-C suppression. These data do not support the simplistic notion that SARM-associated suppression of HDL-C is necessarily proatherogenic; randomized trials are needed to determine SARM’s effects on cardiovascular events.

Cow's Milk Intake and Risk of Coronary Heart Disease in Korean Postmenopausal Women.

Numerous studies have reported conflicting results associated with cow’s milk intake and coronary heart disease (CHD). However, studies involving postmenopausal women are very limited. This study was therefore undertaken to identify the relationship between cow’s milk intake and CHD risk in postmenopausal women, using data from the 6th period of the Korea National Health and Nutrition Examination Survey (2013–2015). A total of 1825 postmenopausal women, aged 50–64 years old, were included in the final analysis. The frequency of cow’s milk consumption for each subject was determined using the semi-quantitative food frequency questionnaire, and was classified into four groups (Q1–Q4): Q1, group that did not drink milk (no milk, n = 666); Q2, 0 < frequency of milk intake per week ≤ 1 (n = 453); Q3, 1 < frequency of milk intake per week ≤ 3 (n = 319); and Q4, frequency of milk intake >3 times per week (n = 387). General characteristics, such as education, living area, household income, and obesity level, were compared between the four groups. Percentages of daily nutrient intake compared to the dietary reference intake for Koreans (KDRIs) were determined, and the Framingham Risk Score (FRS), atherogenic index (AI), and atherogenic index of plasma (AIP) were determined as the CHD risk indicators. Except household income, no significant difference was obtained among the four groups with respect to age, education, living area, or obesity. Compared to KDRIs, the intake ratio of calcium, phosphorus, and riboflavin were significantly higher in the Q4 group than in the Q1–Q3 groups. Blood HDL-cholesterol was significantly higher in Q4 than in Q1. The CHD risk factors FRS (%), AI, and AIP were significantly lower in the Q4 group as compared to the other groups (CHD risk (%): Q1 9.4, Q4 8.5; AI: Q1 3.06, Q4 2.83; API: Q1 0.37, Q2 0.31, Q4 0.32). FRS was determined to be significantly and positively correlated to AI or AIP, and negatively correlated with the cow’s milk intake frequency and calcium intake. In conclusion, compared to women who do not consume cow’s milk, postmenopausal women who consume cow’s milk frequently have a better nutritional status of calcium, phosphorus, and vitamin B12, higher HDL levels, and a lower level of CHD risk indicators, such as FRS, AI, and AIP, contributing to decreased CHD risk in a 10-year period. Therefore, to prevent the risk of CHD in postmenopausal women, there needs to be a greater emphasis for cow’s milk consumption four or more times per week.

The effects of exercise training on lipid metabolism and coronary heart disease.

Blood lipoproteins are formed by various amounts of cholesterol (C), triglycerides (TGs), phospholipids, and apolipoproteins (Apos). ApoA1 is the major structural protein of high-density lipoprotein (HDL), accounting for ~70% of HDL protein, and mediates many of the antiatherogenic functions of HDL. Conversely, ApoB is the predominant low-density lipoprotein (LDL) Apo and is an indicator of circulating LDL, associated with higher coronary heart disease (CHD) risk. Thus, the ratio of ApoB to ApoA1 (ApoB/ApoA1) is used as a surrogate marker of the risk of CHD related to lipoproteins. Elevated or abnormal levels of lipids and/or lipoproteins in the blood are a significant CHD risk factor, and several studies support the idea that aerobic exercise decreases CHD risk by partially lowering serum TG and LDL-cholesterol (LDL-C) levels and increasing HDL-C levels. Exercise also exerts an effect on HDL-C maturation and composition and on reverse C transport from peripheral cells to the liver to favor its catabolism and excretion. This process prevents atherosclerosis, and several studies showed that exercise training increases heart lipid metabolism and protects against cardiovascular disease. In these and other ways, it more and more appears that regular exercise, nutrition, and strategies to modulate lipid profile should be viewed as an integrated whole. The purpose of this review is to assess the effects of endurance training on the nontraditional lipid biomarkers, including ApoB, ApoA1, and ApoB/ApoA1, in CHD risk.

Genetic polymorphisms of the SHBG gene can be the effect on SHBG and HDL-cholesterol levels in Coronary Heart Disease: a case-control study.

Sex hormone binding globulin (SHBG) level is positively associated with the high-density lipoprotein cholesterol (HDL-C) levels. The aim of this study was to investigate the effects of the SHBG gene variations (D356N, rs1799941, and P156L) on SHBG and HDL-C levels and Coronary Heart Disease (CHD) risk. The SHBG D356N (rs6259,G > A), P156L (rs6258,C > T), and rs1799941(G > A) polymorphisms were determined in 131 male CHD patients and 55 male controls by PCR-RFLP and real-time PCR techniques. SHGB levels were measured by Electro-chemiluminescence immunoassay (ECLIA). In the patients who had SHBG levels lower than threshold 35nmol/l value, the risk of being HDL-C levels lower than threshold 0.90mmol/l value was observed statistically significant (p = 0.017; OR 2.522, 95% CI 1.170-5.438). The rs1799941 GG was associated with increased CHD risk when compared with the A allele carriers (GA + AA) (p = 0.019, OR 2.222, 95% CI 1.130-4.371). In addition, the rs1799941 GG genotype and D356NN allele were associated with lower SHBG in the CHD group (p < 0.01). The logistic regression analysis also revealed the rs1799941 GG genotype was significantly associated with low SHBG in CHD patients. It was observed that Haplotype-1(rs1799941 G allele-P156L P allele-D356N D allele) was associated with increased CHD risk, while Haplotype-2 (rs1799941 rare A allele-P156L C allele- D356N G allele) was correlated with the decreased CHD risk (p = 0.0167). Our findings suggest that there is a positive correlation between SHBG and HDL-C levels in CHD patients, and this association might be affected by SHBG gene variations.

Psychological Traits, Heart Rate Variability, and Risk of Coronary Heart Disease in Healthy Aging Women-The Women's Health Initiative.

Psychological traits such as optimism and hostility affect coronary heart disease (CHD) risk, but mechanisms for this association are unclear. We hypothesized that optimism and hostility may affect CHD risk via changes in heart rate variability (HRV). We conducted a longitudinal analysis using data from the Women's Health Initiative Myocardial Ischemia and Migraine Study. Participants underwent 24-hour ambulatory electrocardiogram monitoring 3 years after enrollment. Optimism (Life Orientation Test-Revised), cynical hostility (Cook-Medley), demographics, and coronary risk factors were assessed at baseline. HRV measures included standard deviation of average N-N intervals (SDNN); standard deviation of average N-N intervals for 5 minutes (SDANN); and average heart rate (HR). CHD was defined as the first occurrence of myocardial infarction, angina, coronary angioplasty, and bypass grafting. Linear and Cox regression models adjusted for CHD risk factors were used to examine, respectively, associations between optimism, hostility, and HRV and between HRV and CHD risk. Final analyses included 2655 women. Although optimism was not associated with HRV, hostility was inversely associated with HRV 3 years later (SDANN: adjusted β = -0.54; 95% CI = -0.97 to -0.11; SDNN: -0.49; 95% CI = -0.93 to -0.05). HRV was inversely associated with CHD risk; for each 10-millisecond increase in SDNN or SDANN, there was a decrease in CHD risk of 9% (p = .023) and 12% (p = .006), respectively. HRV did not play a major role in explaining why more optimistic women seem to be somewhat protected from CHD risk. Although hostility was inversely associated with HRV, its role in explaining the association between hostility and CHD risk remains to be established.

Association between miR-499 rs3746444 polymorphism and coronary heart disease susceptibility: An evidence-based meta-analysis of 5063 cases and 4603 controls

MicroRNA-499 (miR-499) rs3746444 polymorphism has been associated with the risk of coronary heart disease (CHD). However, results from several studies are inconsistent. This meta-analysis aimed to further investigate the possible association between miR-499 rs3746444 polymorphism and CHD risk. A total of 9 case-control studies included 5063 CHD cases and 4603 healthy subjects. The A allele at rs374644 was associated with significantly decreased CHD risk in the total population according to the allelic model (OR = 0.80, 95% CI = 0.68–0.93, P = 0.005), homozygous model (OR = 0.52, 95% CI = 0.39–0.71, P < 0.001) and heterozygous model (OR = 0.57, 95% CI = 0.43–0.77, P < 0.001). A similar trend was found specifically in Asian and Chinese populations. In contrast, the wild-type GG genotype at rs374644 was associated with significantly increased CHD risk in the total population, according to the dominant model (OR = 1.83, 95% CI = 1.39–2.42, P < 0.001), and a similar trend was found in Asian and Chinese populations. These results indicate that in the total population, as well as in Asian and Chinese populations, the wild-type GG genotype at rs374644 may be related to increased susceptibility to CHD, while the A allele may be protective against CHD.

How do the experiences and beliefs of adults and children with heterozygous familial hypercholesterolaemia influence their adherence to treatment? A systematic review of qualitative evidence protocol

BackgroundHeterozygous familial hypercholesterolaemia (FH) is a genetic disorder characterised by elevated levels of low density lipoprotein (LDL) cholesterol from birth, estimated to affect 1 in 250 of the UK population. Left untreated, FH substantially increases an individual’s risk of premature coronary heart disease (CHD) and associated mortality. This risk can be minimised with timely diagnosis and successful treatment with medication and lifestyle changes, as advocated in national and international guidelines. Despite these recommendations, the limited research available suggests adherence to treatment may be sub-optimal. This review will identify and synthesise the available qualitative research regarding the experiences and beliefs of adults and children with FH in relation to their condition and its treatment, and the influence of these upon treatment adherence.MethodsThe following electronic databases will be searched from their inception: Cochrane library, MEDLINE, Embase, PsycINFO (via OVID) and CINAHL. Studies available in English and reporting primary qualitative data will be included. Database searching will be supplemented with searches in relevant specialist websites. The references of identified papers will also be hand searched. Two reviewers will independently screen titles and abstracts of identified studies, with full texts of potentially relevant papers retrieved for review against pre-defined inclusion and exclusion criteria. The Critical Appraisal Skills Programme (CASP) Qualitative Research checklist will be used to assess quality of the included studies, and the results will be taken into consideration when reporting the findings. A data extraction tool will be created for use in this review to extract study findings relevant to the review questions. A thematic synthesis approach will be taken to analyse the results.DiscussionAdherence to treatment recommendations is crucial for the successful management of FH and subsequent decrease in risk of CHD later in life. Common identified themes could provide an understanding of the beliefs and experiences which influence adherence to treatment recommendations and provide an insight into perceived barriers and facilitators. The findings are intended to be used in the development of future interventions or guidelines regarding treatment of children and adults with FH.Systematic review registrationPROSPERO registration number: CRD42018085946

Association between PPAP2B gene polymorphisms and coronary heart disease susceptibility in Chinese Han males and females.

Little is known about gender-related differences in the association between PPAP2B single nucleotide polymorphisms (SNPs) and coronary heart disease (CHD) in Chinese Han males and females. We therefore conducted a case-control study with 456 cases and 685 healthy controls divided into male and female subgroups. Five PPAP2B polymorphisms (SNPs) were selected and genotyped using Sequenom Mass-ARRAY technology. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression adjusting for age and gender. Allelic model analysis revealed that for PPAP2B rs1759752, allele frequency distributions differed between cases and controls in the male subgroup (p = 0.015, OR: 1.401, 95%CI: 1.066–1.481). Genetic model analysis revealed that in the male subgroup, rs1759752 was associated with increased CHD risk in the dominant model (p = 0.035) and overdominant model (p = 0.045). In the female subgroup, rs12566304 was associated with a decreased CHD risk in the codominant model (p = 0.038) and overdominant model (p = 0.031). Additionally, the “GC” haplotypes of rs1759752 and rs1930760 were protective against CHD in males. These observations shed new light on gender-related differences in the association between PPAP2B gene polymorphisms and CHD susceptibility in the Chinese Han population.

Association between Toll-like receptor 4 Asp299Gly polymorphism and coronary heart disease susceptibility.

Published data on the association between Toll-like receptor 4 (TLR4) Asp299Gly polymorphism and coronary heart disease (CHD) susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. English-language studies were identified by searching PubMed and Embase databases (up to November 2016). All epidemiological studies were regarding Caucasians because no TLR4 Asp/Gly and Gly/Gly genotypes have been detected in Asians. A total of 20 case-control studies involving 14,416 cases and 10,764 controls were included in the meta-analysis. Overall, no significant associations were found between TLR4 Asp299Gly polymorphism and CHD susceptibility in the dominant model (OR=0.89; 95%CI=0.74 to 1.06; P=0.20) pooled in the meta-analysis. In the subgroup analysis by CHD, non-significant associations were found in cases compared to controls. When stratified by control source, no significantly decreased risk was found in the additive model or dominant model. The present meta-analysis suggests that the TLR4 Asp299Gly polymorphism was not associated with decreased CHD risk in Caucasians.

Association Between Rotating Night Shift Work and Risk of Coronary Heart Disease Among Women.

Prospective studies linking shift work to coronary heart disease (CHD) have been inconsistent and limited by short follow-up. To determine whether rotating night shift work is associated with CHD risk. Prospective cohort study of 189,158 initially healthy women followed up over 24 years in the Nurses' Health Studies (NHS [1988-2012]: N = 73,623 and NHS2 [1989-2013]: N = 115,535). Lifetime history of rotating night shift work (≥3 night shifts per month in addition to day and evening shifts) at baseline (updated every 2 to 4 years in the NHS2). Incident CHD; ie, nonfatal myocardial infarction, CHD death, angiogram-confirmed angina pectoris, coronary artery bypass graft surgery, stents, and angioplasty. During follow-up, 7303 incident CHD cases occurred in the NHS (mean age at baseline, 54.5 years) and 3519 in the NHS2 (mean age, 34.8 years). In multivariable-adjusted Cox proportional hazards models, increasing years of baseline rotating night shift work was associated with significantly higher CHD risk in both cohorts. In the NHS, the association between duration of shift work and CHD was stronger in the first half of follow-up than in the second half (P=.02 for interaction), suggesting waning risk after cessation of shift work. Longer time since quitting shift work was associated with decreased CHD risk among ever shift workers in the NHS2 (P<.001 for trend). [table: see text] Among women who worked as registered nurses, longer duration of rotating night shift work was associated with a statistically significant but small absolute increase in CHD risk. Further research is needed to explore whether the association is related to specific work hours and individual characteristics.

Abstract MP39: Plasma Phospholipid Fatty Acid and Coronary Heart Disease Risk

Introduction: The 2013 AHA/ACC Guideline recommended limiting saturated fatty acids (SFA) and substituting SFA with monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids (PUFA) in diet. Dietary intake data derived from self-reports is prone to measurement error and studies have been criticized for this reason. An objective alternative approach to examining the role of different dietary fatty acids on coronary heart disease (CHD) risk is to measure plasma phospholipid fatty acid (PL-FA) profiles, which reflect both dietary intake and endogenous metabolism, hence are proximal to the pathophysiologic processes of CHD. Our aim was to evaluate the role of plasma PL-FA profiles on CHD risk both directly and by estimating the theoretical effects of plasma “substitution” of various fatty acids for each other on CHD risk, and evaluate the consistence with the AHA/ACC Guideline. Hypothesis: Plasma SFA is associated with increased CHD risk, and “substituting” plasma SFA with MUFA, PUFA n-6 or n-3 is associated with lower CHD risk. Methods: We performed a nested case-control study with 2428 postmenopausal women in Women’s Health Initiative Observational Study (1214 CHD cases-controls pairs matched for baseline age, enrollment date, ethnicity and hysterectomy). Plasma PL-FA profiles were measured using gas chromatography methodology and expressed as molar percentage (mol%). Multivariate conditional logistic regression was used to calculate ORs for CHD risk associated with 1 mol% PL-FA increase, and “substitutions” of various fatty acids for each other, adjusting for matching factors, physical activity, body mass index (BMI), smoking, family history of diabetes, anticoagulant medication, hormone therapy, hypertension, diabetes mellitus, dyslipidemia and alternative healthy eating index. In addition, we tested the interactions of BMI and hormone therapy with PL-FAs. Results: In multivariate conditional logistic regression analysis, plasma PL SFA was associated with increased CHD risk (OR=1.16, 95% CI 1.09 to 1.24) and PUFA n-3 was associated with decreased CHD risk (OR=0.92, 95% CI 0.86 to 0.97). No significant associations were observed for MUFA, PUFA n-6 and trans -fatty acids. “Substituting” 1 mol% SFA with an equivalent proportion of MUFA, PUFA n-6, or n-3 were associated with lower CHD risk (OR=0.81, 95% CI 0.74 to 0.88; OR=0.77, 95% CI 0.70 to 0.84;and OR=0.85, 95%CI 0.80 to 0.92, respectively). “Substituting” PUFA n-6 with n-3 was associated with lower CHD risk (OR=0.92, 95% CI 0.86 to 0.98) while no significant effect was found for “substituting” PUFA n-6 with MUFA. No significant interactions were obtained of BMI and hormone therapy with PL-FAs. Conclusion: This plasma PL-FA “substitution” analysis is consistent with the AHA/ACC Guideline and suggests that “substituting” PL SFA with MUFA, PUFA n-6 or n-3, and “substituting” PUFA n-6 with n-3 is associated with lower CHD risk.

Radiation Dose-Response Relationship for Risk of Coronary Heart Disease in Survivors of Hodgkin Lymphoma.

Cardiovascular diseases are increasingly recognized as late effects of Hodgkin lymphoma (HL) treatment. The purpose of this study was to identify the risk factors for coronary heart disease (CHD) and to quantify the effects of radiation dose to the heart, chemotherapy, and other cardiovascular risk factors. We conducted a nested case-control study in a cohort of 2,617 5-year HL survivors, treated between 1965 and 1995. Cases were patients diagnosed with CHD as their first cardiovascular event after HL. Detailed treatment information was collected from medical records of 325 cases and 1,204 matched controls. Radiation charts and simulation radiographs were used to estimate in-field heart volume and mean heart dose (MHD). A risk factor questionnaire was sent to patients still alive. The median interval between HL and CHD was 19.0 years. Risk of CHD increased linearly with increasing MHD (excess relative risk [ERR]) per Gray, 7.4%; 95% CI, 3.3% to 14.8%). This results in a 2.5-fold increased risk of CHD for patients receiving a MHD of 20 Gy from mediastinal radiotherapy, compared with patients not treated with mediastinal radiotherapy. ERRs seemed to decrease with each tertile of age at treatment (ERR/Gy(<27.5years), 20.0%; ERR/Gy(27.5-36.4years), 8.8%; ERR/Gy(36.5-50.9years), 4.2%; P(interaction) = .149). Having ≥ 1 classic CHD risk factor (diabetes mellitus, hypertension, or hypercholesterolemia) independently increased CHD risk (rate ratio, 1.5; 95% CI, 1.1 to 2.1). A high level of physical activity was associated with decreased CHD risk (rate ratio, 0.5; 95% CI, 0.3 to 0.8). The linear radiation dose-response relationship identified can be used to predict CHD risk for future HL patients and survivors. Appropriate early management of CHD risk factors and stimulation of physical activity may reduce CHD risk in HL survivors.

The mechanisms by which antidepressants may reduce coronary heart disease risk.

BackgroundDepression is known to increase the risk for coronary heart disease (CHD) likely through various pathogenetic actions. Understanding the links between depression and CHD and the effects of mediating these links may prove beneficial in CHD prevention.MethodsAn integrated model of CHD was used to elucidate pathogenetic pathways of importance between depression and CHD. Using biomarker relative risk data the pathogenetic effects are representable as measurable effects based on changes in biomarkers.ResultsA ‘connection graph’ presents interactions by illustrating the relationship between depression and the biomarkers of CHD. The use of selective serotonin reuptake inhibitors (SSRIs) is postulated to have potential to decrease CHD risk. Comparing the ‘connection graph’ of SSRI’s to that of depression elucidates the possible actions through which risk reduction may occur.ConclusionsThe CHD effects of depression appear to be driven by increased inflammation and altered metabolism. These effects might be mediated with the use of SSRI’s.

Associations of the uric acid related genetic variants in SLC2A9 and ABCG2 loci with coronary heart disease risk.

BackgroundMultiple studies investigated the associations between serum uric acid and coronary heart disease (CHD) risk. However, further investigations still remain to be carried out to determine whether there exists a causal relationship between them. We aim to explore the associations between genetic variants in uric acid related loci of SLC2A9 and ABCG2 and CHD risk in a Chinese population.ResultsA case–control study including 1,146 CHD cases and 1,146 controls was conducted. Association analysis between two uric acid related variants (SNP rs11722228 in SLC2A9 and rs4148152 in ABCG2) and CHD risk was performed by logistic regression model. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Compared with subjects with A allele of rs4148152, those with G allele had a decreased CHD risk and the association remained significant in a multivariate model. However, it altered to null when BMI was added into the model. No significant association was observed between rs11722228 and CHD risk. The distribution of CHD risk factors was not significantly different among different genotypes of both SNPs. Among subjects who did not consume alcohol, the G allele of rs4148152 showed a moderate protective effect. However, no significant interactions were observed between SNP by CHD risk factors on CHD risk.ConclusionsThere might be no association between the two uric acid related SNPs with CHD risk. Further studies were warranted to validate these results.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0162-7) contains supplementary material, which is available to authorized users.

Positive association between PPARD rs2016520 polymorphism and coronary heart disease in a Han Chinese population.

PPARD encodes peroxisome proliferator-activated re-ceptor delta, which has been shown to play an important role in control-ling lipid metabolism and atherosclerosis. In this case-control study, we explored the relationship between PPARD rs2016520 polymorphism and coronary heart disease (CHD) in a Han Chinese population. A to-tal of 657 CHD cases and 640 controls were included in the associa-tion study. rs2016520 polymorphism genotyping was performed using the melting temperature-shift polymerase chain reaction method. The PPARD rs2016520-G allele reduced CHD risk by 17.9% (χ(2) = 5.061, P = 0.025, OR = 0.821, 95%CI = 0.692-0.975). Furthermore, a signifi-cant difference in CHD risk was observed for the PPARD rs2016520 polymorphism in the dominant model (AG + GG vs AA: χ(2) = 4.751, degrees of freedom (df) = 1, P = 0.029, OR = 0.784, 95%CI = 0.631- 0.976). Analysis by age suggested that the G-allele decreased CHD risk by 14.8% in ages greater than 65 years (χ(2) = 4.446, P = 0.035, OR = 0.852, 95%CI = 0.684-1.060). In contrast, meta-analysis of PPARD rs2016520 among 3732 cases and 5042 controls revealed no associa-tion between PPARD rs2016520 and CHD (P = 0.19). We found that the PPARD rs2016520-GG genotype decreased CHD risk in a Han Chinese population. Moreover, we found an association between serum high-density lipoprotein cholesterol level and PPARD rs2016520 in senior individuals aged ≥ 65 years. The meta-analysis revealed no association between PPARD rs2016520 and CHD, suggesting ethnic differences in the association between the PPARD locus and CHD.

Walnut-enriched diet reduces fasting non-HDL-cholesterol and apolipoprotein B in healthy Caucasian subjects: A randomized controlled cross-over clinical trial

BackgroundWalnut consumption is associated with reduced risk of coronary heart disease (CHD). ObjectiveWe assessed the effect of walnuts on lipid and glucose metabolism, adipokines, inflammation and endothelial function in healthy Caucasian men and postmenopausal women ≥50years old. DesignForty subjects (mean±SEM: age 60±1years, BMI 24.9±0.6kg/m2; 30 females) were included in a controlled, cross-over study and randomized to receive first a walnut-enriched (43g/d) and then a Western-type (control) diet or vice-versa, with each lasting 8weeks and separated by a 2-week wash-out. At the beginning and end of each diet phase, measurements of fasting values, a mixed meal test and an assessment of postprandial endothelial function (determination of microcirculation by peripheral artery tonometry) were conducted. Area under the curve (AUC), incremental AUC (iAUC) and treatment×time interaction (shape of the curve) were evaluated for postprandial triglycerides, VLDL-triglycerides, chylomicron-triglycerides, glucose and insulin. ResultsCompared with the control diet, the walnut diet significantly reduced non-HDL-cholesterol (walnut vs. control: −10±3 vs. −3±2mg/dL; p=0.025) and apolipoprotein-B (−5.0±1.3 vs. −0.2±1.1mg/dL; p=0.009) after adjusting for age, gender, BMI and diet sequence. Total cholesterol showed a trend toward reduction (p=0.073). Fasting VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glucose, insulin, HOMA-IR, and HbA1c did not change significantly. Similarly, fasting adipokines, C-reactive protein, biomarkers of endothelial dysfunction, postprandial lipid and glucose metabolism and endothelial function were unaffected. ConclusionDaily consumption of 43g of walnuts for 8weeks significantly reduced non-HDL-cholesterol and apolipoprotein-B, which may explain in part the epidemiological observation that regular walnut consumption decreases CHD risk.

Hormone replacement therapy and the association with coronary heart disease and overall mortality: Clinical application of the timing hypothesis

Conclusions from randomized controlled trial (RCT) data over the past 10 years has spanned from presumed harm to consistency with observational data that hormone replacement therapy (HRT) decreases the risk for coronary heart disease (CHD) as well as overall mortality in women who are recently postmenopausal. Multiple clinical studies including randomized trials and observational studies converge with animal experimentation to show a consistency that HRT decreases CHD risk and overall mortality in primary prevention when HRT is started at the time of or soon after menopause. The totality of data supports the “timing” hypothesis that posits that HRT effects are dependent on when HRT is started in relation to age and/or time-since-menopause. The totality of data shows that HRT decreases CHD and overall morality when started in women who are less than 60 years old and/or less than 10 years postmenopausal, providing a “window-of-opportunity”. Further evidence shows that women who start HRT when in their 50s and continued for 5–30 years that there is an increase of 1.5 quality-adjusted life-years (QALYs). Additionally, HRT is highly cost-effective at $2438 per QALY gained. The totality of data converges to show a consistency between randomized trials and observational studies that when started in women at or near menopause and continued long-term, HRT decreases CHD and overall mortality compared with women who do not use HRT.This article is part of a Special Issue entitled ‘Menopause’.