Elevated Risk Of Coronary Heart Disease Research Articles

PYCARD gene polymorphisms and susceptibility to periodontal and coronary heart diseases.

Numerous studies have established a link between gene variants within the inflammasome complex and the incidence of periodontitis and cardiovascular illness across various ethnic groups. This study investigated the association between PYCARD gene polymorphism and susceptibility to periodontal disease and coronary heart disease (CHD) and their correlation with clinical periodontal indices. A total of 120 participants were enrolled, categorized into four groups: 30 healthy controls (C), 30 patients with generalized periodontitis (P), 30 patients with atherosclerotic CHD but clinically healthy periodontium (AS-C), and 30 patients with both atherosclerotic CHD and generalized periodontitis (AS-P). We recorded demographic data, collected blood samples, and measured periodontal indices, including plaque index, clinical attachment loss, bleeding on probing, and pocket depth. The genomic variant of the PYCARD gene was analyzed using a conventional polymerase reaction. A significant prevalence of T and G allele mutations and a higher distribution of CT and TT genotypes in PYCARD C/T (rs8056505) and the AG genotype in PYCARD A/G (rs372507365) were observed in groups P, AS-P, and AS-C. These single nucleotide polymorphisms (SNPs) were also positively correlated with the severity of clinical periodontitis indices. Our findings suggest that the increased frequency of T and G alleles and the distribution of CT, TT, and AG genotypes in PYCARD SNPs are significantly associated with an elevated risk for periodontal disease and CHD. These SNPs may participate in the pathogenesis of these conditions. The study reinforces the potential role of these genetic markers as risk factors for both diseases in the Iraqi population.

Somatic and Germline Variants and Coronary Heart Disease in a Chinese Population

The genetic basis of coronary heart disease (CHD) has expanded from a germline to somatic genome, including clonal hematopoiesis of indeterminate potential (CHIP). How CHIP confers CHD risk in East Asian individuals, especially those with small clones (variant allele fraction [VAF] 0.5%-2%) and different genetic backgrounds, was completely unknown. To investigate the CHIP profile in a general Chinese cohort by deep sequencing and further explore the association between CHIP and incident CHD considering germline predisposition. This cohort study used data from 3 prospective cohorts in the project Prediction for Atherosclerotic Cardiovascular Disease Risk in China. Participants without cardiovascular disease or cancer at baseline were enrolled in 2001 and 2008 and had a median follow-up of 12.17 years extending into 2021. CHIP mutations were detected by targeted sequencing (mean depth, 916×). A predefined CHD polygenic risk score (PRS) comprising 531 variants was used to evaluate germline predisposition. The main outcome was first incident CHD. Among 6181 participants, the median (IQR) age was 53.83 years (45.35-62.39 years); 3082 participants (49.9%) were female, and 3099 (50.1%) were male. A total of 1100 individuals (17.80%) harbored 1372 CHIP mutations at baseline. CHIP was independently associated with incident CHD (hazard ratio [HR], 1.42; 95% CI, 1.18-1.72; P = 2.82 × 10-4) and presented a risk gradient with increasing VAF (P = 3.98 × 10-3 for trend). Notably, individuals with small clones, nearly half of CHIP carriers, also demonstrated a higher CHD risk compared with non-CHIP carriers (HR, 1.33; 95% CI, 1.02-1.74; P = .03) and were 4 years younger than those with VAF of 2% or greater (median age, 58.52 vs 62.70 years). Heightened CHD risk was not observed among CHIP carriers with low PRS (HR, 1.02; 95% CI, 0.64-1.64; P = .92), while high PRS and CHIP jointly contributed a 2.23-fold increase in risk (95% CI, 1.51-3.29; P = 6.29 × 10-5) compared with non-CHIP carriers with low PRS. Interestingly, the diversity in CHIP-related CHD risk within each PRS group was substantially diminished when removing variants in the inflammatory pathway from the PRS. This study revealed that elevated CHD risk attributed to CHIP was nonnegligible even for small clones. Inflammation genes involved in CHD could aggravate or abrogate CHIP-related CHD risk.

Predicted visceral adiposity index in relation to risk of coronary heart disease and all-cause mortality: insights from NHANES.

The Visceral Adiposity Index (VAI) is a straightforward and gender-specific marker that combines anthropometric measurements with lipid profiles. The objective of this study was to evaluate the relationship between VAI and coronary heart disease (CHD). The study examined data collected from adults during the NHANES 1999-2018 cycle. The analyses were weighted, and multivariable logistic regression models were employed to investigate the association between VAI and CHD. Additionally, subgroup analyses stratified by age were conducted. To evaluate the impact of VAI levels on survival outcomes, the study utilized the Kaplan-Meier method and performed the log-rank test to evaluate the survival outcome of participants with different VAI levels. The study findings revealed a significant association between VAI and CHD, indicating a non-linear relationship where an increase in VAI was associated with an elevated risk of CHD. High levels of VAI were linked to an increased prevalence of CHD (Q4 vs Q1, OR 1.50, 95% CI 1.12-2.01, P=0.01). Additionally, higher levels of VAI were associated with a poorer overall prognosis in terms of survival outcomes. There were no statistically significant differences in survival outcomes among the population with CHD. The results of this study highlighted a significant association between VAI and CHD, with a non-linear relationship observed. High VAI levels were associated with an increased risk of CHD and poor survival outcomes, emphasizing the importance of understanding and managing this risk factor, particularly in older age groups.

CYP4V2 rs56413992 C > T was associated with the risk of coronary heart disease in the Chinese Han population: a case–control study

PurposeThe research aimed to detect the association between single nucleotide polymorphisms (SNPs) in CYP4V2 gene and coronary heart disease (CHD) risk.MethodsThis case–control study included 487 CHD subjects and 487 healthy individuals. Logistic regression was performed to analyze the connection between five SNPs in CYP4V2 (rs1398007, rs13146272, rs3736455, rs1053094, and rs56413992) and CHD risk, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the connection.ResultsAs a result, we found that rs56413992 T allele (OR = 1.36, 95% CI = 1.09–1.70, p = 0.007) and CT genotype (OR = 1.40, 95% CI = 1.06–1.83, p = 0.017) were significantly associated with an increased risk of CHD in the overall analysis. Precisely, rs56413992 was linked to an elevated risk of CHD in people aged > 60, males, smokers and drinkers. The study also indicated that rs1398007 was linked to an increased CHD risk in drinkers. In addition, rs1053094 was correlated with a decreased risk of CHD complicated with diabetes mellitus (DM), and rs1398007 was correlated with a decreased risk of CHD complicated with hypertension (HTN).ConclusionThis study was the first to experimentally demonstrate that CYP4V2 rs56413992 was associated with the risk of CHD, which will provide a certain reference for revealing the pathogenesis of CHD.

Periodontal disease and subsequent risk of cardiovascular outcome and all-cause mortality: A meta-analysis of prospective studies.

Studies reported periodontal disease (PD) periodontal disease is associated with many systemic diseases, including cardiovascular outcomes and all-cause mortality. However, the precise mechanistic link for these relationship remained unclear. We therefore performed a meta-analysis of cohort studies to investigate the association of PD with the risk of cardiovascular outcomes and all-cause mortality. We systematically searched the databases of PubMed, EmBase, and the Cochrane library to identify eligible studies until April 2023. The investigated outcomes included major adverse cardiovascular events (MACEs), coronary heart disease (CHD), myocardial infarction (MI), stroke, cardiac death, and all-cause mortality. The summary relative risk (RR) with 95% confidence interval (CI) were calculated using the random-effects model. Thirty-nine cohort studies with 4,389,263 individuals were selected for final meta-analysis. We noted PD were associated with elevated risk of MACEs (RR: 1.24; 95%CI: 1.15-1.34; P<0.001), CHD (RR: 1.20; 95%CI: 1.12-1.29; P<0.001), MI (RR: 1.14; 95%CI: 1.06-1.22; P = 0.001), stroke (RR: 1.26; 95%CI: 1.15-1.37; P<0.001), cardiac death (RR: 1.42; 95%CI: 1.10-1.84; P = 0.007), and all-cause mortality (RR: 1.31; 95%CI: 1.07-1.61; P = 0.010). Sensitivity analyses indicated the pooled conclusions for cardiovascular outcomes and all-cause mortality are robustness. The associations of PD with the risk of ardiovascular outcomes and all-cause mortality could affected by region, study design, PD definition, follow-up duration, and study quality. This study found the risk of cardiovascular outcomes and all-cause mortality were elevated in PD patients, and the intervention for PD should be applied to prevent the risk of cardiovascular outcomes.

Infertility and Risk of Cardiovascular Disease: A Prospective Cohort Study.

Background Certain symptoms associated with infertility are associated with cardiovascular disease, including menstrual cycle irregularity, early menopause, and obesity; however, few studies have investigated the association between infertility and cardiovascular disease risk. Methods and Results Participants in the NHSII (Nurses' Health Study II) who reported infertility (12 months of trying to conceive without success, including women who subsequently conceived) or who were gravid, with no infertility were followed from 1989 until 2017 for development of incident, physician-diagnosed coronary heart disease (CHD) (myocardial infarction, coronary artery bypass grafting, angioplasty, stent) and stroke. Time-varying Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs and were adjusted a priori for potential confounding variables. Among 103 729 participants, 27.6% reported having ever experienced infertility. Compared with gravid women who had not reported infertility, women with a history of infertility had greater risk of CHD (HR, 1.13 [95% CI, 1.01-1.26]) but not stroke (HR, 0.91 [95% CI, 0.77-1.07]). The association between history of infertility and CHD was strongest among women who reported infertility at an earlier age (HR for infertility first reported at ≤25 years, 1.26 [95% CI, 1.09-1.46]; HR at 26-30 years, 1.08 [95% CI, 0.93-1.25]; HR at >30 years, 0.91 [95% CI, 0.70-1.19]). When we investigated specific infertility diagnoses, elevated risk of CHD was observed among women whose infertility was attributed to an ovulatory disorder (HR, 1.28 [95% CI, 1.05-1.55]) or endometriosis (HR, 1.42 [95% CI, 1.09-1.85]). Conclusions Women with infertility may be at an increased risk of CHD. Risk differed by age at first infertility diagnosis and was restricted to ovulatory- and endometriosis-related infertility.

Mediating effect of metabolic diseases on the relationship between hyperuricemia and coronary heart disease

Background and aimsStudies have shown that elevated serum uric acid (SUA) may increase the risk of coronary heart disease (CHD). However, it is still disputable how mediate effects between metabolic diseases and hyperuricemia affect the incidence of CHD. This study aimed to explore whether metabolic diseases may mediate the connection from hyperuricemia at baseline to the elevated incidence risk of CHD during follow-ups. Methods and ResultsBased on the Jinchang cohort, 48 001 subjects were followed for 9 years between June 2011 and December 2019. Multivariate-adjusted Cox regression models were applied to estimate hazard ratios (HRs) of CHD with 95% confidence intervals (CIs). Significantly increased risks of CHD were observed in hyperuricemia (HR:1.46, 95%CI:1.28, 1.67) when compared with normouricemia population. The mediating effect model further demonstrated that metabolic diseases could mediate the association between hyperuricemia and CHD pathogenesis, partially for the combined metabolic diseases with mediation effects of 45.12%, 25.24% for hypertension, 28.58% for overweight or obese status, 29.05% for hypertriglyceridemia, 6.70% for hypercholesterolemia, 3.52% for low high density lipoprotein cholesterol (HDL-C), and 6.51% for high low density lipoprotein cholesterol (LDL-C), respectively. ConclusionsHyperuricemia significantly increased the risk of incident CHD, and this association was partly mediated by metabolic diseases.

Hidden intrapancreatic portal cavernoma by pancreatic cephalic carcinoma Ц an indication for portal vein resection Ц Case Report

Studies have shown that elevated serum uric acid (SUA) may increase the risk of coronary heart disease (CHD). However, it was still disputable how mediate effects between metabolic diseases and hyperuricemia affect the incidence of CHD. This study aimed to explore whether metabolic diseases may mediate the connection from hyperuricemia at baseline to the elevated incidence risk of CHD during follow-ups.Based on the Jinchang cohort, 48 001 subjects were followed for 9 years between June 2011 and December 2019. Multivariate-adjusted Cox regression models were applied to estimate hazard ratios (HRs) of CHD with 95% confidence intervals (CIs). Significantly increased risks of CHD were observed in hyperuricemia (HR:1.46, 95%CI:1.28, 1.67) when compared with normouricemia population. The mediating effect model further demonstrated that metabolic diseases could mediate the association between hyperuricemia and CHD pathogenesis, partially for the combined metabolic diseases with mediation effects of 45.12%, 25.24% for hypertension, 28.58% for overweight or obese status, 29.05% for hypertriglyceridemia, 6.70% for hypercholesterolemia, 3.52% for low high density lipoprotein cholesterol (HDL-C), and 6.51% for high low density lipoprotein cholesterol (LDL-C), respectively.Hyperuricemia significantly increased the risk of incident CHD, and this association was partly mediated by metabolic diseases.

Red meat consumption and all-cause and cardiovascular mortality: results from the UK Biobank study.

To investigate the prospective associations between red meat consumption and all-cause and cardiovascular diseases (CVD) mortality, and to assess the modification effects of lifestyle and genetic risk factors. 180,642 individuals free of CVD or cancer were enrolled from 2006 to 2010 and followed up to 2018 in the UK Biobank. Information on demographics, lifestyles, and medical history was collected through a baseline touchscreen questionnaire. The information on diet was collected through a single touchscreen food-frequency questionnaire. A total of ten single-nucleotide polymorphisms were used to calculate the genetic risk score (GRS) of trimethylamine N-oxide (TMAO), a gut microbiota metabolite from red meat. Adjusted Cox proportional hazard regression models were used to assess the association of red meat consumption with mortality. We documented 3596 deaths [655 CVD deaths, 285 coronary heart disease (CHD) deaths, and 149 stroke deaths] during median 8.6years of follow-up. Compared with the lowest red meat intake (< 1.5 times/week), the highest red meat intake (≥ 3.0 times/week) was associated with a 20%, 53%, and 101% elevated risk for CVD, CHD, and stroke mortality (P for trend = 0.04, 0.007, and 0.02, respectively), but not all-cause mortality. We found that the associations between red meat intake and mortality were not modified by dietary and lifestyle factors, as well as TMAO GRS. In addition, substitution analyses showed that a decrease in red meat consumption and an increase in the consumption of poultry or cereal was significantly associated with 9%-16% lower CVD or CHD mortality risk. Our results indicated that red meat consumption was associated with higher risks of CVD, CHD, and stroke mortality, and the associations were not modified by lifestyle and genetic risk factors. Replacing red meat by poultry or cereal was related to lower risks of CVD and CHD mortality.

A multiethnic association analysis of hyperuricaemia with cardiovascular risk in rural and urban areas in Chinese adults

Comprehensive research on rural–urban disparities in the association of hyperuricaemia (HUA) with cardiovascular disease (CVD) in China, especially among minority groups, is limited. We explored the HUA-CVD relationship between rural and urban areas within ethnic Chinese groups. We included Dong, Miao, and Bouyei adults in Southwest China from the China Multi-Ethnic Cohort Study. Multivariable logistic regression models were used to assess the relationship between HUA and CVD in both residences. We performed stratified analyses by sex and age. The study population included 16,618 people (37.48% Dong, 30.00% Miao, and 32.52% Bouyei) without a reduced estimated glomerular filtration rate. We identified 476 (188 Dong, 119 Miao, and 169 Bouyei) and 175 (62 Dong, 77 Miao, and 36 Bouyei) CVD cases in rural and urban areas. Compared to urban residents, an at least 49% increased CVD risk (adjusted OR 1.49, 95%CI 1.06–2.08 for the Dong ethnic group; 1.55, 1.07–2.25 for the Bouyei ethnic group) and a 1.65-fold elevated coronary heart disease risk (1.65, 1.03–2.64) related to HUA was present in rural residents. Moreover, HUA was positively associated with increased risk of CVD and coronary heart disease in rural women (2.05, 1.26–3.31; 2.11, 1.19–3.75) and rural older adults (1.83, 1.22–2.75; 2.32, 1.39–3.87) among the Bouyei ethnic group, respectively. We found rural elderly individuals with HUA among the Dong ethnic group had a 52% elevated risk of CVD (1.52, 1.05–2.21); furthermore, an at least 79% increased risk of stroke related to HUA was observed in women (2.24, 1.09–4.62) and elderly people (1.79, 1.02–3.13) in rural areas among the Dong ethnic group. But a positive association was not found among the Miao ethnic group. Screening early-onset HUA patients may be helpful for the control and prevention of CVD in rural residents, especially for women and older adults living in a rural community, among the Dong and Bouyei ethnic groups in China.

992-P: Early Menopause and Cardiovascular Disease Risk in Women with and without Diabetes

Background: Early menopause may be associated with higher cardiovascular disease (CVD) risk due to the early cessation of estrogens protection. The presence of diabetes (DM) coupled with early menopause may result in even greater CVD risk in postmenopausal women. We compared CVD risk in women with early vs. normal age menopause with and without DM. Methods: We pooled data from the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. Women with data on menopausal status, age at menopause and DM (yes/no) were included. We excluded pre- or peri-menopausal women, those with hysterectomy/oophorectomy or prevalent CVD. Outcomes were incident coronary heart disease (CHD), ischemic or hemorrhagic stroke, heart failure (HF), and a composite CVD outcome (CHD, stroke or HF). Cox models examined the risk associated with early (&amp;lt;45 yrs) vs. normal age (≥45 yrs) menopause. Covariates included baseline age, race, education, BMI, blood pressure, cholesterol, smoking, alcohol consumption, and hormone therapy use. Results: During a median follow-up of 15 yrs for 5964 postmenopausal women, 684 CHD, 434 stroke, 962 HF and 1535 CVD events occurred. In adjusted models, women with early menopause had elevated risk of CHD (Hazard ratio 1.12, 95% CI 1.03-1.22), stroke (1.09, 1.01-1.18) and HF (1.09, 1.00-1.19) compared to those with normal age menopause. DM was a significant effect modifier to the relationship between early menopause and CHD, stroke or CVD (P for interaction ≤0.05). HRs for early menopause and the outcomes were greater in diabetic than nondiabetic women (CHD 1.34, 1.02-1.78 vs. 1.10, 1.00-1.20; stroke 1.26, 0.98-1.61 vs. 1.07, 0.98-1.16; CVD 1.41, 1.01-1.95 vs. 1.04, 0.94-1.14). Conclusion: Early menopause increases risk for CVD in postmenopausal women; DM places this group at even higher CVD risk. Attention to CVD risk monitoring and management in women with early menopause, with and without diabetes, should be considered. Disclosure Y. Yoshida: None. Z. Chen: None. R. L. Baudier: None. M. Krousel-wood: None. A. H. Anderson: None. V. Fonseca: Consultant; Self; Abbott Diabetes, Asahi Kasei Corporation, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Stock/Shareholder; Self; Amgen Inc., Bravo4health, Mellitus Health. F. Mauvais-jarvis: None. Funding National Institutes of Health (K12HD043451)

Metabolic Dysregulation of the Lysophospholipid/Autotaxin Axis in the Chromosome 9p21 Gene SNP rs10757274

Common chromosome 9p21 single nucleotide polymorphisms (SNPs) increase coronary heart disease risk, independent of traditional lipid risk factors. However, lipids comprise large numbers of structurally related molecules not measured in traditional risk measurements, and many have inflammatory bioactivities. Here, we applied lipidomic and genomic approaches to 3 model systems to characterize lipid metabolic changes in common Chr9p21 SNPs, which confer ≈30% elevated coronary heart disease risk associated with altered expression of ANRIL, a long ncRNA. Untargeted and targeted lipidomics was applied to plasma from NPHSII (Northwick Park Heart Study II) homozygotes for AA or GG in rs10757274, followed by correlation and network analysis. To identify candidate genes, transcriptomic data from shRNA downregulation of ANRIL in HEK-293 cells was mined. Transcriptional data from vascular smooth muscle cells differentiated from induced pluripotent stem cells of individuals with/without Chr9p21 risk, nonrisk alleles, and corresponding knockout isogenic lines were next examined. Last, an in-silico analysis of miRNAs was conducted to identify how ANRIL might control lysoPL (lysophosphospholipid)/lysoPA (lysophosphatidic acid) genes. Elevated risk GG correlated with reduced lysoPLs, lysoPA, and ATX (autotaxin). Five other risk SNPs did not show this phenotype. LysoPL-lysoPA interconversion was uncoupled from ATX in GG plasma, suggesting metabolic dysregulation. Significantly altered expression of several lysoPL/lysoPA metabolizing enzymes was found in HEK cells lacking ANRIL. In the vascular smooth muscle cells data set, the presence of risk alleles associated with altered expression of several lysoPL/lysoPA enzymes. Deletion of the risk locus reversed the expression of several lysoPL/lysoPA genes to nonrisk haplotype levels. Genes that were altered across both cell data sets were DGKA, MBOAT2, PLPP1, and LPL. The in-silico analysis identified 4 ANRIL-regulated miRNAs that control lysoPL genes as miR-186-3p, miR-34a-3p, miR-122-5p, and miR-34a-5p. A Chr9p21 risk SNP associates with complex alterations in immune-bioactive phospholipids and their metabolism. Lipid metabolites and genomic pathways associated with coronary heart disease pathogenesis in Chr9p21 and ANRIL-associated disease are demonstrated.

Impact of secondhand smoke exposure in former smokers on their subsequent risk of coronary heart disease: evidence from the population-based cohort of the Tehran Lipid and Glucose Study.

OBJECTIVESCigarette smoking is an established, strong, and modifiable risk factor for coronary heart disease (CHD). However, little research has investigated CHD risk in former smokers who continue to be exposed to others’ cigarette smoke (former & secondhand smokers).METHODSIn the Tehran Lipid and Glucose Study, a prospective population-based cohort (n=20,069) was followed up for a median period of 14.6 years. A subset of 8,050 participants of 30 years of age and older was analyzed, with first CHD events as the study outcome. Participants were categorized as never, former, current, secondhand, and former & secondhand smokers. Data on smoking intensity (cigarette/d) were also collected. A Cox proportional hazards regression model was applied to estimate the risk of CHD, taking into account the main potential confounders.RESULTSThe mean age of participants was 46.10 ±11.38 years, and they experienced 1,118 first CHD events (with most CHD cases in former smokers) during the follow-up period. The risk of CHD was highest in current smokers, followed in order by former & secondhand, former, and secondhand smokers (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.65 to 2.39; HR, 1.55; 95% CI, 1.15 to 2.08; HR, 1.39; 95% CI, 1.12 to 1.72; HR, 1.27; 95% CI, 1.07 to 1.51, respectively), compared to never smokers. The risk of CHD increased with smoking intensity, which has been proposed as a preferable measure of smoking, indicating a dose-response pattern.CONCLUSIONSThe elevated risk of CHD in former & secondhand smokers was a noteworthy finding, with possible implications for health policy; however, further research is needed.

Up-regulation of long non-coding RNA THRIL in coronary heart disease: Prediction for disease risk, correlation with inflammation, coronary artery stenosis, and major adverse cardiovascular events.

ObjectiveThis study aimed to investigate the role of long non‐coding RNA (lncRNA) THRIL in coronary heart disease (CHD) patients.MethodsA total of 420 patients who underwent coronary arteriography due to suspected symptoms of CHD were enrolled, in which 220 were diagnosed as CHD and 200 were set as control subjects. LncRNA THRIL in plasma samples of CHD patients and control subjects was detected by reverse transcription‐quantitative polymerase chain reaction. Gensini score and biochemical indexes were evaluated in CHD patients and control subjects. Plasma inflammatory cytokines were detected, and major adverse cardiovascular events (MACE) were recorded in CHD patients.ResultsBoth before and after adjustment by age/gender, lncRNA THRIL was increased in CHD patients compared with control subjects (both P < .001), and it well predicted enhanced CHD risk by receiver operating characteristic curves. For coronary artery stenosis, it was positively correlated with Gensini score (P < .001, r = .430). For clinical characteristics, lncRNA THRIL was positively correlated with diabetes mellitus occurrence (P < .001) and fasting blood glucose (FBG) level (P = .029, r = .147). For inflammation, it was positively associated with CRP (P < .001, r = .374), TNF‐α (P < .001, r = .249), IL‐1β (P = .001, r = .222), IL‐8 (P < .001, r = .254), and IL‐17 (P = .011, r = .172), while negatively correlated with IL‐10 (P < .001, r = −.244). For prognosis, lncRNA THRIL was positively associated with MACE accumulating rate (P = .037) in CHD patients.ConclusionLong non‐coding RNA THRIL was increased in CHD patients and well predicted elevated CHD risk. Moreover, it was correlated with enhanced coronary stenosis, systematic inflammation, FBG level, and MACE risk in CHD patients.

Associations Between Midlife (but Not Late-Life) Elevated Coronary Heart Disease Risk and Lower Cognitive Performance: Results From the Framingham Offspring Study.

It is unclear how coronary heart disease (CHD) risk across the adult life span affects late-life cognition. We estimated associations of midlife and late-life elevated CHD risk with cognitive trajectories (general cognitive performance, processing speed/executive function, memory) in later life (after age 55 years or age 70 years) among 2,892 Framingham Offspring Study participants who had completed CHD risk assessments approximately every 4 years since 1971 and had undergone neuropsychological testing between 1999 and 2014. We stratified analyses by apolipoprotein E gene (APOE) Ɛ4 allele carrier status. Using linear mixed-effects models, elevated CHD risk in midlife (age 55 years) was associated with lower levels of general cognitive performance (β=-0.560 standard deviation (SD) units, 95% confidence interval (CI): -0.874, -0.246), executive function (β=-0.624 SD units, 95% CI: -0.916, -0.332), and memory (β=-0.560 SD units, 95% CI: -0.907, -0.213) at age 70 years but not with rates of cognitive change. Late-life (age 70 years) elevated CHD risk, however, was associated with somewhat better levels of general cognitive performance and memory. There were associations between duration of elevated CHD risk during midlife and levels (but not trajectories) of later-life cognitive outcomes. Associations were not modified by APOE-ɛ4 status. These findings suggest that midlife elevated CHD risk is associated with lower cognition, independently of APOE-ɛ4 status, suggesting that risk of vascular disease may not contribute a "second hit" to AD risk.

Abstract 019: Changes in Gut Microbial Metabolites and Risk of Coronary Heart Disease in US Women: the Nurses’ Health Study

Introduction: Circulating levels of gut microbial metabolites, trimethylamine N-oxide (TMAO) and its nutrient precursors of choline and L-carnitine, have been suggested as risk factors for coronary heart disease (CHD). Whether changes in gut microbial metabolites are associated with the CHD incidence remains unknown. Hypothesis: We assessed the hypothesis that long-term (over 10 years) changes in plasma levels of TMAO, choline, and L-carnitine would be associated with the risk of CHD. Methods: This prospective nested case-control study included a total of 768 women (385 incident cases of fatal CHD and nonfatal myocardial infarction and 383 controls) who had data on blood concentrations of TMAO, choline, and L-carnitine at 2 time points, 10 years apart (1989-90, and 2000-01). We identified incident cases of CHD from the date of the second blood collection through 2014. Results: Higher TMAO levels at the second collection were associated with higher risk of CHD (relative risk (RR) 1.22 [95% CI: 1.05, 1.42] per 1 SD increment in log-transformed TMAO) in multivariate analyses controlling for traditional risk factors. Compared with women with low TMAO levels (lower two tertiles) at both time points, the RR was 1.74 (95% CI: 1.05, 2.89) for those with elevated levels of TMAO (the highest tertile) at both time points. Regardless of metabolite levels at the first collection, increases in TMAO or L-carnitine from the first to second collections were significantly associated with an increased risk of CHD (Fig. panels A-B). Women who had increases in both TMAO and L-carnitine had a particularly elevated risk of CHD (RR 2.12, 95% CI: 1.25, 3.59), as compared to those with decreases in both metabolites. Adherence to healthy dietary habits attenuated the associations of TMAO with CHD risk (Fig. panel C). Conclusions: Long-term increases in TMAO were significantly predictive of subsequent risk for CHD among women. The associations may be modified by the nutrient metabolite precursor, L-carnitine, and adherence to healthy dietary habits.

Association Between Self-rated Health, Coronary Artery Calcium Scores, and Atherosclerotic Cardiovascular Disease Risk

The interplay of self-rated health (SRH), coronary artery calcium (CAC) scores, and cardiovascular risk is poorly described. To assess the degree of correlation between SRH and CAC, to determine whether these measures are complementary for risk prediction, and to assess the incremental value of the addition of SRH to established risk tools. The Multi-Ethnic Study of Atherosclerosis (MESA) is a large population-based prospective cohort study of adults aged 45 to 84 years who were recruited from 6 US communities. A total of 6764 participants without baseline cardiovascular disease (CVD) were included in the analysis. Data were collected from July 2000 through August 2002. Follow-up was completed by December 2013, and data were analyzed from October 2018 to December 2018. The EVGGFP (excellent, very good, good, fair, and poor) self-assessment of overall health (assessed before the baseline study examination) and CAC score. The EVGGFP rating was categorized as poor/fair, good, very good, or excellent. Hard coronary heart disease (CHD) events, hard CVD events, and all-cause mortality during a median follow-up of 13.2 years (interquartile range, 12.7-13.7 years). Among the study population of 6764 participants, the mean (SD) age was 62.1 (10.2) years, and 52.9% were women. The EVGGFP rating was strongly associated with age, sex, race/ethnicity, educational and income levels, healthy diet and physical activity, and cardiovascular risk factors. Despite encapsulating many risk variables, no correlation (r = -0.007; P = .57) or association between EVGGFP and the presence (χ2 = 0.84; P = .84) or severity (χ2 = 4.64; P = .86) of CAC was found. During follow-up, 1161 deaths, 637 hard CVD events, and 405 hard CHD events were recorded. In models adjusted for age, sex, race/ethnicity, and CAC, participants who reported excellent health had a 45% lower risk of CVD (hazard ratio [HR], 0.55; 95% CI, 0.39-0.77) and a 42% lower risk of CHD (HR, 0.58; 95% CI, 0.37-0.90) compared with those who reported poor/fair health. Participants in the excellent SRH category who had any CAC had markedly elevated risk of hard CHD (HR, 6.19; 95% CI, 2.1-18.3) and CVD (HR, 6.50; 95% CI, 2.7-15.6) events compared with those with a CAC score of 0. The addition of the EVGGFP rating to CAC improved the area under the curve (C statistic) for CHD events (0.725 vs 0.734; P = .007), CVD events (0.693 vs 0.706; P < .001), and all-cause mortality (0.685 vs 0.707; P < .001). However, the addition of the EVGGFP rating to the combination of CAC and atherosclerotic CVD risk score did not significantly improve C statistics for CHD events (0.751 vs 0.753; P = .39), CVD events (0.739 vs 0.741; P = .18), or all-cause mortality (0.779 vs 0.781; P = .13). Although SRH and CAC integrate many risk variables, this study suggests that they are poorly correlated and have complementary predictive utility. A perception of excellent health does not obviate the need for definitive assessment of CVD risk, whereas fair/poor perceived health may serve as a risk enhancer, arguing for advanced risk assessment in selected clinical scenarios.

Increased cardiovascular risk in thyroid cancer patients taking levothyroxine: a nationwide cohort study in Korea.

Objective Many thyroid cancer patients are exposed to long-term thyroid-stimulating hormone (TSH) suppression, often as lifetime treatment, and are consequently at risk for cardiovascular disease. We investigated the incidence of coronary heart disease (CHD) and ischemic stroke among thyroid cancer patients compared with matched control subjects. Design Retrospective cohort study. Methods A total of 182 419 subjects who received thyroidectomy for thyroid cancer during 2004-2012 were selected from the Korean National Health Insurance data, which cover approximately 97% of the entire Korean population. Propensity score matching was used to select non-cancer controls. Cox proportional hazards regression analysis was used to determine relative risk of coronary heart disease and ischemic stroke. Mean follow-up was 4.32 years. Results Thyroid cancer patients had elevated risk for CHD and ischemic stroke with hazard ratio (HR) of 1.15 (95% confidence interval (CI): 1.10-1.22) and 1.15 (1.09-1.22), respectively. This risk was increased in those who took a higher dosage of levothyroxine (HR: 1.47, 95% CI: 1.34-1.60 for CHD and HR: 1.56, 95% CI: 1.42-1.72 for ischemic stroke among those who took ≥170 μg/day levothyroxine). Although risk of atrial fibrillation was dose-dependently associated with levothyroxine dosage, it represents only a small proportion of ischemic stroke incidence (4.4%, 128/2914). Conclusions The risk for CHD and ischemic stroke was higher in thyroid cancer patients who received thyroidectomy, and the dosage of levothyroxine administered appears to play a major role. Greater caution is suggested for the screening and treatment of thyroid cancer and subsequent TSH suppression therapy, as well as proper management for cardiovascular disease prevention.

Is e-cigarette use associated with coronary heart disease and myocardial infarction? Insights from the 2016 and 2017 National Health Interview Surveys.

Background:This study analyzed the National Health Interview Surveys (NHIS) of 2016 (n = 33,028) and 2017 (n = 26,742) to examine whether e-cigarette use is consistently associated with myocardial infarction (MI) and coronary heart disease (CHD).Methods:Surveys were examined separately and pooled. Logistic regression analysis was used, with demographics, e-cigarette use, smoking and risk factors for CHD (hypertension, hypercholesterolemia, and diabetes) being independent variables. Former smokers were subclassified according to quit duration (⩽ 6 and > 6 years).Results:For MI, an association was observed with some days e-cigarette (but not daily) use in the 2017 survey (OR: 2.11, 95% CI: 1.14–3.88, p = 0.017). No statistically significant association was observed in the pooled analysis (daily e-cigarette use: OR: 1.35, 95% CI: 0.80–2.27, p = 0.267). For CHD, an association was observed with daily e-cigarette use in the 2016 survey (OR: 1.89, 95% CI: 1.01–3.53, p = 0.047). From the pooled analysis, no association was found between any pattern of e-cigarette use and CHD. In single-year and pooled analysis, both MI and CHD were strongly associated with all patterns of smoking, hypertension, hypercholesterolemia, diabetes, and age.Conclusions:The pooled analysis of the 2016 and 2017 NHIS showed no association between e-cigarette use and MI or CHD. The associations between established risk factors, including smoking, and both conditions were remarkably consistent. The inconsistent associations observed in single-year surveys and the cross-sectional design of the NHIS cannot substantiate any link between e-cigarette use and an elevated risk for MI or CHD. Longitudinal studies are needed to explore the effects of e-cigarette use on cardiovascular disease.

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.