Lower Risk Of Coronary Heart Disease Research Articles

Association Between Serine Concentration and Coronary Heart Disease: A Case-Control Study.

Early identification of new residual risk factors for coronary heart disease (CHD) is warranted. In this study, we aim to investigate the association between the serine concentration, an important amino acid in one-carbon metabolism, and CHD in Chinese hospitalized patients. This case-control study included 428 case-control pairs comprising patients with CHD with a maximum coronary artery stenosis degree of >70% and controls with stenosis of <30%. The individuals were matched by age, sex, and date of coronary angiography at Peking University First Hospital from January 1, 2016, to December 31, 2019. Conditional logistic regression was used to investigate the associations between the serine concentration and CHD. Patients with CHD were aged 63.48 ± 10.38 years, and 43.73% were male. Compared with controls, patients with CHD had a slightly lower serine concentration (13.35 ± 4.20 vs 13.77 ± 4.08 μg/mL), but the difference was not significant. In the multivariable conditional logistic regression analysis, for every 1 μg/mL increase in serine concentration, the odds of CHD decreased by 6% (95% confidence interval [CI] 0.90-0.99; P = 0.010). Patients with a serine concentration of ≥13.41 μg/mL had a lower CHD risk than those with a serine concentration of <13.41 μg/mL (odds ratio [OR] 0.57, 95% CI 0.39-0.84; P = 0.004). Subgroup analyses showed that sex interacted with the relationship between serine concentration and CHD (P interaction = 0.039), which was more significant in males (OR 0.93, 95% CI 0.87-0.98; P = 0.013) than in females. This study observed an inverse association between the serine concentration and CHD prevalence in Chinese hospitalized patients, which revealed that serine might play a protective role in CHD.

SGLT2 inhibition, venous thrombolism, and death due to cardiac causes: a mediation Mendelian randomization study.

To investigate the causal role of venous thrombolism mediating sodium-glucose cotransporter 2 (SGLT2) inhibition in death due to cardiac causes using Mendelian randomization (MR). A two-sample two-step MR was used to determine (1) the causal effects of SGLT2 inhibition on death due to cardiac causes; (2) the causal effects of venous thrombolism on death due to cardiac causes; and (3) the mediation effects of venous thrombolism. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene that were associated with both levels of gene expression and hemoglobin A1c. Additionally, employing MR to investigate the causal association between SGLT2 inhibition and cardiac arrest as well as coronary heart disease (CHD). SGLT2 inhibition was associated with a lower risk of death due to cardiac causes (odds ratio [OR] = 0.983, [95% CI = 0.972, 0.993], P = 0.0016). Venous thrombolism was associated with death due to cardiac causes ([OR] = 1.031, [95% CI = 1.005, 1.057], P = 0.0199). Mediation analysis showed evidence of indirect effect of SGLT2 inhibition on death due to cardiac causes through venous thrombolism [β = -0.0015, (95% CI = -0.0032 -0.0002), P = 0.042], with a mediated proportion of 8.9% (95% CI = 1.2%, 18.7%) of the total. Furthermore, SGLT2 inhibition was linked to a lower risk of cardiac arrest ([OR] = 0.097, [95% CI = 0.013, 0.742], P = 0.025). SGLT2 inhibition was linked to a lower risk of CHD ([OR] = 0.957, [95% CI = 0.932, 0.982], P = 0.0009). Our study identified the causal roles of SGLT2 inhibition in venous thrombolism. SGLT2 inhibition may influence death due to cardiac causes through venous thrombolism. Additionally, SGLT2 inhibition was associated with reduced risk of cardiac arrest and CHD.

Changes in Sleep Patterns, Genetic Susceptibility, and Incident Cardiovascular Disease in China

The associations of changes in sleep patterns with incident cardiovascular disease (CVD) are not fully elucidated, and whether these associations are modified by genetic susceptibility remains unknown. To investigate the associations of 5-year changes in sleep patterns with incident CVD and whether genetic susceptibility modifies these associations. This prospective cohort study of the Dongfeng-Tongji cohort was conducted from 2008 to 2018 in China. Eligible participants included those with complete sleep information at baseline survey (2008-2010) and the first follow-up survey (2013); participants who had no CVD or cancer in 2013 were prospectively assessed until 2018. Statistical analysis was performed in November 2023. Five-year changes in sleep patterns (determined by bedtime, sleep duration, sleep quality, and midday napping) between 2008 and 2013, and polygenic risk scores (PRS) for coronary heart disease (CHD) and stroke. Incident CVD, CHD, and stroke were identified from 2013 to 2018. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% CIs. Among 15 306 individuals (mean [SD] age, 65.8 [7.4] years; 8858 [57.9%] female and 6448 male [42.1%]), 5474 (35.78%) had persistent unfavorable sleep patterns and 3946 (25.8%) had persistent favorable sleep patterns. A total of 3669 incident CVD cases were documented, including 2986 CHD cases and 683 stroke cases, over a mean (SD) follow-up of 4.9 (1.5) years. Compared with those with persistent unfavorable sleep patterns, individuals with persistent favorable sleep patterns over 5 years had lower risks of incident CVD (HR, 0.80; 95% CI, 0.73-0.87), CHD (HR, 0.84; 95% CI, 0.76-0.92), and stroke (HR, 0.66; 95% CI, 0.54-0.82) in the subsequent 5-year period. No significant effect modification by PRS was observed for sleep pattern change and CHD or stroke risk. However, sleep pattern changes and PRS were jointly associated with the CHD and stroke risk in a dose-dependent manner, with the lowest risk being among those with persistent favorable sleep patterns combined with low PRS (HR for CHD, 0.65; 95% CI, 0.52-0.82 and HR for stroke, 0.48; 95% CI, 0.29-0.79). In this cohort study of middle-aged and older Chinese adults, individuals with persistent favorable sleep patterns had a lower CVD risk, even among those with higher genetic risk. These findings highlight the importance of maintaining favorable sleep patterns for CVD prevention.

Association between longitudinal change of sleep patterns and the risk of cardiovascular diseases.

To investigate the role of longitudinal change of sleep patterns in the incidence of cardiovascular diseases (CVD). Based on UK Biobank, a total of 18 172 participants were enrolled. Five dimensions of healthy sleep including early chronotype, sleep 7-8 hours/day, free of insomnia, no snoring, and no frequent excessive daytime sleepiness were used to generate a healthy sleep score (HSS) ranging from 0 to 5. Corresponding to the HSS of 0-1, 2-3, and 4-5, the poor, intermediate, and healthy sleep patterns were defined. Based on changes in HSS across assessments 1 and 2, we calculated the absolute difference of HSS. For the change in sleep patterns, we categorized five profiles (stable healthy, worsening, stable intermediate, optimizing, and stable poor sleep patterns). The outcomes were incidence of CVD including coronary heart disease (CHD) and stroke. We assessed the adjusted hazard ratios and 95% confidence intervals (CIs) by Cox hazard models. Compared with participants with stable poor patterns, those who improved their sleep patterns or maintained healthy sleep patterns had a 26% and 32% lower risk of CVD, respectively. Stable healthy sleep pattern was associated with a 29% and 44% reduced risk of CHD and stroke. Per unit, longitudinal increment of the HSS was related to an 8% lower risk of CVD and CHD. Compared with individuals with constant HSS, those with decreased HSS had a 13% higher risk of developing CVD. Optimizing sleep patterns and maintaining a healthy sleep pattern may reduce the risk of CVD.

Associations of Abdominal Muscle Density and Area and Incident Cardiovascular Disease, Coronary Heart Disease, and Stroke: The Multi-Ethnic Study of Atherosclerosis.

Muscle density is inversely associated with all-cause mortality, but associations with cardiovascular disease (CVD) risk are not well understood. This study evaluated the association between muscle density and muscle area and incident total CVD, coronary heart disease (CHD), and stroke in diverse men and women. Adult participants (N=1869) in the Multi-Ethnic Study of Atherosclerosis Ancillary Body Composition Study underwent computer tomography scans of the L2-L4 region of the abdomen. Muscle was quantified by density (Hounsfield units) and area in cm2. Sex-stratified Cox proportional hazard models assessed associations between incident total CVD, incident CHD, and incident stroke across sex-specific percentiles of muscle area and density, which were entered simultaneously into the model. Mean age for men and women at baseline were 64.1 and 65.1 years, respectively, and median follow-up time was 10.3 years. For men, associations between muscle density and incident CVD were inverse but not significant in fully adjusted models (P trend=0.15). However, there was an inverse association between density and CHD (P trend=0.02; HR, 0.26 for 95th versus 10th percentile), and no association with stroke (P trend=0.78). Conversely, for men, there was a strong positive association between muscle area and incident CVD (HR, 4.19 for 95th versus 10th percentile; P trend<0.001). Associations were stronger for CHD (HR, 6.18 for 95th versus 10th percentile; P trend<0.001), and null for stroke (P trend=0.67). Associations for women were mostly null. For men, abdominal muscle density is associated with lower CHD risk, whereas greater muscle area is associated with markedly increased risk of CHD.

Association Between HDL2-C and HDL3-C with Cardiovascular Disease: A Nested Case-Control Study in an Iranian Population.

The contribution of high-density lipoprotein cholesterol (HDL-C) subclasses to incident cardiovascular disease (CVD) and coronary heart disease (CHD) remains a subject of debate. The objective of this study was to investigate these associations in a population with a high prevalence of dyslipidemia and CVD. In a nested case-control study, HDL-C and its subclasses (HDL2-C and HDL3-C) in 370 age and gender-matched case and control subjects were determined. This study employed multivariable-adjusted conditional logistic regression to calculate the odds ratios (ORs) for the associations between HDL-C, HDL2-C, HDL3-C, and HDL2-C/HDL3-C (both as continuous and categorical variables) with incident CVD and CHD. The present study models were adjusted for a comprehensive set of confounders, including body mass index, current smoking, hypertension, type 2 diabetes mellitus, use of lipid-lowering drugs, family history of premature CVD, non-HDL-C, and triglycerides. In multivariate analysis, when considering lipoprotein parameters as continuous variables, a 1-unit increase in HDL-C and HDL3-C was associated with a reduced risk of incident CVD and CHD. For CVD, the ORs (95% confidence intervals [CI]) were 0.95 (0.92 - 0.98) and 0.95 (0.93 - 0.98) for HDL-C and HDL3-C, respectively. The corresponding values for CHD were 0.94 (0.91 - 0.97) and 0.94 (0.91 - 0.97). In the categorical approach to lipoprotein parameters, higher quartiles of HDL-C and HDL3-C, compared to the first quartile, were significantly associated with a lower risk of incident CVD and CHD. The ORs (95% CI) for the fourth quartiles were 0.43 (0.25 - 0.74, P for trend = 0.003) and 0.46 (0.27 - 0.78, P for trend = 0.005) for HDL-C and HDL3-C regarding CVD and 0.32 (0.17 - 0.59) and 0.32 (0.18 - 0.59) (all P for trend = 0.001) regarding CHD, respectively. Paradoxically, across quartiles of HDL2-C/HDL3-C, this lipid ratio was associated with a higher risk of CHD (92% higher risk in the fourth quartile). The results showed that HDL3-C, but not HDL2-C, was primarily responsible for the protective effect of HDL-C against CVD, particularly CHD, in Iranian adults.

Metabolite Signature of Life's Essential 8 and Risk of Coronary Heart Disease Among Low-Income Black and White Americans.

Life's essential 8 (LE8) is a comprehensive construct of cardiovascular health. Yet, little is known about the LE8 score, its metabolic correlates, and their predictive implications among Black Americans and low-income individuals. In a nested case-control study of coronary heart disease (CHD) among 299 pairs of Black and 298 pairs of White low-income Americans from the Southern Community Cohort Study, we estimated LE8 score and applied untargeted plasma metabolomics and elastic net with leave-one-out cross-validation to identify metabolite signature (MetaSig) of LE8. Associations of LE8 score and MetaSig with incident CHD were examined using conditional logistic regression. The mediation effect of MetaSig on the LE8-CHD association was also examined. The external validity of MetaSig was evaluated in another nested CHD case-control study among 299 pairs of Chinese adults. Higher LE8 score was associated with lower CHD risk (standardized odds ratio, 0.61 [95% CI, 0.53-0.69]). The MetaSig, consisting of 133 metabolites, showed significant correlation with LE8 score (r=0.61) and inverse association with CHD (odds ratio, 0.57 [0.49-0.65]), robust to adjustment for LE8 score and across participants with different sociodemographic and health status ([odds ratios, 0.42-0.69]; all P<0.05). MetaSig mediated a large portion of the LE8-CHD association: 53% (32%-80%). Significant associations of MetaSig with LE8 score and CHD risk were found in validation cohort (r=0.49; odds ratio, 0.57 [0.46-0.69]). Higher LE8 score and its MetaSig were associated with lower CHD risk among low-income Black and White Americans. Metabolomics may offer an objective measure of LE8 and its metabolic phenotype relevant to CHD prevention among diverse populations.

Portfolio Diet Score and Risk of Cardiovascular Disease: Findings From 3 Prospective Cohort Studies.

The plant-based Portfolio dietary pattern includes recognized cholesterol-lowering foods (ie, plant protein, nuts, viscous fiber, phytosterols, and plant monounsaturated fats) shown to improve several cardiovascular disease (CVD) risk factors in randomized controlled trials. However, there is limited evidence on the role of long-term adherence to the diet and CVD risk. The primary objective was to examine the relationship between the Portfolio Diet Score (PDS) and the risk of total CVD, coronary heart disease (CHD), and stroke. We prospectively followed 73 924 women in the Nurses' Health Study (1984-2016), 92 346 women in the Nurses' Health Study II (1991-2017), and 43 970 men in the Health Professionals Follow-up Study (1986-2016) without CVD or cancer at baseline. Diet was assessed using validated food frequency questionnaires at baseline and every 4 years using a PDS that positively ranks plant protein (legumes), nuts and seeds, viscous fiber sources, phytosterols (mg/day), and plant monounsaturated fat sources, and negatively ranks foods high in saturated fat and cholesterol. During up to 30 years of follow-up, 16 917 incident CVD cases, including 10 666 CHD cases and 6473 strokes, were documented. After multivariable adjustment for lifestyle factors and a modified Alternate Healthy Eating Index (excluding overlapping components), comparing the highest with the lowest quintile, participants with a higher PDS had a lower risk of total CVD (pooled hazard ratio [HR], 0.86 [95% CI, 0.81-0.92]; Ptrend<0.001), CHD (pooled HR, 0.86 [95% CI, 0.80-0.93]; Ptrend=0.0001), and stroke (pooled HR, 0.86 [95% CI, 0.78-0.95]; Ptrend=0.0003). In addition, a 25-percentile higher PDS was associated with a lower risk of total CVD (pooled HR, 0.92 [95% CI, 0.89-0.95]), CHD (pooled HR, 0.92 [95% CI, 0.88-0.95]), and stroke (pooled HR, 0.92 [95% CI, 0.87-0.96]). Results remained consistent across sensitivity and most subgroup analyses, and there was no evidence of departure from linearity for CVD, CHD, or stroke. In a subset of participants, a higher PDS was associated with a more favorable blood lipid and inflammatory profile. The PDS was associated with a lower risk of CVD, including CHD and stroke, and a more favorable blood lipid and inflammatory profile, in 3 large prospective cohorts.

Blood DNA methylation signature of diet quality and association with cardiometabolic traits.

Diet quality might influence cardiometabolic health through epigenetic changes, but this has been little investigated in adults. Our aims were to identify cytosine-phosphate-guanine (CpG) dinucleotides associated with diet quality by conducting an epigenome-wide association study (EWAS) based on blood DNA methylation (DNAm) and to assess how diet-related CpGs associate with inherited susceptibility to cardiometabolic traits: body mass index (BMI), systolic blood pressure (SBP), triglycerides, type 2 diabetes (T2D), and coronary heart disease (CHD). Meta-EWAS including 5274 participants in four cohorts from Spain, the USA, and the UK. We derived three dietary scores (exposures) to measure adherence to a Mediterranean diet, to a healthy plant-based diet, and to the Dietary Approaches to Stop Hypertension. Blood DNAm (outcome) was assessed with the Infinium arrays Human Methylation 450K BeadChip and MethylationEPIC BeadChip. For each diet score, we performed linear EWAS adjusted for age, sex, blood cells, smoking and technical variables, and BMI in a second set of models. We also conducted Mendelian randomization analyses to assess the potential causal relationship between diet-related CpGs and cardiometabolic traits. We found 18 differentially methylated CpGs associated with dietary scores (P < 1.08 × 10-7; Bonferroni correction), of which 12 were previously associated with cardiometabolic traits. Enrichment analysis revealed overrepresentation of diet-associated genes in pathways involved in inflammation and cardiovascular disease. Mendelian randomization analyses suggested that genetically determined methylation levels corresponding to lower diet quality at cg02079413 (SNORA54), cg02107842 (MAST4), and cg23761815 (SLC29A3) were causally associated with higher BMI and at cg05399785 (WDR8) with greater SBP, and methylation levels associated with higher diet quality at cg00711496 (PRMT1) with lower BMI, T2D risk, and CHD risk and at cg0557921 (AHRR) with lower CHD risk. Diet quality in adults was related to differential methylation in blood at 18 CpGs, some of which related to cardiometabolic health.

Replacing device-measured sedentary time with physical activity is associated with lower risk of coronary heart disease regardless of genetic risk.

Excess sedentary time (ST) is recognized as an important modifiable risk factor for coronary heart disease (CHD). However, whether the associations of genetic susceptibility with CHD incidence can be modified by replacing wearable-device-measured ST with physical activity (PA) is unknown. To examine the associations of wearable-device-measured ST replaced by PA with incident CHD across strata of genetic susceptibility. This study included 77,500 White British (57% female) with valid wrist-worn accelerometry and without prevalent CHD/stroke from UK Biobank. Genetic susceptibility to CHD was quantified through weighted polygenic risk scores for CHD based on 300 single-nucleotide polymorphisms. Wrist-worn accelerometer data were used to derive ST, light PA, and moderate-to-vigorous PA (MVPA). Reallocation of 60min/day of ST into the same amount of MVPA was associated with approximately 9% lower relative risk of CHD for all participants and across strata of genetic risk: replacement of 1min/day of ST associated with <1% lower relative risk of CHD. No evidence of interaction (p: 0.784) was found between genetic risk and ST for CHD risk. Reallocating 60min/day of ST into the same MVPA time was associated with greater absolute CHD risk reductions at high genetic risk (0.27%) versus low genetic risk (0.15%). Replacing any amount of ST with an equal amount of MVPA time is associated with a lower relative risk of CHD, irrespective of genetic susceptibility to CHD. Reductions in CHD absolute risk for replacing ST with MVPA are greater at high genetic risk versus low genetic risk.

Bedtime, sleep pattern, and incident cardiovascular disease in middle-aged and older Chinese adults: The dongfeng-tongji cohort study

ObjectivesTo investigate the associations of bedtime and a low-risk sleep pattern with incident cardiovascular disease (CVD). MethodsA total of 31,500 retirees were included from the Dongfeng-Tongji cohort in 2008–2010 and 2013. Sleep information was collected by questionnaires. CVD events were identified through the health care system until December 31, 2018. Cox proportional hazards regression models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). ResultsDuring an average follow-up of 7.2 years, 8324 cases of incident CVD, including 6557 coronary heart disease (CHD) and 1767 stroke, were documented. U-shaped associations of bedtime with the risks of incident CVD and stroke were observed. Compared with bedtime between 10:01 p.m.-11:00 p.m., the HR (95% CI) for CVD was 1.10 (1.01–1.20) for ≤9:00 p.m., 1.07 (1.01–1.13) for 9:01 p.m.-10:00 p.m., and 1.32 (1.11–1.58) for >12:00 a.m., respectively, mainly driven by stroke risk (22%, 14%, and 70% higher for ≤9:00 p.m., 9:01 p.m.-10:00 p.m., and >12:00 a.m., respectively). The number of low-risk sleep factors, namely bedtime between 10:01 p.m.-12:00 a.m., sleep duration of 7-< 8 h/night, good/fair sleep quality, and midday napping ≤60 min, exhibited dose-dependent relationships with CVD, CHD, and stroke risks. Participants with 4 low-risk sleep factors had a respective 24%, 21%, and 30% lower risk of CVD, CHD, and stroke than those with 0–1 low-risk sleep factor. ConclusionsIndividuals with early or late bedtimes had a higher CVD risk, especially stroke. Having low-risk sleep habits is associated with lower CVD risks.

Standing Blood Pressure and Risk of Falls, Syncope, Coronary Heart Disease, and Mortality.

ACC/AHA guidelines caution against the use of antihypertensive therapy in the setting of low standing systolic BP (SBP) < 110 mm Hg due to unclear benefits. The Atherosclerosis Risk in Communities (ARIC) Study measured supine and standing SBP in adults aged 45-64 years between 1987 and 1989. We used Cox regression to evaluate the associations of low standing SBP (<110 mm Hg) with risk of falls, syncope, coronary heart disease (CHD), and mortality through December 31, 2019. Falls and syncope were ascertained by hospitalization and outpatient claims; CHD events were adjudicated. Associations were examined overall and in strata of hypertension stage, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and sex. Among 12,467 adults followed a median of 24 years (mean age at enrollment 54.1 ± 5.8 years, 55% women, 26% Black adults), 3,000 (24%) had a standing SBP < 110 mm Hg. A standing SBP < 110 mm Hg compared to standing SBP ≥ 110 mm Hg was not significantly associated with falls or syncope, and was associated with a lower risk of CHD events and mortality with HRs of 1.02 (95% CI 0.94, 1.11), 1.02 (0.93, 1.11), 0.88 (0.80, 0.97), and 0.91 (0.86, 0.97), respectively. There were no clinically meaningful differences when stratified by hypertension stage, 10-year ASCVD risk, age, and sex. In this community-based population, low standing SBP was common and not significantly associated with falls or syncope, but was associated with a lower risk of CHD and mortality. These findings do not support screening for low standing BP as a risk factor for adverse events.

1362-P: The Long-Term Cardiovascular Effects of Metformin on Patients with Newly Diagnosed Type 2 Diabetes

Objective: Metformin is the first pharmacological option for preventing and treating type 2 diabetes. However, the use of this drug in preventing cardiovascular disease associated with the development of newly diagnosed type 2 diabetes is unclear. We aimed to examine whether the metformin reduced the incidence of major cardiovascular events over a 20-year follow-up of patients with newly diagnosed type 2 diabetes. Research Design and Methods: We conducted a retrospective observational cohort study of 48,338 patients with type 2 diabetes from Anhui Provincial Hospital between January 1, 2000, and June 30, 2021. Data were collected for patients with newly diagnosed T2D (within 6 months) who did not have prior cardiovascular disease and took metformin at baseline were compared with those who did not using. The primary outcome was the first occurrence of major cardiovascular events including coronary heart disease (CHD), stroke, and hospitalization due to heart failure (HF). The multivariate Cox proportional hazards regression with inverse probability of treatment weighting. Propensity score matching (PSM) was conducted for reducing the biases of baseline characteristics. Results: After matching, newly diagnosed T2D patients who used metformin, compared with those who did not use, had significantly lower risk of HF (HR 0.51, 95% CI 0.28 to 0.93) and CHD (HR 0.37, 95% CI 0.13 to 1.09). No difference in the risk incident stroke (HR 0.89, 95% CI 0.68 to 1.17) was observed. In both the original and PSM groups, use of metformin can reduce the risk of CHD events from newly diagnosed T2D patients (adjusted HR 0.74; 95% CI 0.69-0.87; P = 0.029). Conclusions: In the present retrospective study, metformin use may be beneficial for preventing CHD and HF in newly diagnosed T2D patients. Further randomized controlled trials are needed to confirm these findings. Disclosure T.Yue: None. X.Wang: None. M.Zhao: None. J.Weng: None. S.Luo: None. X.Zheng: None.

Life's Essential 8, Genetic Susceptibility, and Incident Cardiovascular Disease: A Prospective Study.

The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between levels of LE8 and the risk of cardiovascular disease (CVD) outcomes is not known from a large prospective cohort. We aim to analyze the relationship between CVH, indicated by LE8, and risks of coronary heart disease (CHD), stroke, and CVD. Moreover, we sought to test whether the genetic susceptibility to CHD or stroke could be modified by LE8. A total of 137 794 participants free of CVD from the UK Biobank were included. CVH was scored using LE8 and categorized as low, moderate, and high. During a median of 10 years, 8595 CVD cases (6968 CHDs and 1948 strokes) were documented. A higher LE8 score was associated with remarkably lower risks of CHD, stroke, and CVD (P<0.001 for all). Comparing the high CVH to the low CVH, the hazard ratios (95% CI) were 0.34 (0.30-0.38) for CHD, 0.45 (0.37-0.54) for stroke, and 0.36 (0.33-0.40) for CVD. Moreover, the model with LE8 achieved higher accuracy and outperformed the model with Life's Simple 7 for CHD, stroke, and CVD (P<0.001 for all). The protective associations of the LE8 score with CVD outcomes were more pronounced among women (P interaction, <0.001 for CHD and 0.0013 for CVD, respectively) and among younger adults (P interaction, <0.001, 0.007, and <0.001 for CHD, stroke, and CVD, respectively). In addition, a significant interaction was found between the genetic risk of CHD and the LE8 score (P interaction, <0.001). The inverse association was stronger among those with a lower genetic risk of CHD. High level of CVH, defined by LE8, was associated with significantly lower risks of CHD, stroke, and CVD.

Abstract 35: Adherence to Life’s Essential 8, Genetic Susceptibility, and Incident Cardiovascular Disease: A Prospective Study of 137,794 UK Biobank Participants

Introduction: The American Heart Association recently introduced an enhanced approach to assess cardiovascular health (CVH): Life’s essential 8 (LE8). Sleep was included as a new component. The current study sought to analyze the relationship between levels of CVH, indicated by the LE8 score, and risks of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD). Hypothesis: We hypothesized that higher CVH, indicated by the LE8 score, was associated with lower risks of CHD, stroke, and CVD; LE8 might also interact with genetic susceptibility. Methods: The current study included 137,794 participants free of CVD from the UK Biobank. CVH was scored at baseline by LE8 (DASH diet score, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure). The LE8 score ranged from 0 to 100; and was categorized as low (0-49), moderate (50-79), and high (80-100). Weighted genetic risk scores (GRS) for CHD and stroke were calculated. Cox proportional hazard model was used to assess the relationship between LE8 and incident CVD outcomes, and potential interaction with age, gender, and GRS. We also compared the performance of LE8 with Life’s Simple 7 (LS7) using Harrell’s C-index. Results: During a median of 10 years, 8,595 CVD cases (6,968 CHD and 1,948 strokes) were documented. A higher LE8 score was associated with remarkably lower risks of CHD, stroke, and CVD (p&lt;0.001 for all). Comparing the high CVH to the low CVH, the adjusted HRs (95% CI) were 0.34 (0.30, 0.38) for CHD, 0.45 (0.37, 0.54) for stroke, and 0.36 (0.33, 0.40) for CVD. Moreover, the model with LE8 achieved higher accuracy and outperformed the model with LS7 (C-index: 0.7417 vs. 0.7345, p&lt;0.001 for CHD, 0.7208 vs. 0.7165, p&lt;0.001 for stroke, and 0.7339 vs. 0.7276, p&lt;0.001 for CVD). The protective associations of the LE8 score with CVD outcomes were more pronounced among women (p-interaction &lt;0.001 for CHD and 0.0013 for CVD, respectively), and among younger adults (p-interaction &lt;0.001, 0.007, and &lt;0.001 for CHD, stroke, and CVD, respectively). In addition, we found a significant interaction between the GRS of CHD and the LE8 score (p-interaction &lt;0.001). The inverse association was stronger among those with a lower genetic risk of CHD. Conclusions: High level of CVH, defined by LE8, was associated with significantly lower risks of CHD, stroke, and CVD. Such relationships are more pronounced among women, younger adults, and people with a lower genetic predisposition.

Abstract P523: Joint Improvement Scale of Loneliness and Traditional Risk Factor Control, and Incident Cardiovascular Disease in Diabetes Patients

Background: Emerging evidence has shown a higher rate of loneliness and social isolation among patients with diabetes, and loneliness and isolation has been associated with high risk of cardiovascular disease (CVD). Hypothesis: We investigated the extent to which the risks of CVDs could be lowered by improvement of loneliness and social isolation, individually or in conjunction with controlling traditional risk factors in diabetic patients. Methods: A total of 18,783 participants diagnosed with diabetes from the UK Biobank were included. A two-item scale and a three-item scale were used to assess the improvement of loneliness and isolation status, respectively. The degree of traditional risk-factor control was defined as the number of glycated hemoglobin (HbA1c), blood pressure (BP), low-density-lipoprotein cholesterol (LDL-C), smoking and microalbumin reaching the target range. Results: During a mean follow-up of 10.7 years, 3,129 incident total CVD events were documented, including 2,627 coronary heart disease (CHD) and 721 stroke. We found that each point increase in loneliness improvement scale was significantly associated with an 11% lower risk of CVD (HR, 95%CI, 0.89, 0.84-0.93) and a 12% lower risk of CHD (HR, 95%CI, 0.88, 0.83-0.93), but not with stroke. The improvement scale of social isolation was not associated with CVDs. Loneliness showed greater relative importance than lifestyle risk factors in preventing CVD among diabetic patients. We found a significant additive interaction between loneliness and the degree of traditional risk-factor control on the risk of CVDs ( P for additive interaction=0.002). Moreover, compared with non-diabetes controls, the diabetes-related excess CVD risk might be eliminated when three or more risk factors were controlled in non-lonely patients, but more than four are required in lonely patients. Conclusion: Among diabetes patients, improvement of loneliness is associated with a lower risk of CVD and shows an additive interaction with traditional risk factor control.

Abstract MP65: Magnesium-Rich Diet Score is Inversely Associated With Incident Cardiovascular Disease: The Atherosclerosis in Communities (ARIC) Study

Background: Numerous studies have shown inverse associations between serum magnesium (Mg) levels and risk of cardiovascular disease (CVD), but studies of dietary Mg have not been consistent. Aim: The association of a Mg-rich diet score with risks of incident CVD, coronary heart disease (CHD), and ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study was examined. Methods: There were 15,022 Black and White adults without prevalent CVD included in this analysis. Diet was assessed at two visits using an interviewer-administered 66-item food frequency questionnaire. A Mg-rich diet score was created including whole grain products, nuts, fruits, vegetables, legumes, coffee, and tea. Cox proportional hazard regression evaluated the associations of incident CVD, CHD and stroke through 2019 across quintiles of Mg-rich diet score adjusted for demographic characteristics, lifestyle factors, and clinical characteristics. Results: Participants in the highest quintile of Mg-rich diet score compared to the lowest quintile consumed more servings of Mg-rich foods and fiber and less refined grains, red and processed meat, total fat and saturated fat. Over 30 years of follow up, a Mg-rich diet score was inversely associated with incident CVD (HR Q5 vs Q1 =0.88, 95% CI 0.78-0.99, p trend =0.03) and CHD (HR=0.83, 95% CI 0.72-0.96, p trend =0.01); however the diet-stroke association was null (HR=1.08, 95% CI 1.07-1.09, p trend =0.93) (Table). Conclusions: Consuming a diet rich in whole grains, nuts, fruits and vegetables, legumes, coffee and tea is consistent with a lower long-term risk of CVD and CHD.

Abstract P595: Low Serum Cholesterol and Coronary Heart Disease Mortality in Veterans

Background: The lipid hypothesis postulates that lower blood cholesterol is associated with reduced coronary heart disease (CHD) risk, which has been challenged by recent studies that observed a U-shaped relation between cholesterol and mortality. The effect of low cholesterol and CHD risk among Veterans is unclear. Methods: This prospective cohort study included Veterans greater than 18 years of age with baseline outpatient visits from 2002 to 2007 and follow-up to December 30, 2018 in the Veterans Health Administration electronic health record system. Veterans were followed to assess CHD mortality risk in relation to outpatient blood cholesterol levels. We used Cox proportional hazard regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) of CHD mortality associated with total cholesterol (TC). Results: Among 4,467,942 Veterans, 381,871 CHD deaths were recorded. We observed a V-shaped relation between TC and age-, sex, race and smoking-adjusted risk of CHD mortality. The association became U-shaped after adjustment for statin use, body mass index, hypertension, and diabetes. When further adjusted for high-density lipoprotein level, 11 baseline diseases, and applying a 2-year lag analysis, the relation to CHD mortality was J-shaped--flat for TC&lt;180 mg/dL and greater risk was present at higher cholesterol levels. Compared to Veterans with TC between 180-199 mg/dL, risk for CHD mortality (HR (95%CI)) was 1.03 (1.02-1.04), 1.07 (1.06-1.09), 1.15 (1.13-1.18), 1.25 (1.22-1.28) and 1.45 (1.42-1.49) times greater among Veterans with TC (mg/dL) of 200-219, 220-239, 140-259, 260-279 and ≥280, respectively. Transition of the TC- CHD mortality patterns were J-J-J, V-U-J and L-U-J among young, middle, and older veterans (P for interaction between TC and age group &lt; 0.001). Similar J-shaped but weaker relations were observed in statin users at baseline. Conclusions: Based on prospective data for almost 4.5 million adult Veterans, CHD mortality risk steadily increased for TC ≥200mg/dL after adjustment for a range of health conditions. Our results support the lipid hypothesis that lower blood cholesterol is associated with reduced CHD risk and lower prevalence of multimorbidity, mental health disorders, nutritional deficits, and other risk factors for CHD. Furthermore, the hypothesis remained true when TC was low due to use of statins or other lipid-lowering medication. The changes in risk for CHD mortality by TC groups observed in our study (L- to U- to J-shape) highlights the importance of fully adjusting for the presence of multimorbidity and HDL-C to avoid misleading conclusions.

Lifestyle Factors, Genetic Risk, and Cardiovascular Disease Risk among Breast Cancer Survivors: A Prospective Cohort Study in UK Biobank.

Evidence is limited regarding the association between lifestyles and cardiovascular disease (CVD), and the extent to which healthy lifestyles could offset the genetic risk of CVD in females with breast cancer (BC). Females diagnosed as BC, who were free of CVD at baseline, from UK Biobank were included. Five modifiable lifestyle factors were considered to calculate the healthy lifestyle score, namely body mass index (BMI), smoking, alcohol drinking, dietary habits, and physical activity. The polygenetic risk score (PRS) was derived for coronary heart disease (CHD), ischemic stroke (IS), and heart failure (HF). In 13,348 female BC survivors, there were 986 CVD events (736 CHD, 165 IS, and 353 HF) over a median of 8.01 years of follow-up. Participants with 4-5 healthy lifestyle components were associated with a decreased risk of incident CVD (HR: 0.50; 95%CI: 0.37, 0.66), CHD (HR: 0.49; 95%CI: 0.35, 0.69), IS (HR: 0.35; 95%CI: 0.19, 0.65), and HF (HR: 0.59; 95%CI: 0.36, 0.97), compared with those with 0-1 lifestyle components. Evidence for the genetic-lifestyle interaction was observed for CHD (p = 0.034) and HF (p = 0.044). Among participants at high genetic risk, a healthy lifestyle was associated with a lower risk of CHD (HR: 0.37; 95%CI: 0.24, 0.56), IS (HR: 0.37; 95%CI: 0.15, 0.93) and HF (HR: 0.39; 95%CI: 0.21, 0.73). Our findings suggest that BC survivors with a high genetic risk could benefit more from adherence to a healthy lifestyle in reducing CVD risk.

Coronary Artery Calcium Density and Cardiovascular Events by Volume Level: The MESA.

The Agatston coronary artery calcium (CAC) score provides robust cardiovascular disease risk prediction but upweights plaque area by a density factor. Density, however, has been shown to be inversely associated with events. Using CAC volume and density separately improves risk prediction, but it is unclear how to apply this method clinically. We aimed to evaluate the association between CAC density and cardiovascular disease across the spectrum of CAC volume to better understand how to incorporate these metrics into a single score. We performed an analysis of MESA (Multi-Ethnic Study of Atherosclerosis) participants with detectable CAC to evaluate the association between CAC density and events by level of CAC volume using multivariable Cox regression models. In a cohort of 3316 participants, there was a significant interaction (P<0.001) between CAC volume and density for coronary heart disease (CHD) risk (myocardial infarction, CHD death, resuscitated cardiac arrest). Models using CAC volume and density resulted in improvement in the C-index (0.703, SE 0.012 versus 0.687, SE 0.013) and a significant net reclassification improvement (0.208 [95% CI, 0.102-0.306]) compared with the Agatston score for CHD risk prediction. Density was significantly associated with lower CHD risk at volumes ≤130 mm3 (hazard ratio, 0.57 per unit of density [95% CI, 0.43-0.75]), but the inverse association at volumes >130 mm3 was not significant (hazard ratio, 0.82 per unit of density [95% CI, 0.55-1.22]). The lower risk for CHD associated with higher CAC density varied by level of volume, and volume ≤130 mm3 is a potentially clinically useful cut point. Further study is needed to integrate these findings into a unified CAC scoring method.