Risk Of Incident Cardiovascular Disease Research Articles

Proteomics and lipidomics in atherosclerotic cardiovascular disease risk prediction.

Given the limited accuracy of clinically used risk scores such as the Systematic COronary Risk Evaluation 2 system and the Second Manifestations of ARTerial disease 2 risk scores, novel risk algorithms determining an individual's susceptibility of future incident or recurrent atherosclerotic cardiovascular disease (ASCVD) risk are urgently needed. Due to major improvements in assay techniques, multimarker proteomic and lipidomic panels hold the promise to be reliably assessed in a high-throughput routine. Novel machine learning-based approaches have facilitated the use of this high-dimensional data resulting from these analyses for ASCVD risk prediction. More than a dozen of large-scale retrospective studies using different sets of biomarkers and different statistical methods have consistently demonstrated the additive prognostic value of these panels over traditionally used clinical risk scores. Prospective studies are needed to determine the clinical utility of a biomarker panel in clinical ASCVD risk stratification. When combined with the genetic predisposition captured with polygenic risk scores and the actual ASCVD phenotype observed with coronary artery imaging, proteomics and lipidomics can advance understanding of the complex multifactorial causes underlying an individual's ASCVD risk.

Changes in high-density lipoprotein cholesterol with risk of Cardiovascular Disease among initially high-density lipoprotein-high participants

BackgroundHigh-density lipoprotein cholesterol’s (HDL-C) long-held status as a cardiovascular disease (CVD) preventative has been called into question. Most of the evidence, however, focused on either the risk of death from CVD, or on single time point level of HDL-C. This study aimed to determine the association between changes in HDL-C levels and incident CVD in individuals with high baseline HDL-C levels (≥ 60 mg/dL).Methods77,134 people from the Korea National Health Insurance Service-Health Screening Cohort were followed for 517,515 person-years. Cox proportional hazards regression was used to evaluate the association between change in HDL-C levels and the risk of incident CVD. All participants were followed up until 31 December 2019, CVD, or death.ResultsParticipants with the greatest increase in their HDL-C levels had higher risks of CVD (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.05–1.25) and CHD (aHR 1.27, CI 1.11–1.46) after adjusting for age, sex, household income, body mass index, hypertension, diabetes mellitus, dyslipidemia, smoking, alcohol consumption, moderate-to-vigorous physical activity, Charlson comorbidity index, and total cholesterol than those with the lowest increase in HDL-C levels. Such association remained significant even among participants with decreased low-density lipoprotein cholesterol (LDL-C) levels for CHD (aHR 1.26, CI 1.03–1.53).ConclusionsIn people with already high HDL-C levels, additional increases in HDL-C levels may be associated with an increased risk of CVD. This finding held true irrespective of the change in their LDL-C levels. Increasing HDL-C levels may lead to unintentionally elevated risk of CVD.

Genome-wide polygenic risk scores for hypertensive disease during pregnancy can also predict the risk for long-term cardiovascular disease

Hypertensive disorders during pregnancy are associated with the risk of long-term cardiovascular disease after pregnancy, but it has not yet been determined whether genetic predisposition for hypertensive disorders during pregnancy can predict the risk for long-term cardiovascular disease. This study aimed to evaluate the risk for long-term atherosclerotic cardiovascular disease according to polygenic risk scores for hypertensive disorders during pregnancy. Among UK Biobank participants, we included European-descent women (n=164,575) with at least 1 live birth. Participants were divided according to genetic risk categorized by polygenic risk scores for hypertensive disorders during pregnancy (low risk, score ≤25th percentile; medium risk, score 25th∼75th percentile; high risk, score >75th percentile), and were evaluated for incident atherosclerotic cardiovascular disease, defined as the new occurrence of one of the following: coronary artery disease, myocardial infarction, ischemic stroke, or peripheral artery disease. Among the study population, 2427 (1.5%) had a history of hypertensive disorders during pregnancy, and 8942 (5.6%) developed incident atherosclerotic cardiovascular disease after enrollment. Women with high genetic risk for hypertensive disorders during pregnancy had a higher prevalence of hypertension at enrollment. After enrollment, women with high genetic risk for hypertensive disorders during pregnancy had an increased risk for incident atherosclerotic cardiovascular disease, including coronary artery disease, myocardial infarction, and peripheral artery disease, compared with those with low genetic risk, even after adjustment for history of hypertensive disorders during pregnancy. High genetic risk for hypertensive disorders during pregnancy was associated with increased risk for atherosclerotic cardiovascular disease. This study provides evidence on the informative value of polygenic risk scores for hypertensive disorders during pregnancy in prediction of long-term cardiovascular outcomes later in life.

Vasomotor symptoms and risk of cardiovascular disease in peri- and postmenopausal women: A systematic review and meta-analysis

IntroductionVasomotor symptoms (VMS) are the symptoms most frequently experienced by women transitioning to menopause and are a primary indication for menopausal hormone therapy. A growing body of evidence has associated the presence of VMS with future risk for cardiovascular disease (CVD) events. This study aimed to systematically evaluate, qualitatively and quantitatively, the possible association between VMS and the risk for incident CVD. MethodsThis systematic review and meta-analysis included 11 studies evaluating peri- and postmenopausal women in a prospective design. The association between VMS (hot flashes and/or night sweats) and the incidence of major adverse cardiovascular events, including coronary heart disease (CHD) and stroke, was explored. Associations are expressed as relative risks (RR) with 95 % confidence intervals (CI). ResultsThe risk for incident CVD events in women with and without VMS differed according to the age of participants. Women with VSM younger than 60 years at baseline had a higher risk of an incident CVD event than women without VSM of the same age (RR 1.12, 95 % CI 1.05–1.19, I2 0%). Conversely, the incidence of CVD events was not different between women with and without VMS in the age group >60 years (RR 0.96, 95 % CI 0.92–1.01, I2 55%). ConclusionThe association between VMS and incident CVD events differs with age. VMS increases the incidence of CVD only in women under 60 years of age at baseline. The findings of this study are limited by the high heterogeneity among studies, pertaining mainly to different population characteristics, definitions of menopausal symptoms and recall bias.

Mediation analysis in the presence of continuous exposure measurement error.

The difference method is used in mediation analysis to quantify the extent to which a mediator explains the mechanisms underlying the pathway between an exposure and an outcome. In many health science studies, the exposures are almost never measured without error, which can result in biased effect estimates. This article investigates methods for mediation analysis when a continuous exposure is mismeasured. Under a linear exposure measurement error model, we prove that the bias of indirect effect and mediation proportion can go in either direction but the mediation proportion is usually be less biased when the associations between the exposure and its error-prone counterpart are similar with and without adjustment for the mediator. We further propose methods to adjust for exposure measurement error with continuous and binary outcomes. The proposed approaches require a main study/validation study design where in the validation study, data are available for characterizing the relationship between the true exposure and its error-prone counterpart. The proposed approaches are then applied to the Health Professional Follow-up Study, 1986-2016, to investigate the impact of body mass index (BMI) as a mediator for mediating the effect of physical activity on the risk of cardiovascular diseases. Our results reveal that physical activity is significantly associated with a lower risk of cardiovascular disease incidence, and approximately half of the total effect of physical activity is mediated by BMI after accounting for exposure measurement error. Extensive simulation studies are conducted to demonstrate the validity and efficiency of the proposed approaches in finite samples.

Association of Incident Cardiovascular Disease With Time Course and Cumulative Exposure to Multiple Risk Factors

BackgroundThe quantitative relationship of incident cardiovascular disease (CVD) to lifetime cumulative risk factor exposure is not well understood. ObjectivesUsing CARDIA (Coronary Artery Risk Development in Young Adults) study data, we examined the quantitative associations of cumulative exposure over time to multiple, simultaneously operating risk factors with CVD incidence and the incidence of its components. MethodsRegression models were developed quantifying the influence of the time course and severity of multiple CVD risk factors, operating simultaneously, on risk of incident CVD. The outcomes were incident CVD and the incidence of its components: coronary heart disease, stroke, and congestive heart failure. ResultsOur study included 4,958 asymptomatic adults enrolled in CARDIA from 1985 to 1986 (ages 18 to 30 years) who were followed for 30 years. Risk of incident CVD depends on the time course and severity of a series of independent risk factors, the impact of which is mediated by their effects on individual CVD components after age 40 years. Cumulative exposure (AUC vs time) to low-density lipoprotein cholesterol and triglycerides was independently associated with risk of incident CVD. Of the blood pressure variables, areas under the mean arterial pressure vs time curve and the pulse pressure vs time curve were strongly and independently associated with incident CVD risk. ConclusionsThe quantitative description of the link between risk factors and CVD informs the construction of individualized CVD mitigation strategies, design of primary prevention trials, and assessment of public health impact of risk factor-based interventions.

Abstract P418: Dietary Glutamine and Glutamate in Relation to Cardiovascular Disease and Mortality in Adults With Type 2 Diabetes

Background: The potential health effects of dietary glutamine and glutamate have been studied in healthy populations, but evidence among individuals with type 2 diabetes (T2D) who have altered macronutrient metabolism and elevated cardiovascular disease (CVD) risk is limited. Objectives: We aimed to examine dietary glutamine and glutamate in relation to subsequent risk of CVD, including coronary heart disease and stroke, and all-cause and cause-specific mortality among individuals with T2D. Methods: We prospectively followed 15,040 men and women with T2D at baseline or diagnosed during follow-up (Nurses' Health Study: 1980-2014, Health Professionals Follow-Up Study: 1986-2018). Diet was repeatedly assessed using validated food frequency questionnaires every 2-4 years since baseline. Associations of energy-adjusted glutamine and glutamate intake, as well as their ratio, with CVD risk and mortality were assessed using Cox proportional hazards models with adjustments for demographics, dietary and lifestyle factors, and medical history. Results: During 196,955 and 225,371person-years of follow-up in participants with T2D, there were 2,927 incident CVD cases and 4,898 deaths, respectively. Higher intake of glutamine was associated with lower risk of incident CVD, total mortality and CVD mortality: comparing extreme quintiles, the HRs (95%CIs) were 0.88 (0.77, 0.99), 0.85 (0.77, 0.94), and 0.82 (0.69, 0.98), respectively (all P trend <0.05). In contrast, higher intake of glutamate was associated with higher risk of incident CVD, total mortality, and CVD mortality; the HRs were 1.30 (1.15, 1.46), 1.19 (1.08, 1.31), and 1.42 (1.21, 1.67), respectively (all P trend <0.05). Furthermore, comparing extreme quintiles, higher dietary glutamine-to-glutamate ratio was associated with lower risk of CVD incidence (0.84 (0.75, 0.95)), total mortality (0.83 (0.76, 0.91)), and CVD mortality (0.69 (0.59, 0.80)). In addition, compared with participants without increment in glutamine-to-glutamate ratio from pre- to post-diabetes diagnosis, those who increased the ratio had a 15% (3%, 25%) lower CVD mortality. Conclusions: In patients with T2D, dietary glutamine and glutamate demonstrated divergent associations with CVD incidence and mortality, and higher dietary glutamine-to-glutamate ratio was significantly associated with lower CVD incidence and mortality. These data suggest a potential critical role of these two amino acids in the etiology of cardiometabolic diseases and early deaths also among adults with T2D.

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.

Association of frailty with the incidence risk of cardiovascular disease and type 2 diabetes mellitus in long-term cancer survivors: a prospective cohort study

BackgroundComorbidities among cancer survivors remain a serious healthcare burden and require appropriate management. Using two widely used frailty indicators, this study aimed to evaluate whether frailty was associated with the incidence risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) among long-term cancer survivors.MethodsWe included 13,388 long-term cancer survivors (diagnosed with cancer over 5 years before enrolment) free of CVD and 6101 long-term cancer survivors free of T2DM, at the time of recruitment (aged 40–69 years), from the UK Biobank. Frailty was assessed by the frailty phenotype (FP_Frailty, range: 0–5) and the frailty index (FI_Frailty, range: 0–1) at baseline. The incident CVD and T2DM were ascertained through linked hospital data and primary care data, respectively. The associations were examined using Cox proportional hazards regression models.ResultsCompared with non-frail participants, those with pre-frailty (FP_Frailty [met 1–2 of the components]: hazard ratio [HR]=1.18, 95% confidence interval [CI]: 1.05, 1.32; FI_Frailty [0.10< FI ≤0.21]: HR=1.51, 95% CI: 1.32, 1.74) and frailty (FP_Frailty [met ≥3 of the components]: HR=2.12, 95% CI: 1.73, 2.60; FI_Frailty [FI >0.21]: HR=2.19, 95% CI: 1.85, 2.59) had a significantly higher risk of CVD in the multivariable-adjusted model. A similar association of FI_Frailty with the risk of incident T2DM was observed. We failed to find such an association for FP_Frailty. Notably, the very early stage of frailty (1 for FP_Frailty and 0.1-0.2 for FI_Frailty) was also positively associated with the risk of CVD and T2DM (FI_Frailty only). A series of sensitivity analyses confirmed the robustness of the findings.ConclusionsFrailty, even in the very early stage, was positively associated with the incidence risk of CVD and T2DM among long-term cancer survivors, although discrepancies existed between frailty indicators. While the validation of these findings is required, they suggest that routine monitoring, prevention, and interventive programs of frailty among cancer survivors may help to prevent late comorbidities and, eventually, improve their quality of life. Especially, interventions are recommended to target those at an early stage of frailty when healthcare resources are limited.

Pregnancy loss and risk of incident CVD within 5 years: Findings from the Women's Health Initiative.

Previous studies have demonstrated an increased risk of cardiovascular disease (CVD) in women with a history of pregnancy loss. Less is known about whether pregnancy loss is associated with age at the onset of CVD, but this is a question of interest, as a demonstrated association of pregnancy loss with early-onset CVD may provide clues to the biological basis of the association, as well as having implications for clinical care. We conducted an age-stratified analysis of pregnancy loss history and incident CVD in a large cohort of postmenopausal women aged 50-79 years old. Associations between a history of pregnancy loss and incident CVD were examined among participants in the Women's Health Initiative Observational Study. Exposures were any history of pregnancy loss (miscarriage and/or stillbirth), recurrent (2+) loss, and a history of stillbirth. Logistic regression analyses were used to examine associations between pregnancy loss and incident CVD within 5 years of study entry in three age strata (50-59, 69-69, and 70-79). Outcomes of interest were total CVD, coronary heart disease (CHD), congestive heart failure, and stroke. To assess the risk of early onset CVD, Cox proportional hazard regression was used to examine incident CVD before the age of 60 in a subset of subjects aged 50-59 at study entry. After adjustment for cardiovascular risk factors, a history of stillbirth was associated with an elevated risk of all cardiovascular outcomes in the study cohort within 5 years of study entry. Interactions between age and pregnancy loss exposures were not significant for any cardiovascular outcome; however, age-stratified analyses demonstrated an association between a history of stillbirth and risk of incident CVD within 5 years in all age groups, with the highest point estimate seen in women aged 50-59 (OR 1.99; 95% CI, 1.16-3.43). Additionally, stillbirth was associated with incident CHD among women aged 50-59 (OR 3.12; 95% CI, 1.33-7.29) and 60-69 (OR 2.06; 95% CI, 1.24-3.43) and with incident heart failure and stroke among women aged 70-79. Among women aged 50-59 with a history of stillbirth, a non-significantly elevated hazard ratio was observed for heart failure before the age of 60 (HR 2.93, 95% CI, 0.96-6.64). History of stillbirth was strongly associated with a risk of cardiovascular outcomes within 5 years of baseline in a cohort of postmenopausal women aged 50-79. History of pregnancy loss, and of stillbirth in particular, might be a clinically useful marker of cardiovascular disease risk in women.

VEGF Inhibition in Retinal Vein Occlusion Does Not Associate with Cardiovascular Morbidity or Mortality

Intravitreal treatment with VEGF inhibitors has proven safe in clinical trials, but often on selected patient groups and without statistical power to investigate rare safety events. Data on anti-VEGF treatment in patients with retinal vein occlusion (RVO) are sparsely represented, and studies providing population-based, long-term follow-up are needed to assess the risks in routine clinical practice. We aimed to evaluate the association between treatment with anti-VEGF and the risk of incident cardiovascular disease (CVD) and all-cause mortality in patients with RVO, and whether this association was affected by selected risk factors. A cohort study from January 2012 to December 2018 using Danish nationwide registries linked on an individual level. Patients with RVO (n= 7235), exposed (n= 3508), and unexposed (n= 3727) to anti-VEGF, aged ≥ 40 years, alive, and living in Denmark. Cox proportional hazards analysis evaluating the effect of intravitreal VEGF inhibitory treatment on incident CVD and all-cause mortality. A predefined analysis plan specified primary outcomes as hazard ratios (HRs) of a composite CVD endpoint and all-cause mortality in patients treated with anti-VEGF compared with untreated. Secondary outcomes included cumulative dose analysis, HRs on subgroups of CVD, and stratified analyses evaluating the effect of sex, age, diabetes, intensive treatment, and preexisting CVD on the HRs. We found no increased risk of composite CVD (HR, 1.07; 95% confidence interval [CI], 0.89-1.29) or all-cause mortality (HR, 0.88; 95% CI, 0.77-1.00) in patients with RVO treated with anti-VEGF. In the secondary analyses, we found no dose-response relationship. We found an increased risk of intracranial hemorrhage (HR, 1.66; 95% CI, 1.02-2.71), but no increased risks in remaining subgroups of CVD. We found no increased risk associated with selected predisposing risk factors, and no increased risk in patients with preexisting CVD. Treatment with anti-VEGF in patients with RVO is safe, when evaluated in a nationwide, population-based setting. An increased risk of intracranial hemorrhage might be present, but cannot be reliably quantified and should be further elucidated by larger population-based studies including all indications for anti-VEGF treatment. Proprietary or commercial disclosure may be found after the references.

Associations between types and sources of dietary carbohydrates and cardiovascular disease risk: a prospective cohort study of UK Biobank participants

BackgroundRecent studies have reported that the associations between dietary carbohydrates and cardiovascular disease (CVD) may depend on the quality, rather than the quantity, of carbohydrates consumed. This study aimed to assess the associations between types and sources of dietary carbohydrates and CVD incidence. A secondary aim was to examine the associations of carbohydrate intakes with triglycerides within lipoprotein subclasses.MethodsA total of 110,497 UK Biobank participants with ≥ two (maximum five) 24-h dietary assessments who were free from CVD and diabetes at baseline were included. Multivariable-adjusted Cox regressions were used to estimate risks of incident total CVD (4188 cases), ischaemic heart disease (IHD; 3138) and stroke (1124) by carbohydrate intakes over a median follow-up time of 9.4 years, and the effect of modelled dietary substitutions. The associations of carbohydrate intakes with plasma triglycerides within lipoprotein subclasses as measured by nuclear magnetic resonance (NMR) spectroscopy were examined in 26,095 participants with baseline NMR spectroscopy measurements.ResultsTotal carbohydrate intake was not associated with CVD outcomes. Free sugar intake was positively associated with total CVD (HR; 95% CI per 5% of energy, 1.07;1.03–1.10), IHD (1.06;1.02–1.10), and stroke (1.10;1.04–1.17). Fibre intake was inversely associated with total CVD (HR; 95% CI per 5 g/d, 0.96;0.93–0.99). Modelled isoenergetic substitution of 5% of energy from refined grain starch with wholegrain starch was inversely associated with total CVD (0.94;0.91–0.98) and IHD (0.94;0.90–0.98), and substitution of free sugars with non-free sugars was inversely associated with total CVD (0.95;0.92–0.98) and stroke (0.91;0.86–0.97). Free sugar intake was positively associated with triglycerides within all lipoproteins.ConclusionsHigher free sugar intake was associated with higher CVD incidence and higher triglyceride concentrations within all lipoproteins. Higher fibre intake and replacement of refined grain starch and free sugars with wholegrain starch and non-free sugars, respectively, may be protective for incident CVD.

Exposure to various ambient air pollutants and 9 cardiovascular conditions among individuals with diabetes: A prospective analysis of the UK Biobank

Background and aimsThe adverse effects of air pollutants on the risk of most cardiovascular diseases (CVDs) are well-established, but the risk of CVDs such as deep vein thrombosis, pulmonary embolism, or aortic valve stenosis have been underappreciated, especially in the diabetic population. This study aimed to evaluate associations between long-term air pollutants exposure and the risk of incident CVDs among participants with diabetes. MethodsThis study included 27,827 participants with baseline diabetes from the UK Biobank. We then estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CVDs associated with chronic air pollutant exposure in the diabetic population by fitting the Cox proportional hazards model. Moreover, we investigated the cardiovascular effects of air pollutants at concentrations below WHO guideline limits. ResultsAfter multivariable adjustment, long-term NO2 and NOx exposures were positively associated with the development of 8 and 6 types of CVDs in participants with diabetes, respectively. In term of particulate matters, the effect estimates ranged from 1.51 (1.13, 2.03) (coronary artery disease) to 4.65 (2.73, 7.92) (peripheral arterial disease) per 10 μg/m3 increase in PM2.5. Whereas, the effect estimates ranged from 1.15 (1.04, 1.27) (arterial hypertension) to 2.28 (1.40, 3.69) (pulmonary embolism) per 10 μg/m3 increase in PM10. In addition, our study discovered that for most of the cardiovascular events (8 of 9), the deleterious effects of air pollutants persisted even when participants were exposed to air pollutants concentrations below WHO guideline limits. ConclusionsLong-term exposure to ambient NO2, NOx, PM2.5, and PM10, either at normal or low level, increased risk of various cardiovascular outcomes in the diabetic population.

Nuts and Cardiovascular Disease Outcomes: A Review of the Evidence and Future Directions.

Nuts are nutrient-rich foods that contain many bioactive compounds that are beneficial for cardiovascular health. Higher consumption of nuts has been associated with a reduced risk of several cardiovascular diseases (CVD) in prospective cohort studies, including a 19% and 25% lower risk of CVD incidence and mortality, respectively, and a 24% and 27% lower risk of coronary heart disease incidence and mortality, respectively. An 18% lower risk of stroke mortality, a 15% lower risk of atrial fibrillation, and a 19% lower risk of total mortality have also been observed. The role of nuts in stroke incidence, stroke subtypes, peripheral arterial disease and heart failure has been less consistent. This narrative review summarizes recommendations for nuts by clinical practice guidelines and governmental organizations, epidemiological evidence for nuts and CVD outcomes, nut-containing dietary patterns, potential mechanisms of nuts and CVD risk reduction, and future research directions, such as the use of biomarkers to help better assess nut intake. Although there are still some uncertainties around nuts and CVD prevention which require further research, as summarized in this review, there is a substantial amount of evidence that supports that consuming nuts will have a positive impact on primary and secondary prevention of CVD.

Remnant cholesterol, LDL cholesterol and incident cardiovascular disease among Koreans: a national population-based study.

The synergistic association of remnant cholesterol (remnant-C) and low-density lipoprotein cholesterol (LDL-C) levels with incident cardiovascular disease (CVD) in various subgroups of Koreans was investigated. Using the national health insurance data, we included subjects aged between 40 and 70 without a history of CVD and at least two health screenings between 2009 and 2011. The subjects were divided into four groups by LDL-C and remnant-C levels. The primary outcome was CVD, which occurred between 2014 and 2017. Among 3,686,034 (45.6% women) of subjects, 144,004 cardiovascular events occurred. Individuals in both high LDL-C and high remnant-C [hazard ratio (HR) 1.266, 95% confidence interval (CI) 1.243-1.289; 7.9%], high LDL-C only (HR 1.098, 95% CI 1.083-1.113; 21.2%), and high remnant-C only groups (HR 1.102, 95% CI 1.087-1.118; 19.1%) had higher risks of CVD than the reference group (LDL-C < 3.4 mmol/L and remnant-C < 0.8 mmol/L; 51.8%). A continuous and linear increase in CVD risk was found in those with higher remnant-C levels after adjustment for several confounders, including LDL-C levels. The association of remnant-C ≥ 0.8 mmol/L with an increased CVD risk was consistent across various strata. Combined high remnant-C and LDL-C levels confer a higher CVD risk than that individually. Elevated remnant-C values, independent of LDL-C levels, were associated with a risk of incident CVD. Remnant-C levels in addition to LDL-C levels are important considerations in risk stratification for the primary prevention of CVD.

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.

Do associations of physical activity and sedentary behaviour with cardiovascular disease and mortality differ across socioeconomic groups? A prospective analysis of device-measured and self-reported UK Biobank data

ObjectiveTo examine if individual-level and area-level socioeconomic status (SES) modifies the association of moderate-to-vigorous physical activity (MVPA), domain-specific physical activity and sedentary behaviour with all-cause mortality (ACM) and incident cardiovascular...

Pregnancy-Related Complications and Incidence of Atrial Fibrillation: A Systematic Review

Pregnancy-related complications are associated with a higher risk of various incident cardiovascular diseases, but their specific potential relationship with incident atrial fibrillation (AF) is less clear. This systematic review summarises the available evidence from observational studies which have examined associations between pregnancy-related complications and the risk of AF. MEDLINE and EMBASE (Ovid) were searched for studies between 1990 to 10 February 2022. Pregnancy-related complications examined included hypertensive disorders of pregnancy (HDP), gestational diabetes, placental abruption, preterm birth, small-for-gestational-age and stillbirth. Study selection, data extraction and quality assessment were completed independently by two reviewers. Narrative synthesis was used to evaluate the results of the included studies. Nine observational studies were included, with eight eligible for narrative synthesis. Sample sizes ranged from 1839 to 2,359,386. Median follow-up ranged from 2 to 36 years. Six studies reported that pregnancy-related complications were associated with a significantly increased risk of incident AF. Hazard ratios (HRs) (95% confidence intervals) for the four studies that evaluated HDP ranged from 1.1 (0.8-1.6) to 1.9 (1.4-2.7). For the four studies that evaluated pre-eclampsia, HRs ranged from 1.2 (0.9-1.6) to 1.9 (1.7-2.2). Current evidence from observational studies suggests pregnancy-related complications are associated with a significantly higher risk of incident AF. However, only a small number of studies examining each pregnancy-related complication were identified, and considerable statistical heterogeneity was observed. Further large-scale prospective studies are required to confirm the association between pregnancy-related complications and incident AF.

Circulating Vitamin K Is Inversely Associated with Incident Cardiovascular Disease Risk among Those Treated for Hypertension in the Health, Aging, and Body Composition Study (Health ABC)

Circulating Vitamin K Is Inversely Associated with Incident Cardiovascular Disease Risk among Those Treated for Hypertension in the Health, Aging, and Body Composition Study (Health ABC)

Cardiovascular Outcomes according to Comorbidities and Low-Density Lipoprotein Cholesterol in Korean People with Type 2 Diabetes Mellitus.

There are no clear data to support the cardiovascular (CV) risk categories and low-density lipoprotein cholesterol (LDL-C) treatment goals in Korean people with type 2 diabetes mellitus (T2DM). We evaluated the incidence of cardiovascular disease (CVD) according to comorbidities and suggested LDL-C treatment goals in Korean people with T2DM in nationwide cohort data. Using the Korean National Health Insurance Service database, 248,002 people aged 30 to 90 years with T2DM who underwent routine health check-ups during 2009 were included. Subjects with previous CVD were excluded from the study. The primary outcome was incident CVD, defined as a composite of myocardial infarction and ischemic stroke during the follow-up period from 2009 to 2018. The mean age of the study participants was 59.6±10.9 years, and median follow-up period was 9.3 years. CVD incidence increased in the order of DM duration of 5 years or more (12.04/1,000 person-years), hypertension (HT) (12.27/1,000 personyears), three or more CV risk factors (14.10/1,000 person-years), and chronic kidney disease (18.28/1,000 person-years). The risk of incident CVD increased linearly from an LDL-C level of ≥70 mg/dL in most patients with T2DM. In T2DM patients without HT or with a DM duration of less than 5 years, the CVD incidence increased from LDL-C level of ≥100 mg/dL. For primary prevention of CVD in Korean adults with T2DM, it can be helpful to lower LDL-C targets when there are chronic kidney disease, HT, a long duration of diabetes mellitus, or three or more CV risk factors.