Incident Cardiovascular Disease Events Research Articles

Use of bisphosphonates in chronic kidney disease is associated with cardiovascular death.

Chronic kidney disease (CKD) is associated with increased cardiovascular risk, which may be mediated by vascular calcification. Based on evidence that bisphosphonates inhibit vascular calcification, we hypothesized use of bisphosphonates in CKD would be associated with lower incident cardiovascular disease (CVD), CVD-related mortality, and all-cause mortality. This was a longitudinal observational study including 2,593 Framingham Offspring participants. We used propensity score-adjusted Cox regression models to determine the association between bisphosphonate use and outcomes: time to incident CVD, time to CVD-related mortality, and time to all-cause mortality. The data were stratified by presence or absence of CKD, defined as estimated glomerular filtration rate <60 mL/min/1.73m2. The propensity score included age, sex, hypertension, smoking status, diabetes, total cholesterol, high-density lipoprotein, and self-reported history of fracture. In unadjusted and propensity score-adjusted analyses, those with CKD using bisphosphonates had a trend toward increased incident CVD risk (adjusted hazard ratio (HR) 1.66 (95% CI, 93-2.97)) compared to those with CKD not using bisphosphonates. Those with CKD using bisphosphonates also had increased risk of cardiovascular mortality in the propensity score-adjusted model (adjusted HR 2.20 (95% CI, 1.12-4.32)). There was no significant association between bisphosphonate use and all-cause mortality in participants with CKD. Among individuals without CKD, bisphosphonate use was significantly associated with an increase in all-cause mortality in the propensity-score adjusted analysis (adjusted HR 1.59 (95% CI, 1.27-1.98)). However, there was no significant association between bisphosphonate use and incident CVD events (adjusted HR 0.85 95% CI, 0.63-1.16) or CVD-related death (adjusted HR 0.70 (95% CI 0.36-1.37) in those without CKD. Contrary to our hypothesis, bisphosphonate use was associated with a trend toward increased incident CVD and a two-fold higher risk of CVD mortality in CKD.

Abstract 4129036: Air pollution and Cardiovascular Disease Incidence in a Pooled Analysis of 6 U.S. Cohorts

Introduction/Background: Long term air pollution is associated with cardiovascular disease (CVD) incidence, however the effects at low levels in the US are unknown. Research Questions/Hypothesis: To assess the effect of long-term exposure to ambient air pollution CVD incidence (myocardial infarction [MI], stroke, and all CVD) in a pooled analysis of epidemiological cohorts. Materials and Methods: We harmonized data from six cohorts (Cardiovascular Health Study, Nurses’ Health Study II, Multi-Ethnic Study of Atherosclerosis, and Reasons for Geographic And Racial Differences in Stroke Study, Sister Study, and Women’s Health Initiative) with both CVD incidence data and extensive covariate information. We predicted time-varying two-year average concentrations of particulate matter &lt;2.5 microns (PM 2.5 ) and nitrogen dioxide (NO 2 ) from 1990-2019 at participant residential addresses using validated regionalized spatio-temporal models, combining spatio-temporal universal kriging and partial least squares regression with inputs from monitoring data from regulatory and researcher-deployed networks, satellite remote-sensing data and chemical transport modeling. Cox proportional hazards regression models adjusted for individual and area-level information, including smoking status, socio-economic factors, anthropometry, blood pressure, cholesterol, and other clinical variables. Results: Our analysis included over 300,000 participants and 10,229 incident CVD events. The median residential concentration of PM 2.5 was 10.1 µg/m 3 and NO 2 was 9.3 ppb. A 5 µg/m 3 increase in PM 2.5 was not significantly associated with a higher hazard ratio for all outcomes: 1.03 (95%CI: 0.96, 1.10) for CVD incidence, 1.03 (95%CI 0.93, 1.15) for MI, and 1.00 (95%CI 0.90, 1.10) for stroke. We found that a 10ppb increase in NO 2 was associated with a 1.06 (95%CI: 1.01, 1.11) higher hazard ratio for CVD, 1.07 (95%CI: 1.01, 1.11) for MI, and 1.02 (95%CI 0.96, 1.09) for stroke. Conclusions: In this analysis of a large, pooled cohort with excellent exposure, outcome, and covariate information, we found an association of NO 2 exposure—considered a surrogate for traffic-related air pollution—with CVD incidence and MI. Associations with particulate matter were not statistically significant, but could not exclude a small increased risk. We are extending this analysis to include 6 additional cohorts and an additional 700,000 participants to allow for generation of a highly resolved concentration-response function.

Abstract 4127990: Inactive Matrix Gla Protein and Cardiovascular Outcomes: the Multi-Ethnic Study of Atherosclerosis

Background: Matrix Gla protein (MGP) inhibits arterial calcification. Higher inactive MGP, dephosphorylated-uncarboxylated (dp-ucMGP), is positively associated with vascular calcification, possibly portending cardiovascular events. The objective was to determine the association of dp-ucMGP with incident cardiovascular disease (CVD) events and mortality in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: MESA is a cohort study of 45-84 year-old individuals enrolled between 2000-02 with adjudicated outcomes through 2019. Dp-ucMGP was measured at baseline in n=2663 participants with cardiac computed tomography at Exams 1 (2000-02) and 5 (2010-12). Using age-stratified Cox proportional hazard models, adjusted for sex, race-ethnicity, body mass index, systolic blood pressure, statin use, anti-hypertensive medication use, smoking status, physical activity, alcohol use, diabetes, high density lipoprotein, low density lipoprotein, triglycerides, phosphate, and estimated glomerular filtration rate, we determined the association of dp-ucMGP with risk of all CVD (mean follow-up 16 + 4 years), hard CVD (17 + 3 years), hard CHD (17 + 3 years), and all-cause mortality (18 + 2 years). Results: The youngest age quartile (45-53-years-old) with higher dp-ucMGP levels (520-2934 pmol/L) had an increased risk of all CVD (HR 3.01 [95% CI 1.56, 5.80], p=0.001), hard CVD (HR 2.78 [95% CI 1.29, 6.02], p=0.009), hard CHD (HR 3.37 [95% CI 1.29, 8.81], p=0.013) and all-cause mortality (HR 2.69 [95% CI 1.06, 6.79], p=0.037) compared to dp-ucMGP levels between 150-519 pmol/L in maximally adjusted models. There was no relationship with any outcomes for the other age quartiles (Table). Conclusions: Middle aged individuals with elevated dp-ucMGP levels ( &gt; 520 pmol/L) had an increased risk of incident CVD, CHD, and all-cause mortality.

Abstract 4138672: Blood Pressure and Cardiovascular Outcomes in Adults with Diabetes and Chronic Kidney Disease

Background: Most international guidelines recommend intensive blood pressure (BP) targets (e.g., &lt;130/80 mm Hg) for patients with chronic kidney disease (CKD). However, the data supporting these recommendations are limited, particularly for those with concomitant diabetes. Hypothesis: Systolic BP (SBP) &lt;130 mm Hg and diastolic BP (DBP) &lt;80 mm Hg are associated with a reduced risk of cardiovascular disease (CVD) in adults with diabetes and CKD. Aims: To determine the association of BP with incident CVD risk among adults with diabetes and CKD. Methods: From a Korean nationwide health screening database, we identified 373,966 adults aged 20-79 with both diabetes and CKD who: (1) underwent baseline health examinations in 2009-2013; (2) had ≥3 BP measurements; and (3) did not have CVD at baseline. The associations of baseline average SBP and DBP with CVD risk were assessed using multivariable-adjusted cause-specific Cox models. The primary outcome was CVD event, defined as a composite of myocardial infarction, stroke, heart failure, or death from CVD. Results: The median (Q1-Q3) age of the participants was 62 (53-70) years; 40.8% were female. Over a median follow-up of 10.2 years, a total of 40,781 incident CVD events occurred. Compared with SBP 130 to &lt;140 mm Hg as the referent group, the multivariable-adjusted HRs (95% CIs) for CVD event in the SBP ≥150 mm Hg, 140 to &lt;150 mm Hg, 120 to &lt;130 mm Hg, and &lt;120 mm Hg groups were 1.34 (1.29-1.39), 1.11 (1.08-1.14), 0.89 (0.87-0.91), and 0.77 (0.74-0.80), respectively. Compared with DBP 80 to &lt;90 mm Hg as the referent group, the HRs (95% CIs) in the DBP ≥100 mm Hg, 90 to &lt;100 mm Hg, 70 to &lt;80 mm Hg, and &lt;70 mm Hg groups were 1.70 (1.56-1.85), 1.19 (1.15-1.24), 0.88 (0.86-0.90), and 0.83 (0.80-0.87), respectively (Figure A). SBP &lt;130 mm Hg and DBP &lt;80 mm Hg were each associated with a reduced CVD risk in a log-linear manner (Figure B, Figure C). The findings were consistent when examining kidney instead of cardiovascular outcomes. Conclusion: Among patients with diabetes and CKD, SBP below 130 mm Hg and DBP below 80 mm Hg were associated with a reduced risk of CVD.

Abstract 4136040: Wearable Device-Measured Physical Activity and Incident Cardiovascular Diseases In Cancer Survivors

Background: Cardiovascular diseases (CVD) is the leading cause of non-cancer mortality among cancer survivors. Despite the known benefits of physical activity on cardiovascular health in the general population, evidence regarding post-diagnosis physical activity and CVD risk among cancer survivors is limited. Objectives: To explore the associations of wearable device-measured moderate-to-vigorous intensity physical activity (MVPA) with CVD risk in long-term cancer survivors. Methods: The retrospective analysis involved a prospective cohort of 6109 cancer survivors without CVD from the UK Biobank accelerometry subsample. Cancer diagnoses were obtained from national cancer registries (International Classification of Diseases-10 [ICD-10], C00-C97, except for non-melanoma skin cancer, in situ, and non-well-defined cancers), and participants were followed up through December 31, 2022. A machine-learning algorithm was utilized to categorize MVPA into four groups based on guideline-recommend MVPA duration (0-75 min/week, 75-150 min/week, 150-300 min/week, ≥300 min/week). Results: Over a median follow-up of 7.88 years, there were 539 incident CVD events, including 361 incident CAD events, 155 incident HF events, and 109 incident stroke events. A clear inverse linear dose-response relationship between MVPA volume and the incidence of CVD was observed (P for nonlinear=0.49), with no maximal threshold for the benefits. Adjusted CVD incidence rates (95% confidence intervals [CIs]) across MVPA groups (0-75 min/week, 75-150 min/week, 150-300 min/week, ≥300 min/week) were 15.30 (12.90, 18.10), 13.50 (11.00, 16.40), 12.00 (10.20, 14.10), and 9.86 (8.35, 11.60) per 1000 person-years, respectively. Adjusted hazard ratios (95% CI) for CVD, CAD, HF, and stroke in the highest MVPA group (≥300 min/week) compared with those with the lowest MVPA group (0-75 min/week) were 0.63 (0.49, 0.80), 0.68 (0.51, 0.91), 0.66 (0.42,1.06), 0.72 (0.42, 1.23), respectively. Conclusions: Findings from the UK Biobank study suggest that longer durations of MVPA are associated with reduced incident CVD risk in cancer survivors, particularly in CAD risk reduction, underscoring the potential for physical activity to serve as a key component in cardio-oncology care.

Abstract 4124226: Long-term exposure to air pollutants and incidence of cardiovascular disease events and mortality in The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)

Introduction: Exposure to ambient air pollution may increase the risk of cardiovascular disease events and mortality, but prior publications have primarily included administrative cohorts with outcomes that have not been individually reviewed and with air pollution estimates created without cohort-specific exposure monitoring. Multi-Ethnic Study of Atherosclerosis (MESA) is a multi-site cohort study designed specifically to prospectively collect and adjudicate cardiovascular disease (CVD) events. MESA Air recruited additional participants into sub-cohorts for enhanced air pollution variation and sample size. Research Question: The aim of this analysis was to characterize the relationship between long-term exposure to nitrogen dioxide (NO 2 ) and fine particulate matter (PM 2.5 ) and all-cause mortality and CVD events. Methods: Air pollution exposure was assessed using address history with a purpose-built exposure model incorporating cohort-specific monitoring including measurement and validation at participant homes. We used Cox models to assess the risk of rolling 2-year average exposures on all cause-mortality and on a composite CVD endpoint (definite angina, probable angina with revascularization, myocardial infarction, atherosclerosis or other CVD death, resuscitated cardiac arrest, and stroke). Models were stratified for baseline hazard by age, sub-cohort, and recruitment year and were additionally adjusted for age, sex, race/ethnicity, field center, smoking/second-hand smoke, pack-years, physical activity, education, income, neighborhood socioeconomic status, and statin use. Results: MESA Air participants were aged 44-87 years at enrollment between 2000 and 2007; follow-up averaged 14 years. 6,915 participants had follow-up for events, NO 2 exposure, and covariate information. We observed 1,442 deaths and 985 CVD events. The interquartile range over all 2-year averages was 10.5-23.1 ppb for NO 2 and 10.1-14.9 µ/m 3 for PM 2.5 . The adjusted hazard ratio (aHR) for a 10 ppb increment in NO 2 was 1.38 (95% CI: 1.17, 1.64) for all-cause mortality and 1.16 (95% CI: 0.95, 1.42) for incident CVD events. The aHR for a 5 µg/m 3 increment in PM 2.5 was 1.20 (95% CI: 0.99, 1.46) for all-cause mortality and 1.15 (95% CI: 0.95, 1.39) for incident CVD events Conclusions: These results add to growing literature demonstrating an association between air pollution exposure, mortality, and CVD in a cohort with well-characterized clinical endpoints and cohort-specific exposure assessment.

Estimated health benefits, costs, and cost-effectiveness of implementing WHO's sodium benchmarks for packaged foods in India: a modelling study.

Excess dietary sodium intake has been associated with death and disability. WHO has released global sodium benchmarks for packaged foods to support countries to reduce population sodium intake. This study aimed to assess the potential health effect, costs, and cost effectiveness of implementing these WHO sodium benchmarks in India. We used a multiple cohort, proportional multistate, life table (Markov) model to estimate the health gains and cost effectiveness for adults if sodium content in packaged foods complied with the WHO benchmarks compared to the status quo. We used India-specific dietary surveys, food composition tables, foods sales data, and sodium content data from packaged food labels to estimate sodium intake before and after the intervention. Data on blood pressure, cardiovascular disease, and chronic kidney disease burden were obtained from the Global Burden of Diseases, Injuries, and Risk Factors study, and the effect of sodium reduction on blood pressure and disease risk was modelled on the basis of meta-analyses of randomised trials and cohort studies. Intervention and health-care costs were used to estimate net costs, and calculate the incremental cost per health-adjusted life-year (HALY) gained. Costs and HALYs were discounted at 3%. In the first 10 years, compliance with the WHO sodium benchmarks was estimated to avert a mean of 0·3 (95% uncertainty interval [UI] 0·2-0·5) million deaths from cardiovascular diseases and chronic kidney disease, a mean of 1·7 (95% UI 1·0-2·4) million incident cardiovascular disease events, and 0·7 (0·4-1·0) million new chronic kidney disease cases, compared with current practice. Over 10 years, the intervention was projected to be cost saving (100·0% probability), generating 1·0 (0·6 to 1·4) billion HALYs and US$0·8 (95% UI 0·3 to 1·4) million in cost savings. Over the population lifetime, the intervention could prevent 4·2 (2·4-6·0) million deaths from cardiovascular diseases and chronic kidney disease, 14·0 (8·2-20·1) million incident cardiovascular disease events, and 4·8 (2·8-6·8) new chronic kidney disease cases, with an 84·2% probability of being cost-saving and 100·0% probability of being cost-effective. Our modelling data suggest a high potential for compliance with WHO sodium benchmarks for packaged food being associated with substantial health gains and cost savings, making a strong case for India to mandate the implementation of the WHO sodium benchmarks, particularly as packaged food consumption continues to rise. WHO Country Office India.

Estimated health effect, cost, and cost-effectiveness of mandating sodium benchmarks in Australia's packaged foods: a modelling study

Excess dietary sodium is a leading cause of death and disability globally. Because packaged foods are a major source of sodium in many countries, including Australia, mandatory limits for sodium might improve population health. We aimed to estimate the long-term health and economic effect of mandating such thresholds in Australia. We used a multiple cohort, proportional, multistate, life table model to simulate the effect of mandating either the WHO global sodium benchmarks or the currently non-mandatory Australian Healthy Food Partnership (HFP) sodium targets. We compared maintaining the current sodium intake status quo with intervention scenarios, using nationally representative data on dietary intake, sodium in packaged foods, and food sales volume. Blood pressure and disease burden data were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study. The effect of sodium reduction on blood pressure and disease risk was modelled on the basis of meta-analyses of randomised trials and cohort studies. Intervention and health-care costs were used to calculate the incremental cost per health-adjusted life-year (HALY) gained. Costs and HALYs were discounted annually at 3%. Compared with the status quo intervention, mandating the WHO benchmarks could be cost saving over the first 10 years (AUD$223 [95% uncertainty interval 82-433] million saved), with 2743 (1677-3976) cardiovascular disease deaths and 43 971 (26 892-63 748) incident cardiovascular disease events averted, and 11 174 (6800-16 205) HALYs gained. Over the population's lifetime, the intervention was cost effective (100·0% probability). Mandating the HFP sodium targets was also estimated to be cost effective (100·0% probability), but with 29% of the health benefits compared with the WHO benchmarks. Our modelling study supports mandating sodium thresholds for packaged foods as a cost-effective strategy to prevent death and disease in Australia. Although making Australia's voluntary reformulation targets mandatory might save thousands of lives, mandating the WHO global benchmarks could yield substantially greater health gains. None.

Prediction of cardiovascular events and all-cause mortality using race and race-free estimated glomerular filtration rate in African Americans: the Jackson Heart Study.

New Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race adjustment were developed to estimate the glomerular filtration rate (eGFR). We aimed to compare the performance of five CKD-EPI eGFR equations, with or without race, in predicting cardiovascular disease (CVD) events and all-cause mortality in Black Americans from the Jackson Heart Study. JHS is an ongoing population-based prospective cohort study of African Americans in the Jackson, Mississippi, metropolitan area. Five CKD-EPI equations were used to estimate GFR at baseline using serum creatinine (Cr) or cystatin C (cys), including 2009 eGFRcr(ASR [age, sex, race]), 2021 eGFRcr(AS [age and sex]), 2012 eGFRcr-cys(ASR), 2021 eGFRcr-cys(AS), 2012 eGFRcys(AS). Endpoints were incident CVD events and all-cause mortality. Cox proportional hazards regression was used to assess the associations between different eGFRs and outcomes adjusting for atherosclerotic risk factors. Harrell's C-statistics and Net Reclassification Index (NRI) were used to assess the predictive utility. Among 5,129 participants (average age 54.8 ± 12.8 yrs), 1898 were male (37.0%). eGFRcr(AS) provided lower estimates and resulting in a greater proportion of participants categorized as CKD than eGFRcr(ASR), eGFRcr-cys(ASR), eGFRcr-cys(AS) and eGFRcys(AS). A median follow-up of 13.7 and 14.3 years revealed 411 (9.3%) CVD incidents and 1,207 (23.5%) deaths. Lower eGFRs were associated with CVD incidents and all-cause mortality. eGFRcr-cys(ASR), eGFRcr-cys(AS) and eGFRcys(AS) were strongly associated with incident CVD events and all-cause mortality than eGFRcr(ASR) and eGFRcr(AS). A significant discrimination improvement was found in C-statistics for predicting incident CVD events and all-cause mortality after adding each eGFR measure to the basic model including atherosclerotic risk factors. Across a 7.5% 10-year risk threshold, eGFRcys(AS) improved net classification of all-cause mortality (NRI: 2.19, 95%CI: 0.08, 4.65%). eGFR based on creatinine omit race has the lowest mean and detects more CKD patients in Black population. The eGFRs incorporating cystatin C strengthens the association between the eGFR and the risks of incident CVD and all-cause mortality. Cystatin C-based eGFR equations might be more appropriate for predicting CVD and mortality among Black population.

Sleep characteristics in relation to cardiovascular disease incidence and mortality in individuals with diabetes

Abstract Background/Introduction Evidence regarding the potential health effects of sleep characteristics among individuals with type 2 diabetes (T2D) is limited. Purpose We aimed to examine sleep characteristics in relation to subsequent risk of cardiovascular disease (CVD), including coronary heart disease (CHD), and stroke, and all-cause and cause-specific mortality among individuals with T2D. Methods We prospectively followed 21,902 men and women with T2D at baseline or diagnosed during follow-up (Nurses' Health Study: 1986-2018, Health Professionals Follow-Up Study: 1986-2018). Sleep characteristics, including sleep duration, snoring, sleep apnea, and sleep quality, were repeatedly assessed using self-reported questionnaires at baseline and follow-up. Associations of sleep characteristics with CVD risk and mortality were assessed using Cox proportional hazards models with adjustments for demographic, dietary and lifestyle factors, and medical history. Results During 170,355 and 196,458 person-years of follow-up in participants with T2D, there were 2,486 incident CVD events and 3,922 deaths, respectively. Compared with sleeping for 7-8 h/day, the multivariable-adjusted hazard ratios (HRs) of sleeping for ≤5 h/day were 1.21 (1.02, 1.45) for CVD incidence, 1.24 (1.20, 1.51) for CHD incidence, 1.40 (1.24, 1.58) for total mortality, 1.52 (1.20, 1.92) for CVD mortality, and 1.27 (1.01, 1.61) for other non-CVD and non-cancer mortality, while the HRs of ≥10 h/day were 1.42 (1.21, 1.66) for total mortality, and 1.63 (1.20, 2.10) for other non-CVD and non-cancer mortality. Furthermore, compared with participants without habitual snoring, those with habitual snoring had a 21%, 24%, 18%, and 33% higher risk for CVD incidence, CHD incidence, CVD mortality, and total mortality, respectively. Compared with participants without diagnosed sleep apnea, those with sleep apnea had a 27%-58% higher risk for CVD incidence, CVD mortality, and total mortality. In addition, lower habitual sleep quality, including sleep difficulties and restless sleep, was associated with a substantially higher risk of CVD, CHD, or CVD mortality. No associations were observed between sleep characteristics with risk of stroke and cancer mortality in individuals with T2D. Conclusions Short and long sleep durations as well as habitual snoring, sleep apnea, and lower sleep quality were independently associated with higher risks of CVD incidence and mortality, particularly CVD mortality in individuals with T2D.

Using deep learning to detect atherosclerotic plaques on carotid ultrasound images in the UK Biobank

Abstract Background Atherosclerosis is the main underlying cause of cardiovascular disease (CVD). Existing CVD risk assessment tools do not consider the burden of subclinical atherosclerosis. The presence of carotid plaques on carotid ultrasound is a well-known marker of subclinical atherosclerosis. The accumulation of population-scale data on the presence of atherosclerotic plaques, along with deep phenotyping, can allow not only to address the effectiveness of carotid ultrasound in routine clinical practice, but to shed light on the biology of atherosclerosis development. Purpose To develop an effective deep learning model for plaque detection in carotid ultrasound images in the UK Biobank. Methods We used 680 carotid ultrasound images with manually annotated plaques to train a deep learning model employing the YOLOv8 architecture. Different augmentation techniques were used to increase the generalizability of the model. The developed model was applied to automatically detect plaques in raw ultrasound images from 19,507 UK Biobank participants. Logistic and Cox regression were used to explore the associations of plaque presence and number as predicted by the model with conventional CVD risk factors and the risk of future CVD events over follow-up. To explore the genetic architecture of subclinical atherosclerosis, we conducted a genome-wide association study (GWAS) on plaque presence, followed by meta-analysis with data from the CHARGE Consortium. Results Our plaque detection model achieved high classification metrics of accuracy, sensitivity, and specificity (89.3%, 89.5%, and 89.2%, respectively) and detected atherosclerotic plaques in 44% of UK Biobank participants. As expected, plaques were more common among men than women and their prevalence increased linearly with age. Both plaque presence and number of plaques were correlated with conventional CVD risk factors including diabetes, hypertension, and hyperlipidemia, and showed strong associations with future risk of incident CVD events (Hazard Ratio for plaque presence: 1.48 [95%CI: 1.21-1.82], for 2 plaques or more: 1.65, [95% CI: 1.28-2.13]). Incorporating plaque-derived phenotypes minimally altered the C-index of the time-to-event model. GWAS meta-analysis of carotid plaque presence revealed 5 previously known loci, as well as a significant locus including the LPA gene that had not previously been associated with carotid plaque. Conclusion We have developed and implemented an efficient plaque detection model to data from the UK Biobank, which holds significant promise for studying atherosclerosis at a population-wide scale through integration with multiomics data and electronic health records.

Cardiovascular events risk in office-masked nocturnal hypertension defined by home blood pressure monitoring: the J-HOP nocturnal blood pressure study

Abstract Background Elevated nocturnal home blood pressure (BP) has been reported to be associated with increased risk for cardiovascular disease (CVD). Masked hypertension defined by home BP monitoring is also a strong risk factor for adverse CVD outcomes. However, no study has investigated the association between office-masked nocturnal hypertension defined by home BP monitoring and CVD events risk. Purpose This study aimed to examine the association between office-masked nocturnal hypertension defined by home BP monitoring and CVD events risk in a clinical practice-based population. Methods This was a prospective observational study including Japanese participants with CVD or high risk of CVD. Three office BPs were taken on two different occasions. Nocturnal home BP was measured three times per night for two weeks. The association between office-masked nocturnal hypertension and incident total CVD events (including fatal and non-fatal stroke and coronary heart disease) was examined using Cox regression. Results 2,545 participants were followed for the mean of 7.1 years (18,116 person-years), during which 152 (6.0%) CVD events occurred. Mean age (standard deviation) was 63.3 (10.3) years; 49.0% were male; 82.6% took antihypertensive medications. The proportions of participants with normotension (office BP &amp;lt;140/90 mmHg and nocturnal home BP &amp;lt;120/70 mmHg), white-coat hypertension (office BP ≥140/90 mmHg and nocturnal home BP &amp;lt;120/70 mmHg), office-masked nocturnal hypertension (office BP &amp;lt;140/90 mmHg and nocturnal home BP ≥120/70 mmHg), and sustained hypertension (office BP ≥140/90 mmHg and nocturnal home BP ≥120/70 mmHg) were 25.3%, 14.4%, 23.2%, and 37.1%, respectively. The office-masked nocturnal hypertensive group and sustained hypertensive group had higher incidence rates of total CVD events compared with the normotensive group. Relative to normotension, those with both office-masked nocturnal hypertension (adjusted hazard ratio [aHR] 1.72, 95% confidence interval [CI] 1.01–2.92) and sustained hypertension (aHR 1.75, 95%CI 1.03–2.96) had similarly increased CVD risk, even after adjustment for daytime home BP values. Conclusions Screening for office-masked nocturnal hypertension with home BP monitoring identifies a potentially important group of patients with increased risk for incident CVD events for whom additional preventative measures may be appropriate.

The Relationship of Duffy Gene Polymorphism with High-Sensitivity C-Reactive Protein, Mortality, and Cardiovascular Outcomes in Black Individuals

Background: Black adults have higher incidence of all-cause mortality and worse cardiovascular disease (CVD) outcomes when compared to other U.S. populations. The Duffy chemokine receptor is not expressed on erythrocytes in a large majority of Black adults, but the clinical implications of this are unclear. Methods: Here, we investigated the relationship of Duffy receptor status, high-sensitivity C-reactive protein (hs-CRP), and mortality and incident CVD events (coronary heart disease, stroke, and heart failure) in self-identified Black members of three contemporary, longitudinal cohort studies (the Women’s Health Initiative, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis). Data on 14,358 Black participants (9023 Duffy-null and 5335 Duffy-receptor-positive, as defined using single-nucleotide polymorphism (SNP) rs2814778) were included in this analysis. Results: Duffy null was strongly associated with higher hs-CRP (meta-analysis p = 2.62 × 10−9), but the association was largely attenuated, though still marginally significant (p = 0.005), after conditioning on known CRP locus alleles in linkage disequilibrium with the Duffy gene. In our discovery cohorts, Duffy-null status appeared to be associated with a higher risk of all-cause mortality and incident stroke, though these associations were attenuated and non-significant following adjustment for traditional risk factors including hs-CRP. Moreover, the association of Duffy-null status with mortality could not be replicated in an independent sample of Black adults from the UK Biobank. Conclusions: These findings suggest that the higher levels of hs-CRP found in Duffy-null individuals may be in part independent of CRP alleles known to influence circulating levels of hs-CRP. During the follow-up of this community-based sample of Black participants, Duffy-null status was not associated with mortality or incident CVD events independently of traditional risk factors including hs-CRP.

Association between dynapenic obesity and risk of cardiovascular disease: The Hisayama study.

Dynapenic obesity is a condition characterized by high adiposity levels combined with muscle dysfunction. Although high adiposity and muscle loss/dysfunction are thought to synergistically increase the risk of cardiovascular disease (CVD), few studies have addressed the association between dynapenic and sarcopenic obesity and CVD. We aimed to investigate the association of dynapenic obesity with incident CVD events using the data from a population-based prospective longitudinal study in Japan. A total of 2490 community-dwelling Japanese aged 40-79years (42.5% males, mean age 57.7±10.6years) without a history of CVD were followed up for a median of 24years. Handgrip strength was classified as low, medium, or high by age- and sex-specific tertiles. Body mass index (BMI) levels were categorized as lean (<18.5kg/m2), normal (18.5-24.9kg/m2), or obese (≥25.0kg/m2). Dynapenic obesity was defined as having both low handgrip strength and obesity. The outcomes were defined as the first-ever development of CVD (defined as stroke or coronary heart disease). The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the development of CVD were estimated using a Cox proportional hazards model, in which participants with high handgrip strength and normal BMI were used as a reference group. Mediation analyses used serum high-sensitivity C-reactive protein (hs-CRP) and homeostatic model assessment for insulin resistance (HOMA-IR) as mediators. During the follow-up period, 482 participants developed CVD events (324 cases of stroke and 209 of coronary heart disease). The multivariable-adjusted risk of CVD increased significantly among participants with dynapenic obesity compared with the reference group (HR 1.49, 95% CI 1.03-2.17). An analysis by age groups showed a further increase in the risk of CVD among participants with dynapenic obesity aged less than 65years (HR 1.66, 95% CI 1.04-2.65). In mediation analyses for participants aged less than 65years, serum hs-CRP was shown to be a significant mediator explaining 13.8% of the association between dynapenic obesity and the development of CVD, while HOMA-IR explained 12.2% of this relationship. Dynapenic obesity was a significant risk factor for the development of CVD in a general Japanese population. This association was more pronounced among those aged <65years. Inflammation, and possibly glucose metabolism, might partly mediate this association. Our findings suggest that preventing muscle dysfunction as well as appropriate weight control, especially in middle-age, are important for preventing the development of CVD.

A prospective cohort study investigating the association between type 2 diabetes and subsequent cardiovascular events in patients with different blood pressure, HbA1c, and lipid levels.

Globally, there has been a steady increase in the prevalence of type 2 diabetes, and the risk of cardiovascular disease has increased. The relationship between diabetes and the incidence of cardiovascular disease (CVD) at different blood pressure, glycated haemoglobin A1c (HbA1c), and lipid levels remains uncertain. This study aimed to investigate these associations within a population-based cohort. We analysed data from the Guiyang subcentre of the China Cardiometabolic Disease and Cancer Cohort Study, which enrolled participants aged 40 years and older between 2011 and 2012. Subsequently, a follow-up visit was conducted during 2014-2016 to assess incident CVD events. The analysis included a cohort of 7197 adults, of whom 590 were diagnosed with diabetes. Among all the participants, the CVD events linked to diabetes had a multivariable adjusted hazard ratio of 2.37 [95% confidence intervals (CI): 1.38-4.08]. Patients with diabetes had a greater risk of experiencing CVD events if they had high blood pressure [hazard ratios (HR): 1.24, 95% CI: 1.39-4.21] and high lipid levels (HR: 2.19, 95% CI: 1.29-3.70) compared to people with normal blood pressure (HR: 1.23, 95% CI: 0.54-2.82) and lipid levels (HR: 1.26, 95% CI: 0.47-3.41). Our analysis revealed a significant association between diabetes and an increased risk of subsequent CVD events, which can be mitigated through optimal management of the metabolic profile of cardiovascular risk factors.

Influence of physical activity measurement on the association between Life’s Essential 8 and incident cardiovascular disease in older women

ObjectiveThe American Heart Association’s Life’s Essential 8 (LE8) metric includes self-reported physical activity as one of the metrics for assessing cardiovascular health. Self-reported physical activity is prone to misclassification, whereas accelerometer measures are less biased. We examined associations of LE8 and incident cardiovascular disease (CVD) using self-reported and accelerometer-measured physical activity. MethodsParticipants in the Women’s Health Initiative (WHI) Objective Physical Activity and Cardiovascular Health Study (n = 4,243; mean age = 79 ± 7 years) with no CVD history completed the WHI physical activity questionnaire and the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire prior to wearing a hip-worn accelerometer for up to seven days in 2012–2014. LE8 components (physical activity, diet, sleep, body mass index, smoking, blood pressure, non-HDL cholesterol, and glucose) were scored according to guidelines. Scores were created using five physical activity measures: WHI questionnaire (LE8WHI), CHAMPS (LE8CHAMPS), accelerometer-measured physical activity (LE8A), and sample quantiles of accelerometer-measured physical activity (LE8AQ) and daily steps (LE8STEPS). Hazard ratios (HR) for physician-adjudicated CVD were estimated using Cox regression. Results707 incident CVD events occurred over an average 7.5 years. Multivariable HRs (95 % CI) comparing women in the highest vs. lowest quartiles of LE8 scores were: LE8WHI = 0.53 (0.43–0.67), LE8CHAMPS = 0.47 (0.38–0.60), LE8A = 0.44 (0.36–0.56), LE8AQ = 0.44 (0.35–0.55), and LE8STEPS = 0.45 (0.35–0.57). ConclusionsThe LE8-incident CVD association varies by physical activity measurement, however all methods showed reduced risk. Device-measures of physical activity may be more accurate in the LE8, but when impractical to implement, also support use of self-reported measures.

Prediction of Severe Baseline Asymptomatic Carotid Stenosis and Subsequent Risk of Stroke and Cardiovascular Disease.

Risk models to identify patients at high risk of asymptomatic carotid artery stenosis (ACAS) can help in selecting patients for screening, but long-term outcomes in these patients are unknown. We assessed the diagnostic and prognostic value of the previously published Prevalence of ACAS (PACAS) risk model to detect ACAS at baseline and to predict subsequent risk of stroke and cardiovascular disease (CVD) during follow-up. We validated the discrimination and calibration of the PACAS risk model to detect severe (≥70% narrowing) ACAS with patients from the Reduction of Atherothrombosis for Continued Health registry. We subsequently calculated the incidence rates of stroke and CVD (fatal and nonfatal stroke or myocardial infarction or vascular death) during follow-up in 4 risk groups (low, medium, high, and very high, corresponding to sum scores of ≤9, 10-13, 14-17, and ≥18, respectively). Among 26 384 patients, aged between 45 and 80 years, without prior carotid procedures, 1662 (6.3%) had severe baseline ACAS. During ≈70 000 patient-years of follow-up, 1124 strokes and 2484 CVD events occurred. Discrimination of the PACAS model was 0.67 (95% CI, 0.65-0.68), and calibration showed adequate concordance between predicted and observed risks of severe baseline ACAS after recalibration. Significantly higher incidence rates of stroke (Ptrend<0.011) and CVD (Ptrend<0.0001) during follow-up were found with increasing PACAS risk groups. Among patients with high PACAS sum score of ≥14 (corresponding to 27.7% of all patients), severe baseline ACAS prevalence was 11.4%. In addition, 56.6% of incident strokes and 64.9% of incident CVD events occurred in this group. The PACAS risk model can reliably identify patients at high risk of severe baseline ACAS. Incidence rates of stroke and CVD during follow-up were significantly higher in patients with high PACAS sum scores. Selective screening of patients with high PACAS sum scores may help to prevent future stroke or CVD.

Outcomes for older people with screening detected versus existing chronic kidney disease: Cohort study with data linkage

BackgroundChronic Kidney Disease (CKD) is a common health problem, associated with increased risk of cardiovascular disease (CVD), end stage kidney disease (ESKD), and premature death. A third of people aged≥70 years have CKD, many of whom are undiagnosed, but little is known about the value of screening.AimTo compare the risk of adverse health outcomes between people with an existing diagnosis of CKD and those identified on screening. To identify factors associated with mortality in CKD.Design &amp; settingProspective cohort study of 892 primary care patients aged≥60 years with CKD (existing and screening detected) in Oxfordshire, with data linkage to civil death registry and secondary care.MethodHazard Ratios (HR) and 95% Confidence Intervals (CI) were estimated using Cox proportional-hazard models to compare the risk of all-cause mortality, hospitalisation, CVD, ESKD separately, and as a composite between CKD groups, as well as to identify factors associated with mortality.ResultsAfter a median follow-up of 3-5 years, 49 people died, 493 were hospitalised, 57 had an incident CVD event, and 0 had an ESKD event. There was no difference in the composite outcome between those existing CKD and those identified on screening (HR 0.94, CI 0.67-1.33). Older age (HR 1.10, CI 1.06-1.15), male sex (HR 2.31, CI 1.26-4.24), and heart failure (HR 5.18, CI 2.45-10.97) were associated with increased risk of death.ConclusionScreening older people for CKD may be of value, as their risk of short-term mortality, hospitalisation, and CVD is comparable to people routinely diagnosed. Larger studies with longer follow-up in more diverse and representative populations of older adults are needed to corroborate these findings.

Joint and interactive associations of body mass index and genetic factors with cardiovascular disease: a prospective study in UK Biobank

BackgroundBoth body mass index (BMI) and genetic factors independently contribute to cardiovascular disease (CVD). However, it is unclear whether genetic risk modifies the association between BMI and the risk of incident CVD. This study aimed to investigate whether BMI categories and genetic risk jointly and interactively contribute to incident CVD events, including hypertension (HTN), atrial fibrillation (AF), coronary heart disease (CHD), stroke, and heart failure (HF).MethodsA total of 496,851 participants from the UK Biobank with one or more new-onset CVD events were included in the analyses. BMI was categorized as normal weight (< 25.0 kg/m2), overweight (25.0–29.9 kg/m2), and obesity (≥ 30.0 kg/m2). Genetic risk for each outcome was defined as low (lowest tertile), intermediate (second tertile), and high (highest tertile) using polygenic risk score. The joint associations of BMI categories and genetic risk with incident CVD were investigated using Cox proportional hazard models. Additionally, additive interactions were evaluated.ResultsAmong the 496,851 participants, 270,726 (54.5%) were female, with a mean (SD) age was 56.5 (8.1) years. Over a median follow-up (IQR) of 12.4 (11.5–13.1) years, 102,131 (22.9%) participants developed HTN, 26,301 (5.4%) developed AF, 32,222 (6.9%) developed CHD, 10,684 (2.2%) developed stroke, and 13,304 (2.7%) developed HF. Compared with the normal weight with low genetic risk, the obesity with high genetic risk had the highest risk of CVD: HTN (HR: 3.96; 95%CI: 3.84–4.09), AF (HR: 3.60; 95%CI: 3.38–3.83), CHD (HR: 2.76; 95%CI: 2.61–2.91), stroke (HR: 1.44; 95%CI: 1.31–1.57), and HF (HR: 2.47; 95%CI: 2.27–2.69). There were significant additive interactions between BMI categories and genetic risk for HTN, AF, and CHD, with relative excess risk of 0.53 (95%CI: 0.43–0.62), 0.67 (95%CI: 0.51–0.83), and 0.37 (95%CI: 0.25–0.49), respectively.ConclusionsBMI and genetic factors jointly and interactively contribute to incident CVD, especially among participants with high genetic risk. These findings have public health implications for identifying populations more likely to have cardiovascular benefit from weight loss interventions.

Effect of depression treatment on health behaviors and cardiovascular risk factors in primary care patients with depression and elevated cardiovascular risk: data from the eIMPACT trial.

Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk. Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange. The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39). Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed. ClinicalTrials.gov Identifier: NCT02458690.