Cardiovascular Disease Events Research Articles

Comparing five-year and ten-year predicted cardiovascular disease risk in Aotearoa New Zealand: national data linkage study of 1.7 million adults.

There is no consensus on the optimal time horizon for predicting cardiovascular disease (CVD) risk to inform treatment decisions. New Zealand and Australia recommend 5 years, whereas most countries recommend 10 years. We compared predicted risk and treatment-eligible groups using 5-year and 10-year equations. Individual-level linked administrative datasets identified 1,746,665 New Zealanders without CVD, aged 30-74 years in 2006, with follow-up to 2018. Participants were randomly allocated to derivation and validation cohorts. Sex-specific 5-year and 10-year risk prediction models were developed in the derivation cohort and applied in the validation cohort. 28,116 (3.2%) and 62,027 (7.1%) first CVD events occurred during 5-years and 10-years follow-up respectively (cumulative risk, derivation cohort). Median predicted 10-year CVD risk (3.8%) was approximately 2.5 times 5-year risk (1.6%) and 95% of individuals in the top quintile of 5-year risk were also in the top quintile of 10-year risk, across age/gender groups (validation cohort). Using common guideline-recommended treatment thresholds (5% 5-year, 10% 10-year risk), approximately 14% and 28% of women and men respectively were identified as treatment-eligible applying 5-year equations compared to 17% and 32% of women and men applying 10-year equations. Older age was the major contributor to treatment eligibility in both sexes. Predicted 10-year CVD risk was approximately 2.5 times 5-year risk. Both equations identified mostly the same individuals in the highest risk quintile. Conversely, commonly used treatment thresholds identified more treatment-eligible individuals using 10-year equations and both equations identified approximately twice as many treatment-eligible men as women. The treatment threshold, rather than the risk horizon, is the main determinant of treatment eligibility.

Artificial intelligence applied to coronary artery calcium scans (AI-CAC) significantly improves cardiovascular events prediction

Coronary artery calcium (CAC) scans contain valuable information beyond the Agatston Score which is currently reported for predicting coronary heart disease (CHD) only. We examined whether new artificial intelligence (AI) applied to CAC scans can predict non-CHD events, including heart failure, atrial fibrillation, and stroke. We applied AI-enabled automated cardiac chambers volumetry and calcified plaque characterization to CAC scans (AI-CAC) of 5830 asymptomatic individuals (52.2% women, age 61.7 ± 10.2 years) in the multi-ethnic study of atherosclerosis during 15 years of follow-up, 1773 CVD events accrued. The AUC at 1-, 5-, 10-, and 15-year follow-up for AI-CAC vs. Agatston score was (0.784 vs. 0.701), (0.771 vs. 0.709), (0.789 vs. 0.712) and (0.816 vs. 0.729) (p < 0.0001 for all), respectively. AI-CAC plaque characteristics, including number, location, density, plus number of vessels, significantly improved CHD prediction in the CAC 1–100 cohort vs. Agatston Score. AI-CAC significantly improved the Agatston score for predicting all CVD events.

Biomarkers of polyunsaturated fatty acids and cardiovascular risk factors and events in healthy Asian populations: a systematic review.

The associations between circulating polyunsaturated fatty acids (PUFAs) and cardiovascular risk factors and events in healthy Asian populations have been less examined robustly compared to Western populations. This systematic review aimed to summarise current evidence on the associations between n-3 and n-6 PUFAs biomarkers and cardiovascular risk factors and events in healthy Asian populations. PubMed, Embase, Web of Science and Cochrane Library were searched for observational studies from January 2010 until August 2024. Twenty-three studies were eligible, which covered six Asian countries and included events(n=7), traditional risk factors such as blood pressure and lipids(n=4), physical signs such as arterial stiffness(n=4), non-traditional lipid markers(n=1), markers of inflammation(n=4), markers of thrombosis(n=2), and non-invasive imaging-based markers such as carotid intima media thickness(n=5). Biological sample type included plasma(n=6), serum(n=14) and erythrocyte(n=3). Higher circulating total n-3 PUFAs appeared to be associated with lower hypertension risk and specifically eicosapentaenoic acid and docosahexaenoic acid to be associated with lower myocardial infarction risk, reduction in triglycerides and inflammation. Higher circulating linoleic acid was associated with improved lipid profiles and lower inflammation. Limited evidence led to inconclusive associations between circulating n-6 PUFAs biomarkers and cardiovascular disease events and blood pressure. No consistent associations with arterial stiffness, obesity, thrombosis and imaging-based biomarkers were observed for circulating PUFAs biomarkers in Asian populations. Limited studies exist for each outcome, hence results should be interpreted with caution. More high quality and prospective studies in Asian populations are warranted. Several recommendations such as sample size justification and reporting of non-respondents rate are proposed for future studies.

Tuberculosis and increased incidence of cardiovascular disease: Cohort study using US and UK health records.

Limited evidence suggests elevated risks of cardiovascular disease (CVD) among people diagnosed with tuberculosis (TB) disease, though studies have not adjusted for pre-existing CVD risk. We carried out a cohort study using two separate datasets, estimating CVD incidence in people with TB versus those without. Using data from the United States (Veterans Health Administration) and the United Kingdom (Clinical Practice Research Datalink) for 2000-2020 we matched adults with incident TB disease and no CVD history 2-years before TB diagnosis (US n=2,121; UK n=15,820) with up to 10 people without TB on the basis of age, sex, race/ethnicity and healthcare practice. Participants were followed beginning 2-years before TB diagnosis and for 2-years subsequently. The acute period was defined as 3-months before/after TB diagnosis. TB, CVD and covariates were identified from electronic routinely collected data (primary and secondary care; mortality). Poisson models estimated incident rate ratios (IRR) for CVD events in people with TB compared to those without. CVD incidence was consistently higher in people with TB, including during the baseline period (pre-TB) and particularly in the acute period: IRRs were US 3.5 (95% Confidence Interval 2.7-4.4), UK 2.7 (2.2-3.3). Rate Ratios remained high after adjusting for differences in pre-existing CVD risk: US 3.2 (2.2-4.4), UK 1.6 (1.2-2.1). Increased CVD incidence was observed in people with TB versus those without, especially within months of TB diagnosis, persistent after adjustment for differences in pre-existing risk. Enhancing CVD screening and risk management may improve long-term outcomes in people with TB.

Gestational Diabetes Mellitus and Subsequent Risks of Diabetes and Cardiovascular Diseases: the Life Course Perspective and Implications of Racial Disparities.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications worldwide and the prevalence is continuously rising globally. Importantly, GDM is not an isolated complication of pregnancy. Growing evidence suggests that individuals with GDM, compared to those without GDM, have an increased risk of subsequent type 2 diabetes (T2D) and cardiovascular diseases (CVD). Substantial racial and ethnic disparities exist in the risk of GDM. However, the role of race and ethnicity in the progression from GDM to T2D and CVD remains unclear. The purpose of the current review is to summarize recent research about GDM and its life-course impacts on cardiometabolic health, including 1) the peak time of developing T2D and CVD risks after GDM, 2) the racial and ethnic disparities in the risk cardiometabolic diseases after GDM, 3) the biological plausibility and underlying mechanisms, and 4) recommendations for screening and prevention of cardiometabolic diseases among individuals with GDM, collectively to provide an updated review to guide future research. Growing evidence has indicated that individuals with GDM had greater risks of T2D (7.4 to 9.6 times), hypertension (78% higher), and CDV events (74% higher) after GDM than their non-GDM counterparts. More recently, a few studies also suggested that GDM could slightly increase the risk of mortality. Available evidence suggests that key CVD risk factors such as blood pressure, plasma glucose, and lipids levels are all elevated as early as < 1year postpartum in individuals with GDM. The risk of T2D and hypertension is likely to reach a peak between 3-6years after the index pregnancy with GDM compared to normal glycemia pregnancy. Cumulative evidence also suggests that the risk of cardiometabolic diseases including T2D, hypertension, and CVD events after GDM varies by race and ethnicity. However, whether the risk is higher in certain racial and ethnic groups and whether the pattern may vary by the postpartum cardiometabolic outcome of interest remain unclear. The underlying mechanisms linking GDM and subsequent T2D and CVD are complex, often involving multiple pathways and their interactions, with the specific mechanisms varying by individuals of different racial and ethnic backgrounds. Diabetes and CVD risk screening among individuals with GDM should be initiated early during postpartum and continue, if possible, frequently. Unfortunately, adherence to postpartum glucose testing with either obstetrician or primary care providers remained poor among individuals with GDM. A life-course perspective may provide critical information to address clinical and public health gaps in postpartum screening and interventions for preventing T2D and CVD risks in individuals with GDM. Future research investigating the racial- and ethnic-specific risk of progression from GDM to cardiometabolic diseases and the role of multi-domain factors including lifestyle, biological, and socio-contextual factors are warranted to inform tailored and culture-appropriate interventions for high-risk subpopulations. Further, examining the barriers to postpartum glucose testing among individuals with GDM is crucial for the effective prevention of cardiometabolic diseases and for enhancing life-long health.

Enhancing Air Quality Index Activity Guidelines for Preventing Cardiovascular Events in the General Adult Population

BackgroundThe public health relevance of daily Air Quality Index (AQI) activity guidelines for the general adult public in the United States to prevent atherosclerotic cardiovascular disease (ASCVD) events is questionable. ObjectivesThe purpose of the study was to explore the utility of a policy tailoring activity guidance to calculated ASCVD risk rather than uniform recommendations to the general adult public as currently provided. MethodsWe calculated the number needed to treat (NNT) to prevent one ASCVD event per day by following activity recommendations across 10-year ASCVD risk scores (1% to 20%). Second, we modeled the benefits of tailoring recommendations to ASCVD risk. ResultsThe NNT decreased as ASCVD risk and/or AQI levels increased. At AQIs up to 151 (68% of days with AQIs above moderate in the United States), the NNTs remained untenably high (>2.7-55.3 million) across ASCVD risk. Under unhealthy conditions (AQIs 151-200), 28% of elevated AQIs, NNTs <1 million could be achieved by current guidance (15% exposure reduction), but only among the highest-risk individuals (ASCVD 18% to 20%) on the most polluted days (AQIs 192-200). Tailoring guidance to ASCVD risk could yield NNTs <1 million at risk thresholds of 7.5% and 10% if activity restrictions were more stringent (35% to 50% exposure reductions) during unhealthy conditions. ConclusionsASCVD risk has a major influence on the NNT to prevent cardiovascular events by following AQI guidance. It may be possible for a future policy to improve the utility of AQI activity guidance for the general adult public by tailoring activity recommendations to ASCVD risk.

Cost-effectiveness of strengthening blood pressure classification in South Korea: comparing the 2017 ACC/AHA and KSH guidelines

BackgroundHypertension is a significant risk factor for cardiovascular disease (CVD), with hypertension-related deaths increasing annually. While South Korea uses the Korean Society of Hypertension (KSH) guideline of 140/90 mmHg, the American College of Cardiology (ACC) and American Heart Association (AHA) updated their guidelines in 2017 to 130/80 mmHg. This study evaluates the cost-effectiveness of transitioning to the 2017 ACC/AHA guidelines by estimating early treatment impacts and potential CVD risk reduction.MethodsA Markov state-transition simulation model with a 10-year horizon was used to estimate cost-effectiveness, focusing on strengthening target blood pressure. Quality-adjusted life years (QALYs) served as the measure of effectiveness. Cohorts of 10,000 individuals representing South Koreans in their 20s through 80s were compared in scenario analyses from the healthcare system perspective. A 4.5% annual discount rate was applied to costs and effectiveness. Primary outcomes were incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB). The willingness-to-pay (WTP) threshold was < KRW 30,000,000/QALY gained. Probabilistic sensitivity analyses (PSAs) addressed model input parameter uncertainties.ResultsThe base-case analysis showed an ICER value of KRW 1,328,395/QALY gained across all populations. ICER values increased with age, from − KRW 3,138,071/QALY for 20-year-olds to KRW 16,613,013/QALY for individuals over 80. The 60s age group showed the greatest benefit with an incremental QALY gain of 0.46. All scenarios had ICERs below the WTP threshold, with a PSA probability of 98.0% that strengthening blood pressure classification could be cost-effective.ConclusionsThis economic evaluation found that adopting the 2017 ACC/AHA guidelines may result in early treatment, reduce the potential incidence of CVD events, and be cost-effective across all age groups. The study findings have implications for policymakers deciding whether and when to revise official guidelines regarding target blood pressure levels, considering the impacts on public health and budgetary concerns.

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

BackgroundNew 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.MethodsJHS 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.ResultsAmong 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%).ConclusioneGFR 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.

Incidence of Diabetes and Ischemic Heart Disease in COVID-19 Post Pandemic

Background: The long-term effects of COVID-19 Pandemic are currently getting more attention. The majority of individuals with COVID-19 report having symptoms for duration greater than four weeks following their initial appearance. After COVID-19 infection, there is worry that cardiovascular conditions and metabolic conditions may be harmed. The severity of the sickness and COVID-19 vulnerability, meanwhile, are known to be linked to cardiometabolic risk. Aim: To study the incidence of ischemic heart disease and diabetes mellitus post COVID 19 pandemic Methods and Materials: Information for all individuals diagnosed as suffering of COVID-19 were taken at the beginning of the investigation from the health department's release of electronic medical records in February 2021. The main outcomes analyzed were first ever documented CVD as well as DM diagnoses. The data were then collected at different time periods. They were as follows: Before date of indexing. Acute: Follow up till four weeks from index. Post-acute: Five to twelve weeks from date of indexing. Long: Thirteen weeks to fifty-two weeks from date of indexing. Poisson confidence intervals (CIs) were computed. Results: CVD events was 1362 in COVID -19 study group while it was 131 in control study group at phase corresponding to four weeks after the indexed date. CVD events was 781 in COVID -19 study group while it was 298 in control study group at phase corresponding to five to twelve weeks since the date of indexing. CVD events was 781 in COVID -19 study group while it was 298 in control study group at phase corresponding to five to twelve weeks since the date of indexing. CVD events was 2,134 in COVID -19 study group while it was 298 in control study group at phase corresponding to 13 to 52 weeks since the date of indexing. Conclusion: Early on after COVID-19 infection, the risk of CVD is elevated, and this risk is elevated for up to three months. However, it was not observed that there was a long-term rise in the prevalence of CVD or DM in COVID-19 patients who do not already have these illnesses.

Cardiovascular Risks With SGLT2 Inhibitors in Clinical Practice Among Patients With Type 2 Diabetes

Cardiovascular disease (CVD) can be recurrent during type 2 diabetes (T2D) progression in this aging population. The effectiveness of sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy on total (ie, first and subsequent) CVD among patients with T2D in clinical practice remains uncertain. To analyze the comparative association of SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP4i) therapy with total CVD among patients with T2D in clinical practice. This retrospective cohort study used electronic medical records at the National Cheng Kung University Hospital, a leading medical center in Taiwan, from 2015 through 2021. Adult patients with T2D who initiated first use of the study drugs from 2016 through 2019, with up to 6 years of follow-up, were identified. The primary outcomes included total composite CVD events and individual CVD subtypes (ie, atrial fibrillation, coronary heart disease, heart failure, stroke, myocardial infarction, and transient ischemic attack). A shared frailty model analysis was used to assess the association of treatment with repeat CVD events. Data from patients at high risk for CVD recurrence were further analyzed. Data were analyzed from September 1, 2022, to December 31, 2023. Overall, 8384 patients with T2D were identified (mean [SD] age, 63.7 [12.4] years; 4645 [55.4%] male). A total of 1632 propensity score-matched pairs of SGLT2i (mean [SD] age, 57.8 [12.0] years; 673 [41.2%] female and 959 [58.8%] male) and DPP4i (mean [SD] age, 58.2 [12.9] years; 655 [40.1%] female and 977 [59.9%] male) users were included. SGLT2i was associated with reduced total CVD risk vs DPP4i therapy (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98]) but not the first CVD event (with the use of SGLT2i therapy were more prominent for patients at high risk of CVD (ie, HR, 0.70 [95% CI, 0.62-0.80] for individuals with estimated glomerular filtration rate lower than 60 mL/min/1.73 m2; HR, 0.70 [95% CI, 0.64-0.78]; for individuals having any diabetes-related complications; and HR, 0.72 [95% CI, 0.65-0.80] for individuals with a history of CVD) compared with the overall cohort. Among patients at high risk of CVD, greater reduced total CVD burden associated with SGLT2i therapy was observed for women vs men (eg, HR, 0.59 [95% CI, 0.49-0.72] in the subgroup with CVD history). In this cohort study of patients with T2D, the use of SGLT2is vs DPP4is was associated with reduced total cardiovascular burden, suggesting that long-term use of this therapy may optimize treatment benefit among patients with chronic CVD. The SGLT2i-associated benefit among patients with high risk of CVD encourages the prioritization of SGLT2i use for these vulnerable individuals.

Association of estimated glucose disposal rate with incident cardiovascular disease under different metabolic and circadian rhythm states: findings from a national population-based prospective cohort study

BackgroundRecent studies have shown that both metabolic syndrome and circadian rhythm syndrome are firmly associated with the occurrence of cardiovascular disease (CVD), with insulin resistance playing a significant role. The estimated glucose disposal rate (eGDR) is considered to be a reliable surrogate marker for insulin resistance. However, the relationship between eGDR and CVD under different metabolic and circadian rhythm states has not been thoroughly studied, and large-scale prospective cohort studies are needed to clarify this relationship.MethodsThis study is based on the China Health and Retirement Longitudinal Study (CHARLS), recruiting individuals aged 45 and above with complete eGDR data. The eGDR was calculated by the formula: eGDR(mg/kg/min) = 21.158 − (0.09 × WC) − (3.407 × hypertension) − (0.551 × HbA1c) [WC (cm), hypertension (yes = 1/no = 0), and HbA1c (%)] (Zabala et al. in Cardiovasc Diabetol 20(1):202; 2021).Participants were divided into four subgroups based on the quartiles (Q) of eGDR.The cumulative incidence rates and hazard ratios (HR) with 95% confidence intervals (CI) were calculated, with the lowest eGDR quartile (representing the highest degree of insulin resistance) as the reference. Participants were further divided into subgroups based on the diagnosis of Metabolic syndrome (MetS) or circadian syndrome (CircS) to explore the relationship between eGDR and CVD under different metabolic and circadian rhythm conditions. The dose–response relationship between eGDR and CVD incidence was investigated using a restricted cubic spline (RCS) based on a Cox regression model. Receiver operating characteristic (ROC) curves were generated to assess the predictive value of eGDR for CVD incidence. A clinical decision curve analysis (DCA) was also conducted to assess the clinical utility of the basic model.Results6507 participants were included, with a median age of 58 years [52 years, 64 years], and 55% were female. Over a median follow-up duration of 87 months, 679 first-episode CVD events were recorded, including heart disease and stroke. The RCS curves demonstrated a significant dose–response relationship between eGDR and the incidence of first-presentation CVD in different metabolic and circadian rhythm subgroups (all P-values < 0.001, non-linearity P > 0.05). eGDR exhibited a significant linear relationship with all outcomes (non-linearity P < 0.05). The Kaplan–Meier cumulative incidence curves showed that as eGDR levels increased, the cumulative incidence rates of first CVD, heart disease, and stroke gradually decreased from Q1 to Q4 groups. Significant differences were observed across all metabolic and circadian rhythm subgroups (log-rank test P < 0.001). Through the Cox proportional hazards model, we confirmed a significant association between baseline eGDR levels and first-onset CVD, heart disease, and stroke. Subgroup analyses indicated that the predictive ability of eGDR for CVD risk varied across different Body mass index (BMI) (P for interaction = 0.025) and age (P for interaction = 0.045) subgroups. Mediation analysis revealed that CircS partially mediated this association. Furthermore, time-dependent ROC curves demonstrated the potential of eGDR as a predictor of CVD risk, revealing possible differences in the model's application across different cardiovascular conditions.ConclusioneGDR is an independent predictor of CVD risk, with lower eGDR levels being closely associated with a higher risk of CVD (including heart disease and stroke). In populations with MetS or CircS, the association between lower eGDR levels and increased risk is more pronounced.

Associations of smoking status with long-term cardiovascular events in different arterial territories: the EPIC Norfolk prospective population cohort

Abstract Background Smoking cessation is associated with a reduced risk of cardiovascular disease (CVD) events, mainly in ischemic heart disease (IHD) and stroke. However, the impact of smoking status (never, former or current smoking) on long-term CVD events across different arterial territories remains understudied. Knowledge of such associations is important, as it may assist in risk communication and smoking cessation motivation. We therefore investigated associations between smoking status and territory-specific CVD events in a large cohort with ≥20 years follow-up. Methods We included participants without baseline CVD from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population cohort. The strengths of associations between smoking, former smoking and never smoking with the first occurrence of a CVD event were evaluated using a competing risk-adjusted regression model. CVD events were defined as hospitalisation or death due to IHD, ischemic stroke, haemorrhagic stroke, peripheral arterial disease (PAD) or aortic aneurysm (AA). Patients were followed-up until the first event, non-CVD death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, systolic blood pressure, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), diabetes, renal function and body mass index. We compared former and current smoking (at baseline) with never smoking. Results We included 23,581 participants (56% women) with a median baseline age of 58 years [interquartile range (IQR) 51-66]. During median follow up of 21.3 years (IQR 19.0-22.8), 26.4% experienced ≥1 CVD event. The first event of occurrence was IHD in 17.3%, ischemic stroke in 3.6%, haemorrhagic stroke in 1.4%, PAD in 3.1% and AA in 1.4%. Current (vs. never) smoking was associated with IHD [adjusted hazard rate (aHR) 1.53, 95% confidence interval (CI) 1.36-1.72], PAD (aHR 1.29, 95%CI 1.07-1.56) and AA (aHR 4.81, 95%CI 3.54-6.54). Current smoking was not significantly associated with ischemic stroke (aHR 1.20, 95% CI 0.95-1.52) and haemorrhagic stroke (aHR 1.18, 95% CI 0.81-1.70). In former (vs. never) smoking individuals, the association with AA remained statistically significant but less pronounced [aHR 1.69, 95%CI 1.29-2.23]. Conversely, former smoking was not associated with IHD (aHR 1.07, 95%CI 0.99-1.16) or PAD (aHR 1.09, 95%CI 0.95-1.26) (Figure 1). Conclusion After 20-years of follow-up, former smokers, compared to never-smokers, remain at considerably higher risk for CVD events, particularly for aortic aneurysm. This knowledge may assist in treatment decisions and risk communication.

Heterogeneous associations of traditional atherosclerotic risk factors and long-term events in different arterial territories: the EPIC Norfolk prospective population cohort

Abstract Background Atherosclerotic risk factors have been associated with cardiovascular disease (CVD) events in specific arterial territories. However, these observations are limited by relatively short-term follow-up (i.e. ten years) and a focus on a limited number of outcome events. We therefore investigated associations between atherosclerotic risk factors and territory-specific cardiovascular events in a large cohort with ≥20 years follow-up. Methods We included participants without baseline CVD from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population cohort. The strengths of associations between CVD risk factors (smoking, low-density lipoprotein cholesterol (LDL-c), and systolic blood pressure (SBP)) and the first occurrence of a CVD event were evaluated using a competing risk-adjusted regression model. CVD events were defined as hospitalisations or death due to ischemic heart disease (IHD), ischemic stroke, haemorrhagic stroke, peripheral arterial disease (PAD) or aortic aneurysm (AA). Patients were followed-up until the first event, non-CVD death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, diabetes, HDL-c, kidney function and body mass index. LDL-c and SBP were analysed by comparing highest versus lowest quartiles. Smoking (at baseline) was compared to never smoking. Results We included 23,581 participants (56% women) with a median baseline age of 58 years [interquartile range (IQR) 51-66]. During median follow up of 21.3 years (IQR 19.0-22.8), 26.4% of individuals experienced ≥1 CVD event. The first event of occurrence was IHD in 17.3%, ischemic stroke in 3.6%, haemorrhagic stroke in 1.4%, PAD in 3.1% and AA in 1.4%. LDL-c was strongest associated with IHD [adjusted hazard rate (aHR) 1.7, 95% confidence interval (CI) 1.5-1.9], SBP with ischemic stroke (aHR 1.9, 95%CI 1.5-2.5) and smoking with AA (aHR 4.8, 95%CI 3.5-6.5) (Figure 1). Conclusions There is considerable heterogeneity in the associations between atherosclerotic risk factors and long-term, first, territory-specific cardiovascular events. Knowledge of these differences may assist in personalised treatment decisions and risk communication.

Prognostic role of remnant cholesterol and traditional cardiovascular risk factors in young adults: results of long-term follow-up of a cohort of 30-year-old norwegians

Abstract Background There are limited data on the prevalence and impact of traditional cardiovascular (CV) risk factors among young adults. In addition, more knowledge on novel CV risk factors is needed to explain the residual risk beyond that of the traditional risk factors. Increasing evidence suggest a causal role of remnant cholesterol (RC) in the development of atherosclerotic cardiovascular disease (CVD) and subsequent clinical events. However, the role of RC in young adults is unresolved. Purpose We aimed to evaluate the prevalence of traditional risk factors and the respective sex-differences in young adults, as well as their association with long-term CV events. Further, we hypothesized that higher RC concentrations are associated with impaired CV prognosis. Methods In year 2000, all 30-year-old inhabitants of our city were invited to a cross-sectional study including assessment of health status, anthropometric measurements, and non-fasting blood samples. RC was calculated as total cholesterol minus (LDL-C + HDL-C). Long-term clinical follow-up was performed through linkage with mandatory national registries, 22 years after inclusion. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalization for unstable angina and coronary revascularization. Results A total of 5950 individuals were included (56% women). At baseline, men displayed significantly higher systolic and diastolic blood pressure, total cholesterol, LDL-C and triglycerides, as compared with women (Table 1). Also, men had higher levels of RC (Table 1). During a mean follow-up time of 22 years, 108 events (1.8%) occurred. In multivariable Cox regression analysis, non-West-European ancestry (adjusted [a] HR 1.76, 95% confidence interval [CI] 1.03-2.99), diabetes mellitus (aHR 6.39, 95% CI 2.52-16.2), systolic blood pressure (aHR 1.03, 95% CI 1.01-1.04), and LDL-cholesterol (aHR 1.37, 95% CI 1.11-1.68) were associated with an increased risk of CV events during long-term follow-up. Female gender was associated with a reduced risk of CV events (aHR 0.38, 95% CI 0.23-0.64), whereas smoking status did not show any significant association. RC was identified as a significant predictor of CV events (aHR 1.55, 95% CI 1.11-2.18, per 1.0 mmol/L increase). The highest RC quartile (mean RC: 1.1 mmol/L), had the highest event rate (Figure 1, p&amp;lt;0.001 with log-rank test). Conclusion This study uncovers significant sex-differences in modifiable CV risk factors among young adults at the age of 30, which are associated with increased risk for long-term CV events. Interestingly, increasing concentrations of RC at the age of 30 were strongly associated with impaired long-term CV outcome and should be accounted for in early risk prediction.Baseline characteristics.Remnant cholesterol and CVD events.

Association of a healthy plant-based heart-protective diet with reduced cardiovascular disease incidence and mortality: findings from the UK Biobank Study

Abstract Importance Previous research examining the effects of omnivorous and plant-based diets on CVD outcomes has produced inconsistent findings, and the importance of diet quality is overlooked. Objective To assess the relation between adherence to a healthy plant-based, heart-protective diet and the risk of cardiovascular disease (CVD) events. Design: Prospective cohort study. Methods and Results 192,274 (mean age: 56.3±7.9 years, 43.3% males) participants in UK Biobank without CVD at baseline who completed a 24-hour recall questionnaire. Using data generated by Oxford WebQ, we developed a novel heart-protective diet score (HPDS) based on 22 food groups. Cox proportional hazard models were used to study associations. During a median follow-up of 12.3 years, there were 20,692 CVD events and 1,131 CVD deaths. After adjusting for demographics, Townsend deprivation index, lifestyle factors, and history of chronic diseases, participants in the top quartile of the HPDS were at the lower risk of overall CVD (HR: 0.92, 95% CI: 0.88 to 0.95), ischemic heart disease (HR: 0.88 [95% CI: 0.83 to 0.93]), myocardial infarction (HR: 0.82, 95% CI: 0.74 to 0.90), and heart failure (HR: 0.86, 95% CI: 0.78 to 0.95) than those in the bottom quartile. Participants who adhered closely to a healthy plant-based heart-protective diet had the lowest risk of overall CVD (HR: 0.72, 95% CI: 0.61 to 0.86), ischemic heart disease (HR: 0.68, 95% CI: 0.52 to 0.89), myocardial infarction (HR: 0.65, 95% CI: 0.46 to 0.91), and heart failure (HR: 0.51, 95% CI: 0.30 to 0.85) mortality. Conclusions and relevance: Adherence to a healthy plant-based heart-protective diet rich in non-starchy vegetables, fruits, whole grains, legumes, and fish, is associated with a reduced cardiovascular disease incidence and mortality. Further research in diverse ethnic populations is necessary to validate our findings and enhance their generalizability.

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.

Adherence to a sustainable diet, measured via the EAT-Lancet Index, predicts incident short-term and long-term cardiovascular disease incidence: the ATTICA study (2002-2022)

Abstract Background/Introduction The World Heart Federation has estimated that air pollution was the second most fatal modifiable risk factor for cardiovascular disease (CVD), causing approximately 5 million CVD deaths in 2021. Diets and food systems can affect the environment; however, research scarcely focuses on the association between planet-healthy dietary habits and CVD risk. Purpose The purpose of this study was to evaluate the adherence to a sustainable diet and CVD incidence during 20 years of follow-up. Methods Participants initially free-of-CVD from the ATTICA study were used (n=1,958). CVD events were assessed at baseline and at all follow-ups (i.e., 2002, 2012, 2022) according to WHO-ICD-10. Adherence to a sustainable diet was assessed via the EAT-Lancet Index (EAT-LI) (Education and Agriculture Together-EAT) (range: 0-42) based on the published algorithm. Results CVD incidence was 16.2% (n=317 incident cases) at 10-years and 35.3% (n=691 incident cases) at 20-years. Mean EAT-LI was: 17.3 (6.7) for the total sample. EAT-LI was lower in those that had a CVD event during the follow-up, i.e., EAT-LI: 10.5 (6.3) vs 18.5 (5.9) at 10-years (p&amp;lt;0.001) and 10.9 (6.4) vs 20.8 (3.8) at 20-years (p&amp;lt;0.001), in participants with and without a CVD event, respectively. In multi-adjusted analyses, adjusted for age, sex, body mass index trajectories, lifestyle trajectories, and clinical factors (diabetes, hypercholesterolemia, hypertension), higher adherence to a sustainable diet was inversely associated with CVD risk at a short-term and a long-term period (i.e., at 10 and 20 years). Specifically, per 1/42 increase in the EAT-Lancet index, CVD risk was reduced by 11% [Hazard ratio-HR: 0.89, 95%Confidence Interval: 0.86-0.93] and by 16% [HR: 0.84, 95%CI: 0.80-0.89] at 10 and 20 years, respectively. Conclusion Future guidelines for CVD prevention should take into account the sustainable nature of dietary habits, to efficiently nourish the growing world population, and concomitantly protect heart and planet health.

Educational attainment and cardiovascular outcomes in prostate cancer: observations from 3700 men in 6 countries in the RADICAL PC study

Abstract Background Educational attainment has been associated with improved cardiovascular outcomes in individuals with or at high risk for cardiovascular disease (CVD). There is little information on the relationship between education and CVD outcomes in individuals with cancer. Also, we have limited understanding of what mediates the relationship between education and these outcomes. Purpose To evaluate the relationship between educational attainment in patients with PC and CVD event (CVE) or all-cause mortality. Methods We prospectively studied 3,778 men with PC from 55 sites in 7 countries (median age 69 years), 46% on ADT. Inclusion criteria were one of: PC diagnosed in the past 12 months; started ADT within the past 6 months; or plan to start ADT in the next month. Educational attainment was classified as those who attained primary school education vs. those who attained high school education vs. those who attained greater than high school education. Participants were followed for a median of 2.5 years from enrolment to document CVE: myocardial infarction, angina, stroke, cerebrovascular disease, peripheral arterial disease, arterial revascularization, heart failure, venous thromboembolism, and atrial fibrillation. The primary outcome for this analysis was CVE or death. All outcomes were evaluated by Cox proportional hazards models adjusted sequentially for age, race, physical activity levels, tobacco use, and alcohol use. Results Among 3,778 participants, 726 (19%) achieved primary school education, 1,001 (27%) high school, and 2,051 (54%) greater than high school education. On univariate analysis, as compared with participants with greater than high school education, those with high school education and primary school education had respective HR (95% CI) of 1.33 (1.05-1.69) and 2.19 (1.71-2.83). Adding age, race, tobacco, and alcohol use to the Cox model progressively attenuated the association between education and the primary outcome. Eventually, after adjustment for these characteristics and physical activity levels, the relationship between education and the primary outcome was no longer significant (Table). Conclusion This finding suggests that patterns of tobacco and alcohol use and physical activity, which are modifiable behaviors, account for the relationship between education and death or CVE in patients with prostate cancer.Table