CVD Deaths Research Articles

Re‐examination of statistical relationships between dietary fats and other risk factors, and cardiovascular disease, based on two crucial datasets

AbstractCardiovascular disease (CVD) is the major cause of death in many regions around the world, and several of its risk factors might be linked to diets. To improve public health and the understanding of this topic, we look at the recent Minnesota Coronary Experiment (MCE) analysis that used t‐test and Cox model to evaluate CVD risks. However, these parametric methods might suffer from three problems: small sample size, right‐censored bias, and lack of long‐term evidence. To overcome the first of these challenges, we utilize a nonparametric permutation test to examine the relationship between dietary fats and serum total cholesterol. To address the second problem, we use a resampling‐based rank test to examine whether the serum total cholesterol level affects CVD deaths. For the third issue, we use some extra‐Framingham Heart Study (FHS) data with an A/B test to look for meta‐relationship between diets, risk factors, and CVD risks. We show that, firstly, the link between low saturated fat diets and reduction in serum total cholesterol is strong. Secondly, reducing serum total cholesterol does not robustly have an impact on CVD hazards in the diet group. Lastly, the A/B test result suggests a more complicated relationship regarding abnormal diastolic blood pressure ranges caused by diets and how these might affect the associative link between the cholesterol level and heart disease risks. This study not only helps us to deeply analyze the MCE data but also, in combination with the long‐term FHS data, reveals possible complex relationships behind diets, risk factors, and heart disease.

Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study.

We examined the association of attainment of diabetes remission in the context of a 12 year intensive lifestyle intervention with subsequent incidence of chronic kidney disease (CKD) and CVD. The Look AHEAD study was a multi-centre RCT comparing the effect of a 12 year intensive lifestyle intervention with that of diabetes support and education on CVD and other long-term health conditions. We compared the incidence of CVD and CKD among 4402 and 4132 participants, respectively, based on achievement and duration of diabetes remission. Participants were 58% female, and had a mean age of 59 years, a duration of diabetes of 6 year and BMI of 35.8 kg/m2. We applied an epidemiological definition of remission: taking no diabetes medications and having HbA1c <48 mmol/mol (6.5%) at a single point in time. We defined high-risk or very high-risk CKD based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, and CVD incidence as any occurrence of non-fatal acute myocardial infarction, stroke, admission for angina or CVD death. Participants with evidence of any remission during follow-up had a 33% lower rate of CKD (HR 0.67; 95% CI 0.52, 0.87) and a 40% lower rate of the composite CVD measure (HR 0.60; 95% CI 0.47, 0.79) in multivariate analyses adjusting for HbA1c, BP, lipid levels, CVD history, diabetes duration and intervention arm, compared with participants without remission. The magnitude of risk reduction was greatest for participants with evidence of longer-term remission. Participants with type 2 diabetes with evidence of remission had a substantially lower incidence of CKD and CVD, respectively, compared with participants who did not achieve remission. This association may be affected by post-baseline improvements in weight, fitness, HbA1c and LDL-cholesterol. ClinicalTrials.gov NCT00017953 DATA AVAILABILITY: https://repository.niddk.nih.gov/studies/look-ahead/.

Associations between Chinese visceral adiposity index and risks of all-cause and cause-specific mortality: A population-based cohort study.

To determine the associations between the Chinese visceral adiposity index (CVAI) and the risks of all-cause and cause-specific mortality. A total of 3 916 214 Chinese adults were enrolled in a nationwide population cohort covering all 31 provinces of mainland China. The CVAI was calculated based on age, body mass index, waist circumference, and triglyceride and high-density lipoprotein cholesterol concentrations. We used a Cox proportional hazards regression model to determine the hazard ratios and 95% confidence intervals (CIs) for risk of mortality associated with different CVAI levels. The median follow-up duration was 3.8 years. A total of 86 158 deaths (34 867 cardiovascular disease [CVD] deaths, 29 884 cancer deaths, and 21 407 deaths due to other causes) were identified. In general, after adjusting for potential confounding factors, a U-shaped relationship between CVAI and all-cause mortality was observed by restricted cubic spline (RCS). Compared with participants in CVAI quartile 1, those in CVAI quartile 4 had a 23.0% (95% CI 20.0%-25.0%) lower risk of cancer death, but a 23.0% (95% CI 19.0-27.0) higher risk of CVD death. In subgroup analysis, a J-shaped and inverted U-shaped relationship for all-cause mortality and cancer mortality was observed in the group aged < 60 years. The CVAI, an accessible indicator reflecting visceral obesity among Chinese adults, has predictive value for all-cause, CVD, and cancer mortality risks. Moreover, the CVAI carries significance in the field of health economics and secondary prevention. In the future, it could be used for early screening purposes.

Low body mass index is associated with adverse cardiovascular outcomes following PCI in India: ACC-NCDR registry

ObjectiveRegistry-based prospective study was conducted to evaluate association of body mass index (BMI) with major adverse coronary events (MACE) following percutaneous coronary intervention (PCI). MethodsSuccessive patients undergoing PCI were enrolled from April‘19 to March’22 and classified into five BMI categories (<23.0,23.0-24.9,25.0-26.9,27.0–29.9, and ≥30.0 kg/m2). Clinical, angiographic features, interventions and outcomes were obtained by in-person or telephonic follow-up. Primary endpoints were (a) MACE(cardiovascular deaths, acute coronary syndrome or stroke, revascularization, hospitalization and all-cause deaths) and (b)cardiovascular deaths. Cox-proportionate hazard ratios(HR) and 95 % confidence intervals(CI) were calculated. ResultsThe cohort included 4045 patients. Mean age was 60.3 ± 11y, 3233(79.7 %) were men. There was high prevalence of cardiometabolic risk factors. 90 % patients had acute coronary syndrome(STEMI 39.6 %, NSTEMI/unstable angina 60.3 %), 60.0 % had impaired ejection fraction(EF) and multivessel CAD. Lower BMI groups (<23.0 kg/m2) had higher prevalence of tobacco use, reduced ejection fraction(EF), multivessel CAD, stents, and less primary PCI for STEMI. There was no difference in discharge medications and in-hospital deaths. Median follow-up was 24 months (IQR 12–36), available in 3602(89.0 %). In increasing BMI categories, respectively, MACE was in 10.9,8.9,9.5,9.1 and 6.8 % (R2 = 0.73) and CVD deaths in 5.1,4.5,4.4,5.1 and 3.5 % (R2 = 0.39). Compared to lowest BMI category, age-sex adjusted HR in successive groups for MACE were 0.89,0.87,0.79,0.69 and CVD deaths 0.98,0.87,0.95,0.75 with overlapping CI. HR attenuated following multivariate adjustments. ConclusionsLow BMI patients have higher incidence of major adverse cardiovascular events following PCI in India. These patients are older, with greater tobacco use, lower EF, multivessel CAD, delayed STEMI-PCI, and longer hospitalization.

Associations between actigraphy-measured sleep duration, continuity, and timing with mortality in the UK Biobank.

To examine the associations between sleep duration, continuity, timing, and mortality using actigraphy among adults. Data were from a cohort of 88 282 adults (40-69 years) in UK Biobank that wore a wrist-worn triaxial accelerometer for 7 days. Actigraphy data were processed to generate estimates of sleep duration and other sleep characteristics including wake after sleep onset (WASO), number of 5-minute awakenings, and midpoint for sleep onset/wake-up and the least active 5 hours (L5). Data were linked to mortality outcomes with follow-up to October 31, 2021. We implemented Cox models (hazard ratio, confidence intervals [HR, 95% CI]) to quantify sleep associations with mortality. Models were adjusted for demographics, lifestyle factors, and medical conditions. Over an average of 6.8 years 2973 deaths occurred (1700 cancer, 586 CVD deaths). Overall sleep duration was significantly associated with risk for all-cause (p < 0.01), cancer (p < 0.01), and CVD (p = 0.03) mortality. For example, when compared to sleep durations of 7.0 hrs/d, durations of 5 hrs/d were associated with a 29% higher risk for all-cause mortality (HR: 1.29 [1.09, 1.52]). WASO and number of awakenings were not associated with mortality. Individuals with L5 early or late midpoints (<2:30 or ≥ 3:30) had a ~20% higher risk for all-cause mortality, compared to those with intermediate L5 midpoints (3:00-3:29; p ≤ 0.01; e.g. HR ≥ 3:30: 1.19 [1.07, 1.32]). Shorter sleep duration and both early and late sleep timing were associated with a higher mortality risk. These findings reinforce the importance of public health efforts to promote healthy sleep patterns in adults.

Social, behavioral, and metabolic risk factors for racial disparities in cardiovascular disease mortality in US adults

Abstract Background Cardiovascular disease (CVD) mortality is persistently higher in the Black population than in other race and ethnicity groups in the US. Purpose To determine whether social, behavioral, and metabolic risk factors mediate racial disparities in CVD mortality and to assess the contribution of these risk factors to CVD mortality in the US general population. Methods A nationally representative sample of 50,808 individuals aged ≥20 years from National Health and Nutrition Examination Surveys (NHANES) 1999-2018 were included in the analysis. Data on social, behavioral, and metabolic factors were collected in each NHANES survey using standard methods. CVD deaths were ascertained from linkage to the National Death Index with follow-up through 2019. Results Over an average of 9.4 years of follow-up, 2,598 CVD deaths were confirmed. In a multivariable Cox regression model stratified by NHANES cycle and adjusted for age, sex, race, and social, behavioral, and metabolic risk factors simultaneously, individuals who were unemployed, had a lower family income, did not own a home, were not married nor living with a partner, were current smokers, reported no leisure-time physical activity, slept &amp;lt;6 or &amp;gt;8 hours/day, had obesity, hypertension, or diabetes, or had an albumin-to-creatinine ratio ≥30 mg/g or estimated-glomerular filtration rate &amp;lt;60 ml/min/1.73 m2 were at significantly higher risk for CVD mortality. After adjusting for these risk factors, hazard ratios (95% CI) of CVD mortality for Black individuals compared to White individuals decreased from 1.54 (1.34-1.77) to 0.86 (0.75-1.00). Social risk factors explained 72.9% Black-White differences in CVD mortality in a multivariable mediation analysis. The population attributable fractions (95% CI) for the top five risk factors for CVD mortality were 12.5% (5.6-19.3%) for hypertension, 10.6% (6.9-14.3%) for albuminuria, 9.4% (5.3-13.6) for physical inactivity, 9.1% (4.6-13.7%) for family income-to-poverty ratio &amp;lt;300%, and 7.2% (4.5-9.9%) for estimated-glomerular filtration rate &amp;lt;60 ml/min/1.73 m2 in the US general population. Conclusion Social, behavioral, and metabolic risk factors fully explained the Black-White difference in CVD mortality. Hypertension, albuminuria, physical inactivity, low family income, and reduced kidney function are leading risk factors for CVD mortality in the US population.

Myeloid cannabinoid receptor CB1 deficiency confers atheroprotection in a sex-specific manner

Abstract Aim Cardiovascular diseases (CVDs) are the leading cause of death globally, claiming an estimated 17.9 million lives each year. A better understanding of the underlying chronic inflammatory disease mechanisms in atherosclerosis might help finding novel treatments and reduce CVD deaths. In particular, the cannabinoid receptor CB1 has been implicated in atherosclerosis, while its cell-specific effects in this disease are not well understood. Methods Myeloid Cnr1 (CB1 encoding gene) knockout mice were generated on apolipoprotein E deficiency (Apoe-/-) background by crossing CB1flox mice with transgenic mice carrying Cre under control of the lysozyme M (LysM) promoter for selective expression in myeloid cells. Age - and sex-matched groups were analyzed at baseline, 4 and 16 weeks Western diet (0,15% cholesterol). For in vitro experiments, murine bone marrow-derived macrophages (BMDM) were used. Results Male mice with myeloid-specific Cnr1 deficiency on atherogenic background developed smaller lesions and necrotic cores compared to controls, while only minor effects in females were observed. Male Cnr1 deficient mice had reduced arterial monocyte recruitment and macrophage proliferation with less inflammatory phenotype. The sex-specific differences were reproducible in vitro in BMDMs and blunted by female hormone estradiol treatment. Array-based kinase activity profiling of BMDMs stimulated with a synthetic CB1 agonist revealed a CB1-dependent regulation of p53 and cyclin-dependent kinases. Transcriptomic profiling via bulk RNA-sequencing of CB1 agonist-stimulated BMDMs further unveiled chromatin modifications, mRNA processing and mitochondrial respiration among the key processes affected by CB1 signaling, which was supported by metabolic flux assays. Chronic administration of the peripherally-restricted CB1 antagonist JD5037 inhibited plaque progression and macrophage proliferation, again only in male mice. Conclusion Impaired CB1 signaling in macrophages is atheroprotective by limiting their arterial recruitment, proliferation and inflammatory reprogramming. The biological effects of macrophage CB1 signaling seem to be more pronounced in male mice. This highlights the need to consider the biological sex as an important variable in preclinical studies.

Abstract 12190: Cardiovascular Disease Mortality Trends Among Native Hawaiian and Pacific Islander Adults—United States, 2018 to 2022

Introduction: Native Hawaiian and Pacific Islander (NHPI) adults have historically been grouped with Asian adults in US mortality surveillance, potentially masking important differences between these two populations. In 2018, US death certificate race categories were modified, enabling the disaggregation of NHPI national CVD mortality surveillance data from the Asian population. Methods: Using National Vital Statistics System mortality data from 2018 to 2022, we identified CVD deaths among adults aged ≥35 years with ICD-10 codes I00-I99 listed as the underlying cause of death. Of all CVD decedents with non-Hispanic origin and NHPI listed alone or in combination with other race groups on the death certificate, we classified those with NHPI listed as the only race group as NHPI (60.1%). Rate ratios (RR) and 95% confidence intervals (CI) compared age-standardized mortality rates (ASMR) among NHPI adults compared to non-Hispanic Asian adults and US adults overall. Results: From 2018 to 2022, 6,088 CVD deaths (72.0% heart disease, 19.8% stroke) occurred among NHPI adults of Hawaiian (24.5%), Samoan (24.3%), Guamanian (11.0%), or other Pacific Islander (40.2%) descent. The NHPI ASMR was 464.5 CVD deaths per 100,000 (95% CI: 452.4-476.6), second only to the non-Hispanic Black ASMR (590.3 CVD deaths per 100,000, CI: 588.7-591.8; Figure). The ASMR among NHPI adults was significantly higher than non-Hispanic Asian adults (RR: 1.86, CI: 1.81-1.91) and US adults overall (RR: 1.07, 95% CI: 1.04-1.10). Conclusions: Single-race NHPI adults had the second-highest CVD death rate in the US from 2018 to 2022, second only to Black adults, and significantly higher than Asian adults. Surveillance using broader multi-race definitions to identify the NHPI population, further disaggregate by NHPI subgroup, and explore geographic variation is needed to better understand potential health disparities and target interventions to reduce CVD mortality disparities among NHPI adults.

Abstract 16300: Genetic Influences on Cardiovascular Deaths During Various Follow-Up Lengths in the 45-Year Longitudinal Twin Study

Background: Genetic factors are known to affect cardiovascular and coronary heart death. The more deaths occur during the longer follow-up period in a longitudinal study. However, it is unclear whether follow-up lengths affect genetic influences on the mortality from total cardiovascular (CVD) and coronary heart diseases (CHD). Objective: To determine genetic influences on the mortality from CVD and CHD over various years of follow-up in the 45-year longitudinal National Heart, Lung, and Blood Institute (NHLBI) Twin Study. Method: A total of 1024 middle-aged, white male, veteran twins (512 pairs), including 253 monozygotic and 261 dizygotic twin pairs, were initially enrolled during 1969-1973 and then followed up on vital status and causes of death through December 31, 2015. Tetrachoric correlation coefficients were estimated for CHD and CVD death at 20, 30, and 45 years of follow-up, respectively. Genetic and environmental influences on the death were quantified using the best-fitting structural equation model selected with the smallest Akaike's Information Criterion value and the parsimony rule. Results: The age at death ranged from 43.9 to 97.3 years over a 45-year follow-up. Tetrachoric correlation coefficients in dizygotic twins were less than half of that in monozygotic twins over 20, 30, and 45 years of follow-up for CVD but over 20 and 30 years for CHD, respectively. Dominant genetic factors explained 40% (95% CI 5% ~ 68%), 39 % (16% ~ 59%), and 24% (4% ~ 43%) of variation in CVD death over 20, 30, and 45 years of follow-up, respectively, while the remaining variation in CVD death was explained by unique environmental factors during each follow-up period. For CHD death, unique environmental factors explained all variation over 20 and 45 years of follow-up. By contrast, dominant genetic factors explained 26% (95% CI -6% ~ 53%) variation in CHD death over 30 years of follow-up while the remaining variation was explained by unique environmental factors. Conclusion: Dominant genetic factors consistently influence cardiovascular mortality over 20 to 45 years of follow-up, implying a twin study of cardiovascular death can control for genetic confounding during this period.

Abstract 12832: Risk of Extreme Wet Climate Conditions and Racial/Ethnic-Specific Cardiovascular Mortality in Southwest United States

Introduction: Coastal regions are highly vulnerable to extreme climate conditions, which are known to have effects on adult cardiovascular disease mortality (CVDM). Racial/ethnic (R/E) minority populations (ie Non-Hispanic (NH) Black) are known to have a greater incidence of CVDM compared to their NH White counterparts. Consequently, there is a need to document associations between climate extremes and R/E-specific CVDM. Hypothesis: Extreme wet conditions associated with CVDM should vary by R/E, where strongest increased risk is expected for minority populations. Methods: Population-based study using sex, age (45-84 years), and R/E-specific (NH White, Black, Asian, &amp; Hispanic/Latino) CVD deaths [ICD-10 (I00-99)] from CDC for Southwest US (California, Arizona, New Mexico) from Jan 1999 to Dec 2020. Climate exposure categories (mild, moderate, extreme dry/wet) were based on Palmer Drought Severity Index (PDSI), which integrates temperature and precipitation. With population estimates, CVDM rates were associated with PSDI categories using negative binomial regression upon adjusting for diabetes, smoking prevalence, sex, trend, month, state, unemployment rate, and air pollution (PM 2.5 ). Results: From 1999-2020, 1,307,418 (67.6% NH White, 16.1% Hispanic, 7.4% NH Asian, 8.9% NH Black) CVD deaths were recorded. CVDM was associated with a significant increased risk during extreme wet events (compared to extreme drought) only among NH Asian (adjusted rate ratio [RR] 1.08; 95% CI 1.06-1.09) and NH White (RR 1.02; 95% CI 1.01-1.025) in Southwest US (Figure). Insignificant interactions were observed between extreme wet and PM2.5 on CVDM by R/E. Conclusions: Extreme wet climate conditions were associated with an increased risk of CVDM among NH Asian and White adults. Both climate extreme events and R/E should be considered as predisposing risk factors for CVDM. Further studies are needed to assess such CVDM risk factors for other susceptible areas in the US.

Abstract 13727: Cost-Effectiveness of Sotagliflozin in Heart Failure Patients With Preserved and Reduced Ejection Fractions—Results From the SOLOIST-WHF

Background: SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) showed patients with diabetes and recent worsening heart failure (HF), sotagliflozin initiated before or shortly after discharge lowered incident cardiovascular deaths, hospitalizations, and HF urgent visits. In this study, we evaluated the cost-effectiveness of sotagliflozin in all patients and those with preserved (HFpEF ≥50%) and reduced (HFrEF &lt;50%) ejection fraction. Methods: We ran a Markov microsimulation model based on treatment effects from SOLOIST-WHF, healthcare costs and utilities from national sources, and estimated net costs for sotagliflozin of $434 (range from $407 to $612) monthly, to calculate projected lifetime healthcare costs, HF and CVD events, survival, and quality-adjusted life-years (QALYs) for sotagliflozin vs placebo in SOLOIST-WHF eligible patients from a payer perspective. Outcome measured as the incremental cost-effectiveness ratio (ICER), incremental costs / QALYs gained. Sensitivity analyses assessed and quantified uncertainties. Results: Over a lifetime, sotagliflozin compared to placebo added 0.39 QALYs (4.43 vs. 4.04 QALYs) and 0.64 life-years (7.12 vs. 6.48) at an incremental cost of $29,449 (95% uncertainty interval (UI): $26,610-$32,528) for an ICER of $75,510 per QALY gained (UI: $55,640-$98,300). In HFpEF patients, sotagliflozin compared to placebo added 0.43 QALYs (4.53 vs. 4.10 QALYs) and 0.68 life-years (7.14 vs. 6.46) at an incremental cost of $26,615 (UI: $23,376-$29,694) for an ICER of $61,488 per QALY gained (UI: $41,618-$84,280). In HRrEF patients, sotagliflozin added 0.37 QALYs (4.33 vs. 3.96 QALYs) and 0.63 life-years (7.09 vs. 6.46) at an incremental cost of $30,012 (UI: $26,773-$33,251) for an ICER of $77,996 per QALY gained (UI: $58,126-$100,780). The benefit of sotagliflozin in QALY mainly results from the decrease in CVD deaths. Findings were sensitive to drug cost and number of readmissions. Conclusions: This study demonstrates that sotagliflozin priced from $407 to $612 per month is a clinically and economically favorable medication in patients with diabetes, recent worsening heart failure, with both preserved and reduced ejection fraction.

Abstract 16652: Cardiovascular Outcomes of Renin-Angiotensin System Inhibition Amongst Non-Proteinuric Chronic Kidney Disease Patients in the Chronic Renal Insufficiency Cohort

Introduction: Chronic kidney disease is a leading cause of CVD morbidity and mortality. The majority of CKD patients do not have proteinuria. Current therapies, including renin-angiotensin system (RAS) blockers, are only known to be beneficial in proteinuric CKD. Our goal was to evaluate the association of RAS blockade with long-term CVD outcomes and survival among those with non-proteinuric CKD. Methods: The cohort included subjects in the prospective Chronic Renal Insufficiency Cohort Study without proteinuria at study entry. Non-proteinuric CKD was defined as urine protein &lt;0.5g/day. We excluded subjects with heart failure or not on hypertension treatment. We used Cox proportional hazards regression to evaluate the association of RAS blockade vs. other antihypertensive therapy with CVD outcomes and death. The primary outcome was a composite of physician-adjudicated CVD events, including MI, stroke, heart failure hospitalization and death. Baseline covariates were adjusted through inverse probability of treatment weighting including: age, sex, race, education, smoking, BMI, diabetes, blood pressure, eGFR, and statin use. Results: A total of 2,825 of subjects met inclusion criteria. There were 2,068 subjects using vs 757 not using (73% vs 27%) RAS blockade at entry. Users had a similar age (61 vs 62 years) and eGFR (50 vs 51ml/min/1.73m 2 ) to non-users. Users were more likely to be male (66% vs 46%), to have diabetes (59% vs 30%), and to be on a statin (61% vs 50%). No significant association was found between RAS blockade and CVD events (adjusted HR 0.90, 95% CI 0.76-1.07) or mortality (adjusted HR 0.84, 95% CI 0.68-1.04) compared to other antihypertensive therapy. Conclusions: Among adults with non-proteinuric CKD, baseline use of RAS blockade was not associated with a lower risk of long-term events or mortality. Further studies are needed to determine if RAS blockade may play a role in high-risk patients with non-proteinuric CKD.

Abstract 14992: Impact of Coronary Artery Disease on Rate vs. Rhythm-Control of Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is a common arrhythmia that can impair quality of life and increase cardiovascular mortality. Previous studies have shown potentially better outcomes with rate-control agents in patients with coronary artery disease (CAD). Yet, optimal treatment of AF is not yet known. Methods: Leveraging data from the AFFIRM trial, we performed a post-hoc analysis examining outcome differences in patients on rate vs. rhythm-control agents, based on CAD status. The primary outcome was defined as death from any cause; secondary outcomes included ischemic stroke, major bleeding, and hospitalization after baseline. Univariate and multivariate modeling were used to determine risk factors associated with designated outcomes. Results: Of 4060 patients enrolled, 1551 patients had CAD at baseline. There were no differences in treatment randomization based on CAD status; however, more patients with CAD had worse heart function and comorbid CHF. More patients with CAD ultimately used some form of rate-control compared to those without. Overall, CAD patients were more likely to experience death (HR 2.08 [1.79-2.42], P&lt;0.001), specifically those on rhythm-control (HR 1.24 [1.01-1.52], P=0.04, Figure). CAD patients were also more likely to have ischemic stroke (HR 1.24 [1.00-1.53], P=0.05). When comparing CVD vs. non-CVD death, only CAD patients on rhythm-control exhibited a significantly higher rate of CVD death (HR 1.39 [1.03-1.89], P=0.03), while no differences in primary outcomes were noted for all other groups (P&gt;0.05, Figure). In multivariate modeling, the effect of treatment arm on risk of CVD death in CAD patients diminished upon accounting for age, smoking, rhythm at randomization, first episode of AF, CHF, and LVEF&lt;50% (HR 1.18 [0.93-1.50], P=0.17). Conclusions: AF patients with CAD on rhythm-control agents exhibited worse CVD outcomes, which may be more reflective of heart disease severity rather than treatment effects.

2023: The year in cardiovascular disease - the year of new and prospective lipid lowering therapies. Can we render dyslipidemia a rare disease by 2024?

In 2023 there are still even 75% of patients over the target of low-density lipoprotein cholesterol (LDL-C), and hypercholesterolemia is the most common and the worst monitored cardiovascular risk factor. How it is possible, considering the knowledge we have on the role of cholesterol in the process of atherosclerosis, atherosclerotic cardiovascular disease (ASCVD) and its complications, on the methods of lipid disorders diagnosis, prevention, and treatment. Nowadays, almost 4 million deaths per year are attributed to LDL-C, and even 2/3 of all CVD deaths to ASCVD, therefore hypothetically we should easily prevent few to several million of deaths with early diagnosis, and early and intensive non-pharmacological and pharmacological therapies. Moreover, lipidology is now, besides oncology, the area with the highest number of new and ongoing trials with new effective and safe medications that have already appeared and will soon be available. Therefore, we have no doubt that year 2023 should be called the year of new and prospective lipid lowering therapies (LLTs). In this State-of-the-Art paper we summarized the most important trials, studies, and recommendations on the new and prospective LLTs, with suitable graphical summaries that might be helpful for the physicians in their practice with a look to the nearest future with prospective therapies being still under investigation. Let's hope all those medications helps to render dyslipidemia a rare disease in next few years.

Prognostic impact of abnormal sodium burden in heart failure patients with preserved ejection fraction.

Sodium abnormality is common in patients with heart failure (HF) and is associated with adverse clinical outcomes. The aim of this study is to determine the impact of abnormal sodium burden on long-term mortality and hospitalization in HF with preserved ejection fraction (HFpEF). We analysed participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with available baseline and follow-up data (n = 1717). Abnormal sodium burden was defined as the proportion of days with abnormal sodium plasma levels (either <135 mmol/L or > 145 mmol/L). To determine the independent prognostic impact of abnormal sodium burden on the long-term clinical adverse outcomes (The primary outcome was any cause death, the secondary outcomes include cardiovascular disease death, HF hospitalization, any cause hospitalization and the primary endpoint of the original study), a multivariable Cox proportional hazard model and time-updated Cox regression model were performed. Abnormal sodium burden occurred in 717 patients (41.76%). A high abnormal sodium burden was associated with 1.47 (95% CI, 1.15-1.89) higher risk with any cause mortality, 1.51 (95% CI, 1.08-2.09) higher risk with CVD death and 1.31 (95% CI, 1.02-1.69) higher risk with HF hospitalization when compared with no burden group. When sodium level changes over time were accounted for in time-updated models, abnormal sodium level was still associated with poor clinical outcomes. Diuretic and spironolactone usage did not show a statistical interaction effect on the prognostic significance. In HFpEF patients, abnormal sodium burden was an independent predictor long-term any-cause mortality and HF hospitalization.

Triglyceride glucose index as a predictor of mortality in middle-aged and elderly patients with type 2 diabetes in the US

Despite a wealth of research linking the triglyceride glucose index (TyG index) to metabolic diseases. However, little evidence links the TyG index to all-cause or CVD mortality in middle-aged and elderly individuals with type 2 diabetes (T2D). This study analyzed data from 2998 patients with T2D who participated in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. The TyG index and mortality in middle-aged and elderly T2D patients were investigated using Cox regression models. The nonlinear association between the TyG index and mortality can be understood with the help of a restricted cubic spline (RCS). During a median follow-up period of 82 months, 883 fatalities were observed from all causes and 265 from CVD. The TyG index was found to have a U-shaped relationship with all-cause and CVD mortality in T2D, with cutoffs of 8.95 and 9, respectively, according to the RCS. After controlling for other factors, an increase of 1 unit in the TyG index was related to an increase of 33% in all-cause mortality and 50% in CVD mortality when TyG was ≥ 8.95 and 9. When TyG < 8.95 and 9, with the change in the TyG index, the change in all-cause and CVD death was insignificant. Patients with T2D who are middle-aged or older, especially elderly patients, have higher TyG levels associated with increased mortality. In middle-aged and elderly patients with T2D, the TyG index may predict the probability of death from any cause and death from CVD.

A-374 Analytical Performance Assessment and Comparison of Point of Care Testing (POCT) Devices for Blood Lipids Measurements

Abstract Background Cardiovascular diseases (CVDs) are the leading cause of death in the U.S. and worldwide. According to the World Health Organization (WHO), worldwide, 85% of CVD deaths are due to heart disease and strokes, and over 75% occur in low- and middle-income countries (LMICs). Early detection and treatment are key to preventing the consequences of CVD. Point-of-care testing (POCT) devices offer alternatives to screening large populations for CVD risk. Although POCT are increasingly used for screening, only few information is available about their accuracy and reliability. Methods Eight POCT devices for blood lipids that previously successfully participated in the CDC CVD Biomarker Standardization Programs were used in this preliminary study. The analytical performance for all eight devices was assessed using split sample comparisons to the CDC reference measurement procedures for measurements performed in whole blood (WB) and serum. Specifically, the accuracy of total cholesterol (TC) was determined in WB and serum. The accuracy of high-density lipoprotein-cholesterol (HDL-c), and low-density lipoprotein-cholesterol (LDL-c) was determined in serum. The precision of TC, HDL-c, LDL-c, and triglycerides (TG) was determined in WB and serum. Results The reference values of the specimens from 20 donors ranged between 154–279 mg/dL, 36.9–109 mg/dL, and 71.1–182 mg/dL for TC, HDL-c, and LDL-c in serum, and between 145–210 mg/dL for TC in WB. Preliminary assessments found that the mean bias for each instrument ranged from -7.86%–13.82% and from -11.90%–3.24% for TC in WB and serum, respectively. For serum HDL-c samples, the mean bias ranged from −6.81%–15.43%. The mean bias for serum LDL-c samples ranged from −22.40% to 3.08%. For three devices, approximately 30% of the WB measurements and approximately 50% of the serum measurements were reported as outside of the measurement range. The mean imprecision for each instrument ranged from 2.2%–13.75% and from 1.88%–11.76% for TC in WB and serum, respectively. For HDL-c, the mean imprecision ranged from 5.36%–23.21% and from 2.30% to 26.69% in WB and serum, respectively. The mean imprecision ranged from 4.82%–20.34% and from 3.06%–20.54% for LDL-c in WB and serum, respectively. For TG, the mean imprecision ranged from 5.78%–23.91% and from 1.71%–11.02% in WB and serum, respectively. Conclusion These preliminary findings about the analytical performance of POCT devices indicate notable differences in accuracy and precision for lipids measured in WB and serum, with serum measurements being more likely within performance requirements than WB measurements. Some devices appear to be more likely to report values outside the measurement range even though reference values are within the measurement range of the device. Further studies to verify these preliminary findings with more individual donor samples are underway.

Associations of long-term fine particulate matter exposure with all-cause and cause-specific mortality: results from the ChinaHEART project

The chronic effects of fine particulate matter (PM2.5) at high concentrations remains uncertain. We aimed to examine the relationship of long-term PM2.5 exposure with all-cause and the top three causes of death (cardiovascular disease [CVD], cancer, and respiratory disease), and to analyze their concentration-response functions over a wide range of concentrations. We enrolled community residents aged 35-75 years from 2014 to 2017 from all 31 provinces of the Chinese Mainland, and followed them up until 2021. We used a long-term estimation dataset for both PM2.5 and O3 concentrations with a high spatiotemporal resolution to assess the individual exposure, and used Cox proportional hazards models to estimate the associations between PM2.5 and mortalities. We included 1,910,923 participants, whose mean age was 55.6±9.8 years and 59.4% were female. A 10μg/m3 increment in PM2.5 exposure was associated with increased risk for all-cause death (hazard ratio 1.02 [95% confidence interval 1.012-1.028]), CVD death (1.024 [1.011-1.037]), cancer death (1.037 [1.023-1.052]), and respiratory disease death (1.083 [1.049-1.117]), respectively. Long-term PM2.5 exposure nonlinearly related with all-cause, CVD, and cancer mortalities, while linearly related with respiratory disease mortality. The overall effects of long-term PM2.5 exposure on mortality in the high concentration settings are weaker than previous reports from settings of PM2.5 concentrations < 35μg/m³. The distinct concentration-response relationships of CVD, cancer, and respiratory disease mortalities could facilitate targeted public health efforts to prevent death caused by air pollution. The Chinese Academy of Medical Sciences Innovation Fund for Medical Science, the National High Level Hospital Clinical Research Funding, the Ministry of Finance of China and National Health Commission of China, the 111 Project from the Ministry of Education of China.

Cumulative social disadvantage and cardiovascular disease burden and mortality.

To investigate the association between cumulative social disadvantage and cardiovascular burden and mortality in a large cohort of the general population. Cross-sectional (n = 15 010, aged 35 to 74 years, baseline investigation period 2007 to 2012) and longitudinal data (5- and 10-year follow-ups from 2012 to 2022) from the Gutenberg Health Study were used to investigate the association between individual socioeconomic status (SES, measured via a validated questionnaire) and cardiovascular disease (CVD, composite of atrial fibrillation, coronary artery disease, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and/or venous thromboembolism) risk and mortality. Subjects with prevalent CVD had a lower SES sum score, as well as lower education, occupation, and household net-income scores (all P < 0.0001). Logistic regression analysis showed that a low SES (vs. high, defined by validated cut-offs) was associated with 19% higher odds of prevalent CVD [odds ratio (OR) 1.19, 95% CI 1.01; 1.40] in the fully adjusted model. At 5-year follow-up, low SES was associated with both increased cardiovascular [hazard ratio (HR) 5.36, 2.24; 12.82] and all-cause mortality (HR 2.23, 1.51; 3.31). At 10-year follow-up, low SES was associated with a 68% higher risk of incident CVD (OR 1.68, 1.12; 2.47) as well as 86% higher all-cause mortality (HR 1.86, 1.55; 2.24). In general, the education and occupation scores were stronger related to risk of CVD and death than the household net-income score. Low SES was estimated to account for 451.45 disability-adjusted life years per 1000 people (years lived with disability 373.41/1000 and years of life lost 78.03/1000) and an incidence rate of 11 CVD cases and 3.47 CVD deaths per 1000 people per year. The population attributable fraction for CVD incidence after 5 years was 4% due to low SES. Despite universal healthcare access, cumulative social disadvantage remains associated with higher risk of CVD and mortality. Dimensions of education and occupation, but not household net income, are associated with outcomes of interest.

Geographical variation in cardiovascular disease mortality in Norway: The role of life course socioeconomic position and parental health.

Despite substantial geographical variation in cardiovascular (CVD) mortality within countries, little is known about whether this variation can be explained by individuals' life course socioeconomic position (SEP) or differences in family history of premature CVD deaths. Cox proportional hazards models were used to investigate the association between the county of residence at ages 50-59 and CVD death in Norwegians born between 1940 and 1959 and survived to at least age 60, using national data. Individual life course SEP and family history of premature CVD death reduced the geographical variation in CVD mortality across Norwegian counties, but some significant differences remained. Furthermore, CVD risk varied by residents' migration histories between two counties with distinct CVD and socioeconomic profiles.