Non-fatal Cardiovascular Disease Research Articles

Prediction of individual lifetime cardiovascular risk and potential treatment benefit: development and recalibration of the LIFE-CVD2 model to four European risk regions.

The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals. The updated LIFE-CVD (i.e., LIFE-CVD2) models were derived using individual-participant data from 44 cohorts in 13 countries (687,135 individuals without established CVD, 30,939 CVD events in median 10.7 years of follow-up). LIFE-CVD2 uses sex-specific functions to estimate the lifetime risk of fatal and non-fatal CVD events with adjustment for the competing risk of non-CVD death, and is systematically recalibrated to four distinct European risk regions. The updated models showed good discrimination in external validation among 1,657,707 individuals (61,311 CVD events) from eight additional European cohorts in seven countries, with a pooled C-index of 0.795 (95%CI 0.767-0.822). Predicted and observed CVD event risks were well calibrated in population-wide electronic health records data in the UK (CPRD) and Netherlands (ELAN). When using LIFE-CVD2 to estimate potential gain in CVD-free life expectancy from preventive therapy, projections varied by risk region reflecting important regional differences in absolute lifetime risk. For example a 50-year-old smoking woman with a SBP of 140 mm Hg was estimated to gain 0.9 years in the low risk region versus 1.6 years in the very high risk region from lifelong 10 mm Hg SBP reduction. The benefit of smoking cessation for this individual ranged from 3.6 years in the low risk region to 4.8 years in the very high risk region. By taking into account geographical differences in CVD incidence using contemporary representative data sources, the recalibrated LIFE-CVD2 model provides a more accurate tool for the prediction of lifetime risk and CVD-free life expectancy for individuals without previous CVD, facilitating shared decision-making for cardiovascular prevention as recommended by 2021 European guidelines.

Cardiovascular Risk Profile in Master Paralympic Athletes, a High-Risk Undertreated Population: A Cross-Sectional Longitudinal Study.

Recently, European Society of Cardiology (ESC)validated aprediction model to estimate 10-year fatal and non-fatal cardiovascular disease risk (CVDR) in individuals (aged 40-60 years) without previous cardiovascular disease or diabetes(ESC-SCORE2)and to provide indications for treatment. At present, data describing the CVDR in Paralympic athletes (PAs) are scarce and inconsistent. Therefore,we sought to assess the prevalence of risk factors in PAs to estimate their CVDR through SCORE2. Weenrolled 99 PAs aged ≥40 y.o., who participated at 2012-2022 Paralympic Games, competing in 22 different sport disciplines classified according to sport type (power, skills, endurance and mixed) and disabilities: spinal cord injuries (SCI) and non-SCI. CVDR factors,anthropometric measurements and blood samples were collected. Among the 99 PAs (78% males, mean age 45.7±4.7 y.o.), 52.5% had SCI; 54% were dyslipidemic and 23% were smokers. According to ESC-SCORE2, 29% had high and 1% very-high CVDR. Women (compared to men) and endurance (compared to other sport) exhibited better CV profile. SCI showed no differences when compared with non-SCI for CVDR, excepted for a lower HDL and lower exercise performance.None of the dyslipidemic athlete was on pharmacologically treatment, despitethe altered lipid profile had already been detected at younger age. PAs are a selected population, presenting a high CV risk profile, with 30% showing either high or very-high CVDR according to ESC-SCORE2. Dyslipidemiawas the most common risk factor, underestimated and undertreated, emphasizing the need for specific preventive strategies in this special setting of athletes.

The Mediterranean Diet, Its Microbiome Connections, and Cardiovascular Health: A Narrative Review.

The Mediterranean diet (MD), rich in minimally processed plant foods and in monounsaturated fats but low in saturated fats, meat, and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratios, lipids, and inflammation markers, and even prevents the development of fatal and nonfatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns over its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides, and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbiota.

Association of gestational diabetes with long-term risk of premature mortality, and cardiovascular outcomes and risk factors: A retrospective cohort analysis in the UK Biobank.

To investigate the association of gestational diabetes mellitus (GDM) with premature mortality and cardiovascular (CVD) outcomes and risk factors. Parous women recruited to the UK Biobank cohort during 2006-2010 were followed up from their first delivery until 31 October 2021. The data were linked to Hospital Episode Statistics and mortality registries. Multivariate Cox proportional hazard models investigated associations of GDM with all-cause mortality, CVD, diabetes, hypertension and dyslipidaemia. The maximum total analysis time at risk and under observation was 9 694 090 person-years. Among 220 726 women, 1225 self-reported or had a recorded diagnosis of GDM. After adjusting for confounders and behavioural factors, GDM was associated with increased risk for premature mortality [hazard ratio (HR): 1.44, 95% confidence interval (CI): 1.12-1.86], particularly CVD-related death (HR: 2.38, 95% CI: 1.63-3.48), as well as incident total CVD (HR: 1.50, 95% CI: 1.30-1.74), non-fatal CVD (HR: 1.41, 95% CI: 1.20-1.65), diabetes (HR: 14.37, 95% CI: 13.51-15.27), hypertension (HR: 1.49, 95% CI: 1.38-1.60), and dyslipidaemia (HR: 1.30, 95% CI: 1.22-1.39). The total CVD risk was greater in women with GDM who did not later develop diabetes than in those with GDM and diabetes. Women with GDM are at increased risk of premature death and have increased CV risk, emphasizing the importance of interventions to prevent GDM. If GDM develops, the diagnosis represents an opportunity for future surveillance and intervention to reduce CVD risk factors, prevent CVD and improve long-term health.

Income variability and incident cardiovascular disease in diabetes: a population-based cohort study.

Longitudinal change in income is crucial in explaining cardiovascular health inequalities. However, there is limited evidence for cardiovascular disease (CVD) risk associated with income dynamics over time among individuals with type 2 diabetes (T2D). Using a nationally representative sample from the Korean National Health Insurance Service database, 1 528 108 adults aged 30-64 with T2D and no history of CVD were included from 2009 to 2012 (mean follow-up of 7.3 years). Using monthly health insurance premium information, income levels were assessed annually for the baseline year and the four preceding years. Income variability was defined as the intraindividual standard deviation of the percent change in income over 5 years. The primary outcome was a composite event of incident fatal and nonfatal CVD (myocardial infarction, heart failure, and stroke) using insurance claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated after adjusting for potential confounders. High-income variability was associated with increased CVD risk (HRhighest vs. lowest quartile 1.25, 95% CI 1.22-1.27; Ptrend < .001). Individuals who experienced an income decline (4 years ago vs. baseline) had increased CVD risk, which was particularly notable when the income decreased to the lowest level (i.e. Medical Aid beneficiaries), regardless of their initial income status. Sustained low income (i.e. lowest income quartile) over 5 years was associated with increased CVD risk (HRn = 5 years vs. n = 0 years 1.38, 95% CI 1.35-1.41; Ptrend < .0001), whereas sustained high income (i.e. highest income quartile) was associated with decreased CVD risk (HRn = 5 years vs. n = 0 years 0.71, 95% CI 0.70-0.72; Ptrend < .0001). Sensitivity analyses, exploring potential mediators, such as lifestyle-related factors and obesity, supported the main results. Higher income variability, income declines, and sustained low income were associated with increased CVD risk. Our findings highlight the need to better understand the mechanisms by which income dynamics impact CVD risk among individuals with T2D.

Non–High-Density Lipoprotein Cholesterol Levels From Childhood to Adulthood and Cardiovascular Disease Events

Elevated non-high-density lipoprotein cholesterol (non-HDL-C; a recommended measure of lipid-related cardiovascular risk) is common in children and increases risk of adult cardiovascular disease (CVD). Whether resolution of elevated childhood non-HDL-C levels by adulthood is associated with reduced risk of clinical CVD events is unknown. To examine the associations of non-HDL-C status between childhood and adulthood with incident CVD events. Individual participant data from 6 prospective cohorts of children (mean age at baseline, 10.7 years) in the US and Finland. Recruitment took place between 1970 and 1996, with a final follow-up in 2019. Child (age 3-19 years) and adult (age 20-40 years) non-HDL-C age- and sex-specific z scores and categories according to clinical guideline-recommended cutoffs for dyslipidemia. Incident fatal and nonfatal CVD events adjudicated by medical records. Over a mean length of follow-up of 8.9 years after age 40 years, 147 CVD events occurred among 5121 participants (60% women; 15% Black). Both childhood and adult non-HDL-C levels were associated with increased risk of CVD events (hazard ratio [HR], 1.42 [95% CI, 1.18-1.70] and HR, 1.50 [95% CI, 1.26-1.78] for a 1-unit increase in z score, respectively), but the association for childhood non-HDL-C was reduced when adjusted for adult levels (HR, 1.12 [95% CI, 0.89-1.41]). A complementary analysis showed that both childhood non-HDL-C levels and the change between childhood and adulthood were independently associated with the outcome, suggesting that from a preventive perspective, both childhood non-HDL-C levels and the change into adulthood are informative. Compared with those whose non-HDL-C levels remained within the guideline-recommended range in childhood and adulthood, participants who had incident non-HDL-C dyslipidemia from childhood to adulthood and those with persistent dyslipidemia had increased risks of CVD events (HR, 2.17 [95% CI, 1.00-4.69] and HR, 5.17 [95% CI, 2.80-9.56], respectively). Individuals who had dyslipidemic non-HDL-C in childhood but whose non-HDL-C levels were within the guideline-recommended range in adulthood did not have a significantly increased risk (HR, 1.13 [95% CI, 0.50-2.56]). Individuals with persistent non-HDL-C dyslipidemia from childhood to adulthood had an increased risk of CVD events, but those in whom dyslipidemic non-HDL-C levels resolve by adulthood have similar risk to individuals who were never dyslipidemic. These findings suggest that interventions to prevent and reduce elevated childhood non-HDL-C levels may help prevent premature CVD.

Dietary inflammatory potential and the risk of nonfatal cardiovascular diseases in the China Health and Nutrition Survey

BackgroundNo evidence exists to link dietary inflammatory potential to cardiovascular disease (CVD) in China. Furthermore, the precise mechanisms underlying the link between a pro-inflammatory diet and CVD remain incompletely understood. ObjectiveWe aimed to investigate the relationship between dietary inflammatory potential and nonfatal CVD in the Chinese population and to explore the mediating role of insulin resistance. MethodsA total of 4,822 adults participated in the China Health and Nutrition Survey (CHNS) were included in this analysis. The dietary inflammatory index (DII) was used to assess dietary inflammatory potential. Cox proportional hazards models and restricted cubic spline were applied to assess the longitudinal associations. The triglyceride-glucose (TyG) index was calculated to measure insulin resistance. Mediation analysis using a two-stage regression method for survival data to explore the mediating effects of the TyG index on the association between DII score and nonfatal CVD. ResultsDuring a median follow-up of 18 years, 234 incident cases of nonfatal CVD, including 136 stroke and 114 myocardial infarction (MI), were observed. For each standard deviation of DII score, nonfatal CVD incidence increased by 15% [hazard ratio (HR): 1.15, 95% confidence interval (CI): 1.01-1.31], and stroke incidence increased by 22% (HR = 1.22, 95% CI: 1.03-1.45). DII score displayed a linear association with nonfatal CVD and stroke (P for nonlinearity = 0.250 and 0.238, respectively). No significant association was found between the DII score and MI. Mediation analyses showed that the TyG index mediated 5.90% and 9.35% of the total association between DII score and nonfatal CVD and stroke, respectively. ConclusionThis study provides evidence that dietary inflammatory potential is positively associated with nonfatal CVD and stroke in Chinese adults, and the association was partly mediated by insulin resistance.

Replacement of Saturated Fatty Acids from Meat by Dairy Sources in Relation to Incident Cardiovascular Disease: The European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study

BackgroundProspective observational data revealed lower cardiovascular disease (CVD) incidence with modeled replacement of saturated fatty acids (SFA) from total meat by total dairy, but it is unknown what the associations are of replacing SFA from types of meat by types of dairy with CVD incidence. ObjectivesThis study aimed to investigate the associations of replacing SFA from total, red, processed, and poultry meat by SFA from total dairy, milk, cheese, and yogurt with the incidence of CVD. MethodsWe analyzed longitudinal data from 21,841 participants of the European Prospective Investigation into Cancer and Nutrition-Norfolk study (56.4% female; age, 40–79 years). Dietary data were collected by food frequency questionnaires at baseline (1993–1997). Incident fatal or nonfatal CVD (n = 5902), coronary artery disease (CAD; n = 4215), stroke (total: n = 2544; ischemic: n = 1113; hemorrhagic: n = 449) were identified up to 2018. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression for the risk associated with replacement of 2.5% of energy from SFA from meat by dairy, adjusted for sociodemographic, lifestyle, energy, dietary, and cardiometabolic factors. ResultsReplacing SFA from total meat by total dairy was associated with a lower CVD incidence (HR: 0.89; 95% CI: 0.82, 0.96) and CAD (HR: 0.88; 95% CI: 0.80, 0.96). Replacing SFA from processed meat by cheese was associated with lower CVD (HR: 0.77; 95% CI: 0.68, 0.88); CAD (HR: 0.77; 95% CI: 0.66, 0.90), and stroke (HR: 0.81; 95% CI: 0.67, 0.99). Similarly, replacing SFA from red meat by cheese was associated with lower CVD (HR: 0.86; 95% CI: 0.76, 0.97). Higher incidence of stroke was found with replacement of SFA from poultry by milk (HR: 2.06; 95% CI: 1.09, 3.89), yogurt (HR: 2.55; 95% CI: 1.27, 5.13), or cheese (HR: 1.96; 95% CI: 1.04, 3.70), but the CI were relatively large, owing to low, narrow range of poultry SFA intake. ConclusionsFindings indicate that different SFA-rich foods at baseline have differential associations with CVD risk. If confirmed by further studies, these findings could be used to inform specific food-based dietary guidance.

Abstract 2234: Cardiovascular disease risk among men with prostate cancer: Differences by prostate cancer aggressiveness

Abstract Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality among men diagnosed with prostate cancer. We evaluated the extent to which men with prostate cancer develop CVD accounting for potential factors that may contribute to the CVD burden in this population. Methods: We prospectively followed men diagnosed with prostate cancer and free from CVD (stroke and coronary heart disease, including myocardial infarction, coronary artery bypass graft, and percutaneous coronary intervention) before their cancer diagnosis in the Health Professionals Follow-up Study, between 1986 and 2016. Men were categorized by D’Amico prostate cancer risk groups as low-risk (stage T1-2a, Gleason score ≤6, and PSA at diagnosis ≤10 ng/mL), intermediate-risk (T2b and/or Gleason score 7 and/or PSA &amp;gt;10-20), or high-risk (≥T2c/N1/M1 or Gleason score 8-10 or PSA &amp;gt;20). Incident fatal and non-fatal CVD, defined as coronary heart disease and stroke after cancer diagnosis, were centrally adjudicated. CVD risk factors including smoking, hyperlipidemia, hypertension, diabetes mellitus, body mass index, were self-reported on biennial questionnaires. Deaths due to prostate cancer or other causes were treated as competing events when estimating cumulative incidence and cause-specific hazard ratios (HR). Results: Among 5,707 prostate cancer patients, 1,912 had low-risk, 2,261 had intermediate-risk, and 1,534 had high-risk cancer. 1,102 CVD events were documented over up to 30 years of follow-up after cancer diagnosis. The 10-year CVD risk was 8.1% for men with low-risk cancer, 8.8% for intermediate-risk, and 10.4% for high-risk cancer. The cause-specific HRs for CVD were 1.18 (95% CI 1.03, 1.36) in intermediate-risk and 1.59 (95% CI 1.36, 1.85) in high-risk prostate cancer, both compared to low-risk prostate cancer. Men with high-risk cancer tended to be older; after age adjustment, the HRs were 1.15 for intermediate-risk (95% CI 1.00, 1.33) and 1.35 for high-risk cancer (1.35, 95% CI 1.16, 1.58). Associations between cancer risk group and CVD were essentially unchanged after further adjustment for CVD risk factors present at cancer diagnosis, primary cancer treatment modality (surgery, radiation, androgen deprivation therapy, watchful waiting/active surveillance), and calendar year of diagnosis. Discussion: Despite the elevated risk of cancer mortality in men with intermediate-risk and high-risk prostate cancer compared to low-risk prostate cancer, CVD risk remains at least as common over time among these men as among men with low-risk prostate cancer. Incident CVD risk after cancer diagnosis among men with more aggressive cancers, which particularly occur in older men, is not primarily attributable to differences in pre-existing risk factor burden. These findings from a cohort with healthcare access and literacy indicate a need for continued clinical attention to CVD after cancer diagnosis. Citation Format: Caroline Himbert, Anna Plym, Jane B. Vaselkiv, Andreas Pettersson, Philip W. Kantoff, Lorelei A. Mucci, Kenneth J. Mukamal, Konrad H. Stosapck. Cardiovascular disease risk among men with prostate cancer: Differences by prostate cancer aggressiveness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2234.

Abstract 08: Blood Pressure Percentile Charts Better Identify High Risk Young Adults: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Introduction: Current guidelines set a static threshold for diagnosis of hypertension based on absolute blood pressure (BP) levels for all ages. However, BP generally increases with age and relative levels tend to track within individuals from young adulthood on. We aimed to determine whether BP percentiles , compared to the current AHA/ACC clinical thresholds for hypertension, are better able to identify young adults at higher risk for future CVD events. Methods: Among 5,115 CARDIA participants (ppts; mean age 25 yrs; 54% female; 51% Black), we used baseline BP level and over 35 years of follow-up for fatal and non-fatal CVD events. We calculated normative BP percentiles for adults aged 18 and older using NHANES by estimating underlying BP among treated individuals combined with observed BP for untreated individuals (Figure). Using these BP Percentile Charts, we calculated the baseline BP percentile for each ppt. Adjusted survival analyses examined the association between BP percentile (in deciles) and incident CVD events over 30 years. C statistics for models using BP percentiles vs those using current guideline-recommended thresholds were compared to determine relative accuracy. Results: At baseline, mean S/DBP was 112/70 mmHg and &lt;1% were on antihypertensive medications. Adjusted HRs for BP percentile decile demonstrated a dose-response effect with increasing risk associated with higher deciles of SBP. Compared to the 5 th decile young adults with SBPs in the highest decile 90-100% (SBP ≥127 for men and ≥120 for women) had a HR of 1.76 (95% CI 1.10-2.83). C statistics for models using BP percentiles were higher than for models using guideline-recommended thresholds (0.724 vs 0.713). No significant association was seen with DBP deciles. Conclusion: BP percentiles are better able to predict future CVD risk in young adults as compared to current age-invariant thresholds. These methods may help to risk stratify young adults and more accurately identify higher risk individuals for early prevention efforts.

European Lipid Guidelines and Cardiovascular Risk Estimation: Current Status and Future Challenges.

Genetic, experimental, epidemiologic, and clinical data support the causal role of elevated levels of low-density lipoprotein cholesterol (LDL-C) in atherosclerosis and cardiovascular disease (CVD). The recommendations of the 2019 European guidelines are based on the concept of differential CV risk, which in turn defines the LDL-C goals that should be achieved. The 2019 ESC/EAS guidelines for dyslipidaemia use the Systematic COronary Risk Evaluation (SCORE) model to assess CV risk, which provides a 10-year risk of fatal CV event. The SCORE model has recently been updated to reflect current rates of cardiovascular disease in Europe. The new SCORE2 model provides estimates of the 10-year risk of fatal and non-fatal CVD events in people aged 40-69 years, thus improving the identification of individuals at higher risk of a CVD event. However, as in the SCORE age is the main determinant of risk, young people have a relatively low estimated 10-year risk of a CV event even with high levels of one or more causal risk factors. Individuals with familial hypercholesterolaemia, who have elevated LDL-C levels from birth and have a high risk of premature CVD, are one example. The concept of cumulative LDL exposure is thus becoming increasingly important. This is also supported by Mendelian randomisation studies showing that carrying genetic variants associated with lower LDL-C levels reduces CV risk. These observations have introduced the concept of "cholesterol-years", which takes into account both LDL-C levels and time of exposure. It is crucial that future European guidelines pay more attention to this point.

Cardiovascular Risk Profiling Using the Globorisk Calculator among Noncommunicable Disease Patients Attending Primary Health Centers of a Tertiary Care Teaching Hospital in South India: A Cross-Sectional Analytical Study.

Cardiovascular diseases (CVDs) account for over three-quarters of all deaths taking place in developing nations. The present study aims to stratify noncommunicable disease (NCD) patients using the Globorisk chart for predicting their 10-year risk of a major (fatal or nonfatal) CVD event and to estimate the level of agreement between this country-specific chart and the existing World Health Organization (WHO)/International Society of Hypertension (ISH) risk strata. A record-based cross-sectional analytical study was conducted in 2018 among adults attending the NCD clinic of one rural and one urban primary health center in Puducherry. Laboratory and office risk calculators of the Globorisk chart were used to calculate the risk. The median age (interquartile range (IQR)) of the 760 study participants was 58 (50-65) years. When calculated using the Globorisk prediction chart, 22.1% (n = 168) of the participants had a <10% risk for any CVD event in the next 10 years, whereas the same risk was found in 71.1% (n = 540) by using the WHO/ISH risk chart. There was no agreement found between the two risk charts (k = 0.0174; P-value = 0.26). The Globorisk chart was found to identify more patients as belonging to the higher risk category as compared to WHO/ISH charts.

Inclusion of Polypills for Prevention of Cardiovascular Disease in the 23rd World Health Organization Model List of Essential Medicines: A Significant Step Towards Reducing Global Cardiovascular Morbidity and Mortality.

This commentary describes the potential impact of inclusion of polypills for prevention of cardiovascular disease in the 23rd WHO Model List of Essential Medicines, and provides a roadmap for adoption, implementation, sustainment, and scale-up. The World Health Organization's endorsement of polypills is essential for improving global access, particularly in low- and middle-income countries. The greatest health gains are expected in a primary prevention population which has a significantly higher burden of fatal and non-fatal cardiovascular disease compared with the population of individuals with prevalent cardiovascular disease. A focus on adoption, implementation, sustainment, and scale-up of polypills for prevention of cardiovascular disease is needed including increasing supply of available polypills and incorporating polypills into the World Health Organization HEARTS technical package for integration into primary care systems to realize these benefits for population health. Widespread implementation of polypills for prevention of cardiovascular disease has the potential to equitably reduce the impact of cardiovascular disease globally by simplifying treatment options and expanding accessibility across economic levels, both across and within countries.

Association between cardiovascular risk profile and impaired microvascular function in a Swedish middle-aged cohort (the SCAPIS study)

Abstract Aims The aim was to investigate the relationship between microvascular function, cardiovascular risk profile, and subclinical atherosclerotic burden. Methods and results The study enrolled 3809 individuals, 50–65 years old, participating in the population-based observational cross-sectional Swedish CArdioPulmonary bioImage Study. Microvascular function was assessed in forearm skin using an arterial occlusion and release protocol determining peak blood oxygen saturation (OxyP). Cardiovascular risk was calculated using the updated Systematic Coronary Risk Evaluation [SCORE2; 10-year risk of fatal and non-fatal cardiovascular disease (CVD) events]. The OxyP was compared with coronary artery calcification score (CACS) and to plaques in the carotid arteries. Individuals with OxyP values in the lowest quartile (Q1; impaired microvascular function) had a mean SCORE2 of 5.8% compared with 3.8% in those with the highest values of OxyP (Q4), a relative risk increase of 53%. The risk of having a SCORE2 &amp;gt; 10% was five times higher for those in Q1 (odds ratio: 4.96, 95% confidence interval: 2.76–8.93) vs. Q4 when adjusting for body mass index and high-sensitivity C-reactive protein. The OxyP was lower in individuals with CACS &amp;gt; 0 and in those with both carotid plaques and CACS &amp;gt; 0, compared with individuals without subclinical atherosclerotic burdens (87.5 ± 5.6% and 86.9 ± 6.0%, vs. 88.6 ± 5.8%, P &amp;lt; 0.01). Conclusion In a population without CVD or diabetes mellitus, impaired microvascular function is associated with cardiovascular risk profiles such as higher SCORE2 risk and CACS. We suggest that OxyP may serve as a microcirculatory functional marker of subclinical atherosclerosis and CVD risk that is not detected by structural assessments.

Validation of the SCORE2 risk prediction algorithm in a Portuguese population: A new model to estimate 10-year cardiovascular disease incidence in Europe

Introduction and ObjectivesSubjects without cardiovascular (CV) disease (CVD) may suffer from subclinical atherosclerosis, and are at increased risk for atherosclerotic CV events (ASCVE). The ESC/EAS risk SCORE was updated by SCORE2, which estimates 10-year risk of fatal and non-fatal CVD in European populations aged 40–69 years without established CVD or diabetes. Our aim was to compare the two ESC/EAS risk scores and to validate SCORE2 in our population. MethodsA total of 1071 individuals (age 57.2±6.1 years; 75.2% male) without CVD or diabetes, from GENEMACOR study controls, were analyzed over 5.4±3.9 years. The population was stratified into risk categories according to the two scores, and the area under the ROC curve (AUC) and Harrell's C-index assessed the scores’ performance. Calibration was performed using the goodness-of-fit test, and occurrence of the first event assessed by Cox regression. Kaplan–Meier analysis estimated SCORE2 survival. ResultsSCORE stratified subjects into four risk categories: low (7.4%), moderate (46.5%), high (25.3%) and very high (20.8%), and SCORE2 into three: low-to-moderate (24.7%), high (59.0%) and very high (16.2%). SCORE presented good discrimination for CV mortality (AUC=0.838; C-index=0.834, 95% CI: 0.728–0.940), as did SCORE2 for total CV events (AUC=0.744; C-index=0.728, 95% CI: 0.648–0.808). Calibration did not show a disparity between observed and expected ASCVE. The probability of ASCVE was eight times higher in very-high-risk SCORE2 (p=0.001), and three times in the high-risk group (p=0.049). Event-free survival was 99%, 90% and 72% in the low-to-moderate, high and very-high-risk categories, respectively (p<0.0001). ConclusionsSCORE2 improved population stratification by identifying higher-risk patients, enabling early preventive measures. It showed good discriminative ability for all ASCVE.

Four high sensitivity troponin assays and mortality in US adults with cardiovascular disease: The national health and nutrition examination survey, 1999–2004

ObjectiveHigh sensitivity cardiac troponin (hs-cTn) may be useful to monitor residual risk in secondary prevention. Our objective was to study the correlations and comparative associations with mortality of four hs-cTn assays in US adults with known cardiovascular disease (CVD). MethodsWe studied 1,211 adults with a history of CVD who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Using stored samples, we measured hs-cTnT (Roche) and three hs-cTnI assays (Abbott, Siemens, and Ortho). Outcomes were all-cause and CVD mortality, with follow-up through December 31, 2019. ResultsMean age was 64 years, 48 % were female, and 80 % identified as non-Hispanic White. Pearson's correlation coefficients between hs-cTn assays ranged from 0.67 to 0.85. There were 848 deaths (365 from CVD). Among adults with a history of prior non-fatal CVD, each hs-cTn assay (log-transformed, per 1-SD) was independently associated with CVD death (HRs ranging from 1.55 to 2.16 per 1-SD, all p-values <0.05) and with all-cause death (HRs ranging from 1.31 to 1.62 per 1-SD, all p-values <0.05). Associations of hs-cTnT and all-cause and CVD death remained significant after adjusting for hs-cTnI (and vice versa). Associations between hs-cTnI and CVD death remained significant after mutually adjusting for other individual hs-cTnI assays: e.g., HR 2.21 (95 % CI 1.60, 3.05) for Ortho (hs-cTnI) after adjustment for Siemens (hs-cTnI) and HR 1.81 (95 % CI 1.35, 2.43) for Ortho (hs-cTnI) after adjustment for Abbott (hs-cTnI). ConclusionIn US adults with a history of CVD, we found modest correlations between 4 hs-cTn assays. All assays were associated with all-cause and CVD mortality. The hs-cTnT assay was associated with mortality independent of the hs-cTnI assays. Hs-cTnI assays also appeared to be independent of each other. Thus, hs-cTn assays may provide distinct information for residual risk in secondary prevention adults.

White meat consumption and risk of cardiovascular disease and type 2 diabetes: a systematic review and meta-analysis.

The aim was to systematically review the associations among white meat consumption, cardiovascular diseases (CVD), and type 2 diabetes (T2D). Databases MEDLINE, Embase, and Cochrane Central Register of Controlled Trials and Scopus were searched (15th October 2021) for randomized intervention trials (RCTs, ≥ 4 weeks of duration) and prospective cohort studies (≥12 month of follow-up) assessing the consumption of white meat as the intervention/exposure. Eligible outcomes for RCTs were cardiometabolic risk factors and for cohorts, fatal and non-fatal CVD and incident T2D. Risk of bias was estimated using the Cochrane's RoB2 and Risk of Bias for Nutrition Observational Studies. Meta-analysis was conducted in case of ≥3 relevant intervention studies or ≥5 cohort studies using random-effects models. The strength of evidence was evaluated using the World Cancer Research Fund's criteria. The literature search yielded 5,795 scientific articles, and after screening 43 full-text articles, 23 cohort studies and three intervention studies were included. All included intervention studies matched fat content of intervention and control diets, and none of them showed any significant effects on the selected outcomes of white meat when compared to red meat. Findings from the cohort studies generally did not support any associations between white meat intake and outcomes. Meta-analyses were conducted for CVD mortality (RR: 0.95, 95% CI: 0.87-1.02, P = 0.23, I2 = 25%) and T2D incidence (RR: 0.98, 95% CI: 0.87-1.11, P = 0.81, I2 = 82%). The currently available evidence does not indicate a role, beneficial or detrimental, of white meat consumption for CVD and T2D. Future studies investigating potentially different health effects of processed versus unprocessed white meat and substitution of red meat with white meat are warranted.Registration: Prospero registration CRD42022295915.

Cardiovascular health and life expectancy with and without cardiovascular disease in the middle-aged and elderly Chinese population

BackgroundHigh cardiovascular health (CVH) was associated with lower risk of cardiovascular disease (CVD) and longer life expectancy. However, whether life years lived without CVD could increase faster than or at least at the same pace as total lifespan remains unknown. We aimed to explore the associations of CVH status with total life expectancy and life years lived with and without CVD among middle-aged and elderly men and women.MethodsWe included 65,587 participants aged ≥ 45 years from Kailuan study, who were recruited during June 2006 to October 2007. CVH was scored and classified (low [0–49 points], moderate [50–79 points] and high [80–100 points]) with Life’s Essential 8, incorporating evaluations of health behaviors and factors. All-cause mortality and incident non-fatal CVD were recorded from baseline to December 31, 2020. The multi-state life table was adopted to explore the associations of CVH status with total life expectancy and life years lived with and without CVD.ResultsSix thousand fifty eight cases of incident non-fatal CVD and 10,580 cases of deaths were identified. Men aged 45 years with low, moderate, and high CVH had a life expectancy of 33.0, 36.5 and 38.5 years, of which 7.8 (23.6%), 6.0 (16.3%) and 3.7 years (9.6%) were spent with CVD. For women, the corresponding life expectancy was 36.6, 43.6 and 48.6 years, and the remaining life years lived with CVD were 7.8 (21.3%), 6.0 (13.7%) and 4.5 years (9.3%), respectively. The benefits of high CVH were persistent across lifespan from age 45 to 85 years and consistent when CVH was evaluated with health behaviors and factors alone.ConclusionsHigh CVH compared with low CVH was associated with longer total life expectancy and fewer years spent with CVD, indicating that promoting CVH is of great importance for CVD prevention and healthy ageing in China.

Mortality and Morbidity Among Individuals With Hypertension Receiving a Diuretic, ACE Inhibitor, or Calcium Channel Blocker

The long-term relative risk of antihypertensive treatments with regard to mortality and morbidity is not well understood. To determine the long-term posttrial risk of primary and secondary outcomes among trial participants who were randomized to either a thiazide-type diuretic, calcium channel blocker (CCB), or angiotensin-converting enzyme (ACE) inhibitor with up to 23 years of follow-up. This prespecified secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a multicenter randomized, double-blind, active-controlled clinical trial, followed up with participants aged 55 years or older with a diagnosis of hypertension and at least 1 other coronary heart disease risk factor for up to 23 years, from February 23, 1994, to December 31, 2017. Trial participants were linked with administrative databases for posttrial mortality (N = 32 804) and morbidity outcomes (n = 22 754). Statistical analysis was performed from January 2022 to October 2023. Participants were randomly assigned to receive a thiazide-type diuretic (n = 15 002), a CCB (n = 8898), or an ACE inhibitor (n = 8904) for planned in-trial follow-up of approximately 4 to 8 years and posttrial passive follow-up for up to 23 years. The primary end point was mortality due to cardiovascular disease (CVD). Secondary outcomes included all-cause mortality, combined fatal and nonfatal (morbidity) CVD, and both mortality and morbidity for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer. A total of 32 804 participants (mean [SD] age, 66.9 [7.7] years; 17 411 men [53.1%]; and 11 772 Black participants [35.9%]) were followed up for all-cause mortality and a subgroup of 22 754 participants (mean [SD] age, 68.7 [7.2] years; 12 772 women [56.1%]; and 8199 Black participants [36.0%]) were followed up for fatal or nonfatal CVD through 2017 (mean [SD] follow-up, 13.7 [6.7] years; maximum follow-up, 23.9 years). Cardiovascular disease mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively, at 23 years after randomization (adjusted hazard ratio [AHR], 0.97 [95% CI, 0.89-1.05] for CCB vs diuretic; AHR, 1.06 [95% CI, 0.97-1.15] for ACE inhibitor vs diuretic). The long-term risks of most secondary outcomes were similar among the 3 groups. Compared with the diuretic group, the ACE inhibitor group had a 19% increased risk of stroke mortality (AHR, 1.19 [95% CI, 1.03-1.37]) and an 11% increased risk of combined fatal and nonfatal hospitalized stroke (AHR, 1.11 [95% CI, 1.03-1.20]). In this secondary analysis of a randomized clinical trial in an adult population with hypertension and coronary heart disease risk factors, CVD mortality was similar between all 3 groups. ACE inhibitors increased the risk of stroke outcomes by 11% compared with diuretics, and this effect persisted well beyond the trial period. ClinicalTrials.gov Identifier: NCT00000542.

Chronic stress and cardiovascular events: Findings from the CARDIA Study

Higher levels of perceived stress are associated with adverse cardiovascular health. It is plausible that these associations are attenuated among individuals with positive psychological factors such as social support and health-enhancing behaviors. Therefore, this study examined longitudinal associations of chronic stress with cardiovascular disease (CVD) events, and whether social support and physical activity (PA) modify these associations. Data from 3,401 adults (mean age 40.2 years; 46.7% Black; 56.2% women) from the Coronary Artery Risk Development in Young Adults (CARDIA) study, with no prior CVD event in 2000-2001 were analyzed. Chronic stress lasting ≥6 months across 5 life domains (work, financial, relationships, health of self, and health of close other) was self-reported. Adjudicated CVD events (fatal/or nonfatal CVD event) were ascertained yearly through 2020. PA and social support were self-reported via questionnaires. Statistical analyses were conducted in 2023 using multivariable stepwise Accelerated Failure Time analysis to assess associations between key study variables. The mean chronic stress score was 1.30±1.33 stressors and, by 2020, 220 participants had experienced a CVD event. Chronic stress was associated with lowered survival (time ratio: 0.92; 95% CI: 0.854-0.989), when adjusted for sociodemographic and lifestyle variables but no longer significant when adjusting for clinical factors. Neither PA nor social support were significant modifiers (all ps>0.05). Chronic stress was associated with the risk of having a CVD event among middle-aged adults, due at least in part to clinical mediators. Studies should continue exploring positive psychosocial and behavioral factors that may modify this association.