Total CVD Research Articles

Reverse epidemiology of obesity paradox: Fact or fiction?

Obesity paradox refers to the clinical observation that when acute cardiovascular decompensation occurs, patients with obesity may have a survival benefit. This apparently runs counter to the epidemiology of obesity, which may increase the risk for non-communicable diseases (NCDs). The scientific community is split on obesity paradox, with some supporting it, while others call it BMI paradox. This review: (a) defines the obesity paradox, and its proposed role in overall mortality in NCDs; (b) delineates evidence for and against obesity paradox; (c) presents the importance of using different indices of body mass to assess the risk in NCDs; (d) examines the role of metabolically healthy obesity in obesity paradox, and emerging importance of cardio-respiratory fitness (CRF) as an independent predictor of CVD risk and all-cause mortality in patients with/without obesity. Evidence suggests that the development of obesity and insulin resistance are influenced by genetic (or ethnic) make up and dietary habits (culture) of the individuals. Hence, this review presents lean diabetes, which has higher total CVD and non-CVD mortality as compared to diabetics with obesity and the possibility of maternal factors programming cardiometabolic risk during fetal development, which may lead to a paradigm shift in our understanding of obesity.

Is too much sugar bitter? The impacts of sugars on health.

This paper reviews the associations between sugars consumption and non-communicable diseases. Systematic reviews demonstrate associations between sugars intake and dental caries, weight gain, type 2 diabetes and cardiovascular diseases. Children consuming more sugar-sweetened beverages (SSBs) are 1.55 times more likely to be overweight. In adults, higher consumption of SSBs is associated with a 27% higher relative risk of developing type 2 diabetes. In adults, greater free sugar consumption was positively associated with total CVD (HR 1.07; 95% CI: 1.03-1.10), ischaemic heart disease (HR 1.06; 95%CI: 1.02,1.10), and stroke (HR 1.10, 95% CI: 1.04, 1.17). Those consuming sugars higher than the recommended level of 10% of total energy are more likely to develop dental caries; 42 out of 50 studies involving children and 5 out of 5 in adults reported at least one positive association between sugars and caries. Reduction in sugars consumption requires a myriad of interventions to reduce supply and demand at national and global levels, fiscal policies, alongside high-quality research and promoting environments to reduce the burden of NCDs.

Reduced Risk of Cardiovascular Diseases after Bariatric Surgery Based on the New PREVENT Equations.

We applied the novel Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations to evaluate cardiovascular-kidney-metabolic (CKM) health and estimated CVD risk, including heart failure (HF), after bariatric surgery. Among 7804 patients (20-79 years) undergoing bariatric surgery at Vanderbilt University Medical Center during 1999-2022, CVD risk factors at pre-surgery, 1-year, and 2-year post-surgery were extracted from electronic health records. The 10- and 30-year risks of total CVD, atherosclerotic CVD (ASCVD), coronary heart disease (CHD), stroke, and HF were estimated for patients without a history of CVD or its subtypes at each time point, using the social deprivation index-enhanced PREVENT equations. Paired t-tests or McNemar tests were used to compare pre- with post-surgery CKM health and CVD risk. Two-sample t-tests were used to compare CVD risk reduction between patient subgroups defined by age, sex, race, operation type, weight loss, and history of diabetes, hypertension, and dyslipidemia. CKM health was significantly improved after surgery with lower systolic blood pressure, non-high-density-lipoprotein cholesterol (non-HDL), and diabetes prevalence, but higher HDL and estimated glomerular filtration rate (eGFR). The 10-year total CVD risk decreased from 6.51% at pre-surgery to 4.81% and 5.08% at 1- and 2-year post-surgery (relative reduction: 25.9% and 16.8%), respectively. Significant risk reductions were seen for all CVD subtypes (i.e., ASCVD, CHD, stroke, and HF), with the largest reduction for HF (relative reduction: 55.7% and 44.8% at 1- and 2-year post-surgery, respectively). Younger age, White race, >30% weight loss, diabetes history, and no dyslipidemia history were associated with greater HF risk reductions. Similar results were found for the 30-year risk estimates. Bariatric surgery significantly improves CKM health and reduces estimated CVD risk, particularly HF, by 45-56% within 1-2 years post-surgery. HF risk reduction may vary by patient's demographics, weight loss, and disease history, which warrants further research.

Early Menarche as a Protective Factor Against Cardiovascular Events: A Systematic Review and Meta-analysis.

Women are often neglected in cardiovascular health prevention. Age at menarche (AAM) has been linked to cardiovascular (CVD) disease in women and is potentially identified as one of the significant CVD risk factor. However, there is still limited comprehensive evidence addressing this issue. This systematic review and meta-analysis aimed to investigate how early menarche affects the outcome of all-cause mortality, CVD mortality, total cardiovascular disease event, stroke (ischemic, hemorrhagic, and total stroke), and coronary heart disease (CHD). The Cochrane Library, MEDLINE, Embase, ScienceDirect, and Google Scholar databases were searched from March 2013 to March 2023 for cohorts investigating the effect of early onset of menarche on CVD events with a minimum follow-up period of 5 years. Studies that observed specific population and/or included women with a history of CVD at baseline were excluded. The Newcastle-Ottawa scale was used for risk of bias assessment for each cohort included. The data were presented as dichotomous measure using risk ratios. I2 statistics were utilized to evaluate the heterogeneity of presented data. Thirteen cohorts included 18 626 799 female patients with ages ranging from 43 to 62.6 years. These reported 6 estimates each for CHD (5 483 298 patients) and all-cause mortality (1 595 878 patients), 5 estimates each for total stroke (2 941 321 patients) and CVD mortality (1 706 742 patients), 4 estimates each for total CVD events (3 988 311 patients) and ischemic stroke (2 434 580 patients), and 1 estimate for hemorrhagic stroke (66 104 patients). Our study found that events of CHD were significantly lower in early menarche (RR 0.57; 95% CI 0.41-0.78; P <.00001), as well as total stroke (RR 0.51; 95% CI 0.35-0.73; P =.0003), CVD mortality (RR 0.47; 95% CI 0.22-0.98; P =.04), total CVD events (RR 0.44; 95% CI 0.25-0.76; P =.003), ischemic stroke (RR 0.31; 95% CI 0.15-0.61; P <.0008), and hemorrhagic stroke (RR 0.12; 95% CI 0.07-0.20; P <.00001); and insignificantly higher in all-cause mortality (RR 0.90, 95% CI 0.76-1.06, P =.20). In our study, cardiovascular events are lower in women with early menarche; hence, the later age of menarche is a potential risk factor to be considered when assessing CVD risk in a patient. However, our sample characteristics were heterogenous, and we did not consider other female hormonal factors that might potentially contribute to the CVD outcomes observed; thus, further studies are needed to clarify.

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.

Sodium Intake and Cause-Specific Mortality Among Predominantly Low-Income Black and White US Residents

Epidemiologic evidence regarding the outcomes of dietary sodium intake on mortality remains limited for low-income individuals, particularly Black people. To investigate the associations of excessive dietary sodium with all-cause and cause-specific mortality among predominantly low-income Black and White Americans. This cohort study included participants aged 40 to 79 years from the Southern Community Cohort Study who were recruited at Community Health Centers in 12 southeastern states from 2002 to 2009. Analyses were conducted between March 2022 and June 2023. Dietary sodium intake was assessed using a validated food frequency questionnaire at baseline. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality outcomes (all-cause, cardiovascular disease [CVD], coronary heart disease [CHD], stroke, heart failure, cancer, and other) associated with sodium intake. Nonlinear associations and population-attributable risk (PAR) of the mortality burden associated with excess sodium were further assessed. Among the 64 329 participants, 46 185 (71.8%) were Black, 18 144 (28.2%) were White, and 39 155 (60.9%) were female. The mean (SD) age at study enrollment was 51.3 (8.6) years for Black participants and 53.3 (9.3) years for White counterparts. Mean (SD) dietary sodium intake was 4512 (2632) mg/d in Black individuals and 4041 (2227) mg/d in White individuals; 37 482 Black individuals (81.2%) and 14 431 White individuals (79.5%) exceeded the current dietary recommendations of 2300 mg/d. During a median (IQR) follow-up of 13.8 (11.3-15.8) years, 17 811 deaths were documented, including 5701 from CVD. After adjustment for potential confounders, in Black individuals, HRs per 1000-mg increase in daily sodium intake were 1.07 (95% CI, 1.03-1.10) and 1.08 (95% CI, 1.02-1.14) for deaths from total CVD and CHD, respectively; while in White individuals, the corresponding HRs were 1.08 (95% CI, 1.02-1.14) and 1.13 (95% CI, 1.03-1.23). No significant associations were found for cancer mortality. PAR estimates suggest that sodium intake above the recommended threshold may account for 10% of total CVD, 13% of CHD, and 30% of heart failure deaths in this low-income southern population. In this cohort study of 64 329 low-income Americans, nearly 80% of study participants consumed sodium exceeding the current recommended daily amount, which was associated with 10% to 30% of CVD mortality. Public health programs targeted to reduce sodium intake among this underserved population may be beneficial.

Abstract P370: Prevalence of the AHA Life's Essential 8 in Midlife Women and Its Prospective Associations With Total Mortality and Cardiovascular Diseases Events: The Study of Women’s Health Across the Nation (SWAN)

Objective: Midlife women face significant acceleration in CVD risk during the menopause transition. We aim to determine the cardiovascular health (CVH) as measured by Life's Essential 8 (LE8) in midlife women and to test the associations of midlife LE8 with future CVD events/total mortality. Methods: Participants were from the SWAN study, a multi-ethnic study of the menopause transition. LE8 includes diet, physical activity (PA), nicotine exposure, sleep, BMI, and blood lipids/glucose/pressure. The total and each LE8 scores (0 [lowest] - 100 [highest]) were calculated using AHA definitions. Scores were grouped into low (0-49), intermediate (50-74) and high (75-100) to characterize women. CVD events were self-reported between visits 1-16 and included: myocardial infarction, stroke, heart failure and revascularization. A subset of the events was adjudicated via medical record. Death certificates were obtained. Cox proportional hazards model was used to test the association between continuous LE8 metrics and CVD events/total mortality. Results: A total of 3302 women (mean age 46±3 years, 54% premenopausal) free of CVD at baseline were included. Among them, 28% achieved high total LE8 scores (mean 83±6) and many women had low scores on sleep, PA and diet ( Figure ). During a median (IQR) follow-up of 19 (7) years, 156 deaths and 202 CVD events were recorded. Higher midlife LE8 scores were associated with significantly lower risk of total mortality and CVD events adjusting for demographic and health factors ( Figure ). For individual components, BMI, blood lipids/glucose/pressure, nicotine exposure and sleep were associated with CVD events; BMI, blood glucose/pressure, nicotine exposure and PA were associated with total mortality ( Figure ). Conclusions: The prevalence of healthy diet, physical activity and healthy sleep is low in midlife women. Lower CVH is an independent risk factor of subsequent risk of CVD events/total mortality in midlife women. The findings highlight the need to promote healthy behaviors in midlife women.

Cholesterol associated genetic risk score and acute coronary syndrome in Czech males.

Despite a general decline in mean levels across populations, LDL-cholesterol levels remain a major risk factor for acute coronary syndrome (ACS). The APOB, LDL-R, CILP, and SORT-1 genes have been shown to contain variants that have significant effects on plasma cholesterol levels. We examined polymorphisms within these genes in 1191 controls and 929 patients with ACS. Only rs646776 within SORT-1 was significantly associated with a risk of ACS (P < 0.05, AA vs. + G comparison; OR 1.21; 95% CI 1.01-1.45). With regard to genetic risk score (GRS), the presence of at least 7 alleles associated with elevated cholesterol levels was connected with increased risk (P < 0.01) of ACS (OR 1.26; 95% CI 1.06-1.52). Neither total mortality nor CVD mortality in ACS subjects (follow up-9.84 ± 3.82years) was associated with the SNPs analysed or cholesterol-associated GRS. We conclude that, based on only a few potent SNPs known to affect plasma cholesterol, GRS has the potential to predict ACS risk, but not ACS associated mortality.

Abstract 13681: Association of Serum Trimethylamine N-oxide Levels With Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies

Background: Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite of red meat, has emerged as a potential biomarker for CVD and all-cause mortality. It is also found in preformed amounts in fish. However, the association between serum TMAO levels and CVD outcomes remain unclear. Aim: To conduct a systematic review and dose-response meta-analysis evaluating the association between serum TMAO and CVD and all-cause mortality in prospective cohort studies. Methods: A comprehensive literature search was conducted in MEDLINE, EMBASE, and Cochrane Library up to and including March 6, 2023. A manual search through references found in reviews and meta-analyses was also conducted. Studies reporting hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs) for the association between serum TMAO levels and CVD or all-cause mortality in adults ≥ 18 years with follow-up of ≥ 1 year were included. Random-effects models were utilized for pooled risk estimates and assess the dose-response. GRADE was used to evaluate certainty of evidence. Results: 2459 papers, 44 prospective cohort studies were included involving 84771 participants included in final analysis (fig.1). Pooled analyses revealed a significant positive association between elevated serum TMAO levels and the risk of total CVD (RR 1.29 [1.16-1.44]), CVD mortality (RR 1.51 [1.23-1.87]) and all-cause mortality (RR 1.30 [1.21,1.39]). Non-significant associations were found for MI, stroke, total CHD, MI mortality and CHD mortality. All outcomes were of low to very low certainty.Dose response analysis revealed a significant linear association with all-cause mortality (RR 1.01 [95% CI 1.01, 1.02] per 2μM/L) up to a threshold of 6μM/L and total CVD (RR 1.04 [1.02-1.06]). Conclusion: This study provides evidence supporting the positive association of serum TMAO levels with increased risk of total CVD, CVD mortality and all-cause mortality. A recent review found 13/15 studies demonstrated a strong positive correlation between TMAO and fish intake, complicating the hypotheses relating TMAO in red meat and CVD risk. Thus, further assessments of diet components are needed to explore the clinical implications of the associations found in our study.

Abstract 13805: Associations of Subclavian Artery Calcification With Future Cardiovascular Events and Death: The Multi-Ethnic Study of Atherosclerosis

Introduction: Atherosclerosis affects the upper limbs and may be a marker of diffuse atherosclerosis and increased risk for cardiovascular events. Hypothesis: Subclavian artery calcification (SAC) and thoracic aorta calcification (TAC) obtained by chest CT provide additional information about future CV events and death beyond coronary artery calcification (CAC) and CV risk factors. Methods: Chest CT scans of MESA participants (N = 2519) at exam 5 (2016-18) were interrogated for the presence and extent of SAC, TAC, and CAC. Proportional hazards regression was conducted for associations with incident total CVD events (n = 209), adjusted for age, race/ethnicity, and sex, then SAC, TAC, and CAC adjusted for demographics and each other, and finally adding adjustment for CV risk factors. Results: The mean age of the sample was 68.3±9.2 years; 48% were male, 27% Black, 13% Chinese, 22% Hispanic, 38% White. The prevalence of any calcification was 62% for SAC, while being 60 and 69% for TAC and CAC, respectively. Among those with any calcification, N and median Agatston score were SAC: 1704, 76; TAC: 1655, 152; CAC 1896, 135. CAC predicted future events in all models (Table). After adjustment for demographics, the ln(Agatston score +1) in each calcified vascular bed predicted future CVD. Mean±SD of the predictors were ln(SAC+1): 2.4±2.4, ln(TAC+1) 2.7±2.9 and ln(CAC+1) 3.1±2.6. SAC, but not TAC, was still predictive after mutual adjustment. SAC was marginally predictive (HR: 1.08, p = 0.06) when CV risk factors were also included in the model. Conclusions: Calcification was common in all 3 vascular beds, but there is no evidence that predictions using SAC and TAC are independent of CAC. We speculate that although the tendency to calcify is similar across vascular beds, CAC is most relevant for incident CVD.

The global estimate of premature cardiovascular mortality: a systematic review and meta-analysis of age-standardized mortality rate

BackgroundCardiovascular disease (CVD) is a significant cause of premature mortality worldwide, with a growing burden in recent years. Despite this, there is a lack of comprehensive meta-analyses that quantify the extent of premature CVD mortality. Study addressed this gap by estimating the pooled age-standardized mortality rate (ASMR) of premature CVD mortality.MethodsWe conducted a systematic review of published CVD mortality studies that reported ASMR as an indicator for premature mortality measurement. All English articles published as of October 2022 were searched in four electronic databases: PubMed, Scopus, Web of Science (WoS), and the Cochrane Central Register of Controlled Trials (CENTRAL). We computed pooled estimates of ASMR using random-effects meta-analysis. We assessed heterogeneity from the selected studies using the I2 statistic. Subgroup analyses and meta regression analysis was performed based on sex, main CVD types, income country level, study time and age group. The analysis was performed using R software with the “meta” and “metafor” packages.ResultsA total of 15 studies met the inclusion criteria. The estimated global ASMR for premature mortality from total CVD was 96.04 per 100,000 people (95% CI: 67.18, 137.31). Subgroup analysis by specific CVD types revealed a higher ASMR for ischemic heart disease (ASMR = 15.57, 95% CI: 11.27, 21.5) compared to stroke (ASMR = 12.36, 95% CI: 8.09, 18.91). Sex-specific differences were also observed, with higher ASMRs for males (37.50, 95% CI: 23.69, 59.37) than females (15.75, 95% CI: 9.61, 25.81). Middle-income countries had a significantly higher ASMR (90.58, 95% CI: 56.40, 145.48) compared to high-income countries (21.42, 95% CI: 15.63, 29.37). Stratifying by age group indicated that the age groups of 20–64 years and 30–74 years had a higher ASMR than the age group of 0–74 years. Our multivariable meta-regression model suggested significant differences in the adjusted ASMR estimates for all covariates except study time.ConclusionsThis meta-analysis synthesized a comprehensive estimate of the worldwide burden of premature CVD mortality. Our findings underscore the continued burden of premature CVD mortality, particularly in middle-income countries. Addressing this issue requires targeted interventions to mitigate the high risk of premature CVD mortality in these vulnerable populations.

Association of ultra-processed foods consumption with risk of cardio-cerebrovascular disease: A systematic review and meta-analysis of cohort studies

AimsThe epidemiological evidence regarding the impact of ultra-processed foods (UPFs) on the risk of cardio-cerebrovascular diseases (CCVDs) is controversial. The aim of this systematic review and meta-analysis is to examine the association between UPF consumption and the risk of CCVDs within cohort studies. Data synthesisA systematic literature search was conducted across multiple databases, including PubMed/Medline, Embase, Web of Science, Scopus, and the Cochrane Library databases, covering the inception of these databases up until January 1st, 2023. A total of 39 cohort studies involving 63,573,312 human participants were deemed eligible according to the inclusion criteria. Utilizing random-effects models, risk ratios (RRs) were estimated to determine the pooled results. Our findings indicate a significant association between a higher consumption of UPF and an increased likelihood of CCVDs (RR: 1.08, 95% CI: 1.01–1.16, I2 = 89%; p < 0.01) compared to individuals who either abstain from or consume lesser amounts of UPF. Nonlinear dose-response meta-analyses showed that a consistent high intake of UPFs was associated with an elevated risk of developing CCVDs (p non-linearity <0.001). Notably, the risk of CCVDs escalated by approximately 7% with an UPF intake of up to 1 serving per day. Subgroup analysis further revealed a significant augmentation in the risk of total CVD and hypertension with increased UPF consumption. ConclusionsA higher intake of UPF significantly increases the risk of developing CCVDs. Prospective studies controlling for confounding factors are needed to validate the relationship between UPF intake and the development of CCVDs.

1350-P: Risk Models for the Development of Cardiovascular and Microvascular Events in Adults with Type 2 Diabetes in the FIELD Study

Background: There are a few prediction models for chronic complications in people with type 2 diabetes (T2D). This study developed such risk models. Methods: Data from 9795 adults with T2D in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial were used to develop risk prediction models for total CVD events, cardiovascular mortality, amputations and new microvascular events using 27 candidate traditional risk factors and additional novel biomarkers (incl. vascular and systemic inflammation, oxidative stress; n=26) using exhaustive search methods. Results: There were 1295 total first CVD events, 267 CVD deaths, 115 amputations and 1530 new microvascular events. A total of 19 and 18 traditional risk factors were selected in the clinical risk models for total CVD events and CVD mortality, with AUC of 0.723 and 0.821 respectively. For individual microvascular complications, the AUC of their models ranged from 0.656 to 0.895. The addition of novel biomarkers to the clinical risk models only resulted in modestly higher AUC (Table below). Conclusion: New clinical risk models can be implemented as risk prediction tools for chronic complications in adults with T2D, including for sight-threatening retinopathy and amputations. Novel biomarkers may guide future research on disease mechanisms, but had limited predictive value over clinical variables. Disclosure K.Ong: None. M.Taskinen: Board Member; Novo Nordisk, Consultant; Eli Lilly and Company, Novartis, Akcea, Research Support; Novo Nordisk. R.J.Simes: None. A.Jenkins: Advisory Panel; Insulet Corporation, Board Member; Insulin for Life, Research Support; Abbott Diabetes, Medtronic, Hemsley Charitable Trust, Juvenile Diabetes Research Foundation (JDRF), National Institutes of Health. A.C.Keech: None. On behalf of the field study investigators: n/a. R.L.O'connell: None. A.S.Januszewski: None. M.W.Donoghoe: None. V.Gebski: None. D.Sullivan: None. K.Rye: None. R.S.Scott: None. J.D.Best: None. Funding Laboratories Fournier; National Health and Medical Research Council of Australia (457103, 1024105, 1037786)

Association of Healthful Plant-based Diet Adherence With Risk of Mortality and Major Chronic Diseases Among Adults in the UK

Plant-based diets have gained popularity for both environmental and health reasons, but a comprehensive assessment of their quality in relation to risk of mortality and major chronic diseases is lacking. To examine whether healthful vs unhealthful plant-based dietary patterns are associated with mortality and major chronic diseases among UK adults. This prospective cohort study used data from adults in the UK Biobank, a large-scale population-based study. Participants were recruited between 2006 and 2010 and followed up using record linkage data until 2021; follow-up for different outcomes ranged between 10.6 and 12.2 years. Data analysis was conducted from November 2021 to October 2022. Adherence to a healthful vs unhealthful plant-based diet index (hPDI vs uPDI) derived from 24-hour dietary assessments. The main outcomes were hazard ratios (HRs) and 95% CIs of mortality (overall and cause specific), cardiovascular disease (CVD [total, myocardial infarction, ischemic stroke, and hemorrhagic stroke]), cancer (total, breast, prostate, and colorectal), and fracture (total, vertebrae, and hip) across quartiles of hPDI and uPDI adherence. This study included 126 394 UK Biobank participants. They had a mean (SD) age of 56.1 (7.8) years; 70 618 (55.9%) were women. The majority of participants (115 371 [91.3%]) were White. Greater adherence to the hPDI was associated with lower risks of total mortality, cancer, and CVD, with HRs (95% CIs) of 0.84 (0.78-0.91), 0.93 (0.88-0.99), and 0.92 (0.86-0.99), respectively, for participants in the highest hPDI quartile compared with the lowest. The hPDI was also associated with lower risks of myocardial infarction and ischemic stroke, with HRs (95% CIs) of 0.86 (0.78-0.95) and 0.84 (0.71-0.99), respectively. By contrast, higher uPDI scores were associated with higher risks of mortality, CVD, and cancer. The associations observed did not show heterogeneity across strata of sex, smoking status, body mass index, or socioeconomic status or with polygenic risk scores (specifically with regard to CVD end points). The findings of this cohort study of middle-aged UK adults suggest that a diet characterized by high-quality plant-based foods and lower intakes of animal products may be beneficial for health, irrespective of established chronic disease risk factors and genetic predisposition.

State-Level Cardiovascular Mortality Rates Among Hispanic, Non-Hispanic Black, and Non-Hispanic White Populations, 1990 to 2019

Cardiovascular disease (CVD) is the leading cause of death in the US, with considerable variation by both state and race and ethnicity group. Consistent, comparable measures of mortality by specific CVD cause at the state level and by race and ethnicity have not previously been available and are necessary for supporting policy decisions aimed at reducing health inequities. To quantify and describe levels and trends of mortality due to overall CVD and its component causes for 3 mutually exclusive race and ethnicity groups and by state. This cross-sectional study used Census data, population surveys, and US vital registration records to estimate cause-specific cardiovascular mortality by state and by the following race and ethnicity groups, defined by the US Office of Management and Budget: Hispanic of any race, non-Hispanic Black (hereafter, Black), and non-Hispanic White (hereafter, White). Data were analyzed from January 2020 to September 2022. State of residence at time of death; Hispanic ethnicity and Black or White race. CVD death counts and mortality rates. An estimated 25 397 029 persons died of cardiovascular diseases from 1990 to 2019. The mean (SD) age of individuals was 78.20 (14.01); 13 087 290 individuals (51.53%) were female and 12 309 739 (48.47%) were male; 2 921 650 (11.50%) were Black, 1 159 498 (4.57%) were Hispanic, and 21 315 880 (83.93%) were White. Age-standardized CVD mortality per 100 000 persons in 2019 was 194.4 (95% uncertainty interval [UI], 172.7 to 207.4), 107.7 (95% UI, 92.9 to 121.4), and 153.8 (95% UI, 133.8 to 163.8) among Black, Hispanic, and White populations, respectively. The median (IQR) percentage change across states was smaller for 2010 to 2019 compared with 1990 to 2000 for both White female and White male populations (-6.8 [-10.1 to -4.3] vs -10.2 [-12.9 to -5.9] and -4.6 [-8.6 to -2.5] vs -16.5 [-19.3 to -15.4]). For the Black and Hispanic groups, the percentage change (IQR) was larger for the female populations for the latter time period (-15.1 [-18.9 to -11.7] vs -12.6 [-19.6 to -7.8] and -23.5 [-29.2 to -18.5] vs -8.2 [-17.8 to 5.96]). The converse was observed among male individuals in both groups, with smaller percentage change (IQR) values in 2010 to 2019 compared with 1990 to 2000 (-13.1 [-18.7 to -8.6] vs -18.6 [-25.5 to -14.7] among the Black male population and -20.4 [-25.6 to -15.6] vs -21.5 [-31.1 to -5.7] among the Hispanic male population). There was substantial variability at the state level for death due to total CVD and component causes in 2019 and changes in CVD mortality from 1990 through 2019. The findings of this study indicate that CVD mortality varied widely by state and race and ethnicity group. Changes over the time period were not consistent for all groups and varied by cardiovascular subcause. These results highlight ongoing health disparities in cardiovascular mortality.

Ultra-processed foods and mortality: analysis from the Prospective Urban and Rural Epidemiology study

BackgroundHigher intake of ultra-processed foods (UPFs) has been associated with increased risk of CVD and mortality in observational studies from Western countries but data from non-Western countries are limited. ObjectivesWe aimed to assess the association between consumption of UPFs and risk of mortality and major CVD in a cohort from multiple world regions. DesignThis analysis includes 138,076 participants without a history of CVD between the ages of 35 and 70 y living on 5 continents, with a median follow-up of 10.2 y. We used country-specific validated food-frequency questionnaires to determine individuals’ food intake. We classified foods and beverages based on the NOVA classification into UPFs. The primary outcome was total mortality (CV and non-CV mortality) and secondary outcomes were incident major cardiovascular events. We calculated hazard ratios using multivariable Cox frailty models and evaluated the association of UPFs with total mortality, CV mortality, non-CV mortality, and major CVD events. ResultsIn this study, 9227 deaths and 7934 major cardiovascular events were recorded during the follow-up period. We found a diet high in UPFs (≥2 servings/d compared with 0 intake) was associated with higher risk of mortality (HR: 1.28; 95% CI: 1.15, 1.42; P-trend < 0.001), CV mortality (HR: 1.17; 95% CI: 0.98, 1.41; P-trend = 0.04), and non-CV mortality (HR: 1.32; 95% CI 1.17, 1.50; P-trend < 0.001). We did not find a significant association between UPF intake and risk of major CVD. ConclusionsA diet with a high intake of UPFs was associated with a higher risk of mortality in a diverse multinational study. Globally, limiting the consumption of UPFs should be encouraged.

Association of Ginseng Consumption With All-cause and Cause-specific Mortality: Shanghai Women's Health Study.

BackgroundGinseng, an herbal remedy, has been commonly used in Asian countries to promote longevity and health for over 2,000 years. However, the association of ginseng consumption with all-cause and cause-specific mortality is still unclear. We analyzed the association of total and major cause-specific mortality (cardiovascular disease [CVD], cancer, and other death) with consumption of ginseng (primarily American and white ginseng).MethodsThis study included 56,183 female participants with an average follow-up of 14.7 years in the Shanghai Women’s Health Study, an ongoing prospective cohort study. Data were assessed via an in-person interview conducted at baseline recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ginseng-mortality associations after adjusting for confounders.ResultsCompared with those who never used ginseng, regular ginseng use was associated with significantly reduced all-cause mortality (HR 0.92; 95% CI, 0.87–0.98). This inverse association was seen primarily among those who consumed ginseng for perceived general health benefit (HR 0.90; 95% CI, 0.85–0.96). A significant dose-response association was observed between duration of ginseng use and total mortality (HR 0.85, for using ≥6 years vs never use; P for trend <0.001), CVD mortality (HR 0.83; P for trend = 0.019), and other-cause mortality (HR 0.76; P for trend = 0.001). However, no dose-response association was observed between amount of ginseng consumption and mortality outcomes.ConclusionRegular ginseng consumption, particularly over a long duration, was associated with decreased risk of all causes of death, death due to CVD, and death due to certain other diseases.

Comparison between the European SCORE and the updated SCORE2 for cardiovascular outcomes

Abstract Introduction The European Systematic Coronary Risk Evaluation (SCORE) has predicted a 10-year risk of CVD since 1986. It included only fatal CVD outcomes, underestimating the total CVD burden, especially for younger people. To counteract this issue, a new score was created (SCORE2) to estimate 10-year fatal and non-fatal CVD risk in Europeans without previous CVD or diabetes aged 40–69 years. Purpose Establish a comparison between SCORE and SCORE2 in terms of CV outcomes in a moderate-risk population. Methods A population of 1,178 individuals without CVD (mean age 53.3±6.9 years; 73.9 male) was stratified into three risk categories for SCORE and SCORE2: low, moderate and high-risk. Using t-test and Chi-square, we compared the two scores in terms of means and risk categories. Kaplan-Meier estimator evaluated MACE occurrence for each category of the two scores during an extended follow-up (mean of 5.2±3.4 years). MACE discriminative capacity of SCORE and SCORE2 was evaluated through C-index methodology. Results The means of the two scores were significantly different (p&amp;lt;0.0001): 2.1±2.4 for SCORE and 6.0±3.3 for SCORE2. 51% of the individuals with high-risk SCORE2 presented the lowest value of SCORE (0–5%). Kaplan-Meier curves showed that the highest category had a worst survival for each score. SCORE2 showed a better discriminative capacity for MACE (C-index 0.678) relatively to SCORE (C-index 0.591), with statistical significance (p&amp;lt;0.0001). Conclusion SCORE2 enhanced the identification of individuals at higher risk of developing CVD and better discriminated MACE occurrence relatively to SCORE. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPERAM

Nordic dietary patterns and cardiometabolic outcomes: a systematic review and meta-analysis of prospective cohort studies and randomised controlled trials

Aims/hypothesisNordic dietary patterns that are high in healthy traditional Nordic foods may have a role in the prevention and management of diabetes. To inform the update of the EASD clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of Nordic dietary patterns and cardiometabolic outcomes.MethodsWe searched MEDLINE, EMBASE and The Cochrane Library from inception to 9 March 2021. We included prospective cohort studies and RCTs with a follow-up of ≥1 year and ≥3 weeks, respectively. Two independent reviewers extracted relevant data and assessed the risk of bias (Newcastle–Ottawa Scale and Cochrane risk of bias tool). The primary outcome was total CVD incidence in the prospective cohort studies and LDL-cholesterol in the RCTs. Secondary outcomes in the prospective cohort studies were CVD mortality, CHD incidence and mortality, stroke incidence and mortality, and type 2 diabetes incidence; in the RCTs, secondary outcomes were other established lipid targets (non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides), markers of glycaemic control (HbA1c, fasting glucose, fasting insulin), adiposity (body weight, BMI, waist circumference) and inflammation (C-reactive protein), and blood pressure (systolic and diastolic blood pressure). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence.ResultsWe included 15 unique prospective cohort studies (n=1,057,176, with 41,708 cardiovascular events and 13,121 diabetes cases) of people with diabetes for the assessment of cardiovascular outcomes or people without diabetes for the assessment of diabetes incidence, and six RCTs (n=717) in people with one or more risk factor for diabetes. In the prospective cohort studies, higher adherence to Nordic dietary patterns was associated with ‘small important’ reductions in the primary outcome, total CVD incidence (RR for highest vs lowest adherence: 0.93 [95% CI 0.88, 0.99], p=0.01; substantial heterogeneity: I2=88%, pQ<0.001), and similar or greater reductions in the secondary outcomes of CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). Inverse dose–response gradients were seen for total CVD incidence, CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). No studies assessed CHD or stroke mortality. In the RCTs, there were small important reductions in LDL-cholesterol (mean difference [MD] −0.26 mmol/l [95% CI −0.52, −0.00], pMD=0.05; substantial heterogeneity: I2=89%, pQ<0.01), and ‘small important’ or greater reductions in the secondary outcomes of non-HDL-cholesterol, apolipoprotein B, insulin, body weight, BMI and systolic blood pressure (p<0.05). For the other outcomes there were ‘trivial’ reductions or no effect. The certainty of the evidence was low for total CVD incidence and LDL-cholesterol; moderate to high for CVD mortality, established lipid targets, adiposity markers, glycaemic control, blood pressure and inflammation; and low for all other outcomes, with evidence being downgraded mainly because of imprecision and inconsistency.Conclusions/interpretationAdherence to Nordic dietary patterns is associated with generally small important reductions in the risk of major CVD outcomes and diabetes, which are supported by similar reductions in LDL-cholesterol and other intermediate cardiometabolic risk factors. The available evidence provides a generally good indication of the likely benefits of Nordic dietary patterns in people with or at risk for diabetes.RegistrationClinicalTrials.gov NCT04094194.FundingDiabetes and Nutrition Study Group of the EASD Clinical Practice.Graphical abstract

Association of increased risk of cardiovascular diseases with higher levels of perfluoroalkylated substances in the serum of adults.

Evidence showing the association of perfluoroalkylated substance (PFAS) exposure with CVD risk is scarce. The objective of this study was to explore the relationships of CVD risk with mixed or individual serum PFAS levels among general adults. We analyzed combined data of 7904 adults who participated in the National Health and Nutrition Examination Survey 2003-2012 with a Bayesian kernel machine regression (BKMR) to examine the relationships of individual or mixed PFAS exposure with total CVD risk. A logistic regression model and restricted cubic spline (RCS) regression with multivariate adjustment were conducted to assess the relationships between individual serum PFAS levels and the risk of total CVD or its subtypes. A mediation model was applied to investigate how C-reactive protein (CRP) levels mediate the strength of the association. The BKMR results indicated a positive relationship between mixed PFAS exposure and total CVD risk; among the PFASs, perfluorooctane sulfonic acid (PFOS) had the highest posterior inclusion probability. As determined by logistic regression, a log-unit change in PFOS levels was positively related to a higher risk of heart attack and stroke in males (both P < 0.05). A nonlinear relationship was found between PFOS levels and stroke risk (P for nonlinearity = 0.04), as illustrated in the RCS plot. The mediation analysis showed that CRP levels mediated 8% and 1.2% of the relationship between serum PFOS and PFNA levels, respectively, and the prevalence of stroke. A significant relationship between higher serum PFAS concentrations and an increased risk of CVD was observed, mainly in males.