Nonfatal Coronary Heart Disease Research Articles

Socioeconomic Disadvantage in Pregnancy and Postpartum Risk of Cardiovascular Disease

Pregnancy is an educable and actionable life stage to address social determinants of health (SDOH) and lifelong cardiovascular disease (CVD) prevention. But the link between a risk score that combines multiple neighborhood-level social determinants in pregnancy and the risk of long-term CVD remains to be evaluated. To examine whether neighborhood-level socioeconomic disadvantage measured by the Area Deprivation Index (ADI) in early pregnancy is associated with a higher 30-year predicted risk of CVD postpartum, as measured by the Framingham Risk Score. An analysis of data from the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study longitudinal cohort. Participant home addresses during early pregnancy were geocoded at the Census-block level. The exposure was neighborhood-level socioeconomic disadvantage using the 2015 ADI by tertile (least deprived [T1], reference; most deprived [T3]) measured in the first trimester. Outcomes were the predicted 30-year risks of atherosclerotic CVD (ASCVD, composite of fatal and non-fatal coronary heart disease and stroke) and total CVD (composite of ASCVD plus coronary insufficiency, angina pectoris, transient ischemic attack, intermittent claudication, and heart failure) using the Framingham Risk Score measured 2-to-7 years after delivery. These outcomes were assessed as continuous measures of absolute estimated risk in increments of 1%, and, secondarily, as categorical measures with high-risk defined as an estimated probability of CVD >10%. Multivariable linear regression and modified Poisson regression models adjusted for baseline age and individual-level social determinants, including health insurance, educational attainment, and household poverty. Among 4,309 nulliparous individuals at baseline, the median age was 27 years (IQR: 23-31) and the median ADI was 43 (IQR: 22-74). At 2-to-7 years postpartum (median: 3.1 years, IQR: 2.5, 3.7), the median 30-year risk of ASCVD was 2.3% (IQR: 1.5, 3.5) and of total CVD was 5.5% (IQR: 3.7, 7.9); 2.2% and 14.3% of individuals had predicted 30-year risk >10%, respectively. Individuals living in the highest ADI tertile had a higher predicted risk of 30-year ASCVD % (adj. ß: 0.41; 95% CI: 0.19, 0.63) compared with those in the lowest tertile; and those living in the top two ADI tertiles had higher absolute risks of 30-year total CVD % (T2: adj. ß: 0.37; 95% CI: 0.03, 0.72; T3: adj. ß: 0.74; 95% CI: 0.36, 1.13). Similarly, individuals living in neighborhoods in the highest ADI tertile were more likely to have a high 30-year predicted risk of ASCVD (aRR: 2.21; 95% CI: 1.21, 4.02) and total CVD ≥10% (aRR: 1.35; 95% CI: 1.08, 1.69). Neighborhood-level socioeconomic disadvantage in early pregnancy was associated with a higher estimated long-term risk of CVD postpartum. Incorporating aggregated SDOH into existing clinical workflows and future research in pregnancy could reduce disparities in maternal cardiovascular health across the lifespan, and requires further study.

Associations between Cholesterol Intake, Food Sources and Cardiovascular Disease in Chinese Residents.

Cholesterol is a nutrient commonly found in the human diet. The relationship between dietary cholesterol, its sources, and cardiovascular disease (CVD) is still a topic of debate. This study aimed to investigate the association between dietary cholesterol, its sources, and cardiovascular events in a Chinese population. The present study analyzed data from the China Health and Nutrition Survey (CHNS) cohort between 1991 and 2015. This study analyzed data from 3903 participants who were 40 years of age or older at baseline and had no history of cardiovascular disease, diabetes, or hypertension. During a median follow-up of 14 years, 503 cardiovascular disease events were identified through follow-up questionnaires administered every 2-3 years. The events included fatal and nonfatal coronary heart disease, stroke, heart failure, and other cardiovascular disease deaths. Cox regression was used to estimate risk ratios (HR) for CVD events after adjusting for demographic, socioeconomic, and behavioral factors. It was discovered that sources of dietary cholesterol varied among different subgroups of the population. The top three sources of cholesterol among all participants were eggs, red meat, and seafood, accounting for 57.4%, 28.2%, and 9.0% of total daily cholesterol intake, respectively. The present study found that there was a significant association between total dietary cholesterol intake, and the risk of developing cardiovascular disease (adjusted HR [95% CI]: total cholesterol (highest and lowest quartiles compared) 1.57 [1.17-2.11]). Cholesterol from poultry, seafood, and eggs was also significantly associated with a reduced risk of CVD (adjusted HR [95% CI]: poultry 0.18 [0.04-0.82], seafood 0.11 [0.02-0.54], and eggs 0.16 [0.03-0.73]). After adjusting for daily caloric intake, daily fat intake, and daily saturated fat intake, the previously observed association between red meat cholesterol and cardiovascular events (unadjusted HR [95% CI]: 0.44 [0.35-0.55]) was no longer statistically significant (adjusted HR [95% CI]: 0.21 [0.04-1.01]).

Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study

BackgroundThe residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event.MethodsData on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined.ResultsThe 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log–alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure.ConclusionThis study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Sex differences in risk factors for coronary heart disease events: a prospective cohort study in Iran

We investigated sex-specific associations and their differences between major cardiovascular risk factors and the risk of incident coronary heart disease (CHD) and hard CHD (defined as nonfatal myocardial infarction and CHD death). A total of 7518 (3377 men) participants from the Tehran Lipid and Glucose Study were included. Cox models were used to estimate the hazard ratios (HRs) and women-to-men ratios of HRs for CHD events associated with each risk factor. During 20 years of follow-up (1999–2018), 1068 (631 men) and 345 (238 men) new cases of CHD and hard CHD, respectively, were documented. In total population, the incidence rates per 1000 person-years were 9.5 (9.0–10.1) and 2.9 (2.6–3.2) for CHD and hard CHD, respectively. Hypertension, diabetes, pre-diabetes, and a high waist-to-hip ratio (WHR) were associated with a greater HR of hard CHD in women than men; the women-to-men HRs were 2.85 [1.36–5.98], 1.92 [1.11–3.31], 2.04 [1.09–3.80] and 1.42 [1.10–1.82], respectively. Diabetes was associated with a higher HR of CHD in women than men (ratio of HRs 1.49 (1.10–2.01). In conclusion, we found that hypertension, diabetes, pre-diabetes, and high WHR conferred a greater excess risk of CHD events in women than in men, suggesting that Iranian women may require greater attention for the prevention of CHD events.

Kidney function and future risk of atherosclerotic cardiovascular disease: a study from, approximately half million adults

Abstract Background Data are lacking regarding contribution of kidney function towards atherosclerotic cardiovascular diseases (ASCVD) in young to middle aged adults. Purpose To evaluate the impact of kidney function on future risk of ASCVD in a large, young contemporary population without prior ASCVD. Methods This observational cohort study included young to middle aged adults (ages 30-55 years) without established ASCVD (as of January 1, 2006) who were members of an integrated healthcare delivery system in Northern California. Adjusted multivariate models (age, sex, race, diabetes, hypertension, HDL-C, LDL-C, total cholesterol, smoking, albuminuria) were specified to estimate risk ratios (RRs) for incident ASCVD events by kidney function (eGFR mL/min/1.732). Incident ASCVD events were defined as a composite of nonfatal myocardial infarction, ischemic stroke, or coronary heart disease death through December 31, 2020. Results A total of 426,735 individuals met the selection criteria. Mean age was 45.4 (±7.0) years. Fifty-five percent were women, and the median follow-up was 12.7 (IQR=11) years. In fully adjusted models, risk of future ASCVD, compared to patients with eGFR ≥ 60 was 1.7 (95% CI 1.5-1.9) for eGFR 30-59 RR and RR of 2.2 (95% CI 1.8- 2.7) for eGFR &amp;lt; 30. The kidney function-ASCVD associations were similar by sex for eGFR 30-59, but risks were accentuated among women with eGFR&amp;lt;30 (figure). Conclusions There was increased risk of future ASCVD with worsening kidney function. This risk was more pronounced among women. Using eGFR as part of risk assessment can inform targeting early interventions to prevent both kidney disease and subsequent ASCVD, especially in the era where effective pharmacotherapy such as SGLT2-Inhibitors have demonstrated renal and cardioprotective effects in high-risk populations.

Combined population genomic screening for three high-risk conditions in Australia: a modelling study

No previous health-economic evaluation has assessed the impact and cost-effectiveness of offering combined adult population genomic screening for mutliple high-risk conditions in a national public healthcare system. This modeling study assessed the impact of offering combined genomic screening for hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia to all young adults in Australia, compared with the current practice of clinical criteria-based testing for each condition separately. The intervention of genomic screening, assumed as an up-front single cost in the first annual model cycle, would detect pathogenic variants in seven high-risk genes. The simulated population was 18-40 year-olds (8,324,242 individuals), modelling per-sample test costs ranging AU$100-$1200 (base-case AU$200) from the year 2023 onwards with testing uptake of 50%. Interventions for identified high-risk variant carriers follow current Australian guidelines, modelling imperfect uptake and adherence. Outcome measures were morbidity and mortality due to cancer (breast, ovarian, colorectal and endometrial) and coronary heart disease (CHD) over a lifetime horizon, from healthcare-system and societal perspectives. Outcomes included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER), discounted 5% annually (with 3% discounting in scenario analysis). Over the population lifetime (to age 80 years), the model estimated that genomic screening per-100,000 individuals would lead to 747 QALYs gained by preventing 63 cancers, 31 CHD cases and 97 deaths. In the total model population, this would translate to 31,094 QALYs gained by preventing 2612 cancers, 542 non-fatal CHD events and 4047 total deaths. At AU$200 per-test, genomic screening would require an investment of AU$832 million for screening of 50% of the population. Our findings suggest that this intervention would be cost-effective from a healthcare-system perspective, yielding an ICER of AU$23,926 (∼£12,050/€14,110/US$15,345) per QALY gained over the status quo. In scenario analysis with 3% discounting, an ICER of AU$4758/QALY was obtained. Sensitivity analysis for the base case indicated that combined genomic screening would be cost-effective under 70% of simulations, cost-saving under 25% and not cost-effective under 5%. Threshold analysis showed that genomic screening would be cost-effective under the AU$50,000/QALY willingness-to-pay threshold at per-test costs up to AU$325 (∼£164/€192/US$208). Our findings suggest that offering combined genomic screening for high-risk conditions to young adults would be cost-effective in the Australian public healthcare system, at currently realistic testing costs. Other matters, including psychosocial impacts, ethical and societal issues, and implementation challenges, also need consideration. Australian Government, Department of Health, Medical Research Future Fund, Genomics Health Futures Mission (APP2009024). National Heart Foundation Future Leader Fellowship (102604).

Abstract 14790: Association of Neighborhood Socioeconomic Disadvantage in Early Pregnancy and 30-Year Predicted Probability of Cardiovascular Disease 2-7 Years Postpartum

Introduction: To determine whether neighborhood socioeconomic disadvantage as measured by the Area Deprivation Index (ADI) in early pregnancy is associated with higher 30-year predicted risk of cardiovascular disease (CVD) by the Framingham Risk Score. Methods: A secondary analysis of data from the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study (HHS) longitudinal cohort. Participant home addresses in the first trimester were geocoded at the census-tract level. The exposure was neighborhood socioeconomic disadvantage using the 2015 ADI by tertile (least deprived [T1], reference; most deprived [T3]). The primary outcome was the predicted 30-year risk of hard CVD using the Framingham Risk Score (composite of fatal and non-fatal coronary heart disease and stroke). The secondary outcome was predicted 30-year risk of total CVD (composite of “hard” CVD plus coronary insufficiency and angina pectoris, stroke, transient ischemic attack, intermittent claudication and heart failure). Outcomes were assessed categorically as high-risk defined as a predicted probability of CVD &gt; 10%, and secondarily as a continuous measure of absolute risk (%). Modified Poisson and linear regression models adjusted for age, insurance, education, and income. Results: Among 4,310 nulliparous individuals, the median age was 27 years (IQR: 23-31), and the median ADI was 43 (IQR: 22-74). At 2-7 years postpartum (median: 4 years), the median 30-year risk of hard CVD was 2.3% (IQR: 1.5-3.5), and total CVD was 5.5% (IQR: 3.7-7.9). Individuals living in neighborhoods in the highest tertile of socioeconomic disadvantage were more likely to have a high 30-year predicted risk of hard CVD (≥10%) compared with those in the lowest tertile (aRR: 2.25; 95% CI: 1.23, 4.11), with similar results for high 30-year predicted risk of total CVD (aRR: 1.36; 95% CI: 1.09, 1.69). Living in the highest ADI tertile was associated with a higher absolute risk of 30-year hard (adj. ß: 0.41; 95% CI: 0.19, 0.63) and total CVD (adj. ß: 0.76; 95% CI: 0.38, 1.14) when analyzed as a continuous outcome. Conclusions: Neighborhood socioeconomic disadvantage in early pregnancy is associated with higher predicted risk of 30-year CVD 2-7 years after delivery.

Educational Attainment and Lifetime Risk of Cardiovascular Disease

Education is a social determinant of health. Quantifying its association with lifetime cardiovascular disease (CVD) risk has public health importance. To calculate lifetime risk estimates of incident CVD and CVD subtypes and estimate years lived with and without CVD by education. Included community-based cohort studies with adjudicated cardiovascular events used pooled individual-level data from 1985 to 2015 of 6 prospective cohort studies. The study team assessed the association between education and lifetime CVD risk with modified Kaplan-Meier and Cox models accounting for competing risk of noncardiovascular death. The study team estimated years lived with and without CVD by education with the Irwin restricted mean and the utility of adding educational attainment to CVD risk assessment. Participants (baseline 40 to 59 years old and 60 to 79 years old) were without CVD at baseline and had complete education, cardiovascular risk factors, and prospective CVD outcomes data. Data were analyzed from January 2022 to September 2022. Educational attainment (less than high school, high school completion, some college, or college graduate). Cardiovascular events (fatal and nonfatal coronary heart disease, heart failure, and stroke; CVD-related deaths; and total CVD encompassing any of these events). There were 40 998 participants (23 305 female [56.2%]) with a mean (SD) age of 58.1 (9.7) years for males and 58.3 (9.9) years for females. Compared with college graduates, those with less than high school or high school completion had higher lifetime CVD risks. Among middle-aged men, the competing hazard ratios (HRs) for a CVD event were 1.58 (95% CI, 1.38-1.80), 1.30 (95% CI, 1.10-1.46), and 1.16 (95% CI, 1.00-1.34) in those with less than high school, high school, and some college, respectively, compared with those with college completion. Among women, these competing HRs were 1.70 (95% CI, 1.49-1.95), 1.19 (95% CI, 1.05-1.35), and 0.98 (95% CI, 0.83-1.15). Individuals with higher education had longer duration of life prior to incident CVD. Education provided limited contribution toward enhancing CVD risk prediction. Lower education was associated with lifetime CVD risk across adulthood; higher education translated to healthy longevity. Educational policy initiatives may associate with long-term health benefits.

Obesity, metabolic health and clinical outcomes after incident cardiovascular disease: A nationwide population-based cohort study.

The association between metabolic syndrome and increased cardiovascular disease (CVD) risk is well-established. However, in patients with incident CVD, the relationship between obesity, metabolic health, and subsequent CVD and mortality outcomes are less well-established. This study investigated the association between body mass index (BMI), metabolic health and the risk of subsequent cardiovascular mortality and morbidity outcomes in patients with incident CVD events. This cohort study identified 130685 patients from the nationwide Clinical Practice Research Datalink (CPRD GOLD) and Hospital Episode Statistics (HES) databases in the United Kingdom. Patients were ≥18years with incident CVD [coronary heart disease (CHD), stroke, or peripheral vascular disease (PVD)] between 1 January 1998 and 31 December 2017. BMI (in kg/m2 ) was categorized as underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9) and obese (≥30). Within each BMI category, patients were grouped by increasing count of 1, 2 or 3 metabolic risk factors [RF] (dyslipidaemia, diabetes mellitus and hypertension) and were regarded as metabolically unhealthy while absence of these factors was considered metabolically healthy (MH). Multivariable Cox regression was used to assess the risk (hazard ratio with 95% confidence interval) of subsequent outcomes (non-fatal CHD, stroke, PVD, incident heart failure, CVD-mortality and all-cause mortality) in BMI subgroups with incremental count of metabolic RFs. During a median follow-up of 13.0years, a higher BMI was associated with reduced risk for stroke, PVD, CVD-mortality and all-cause mortality within each metabolic risk category, while increasing metabolic RFs within each BMI subgroup accounted for increasing risks. When compared with patients with normal BMI and no RF, CVD-mortality risk in overweight patients with no RF was 0.76 (0.70-0.84), and in obese patients with no RF was 0.85 (0.76-0.96). The respective risk for all-cause mortality in patients with overweight and no RF was 0.69 (0.65-0.72), and in obese patients with no RF was 0.75 (0.70-0.79). Subsequent outcomes of stroke and PVD showed similar trends. In contrast, the risk of subsequent non-fatal CHD events and incident HF increased with higher BMI and with incremental metabolic risk factors within each BMI category. Underweight was constantly associated with increased risk for all outcomes regardless of the presence of metabolic RFs except for non-fatal CHD events. In patients with incident CVD, overweight and obesity were related to a more favourable prognosis for subsequent stroke, PVD and mortality (CVD-related and all-cause) irrespective of the presence of other metabolic risk factors.

Endocan is Related to Increased Cardiovascular Risk in Type 2 Diabetes Mellitus Patients.

Aim: Type 2 diabetes mellitus (T2D) patients have an increased risk for cardiovascular disease (CVD). Different algorithms are used for the CVD risk quantification and United Kingdom Prospective Diabetes Study (UKPDS) score was among the most validated. Endocan is a novel endothelial dysfunction marker. The aim was to explore the potential relationship between serum endocan level and UKPDS risk engine score [which enables calculation of the 10-year risk of nonfatal and fatal coronary heart disease (eCHD) and stroke] in T2D patients. Materials and Methods: The study included a cohort of 104 patients with T2D (of them 52.8% men), with median age 66 years and body mass index (BMI) = 30.7 kg/m2. Patients were divided into: low (<15%), moderate (≥15% and <30%), and high-risk UKPDS category (≥30%). Results: In multivariable regression analysis (when adjusted for sex, BMI and/or hip circumference), endocan was the independent predictor for moderate and high estimated risks (nonfatal eCHD, fatal eCHD, and nonfatal stroke risk). In the Model for high nonfatal eCHD [areas under curve (AUC) = 0.895] and high fatal eCHD (AUC = 0.860) endocan indicated good clinical accuracy, and an excellent accuracy in discriminating patients with high risk for nonfatal stroke risk (AUC = 0.945). Conclusion: Endocan was the independent predictor for moderate and high estimated risks (i.e., nonfatal and fatal CHD and nonfatal stroke risk scores) in T2D patients. When included in models with sex and obesity indices endocan demonstrated good clinical accuracy in discriminating T2D patients with high risk for nonfatal and fatal eCHD and nonfatal stroke risk from those patients with low risk.

Risk of atherosclerotic cardiovascular disease in patients with premature ASCVD: A study from approximately 1 million young adults

Abstract Funding Acknowledgements Type of funding sources: None. Background Risk of atherosclerotic cardiovascular disease (ASCVD) attributable to premature ASCVD remains poorly understood. Purpose To evaluate the risk of ASCVD among those with premature ASCVD versus those without in a large contemporary population. Methods This observational cohort study included young adults (ages 30-55 years) with and without prior ASCVD (as of January 1, 2006) who were members of an integrated healthcare delivery system in Northern California. Adjusted multivariate models were specified to estimate risk ratios (RRs) for incident ASCVD events by ASCVD status at baseline. Incident ASCVD events were defined as a composite of nonfatal myocardial infarction, ischemic stroke, or coronary heart disease death through December 31, 2020. Results A total of 929,214 individuals met the selection criteria of no prior ASCVD and 5,703 with prior ASCVD. Mean age was 43.9 (±7.3) years and 50.0 (±5.2) years, respectively. Fifty-two and thirty percent were women in each cohort, and the median follow-up was 11.8 and 8.3 years, respectively. Crude ASCVD rate was 2.1 and 24.5 events per 1,000 person-years, respectively. Age-adjusted Kaplan-Meier curves for ASCVD in individuals with and without prior ASCVD in Figure. In models adjusted for demographics (sex, age, race) and traditional risk factors (diabetes, hypertension, LDL-cholesterol, HDL-cholesterol, total cholesterol, smoking), individuals with prior ASCVD had RR of 4.6 (95% CI 4.3-5.0) for CHD, RR of 3.0 (95% CI 2.7-3.4) for stroke and RR of 4.1 (95% CI 3.8-4.3) for ASCVD. Conclusions Risk of ASCVD among those with prior ASCVD was several-fold greater compared to those without prior ASCVD. Continued efforts for secondary prevention are needed in this vulnerable high-risk population.

Abstract MP11: Ultra-Processed Food Consumption and Cardiovascular Disease in the European Prospective Investigation Into Cancer and Nutrition Study

Introduction: Diets containing many ultra-processed foods (UPF) are linked to unfavourable health. UPF are defined by the NOVA classification as industrial food and drinks made from substances not used in domestic culinary preparations, such as hydrogenated fats, modified starches, and other food additives. There is evidence suggesting a link between UPF consumption and cardiovascular disease (CVD) incidence, but this association has not been tested in a large European cohort. Using data from the pan-European Prospective Investigation into Cancer and nutrition (EPIC) study, we assessed the hypothesis that higher consumption of UPF is associated with an increased risk of incident fatal and non-fatal CHD and stroke in the EPIC-Heart cohort. Methods: Case-cohort design nested in the EPIC cohort including 36,415 adults from Denmark, Germany, Italy, the Netherlands, Spain, Sweden, and the UK. Socio-demographic, lifestyle factors and usual dietary intake were assessed at time of recruitment (1992 - 2000) using country-specific validated questionnaires. Consumption of UPF was expressed in percentage of grams per day. CVD cases ascertainment varied across EPIC centres and included hospital admissions, linkage to registers, self-report and mortality data. Proportion of missing values ranged from 0.95% for smoking status to 14.2% for history of diabetes. We performed multiple imputation on all covariates with missing values. Cox proportional hazard models with age as the underlying time variable stratified by sex, centre and age were used to test the longitudinal association between UPF consumption and coronary heart disease (CHD) and stroke incidence adjusted for confounders. We applied prentice weights to our cox proportional hazard models to account for the case-cohort design. Results: The mean contribution of UPF to the overall diet in grams was 14.2% in men and 12.8% in women. After a median follow-up time of 9.7 years, it was documented 11,973 non-fatal and 2,281 fatal CHD events, and 6,765 non-fatal and 899 fatal stroke events. In models adjusted for education, smoking, physical activity, body mass index, height, diabetes, high blood pressure, alcohol, energy, and sodium intake, and the Mediterranean diet score, each 10% increase in the consumption of grams from UPF was associated with an increased risk of non-fatal CHD (HR 1.13, 95%CI 1.02 - 1.26), fatal CHD (HR 1.33, 95%CI 1.09 - 1.62) and fatal stroke (HR 1.40, 95%CI 1.07 - 1.85), but not with non-fatal stroke (HR 1.11, 95%CI 0.98 - 1.24). Complete-case analysis showed similar results. Conclusion: In this large prospective cross-European study we found that higher proportion of UPF in the diet was associated with an increased risk of non-fatal CHD and fatal CHD and stroke. These findings corroborate other large-scale cohort studies indicating that the increasing consumption of ultra-processed intake may contribute to higher CVD incidence.

Abstract P221: Intake of Ultra-Processed Foods in Relation to Cardiovascular Disease Incidence in US Men and Women With Diabetes Mellitus

Introduction: Recent evidence suggests that intake of ultra-processed foods (UPF) is related to unfavorable cardio-metabolic risk profiles among generally healthy populations. However, evidence on the relationship between UPF intake and cardiovascular disease (CVD) among patients with type 2 diabetes (T2D) is lacking. Hypothesis: We assessed the hypothesis that higher intake of dietary UPF is associated with higher risks of CVD among individuals with T2D. Methods: We prospectively followed 13,272 men and women participating in the Health Professionals Follow-Up Study (HPFS) and Nurses’ Health Study (NHS) with T2D at baseline and during follow-up (HPFS: 1986-2018; NHS: 1980-2014). Diet was repeatedly assessed using validated food frequency questionnaires every 2-4 years. UPF were categorized according to the Nova classification. CVD was defined as fatal and non-fatal coronary heart disease (CHD) (including nonfatal myocardial infarction, coronary artery bypass graft surgery, and coronary angioplasty and stent) and fatal and non-fatal stroke. Associations of UPF consumption with risks of CVD were assessed using Cox regression. Results: During 165,761 person-years of follow-up, 1,826 total CHD and 529 total stroke were identified and confirmed. After adjusting for demographics, lifestyle, medical history, dietary factors, and diabetes medication use, higher total intake of UPF was associated with higher risk of CHD. The multivariable-adjusted HRs (95% CIs) were 1.20 (1.02, 1.43) ( P trend = 0.03) when comparing the highest and lowest quintiles (Q5 vs. Q1) or 1.03 (1.01, 1.04) for each 1 serving/day increment of UPF. No association between UPF intake and risk of stroke was observed (Q5 vs. Q1: 0.92 (0.67, 1.24)). These results were consistent across subgroups in analyses stratified by age, sex, BMI, diet quality, physical activity, smoking, diabetes medication use, or diabetes duration. In addition, compared with participants who had a stable or decreased consumption of UPF (≤0 change in UPF) from pre- to post-diabetes diagnosis, participants who increased consumption of UPF (&gt;0 increment of UPF intake) after diabetes diagnosis had a 15% (1%, 31%) higher risk of CHD. Conclusions: Among participants with T2D, higher dietary UPF consumption was associated with a higher risk of CHD, but not stroke. These results provide further support for the current recommendations to limit UPF consumption for the prevention of CHD among patients with diabetes.

Nuts and seeds consumption and risk of cardiovascular disease, type 2 diabetes and their risk factors: a systematic review and meta-analysis.

We aimed to systematically review studies and evaluate the strength of the evidence on nuts/seeds consumption and cardiometabolic diseases and their risk factors among adults. A protocol was pre-registered in PROSPERO (CRD42021270554). We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to September 20, 2021 for prospective cohort studies and ≥12-week randomized controlled trials (RCTs). Main outcomes were cardiovascular disease (CVD), coronary heart disease (CHD), stroke and type 2 diabetes (T2D), secondary total-/low density lipoprotein (LDL)-cholesterol, blood pressure and glycaemic markers. Data extraction and risk of bias (RoB) assessments (using RoB 2.0 and RoB-NObS) were performed in duplicate. Effect sizes were pooled using random-effects meta-analyses and expressed as relative risk (RR) or weighted mean differences with 95% confidence intervals (CI); heterogeneity quantified as I 2. One-stage dose-response analyses assessed the linear and non-linear associations with CVD, CHD, stroke and T2D. The strength of evidence was classified per the World Cancer Research Fund criteria. After screening 23,244 references, we included 42 papers from cohort studies (28 unique cohorts, 1,890,573 participants) and 18 RCTs (2,266 participants). In the cohorts, mainly populations with low consumption, high versus low total nuts/seeds consumption was inversely associated with total CVD (RR 0.81; 95% CI 0.75, 0.86; I 2 = 67%), CVD mortality (0.77; 0.72, 0.82; I 2 = 59.3%), CHD (0.82; 0.76, 0.89; I 2 = 64%), CHD mortality (0.75; 0.65, 0.87; I 2 = 66.9%) and non-fatal CHD (0.85; 0.75, 0.96; I 2 = 62.2%). According to the non-linear dose-response analyses, consumption of 30 g/day of total nuts/seeds was associated with RRs of similar magnitude. For stroke and T2D the summary RR for high versus low intake was 0.91 (95% CI 0.85, 0.97; I 2 = 24.8%) and 0.95 (0.75, 1.21; I 2 = 82.2%). Intake of nuts (median ~50 g/day) lowered total (-0.15 mmol/L; -0.22, -0.08; I 2 = 31.2%) and LDL-cholesterol (-0.13 mmol/L; -0.21, -0.05; I 2 = 68.6%), but not blood pressure. Findings on fasting glucose, HbA1c and insulin resistance were conflicting. The results were robust to sensitivity and subgroup analyses. We rated the associations between nuts/seeds and both CVD and CHD as probable. There was limited but suggestive evidence for no association with stroke. No conclusion could be made for T2D. There is a probable relationship between consumption of nuts/seeds and lower risk of CVD, mostly driven by CHD, possibly in part through effects on blood lipids. More research on stroke and T2D may affect the conclusions. The evidence of specific nuts should be further investigated.

Prospective Association of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis.

Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines. Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance-weighted random effects models. The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults. For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician-patient communication and population health to reduce the risk of CVD.

Menstrual Cycle Regularity and Length Across the Reproductive Lifespan and Risk of Cardiovascular Disease

Menstrual cycle characteristics may be associated with an increased risk of cardiovascular disease (CVD). However, existing studies are limited, and few have explored the mediating role of established CVD risk factors. To explore the associations of menstrual cycle characteristics across the reproductive lifespan with the risk of CVD and to what extent these associations were mediated by hypercholesterolemia, chronic hypertension, and type 2 diabetes. This cohort study prospectively followed Nurses' Health Study II participants between 1993 and 2017 who reported menstrual cycle regularity and length for ages 14 to 17 years and 18 to 22 years at enrollment in 1989 and updated current cycle characteristics in 1993 (at ages 29 to 46 years). Data analysis was performed from October 1, 2019, to January 1, 2022. Menstrual cycle regularity and length across the reproductive lifespan. Incident CVD events of interest, including fatal and nonfatal coronary heart disease (CHD; myocardial infarction [MI] or coronary revascularization) and stroke. A total of 80 630 Nurses' Health Study II participants were included in the analysis, with a mean (SD) age of 37.7 (4.6) years and body mass index of 25.1 (5.6) at baseline. Over 24 years of prospective follow-up, 1816 women developed their first CVD event. Multivariable Cox proportional hazards models showed that, compared with women reporting very regular cycles at the same ages, women who had irregular cycles or no periods at ages 14 to 17, 18 to 22, or 29 to 46 years had hazard ratios for CVD of 1.15 (95% CI, 0.99-1.34), 1.36 (95% CI, 1.06-1.75), and 1.40 (95% CI, 1.14-1.71), respectively. Similarly, compared with women reporting a cycle length of 26 to 31 days, women reporting a cycle length 40 days or more or a cycle too irregular to estimate from ages 18 to 22 or 29 to 46 years had hazard ratios for CVD of 1.44 (95% CI, 1.13-1.84) and 1.30 (95% CI, 1.09-1.57), respectively. Mediation analyses showed that subsequent development of hypercholesteremia, chronic hypertension, and type 2 diabetes only explained 5.4% to 13.5% of the observed associations. In this cohort study, both irregular and long menstrual cycles were associated with increased rates of CVD, which persisted even after accounting for subsequently established CVD risk factors.

Temporal Trends in Incidence of Premature Cardiovascular Disease Over the Past 7 Decades: The Framingham Heart Study.

Background Premature onset of cardiovascular disease (CVD) imposes a significant societal burden and challenges prevention efforts. Methods and Results Trends in the incidence of premature CVD (before age 55, 60, or 65 years, separate analysis for each threshold) were evaluated in 14 464 Framingham Heart Study participants over 7 decades of observation (1950-2019). The change in the incidence of premature CVD (per decade) in men and women was assessed using overdispersed Poisson regression (accounting for cohort effects), adjusting for age at entry and age at onset of premature CVD within each decade. CVD was defined as a composite of fatal or nonfatal coronary heart disease, stroke or transient ischemic attack, peripheral vascular disease, and heart failure. There were 2223 first CVD events (832 in women) before age 65 years during 282 481 person-years of observations (154 587 in women) between 1950 and 2019. The age-adjusted CVD incidence before age 65 years decreased from 14.8 per 1000 person-years (1950-1959) to 4.69 per 1000 person-years (2010-2019) in men and from 7.23 per 1000 person-years (1950-1959) to 1.73 per 1000 person-years (2010-2019)in women. In adjusted analyses, the incidence of premature CVD decreased per decade in men (18.4% [95% CI, 12.0%-24.0%], for onset before age 55 years; 19.5% [95% CI, 12.0%-27.0%], for onset before age 60 years; 21.3% [95% CI, 16.0%-27.0%], for onset before age 65 years) and women (15.1% [95% CI, 7.0%-22.0%], for onset before age 55 years; 14.0% [95% CI, 6.0%-22.0%], for onset before age 60 years; 18.2% [95% CI, 12.0%-24.0%], for onset before age 65 years). The decline in premature CVD was accompanied by a reduction in smoking and increased use of lipid-lowering treatments across the decades. Incidence of premature coronary heart disease decreased, whereas the contribution of stroke to premature CVD burden increased over time. Conclusions The incidence of premature CVD has decreased among White adults in the Framingham cohort over the past 70 years; the residual burden of premature stroke warrants further study. Additional studies of trends in premature CVD in more racially and geographically diverse populations are warranted to elucidate the generalizability of these findings.

Physical activity from young adulthood to middle age and premature cardiovascular disease events: a 30-year population-based cohort study

BackgroundAlthough physical activity is generally protective of cardiovascular disease (CVD), less is known about how young adult physical activity relates to premature CVD events. The objective of this study was to determine the association between level and change in physical activity from young adulthood to middle age and incidence of premature CVD events before age 60.MethodsWe analyzed data collected across four urban sites from nine visits over 30 years of follow-up (1985–2016) from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective community-based cohort study of 5115 Black and White women and men aged 18–30 years at baseline (1985–1986). Linear mixed models were used to develop individualized moderate-to-vigorous intensity self-reported physical activity trajectories per participant. Fatal and nonfatal coronary heart disease (CHD), heart failure, and stroke outcomes were analyzed separately and as a combined CVD event outcome.ResultsOverall, physical activity declined in young adults as they progressed through middle age. Lower physical activity scores (per 100 exercise units) in 18 year-olds were associated with higher odds of premature CHD (AOR 1.14, 95% CI 1.02–1.28), heart failure (AOR 1.21, 95% CI 1.05–1.38), stroke (AOR 1.20, 95% CI 1.04–1.39), and any CVD (AOR 1.15, 95% CI 1.06–1.24) events. Each additional annual 1-unit reduction in the physical activity score was associated with a higher annual odds of incident heart failure (1.07, 95% CI 1.02–1.13), stroke (1.06, 95% CI 1.00–1.13), and CVD (1.04, 95% CI 1.01–1.07) events. Meeting the minimum (AOR 0.74, 95% CI 0.0.57–0.96) and twice the minimum (AOR 0.55, 95% CI 0.34–0.91) Department of Health and Human Services physical activity guidelines through follow up was protective of premature CVD events.ConclusionsGiven recent trends in declining physical activity with age and associated premature CVD events, the transition from young adult to midlife is an important time period to promote physical activity.

Marital status and genetic liability independently predict coronary heart disease incidence.

Married individuals have a lower coronary heart disease (CHD) risk than non-married, but the mechanisms behind this are not fully understood. We analyzed whether genetic liability to CHD may affect these associations. Marital status, a polygenic score of CHD (PGS-CHD), and other risk factors for CHD were measured from 35,444 participants (53% female) in Finnish population-based surveys conducted between 1992 and 2012. During the register-based follow-up until 2020, there were 2439 fatal and non-fatal incident CHD cases. The data were analyzed using linear and Cox regression models. Divorced and cohabiting men and women had a higher genetic risk of CHD than married individuals, but the difference was very small (0.023-0.058 standard deviation of PGS-CHD, p-values 0.011-0.429). Both marital status and PGS-CHD were associated with CHD incidence, but the associations were largely independent. Adjusting for behavioral and metabolic risk factors for CHD explained part of these associations (11-20%). No interaction was found between marital status and PGS-CHD for CHD incidence. We showed minor differences between the marital status categories in PGS-CHD and demonstrated that marital status and genetic liability predicted CHD incidence largely independently. This emphasizes the need to measure multiple risk factors when predicting CHD risk.

Depression increased risk of coronary heart disease: A meta-analysis of prospective cohort studies.

BackgroundDepression, as an independent risk factor, can lead to a substantially increased risk of coronary heart disease (CHD). The overall body of evidence involving depression and CHD is not consistent. Therefore, we performed an update meta-analysis to evaluate the association between depression and the risk of patients with CHD.MethodsStudies were identified through a comprehensive literature search of the PubMed, Embase, and the Cochrane Library database from its inception to 28 September 2021 for titles/abstracts with restricted to English language articles. The literature was screened according to the inclusion and exclusion criteria. Along with data extraction, we evaluated the quality of eligible studies using the Newcastle-Ottawa Scale (NOS). The primary outcome was fatal or non-fatal CHD. We calculated relative risk (RR) with 95% confidence intervals (CIs) using a random-effects models. The protocol was registered in the PROSPERO registration (registration number CRD42021271259).ResultsFrom 9,151 records, we included 26 prospective cohort studies published from 1998 to 2018, consisting of 402,597 patients. Either in depression-exposured group or non-depression-exposured group, the mean age of all participants ranged from 18 to 99 years. Moreover, the NOS scores of these studies are eventually indicated that the quality of these eligible studies was reliable. In general, the pooled results showed that patients with depression had a higher risk of CHD compared to patients without depression (RR = 1.21, 95% CI: 1.14–1.29). Additionally, the funnel plot appeared to be asymmetry, indicating there existing publication bias for the pooled results between depression and CHD. A sensitivity analysis was used to assess the stability of the relationship between depression and CHD that indicating the results robust (RR = 1.15, 95% CI: 1.09–1.21).ConclusionDepression may increase risk of CHD. Future studies on the share pathogenic mechanisms of both depression and CHD may develop novel therapies.