Coronary Heart Disease Outcomes Research Articles

A Proteomics-Based Approach for Prediction of Different Cardiovascular Diseases and Dementia.

Many studies have explored whether individual plasma protein biomarkers improve cardiovascular disease risk prediction. We sought to investigate the use of a plasma proteomics-based approach in predicting different cardiovascular outcomes. Among 51 859 UK Biobank participants (mean age, 56.7 years; 45.5% male) without cardiovascular disease and with proteomics measurements, we examined the primary composite outcome of fatal and nonfatal coronary heart disease, stroke, or heart failure (major adverse cardiovascular events), as well as additional secondary cardiovascular outcomes. An exposome-wide association study was conducted using relative protein concentrations, adjusted for a range of classic, demographic, and lifestyle risk factors. A prediction model using only age, sex, and protein markers (protein model) was developed using a least absolute shrinkage and selection operator-regularized approach (derivation: 80% of cohort) and validated using split-sample testing (20% of cohort). Their performance was assessed by comparing calibration, net reclassification index, and c statistic with the PREVENT (Predicting Risk of CVD Events) risk score. Over a median 13.6 years of follow-up, 4857 participants experienced first major adverse cardiovascular events. After adjustment, the proteins most strongly associated with major adverse cardiovascular events included NT-proBNP (N-terminal pro B-type natriuretic peptide; hazard ratio [HR], 1.68 per SD increase), proADM (pro-adrenomedullin; HR, 1.60), GDF-15 (growth differentiation factor-15; HR, 1.47), WFDC2 (WAP four-disulfide core domain protein 2; HR, 1.46), and IGFBP4 (insulin-like growth factor-binding protein 4; HR, 1.41). In total, 222 separate proteins were predictors of all outcomes of interest in the protein model, and 86 were selected for the primary outcome specifically. In the validation cohort, compared with the PREVENT risk factor model, the protein model improved calibration, net reclassification (net reclassification index +0.09), and c statistic for major adverse cardiovascular events (+0.051). The protein model also improved the prediction of other outcomes, including ASCVD (c statistic +0.035), myocardial infarction (+0.023), stroke (+0.024), aortic stenosis (+0.015), heart failure (+0.060), abdominal aortic aneurysm (+0.024), and dementia (+0.068). Measurement of targeted protein biomarkers produced superior prediction of aggregated and disaggregated cardiovascular events. This study represents an important proof of concept for the application of targeted proteomics in predicting a range of cardiovascular outcomes.

Prevalence and predictors of coronary heart disease among individuals with and without obesity in North Dakota.

Coronary heart disease (CHD) is the most common cardiovascular disease in the United States and heart disease is the leading cause of death in North Dakota. Although obesity is a major risk factor for CHD, some studies have reported an inverse relationship between body mass index (BMI) and CHD outcomes. Understanding the epidemiology of CHD among individuals with and without obesity is essential to guide health planning. Therefore, the objectives of this study were to estimate the prevalence and identify predictors of CHD among North Dakota adults with and without obesity. Behavioral Risk Factor Surveillance System data from 2017 to 2021 were provided by the North Dakota Department of Health and Human Services. Weighted prevalence estimates and 95% confidence intervals (CIs) were computed for CHD and potential risk factors among respondents with and without obesity (BMI ≥30 kg/m2). Multivariable logistic regression was used to identify significant predictors of CHD in both groups. A total of 17,092 respondents were included in the study. Respondents with obesity had a higher prevalence of CHD (4.7%, 95% CI: 4.2-5.4) than those without obesity (3.0%, 95% CI: 2.7-3.4). Predictors of CHD among both groups included age, sex, self-reported general health, high blood pressure, high cholesterol, chronic obstructive pulmonary disease, and diabetes. Having a personal doctor (Odds Ratio [OR] = 1.91, 95% CI: 1.13-3.23) and arthritis (OR = 1.72, 95% CI: 1.34-2.22) were significant predictors of CHD among respondents without obesity, but not among those without obesity. While the prevalence of CHD was significantly higher among adults with obesity compared to those without obesity, the findings of the stratified analysis indicated that predictors of the condition tended to be similar for the two groups. This study provides useful information to guide health planning and control programs that aim to reduce the burden of CHD in North Dakota.

Ultra-processed food consumption and risk of coronary heart diseases: UK Whitehall II cohort study

Abstract In recent decades, ultra-processed foods (UPFs) intake has increased drastically, sparking concerns about their potential impact on cardiometabolic diseases. However, large-scale cohort studies tracking UPF consumption at multiple time points remain limited. This study explores the prospective association between repeated measures of UPF intake and the risk of coronary heart disease (CHD), along with its secondary endpoints, within the UK Whitehall II study. The analytical sample tracked 7,138 midlife British participants without CHD from baseline. UPF consumption was measured using validated food frequency questionnaire (127 items) and classified by the NOVA system during three phases: 1991/1994 (phase 3), 1997/1999 (phase 5), and 2002/2003 (phase 7). This study assessed the onset of CHD and its secondary endpoints, including CHD and all-cause mortality, through medical exams and hospital records up to 2016 and 2021, respectively. Cox proportional hazards regression models adjusted for socio-demographics, lifestyle factors and total energy intake were used to explore the prospective association between cumulative average UPF intake (in quintiles) and CHD outcomes. During a median follow-up of 13 and 19 years, 589 cases and 1,314 deaths were documented. In multivariable adjusted cox models, the highest UPF consumption quintile versus the lowest quintile was associated with higher CHD incidence [HR:1.26; 95% Confidence Interval (CI): 1.02-1.55; p = 0.03]. Additional adjustment of total energy intake increased the CHD risk by 28% [HR:1.28; 95% CI: 1.03-1.58; p = 0.02]. No significant relationships were found between cumulative average UPF intake and CHD or all-cause mortality. In UK midlife adults, higher UPF intake is prospective associated with increased CHD risk. Although additional research is warranted, these findings emphasize the importance of public awareness and food policy interventions to reduce UPF intake for alleviating the population burden of CVD. Key messages • Our study suggests the need for increased efforts to implement population wide strategies on regulating food processing, such as taxation and front of package warning labelling of UPF. • Our study emphasizes UPF’s role in cardiovascular prevention, highlighting the need for nutrition counseling on UPF consumption for those at risk of CVD.

Development and external validation of a risk prediction model for depression in patients with coronary heart disease

BackgroundDepression is an independent risk factor for adverse outcomes of coronary heart disease (CHD). This study aimed to develop a depression risk prediction model for CHD patients. MethodsThis study utilized data from the National Health and Nutrition Examination Survey (NHANES). In the training set, reference literature, logistic regression, LASSO regression, optimal subset algorithm, and machine learning random forest algorithm were employed to screen prediction variables, respectively. The optimal prediction model was selected based on the C-index, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI). A nomogram for the optimal prediction model was constructed. 3 external validations were performed. ResultsThe training set comprised 1375 participants, with a depressive symptoms prevalence of 15.2 %. The optimal prediction model was constructed using predictors obtained from optimal subsets algorithm (C-index = 0.774, sensitivity = 0.751, specificity = 0.685). The model includes age, gender, education, marriage, diabetes, tobacco use, antihypertensive drugs, high-density lipoprotein cholesterol (HDLC), and aspartate aminotransferase (AST). The model demonstrated consistent discrimination ability, accuracy, and clinical utility across the 3 external validations. LimitationsThe applicable population of the model is CHD patients. And the clinical benefits of interventions based on the prediction results are still unknown. ConclusionWe developed a depression risk prediction model for CHD patients, which was presented in the form of a nomogram for clinical application.

Diagnostic and prognostic value of serum Cys-C, retinol-binding protein, and ischemia-modified albumin in patients with coronary heart disease: A diagnostic accuracy study.

The use of 3 biomarkers - cystatin-C (Cys-C), retinol-binding protein (RBP), and ischemia-modified albumin (IMA) - for the clinical classification and outcome of coronary heart disease (CHD) has not been adequately evaluated. We explored the serum levels of these 3 markers and evaluated their diagnostic and prognostic values in patients with CHD. This retrospective case-control study, conducted between June 2017 and June 2018, included 201 patients with CHD hospitalized at the Henan Provincial People's Hospital and 127 healthy individuals from Henan Provincial People's Hospital as controls. Cys-C, RBP, IMA levels, and other laboratory parameters in the 2 groups were determined, and patient outcomes were analyzed. Cys-C, RBP, and IMA levels were higher in the case group than in the control group (P < .05). Logistic regression analysis confirmed that these 3 biomarkers were independent risk factors for CHD. Each indicator has clinical significance in the diagnosis and prognosis of CHD, with RBP being the most significant. The AUC value for CHD detection using a combination of the 3 indicators was 0.783, and the sensitivity and specificity values were 78% and 74.6%, respectively. Simultaneous detection of Cys-C, RBP, and IMA could be an optimal method for early diagnosis and prognosis of CHD.

Television Viewing from Young Adulthood to Middle Age and Premature Cardiovascular Disease Events: A Prospective Cohort Study

BackgroundPrevious literature has explored the relationship between television viewing and cardiovascular disease (CVD) in adults; however, there remains a paucity of longitudinal data describing how young adult television viewing relates to premature CVD events.ObjectiveTo ascertain the relationship between level and annualized changes in television viewing from young adulthood to middle age and the incidence of premature CVD events before age 60.DesignThe Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective community-based cohort with over 30 years of follow-up (1985–present).ParticipantsBlack and White men and women who were 18–30 years old at baseline (1985–1986).Main MeasuresIndependent variables: Individualized television viewing trajectories were developed using linear mixed models. Dependent variables: Fatal and nonfatal coronary heart disease (CHD), heart failure, and stroke outcomes were analyzed separately and as a combined CVD event outcome.Key ResultsAmong 4318 included participants, every 1-h increase in daily hours of television viewing at age 23 was associated with higher odds of incident CHD (adjusted odds ratio [AOR] 1.26, 95% confidence interval [CI] 1.06–1.49) and incident CVD events (AOR 1.16, 95% CI 1.03–1.32). Each additional hour of daily television viewing annually was associated with higher annual odds of CHD incidence (AOR 1.55, 95% CI 1.06–2.25), stroke incidence (AOR 1.58, 95% CI 1.02–2.46), and CVD incidence (AOR 1.32, 95% CI 1.03–1.69). Race and sex modified the association between television viewing level at age 23 and CHD, heart failure, and stroke, with White men most consistently having significant associations.ConclusionsIn this prospective cohort study, greater television viewing in young adulthood and annual increases in television viewing across midlife were associated with incident premature CVD events, particularly CHD. Young adulthood as well as behaviors across midlife may be important periods to promote healthy television viewing behavior patterns.

Growth differentiation factor-15 predicts all-cause death and major adverse cardiovascular events in patients with coronary heart disease: a prospective cohort study.

The prognostic value of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in coronary heart disease (CHD) patients remains limited. Our study examines the association between GDF-15 and adverse outcomes over an extended period in CHD patients and firstly assesses the incremental prognostic effect of incorporating GDF-15 into the Framingham risk score (FRS)-based model. This single-center prospective cohort study included 3,321 patients with CHD categorized into 2,479 acute coronary syndrome (ACS) (74.6%) and 842 non-ACS (25.4%) groups. The median age was 61.0 years (range: 53.0-70.0), and 917 (27.6%) were females. Mortality and major adverse cardiovascular events (MACEs) included cardiovascular mortality, myocardial infarction (MI), stroke, and heart failure (HF) (inclusive of HF episodes requiring outpatient treatment and/or hospital admission). Cox regression models assessed the associations between GDF-15 and the incidence of all-cause mortality and MACEs. Patients were stratified into three groups based on GDF-15 levels: the first tertile group (< 1,370 ng/L), the second tertile group (1,370-2,556 ng/L), and the third tertile group (> 2,556 ng/L). The C-index, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA) were used to assess incremental value. Over a median 9.4-year follow-up, 759 patients (22.9%) died, and 1,291 (38.9%) experienced MACEs. The multivariate Cox model indicated that GDF-15 was significantly associated with all-cause mortality (per ln unit increase, HR = 1.49, 95% CI: 1.36-1.64) and MACEs (per ln unit increase, HR = 1.29, 95% CI: 1.20-1.38). These associations persisted when GDF-15 was analyzed as an ordinal variable (p for trend < 0.05). Subgroup analysis of ACS and non-ACS for the components of MACEs separately showed a significant association between GDF-15 and both cardiovascular mortality and HF, but no association was observed between GDF-15 and MI /stroke in both ACS and non-ACS patients. The addition of GDF-15 to the FRS-based model enhanced the discrimination for both all-cause mortality (∆ C-index = 0.009, 95% CI: 0.005-0.014; IDI = 0.030, 95% CI: 0.015-0.047; continuous NRI = 0.631, 95% CI: 0.569-0.652) and MACEs (∆ C-index = 0.009, 95% CI: 0.006-0.012; IDI = 0.026, 95% CI: 0.009-0.042; continuous NRI = 0.593, 95% CI: 0.478-0.682). DCA suggested that incorporating GDF-15 into the FRS-based model demonstrated higher net benefits compared to FRS-based models alone (All-cause mortality: FRS-based model: area under the curve of DCA (AUDC) = 0.0903, FRS-based model + GDF-15: AUDC = 0.0908; MACEs: FRS-based model: AUDC = 0.1806, FRS-based model + GDF-15: AUDC = 0.1833). GDF-15 significantly associates with the long-term prognosis of all-cause mortality and MACEs in CHD patients and significantly improves the prognostic accuracy of the FRS-based model for both outcomes.

Occupational Physical Activity and Fitness in Predicting Cardiovascular Mortality among European Cohorts of Middle-Aged Men: A 60-Year Follow-Up in the Seven Countries Study

Aim and Background: To determine whether occupational physical activity (OPA) and physical fitness (Fitscore) predict cardiovascular disease (CVD) mortality and its components. Methods: Among middle-aged men (N = 5482) of seven cohorts of the Seven Countries Study (SCS), several baseline risk factors were measured, and there was a follow-up for 60 years until virtual extinction. OPA was estimated from the type of work while Fitscore was derived from linear combinations of levels of arm circumference, heart rate and vital capacity computed as a factor score by principal component analysis. The predictive adjusted power of these characteristics was obtained by Cox models for coronary heart disease (CHD), heart diseases of uncertain etiology (HDUE), stroke and CVD outcomes. Results: Single levels of the three indicators of fitness were highly related to the three levels of OPA and Fitscore. High levels of both OPA and Fitscore forced into the same models were associated with lower CVD, CHD, HDUE and stroke mortality. When assessed concomitantly in the same models, hazard ratios (high versus low) for 60-year CVD mortality were 0.88 (OPA: 95% CI: 0.78–0.99) and 0.68 (Fitscore 95% CI: 0.61–0.75), and the predictive power of Fitscore outperformed that of OPA for CHD, HDUE and stroke outcomes. Similar results were obtained in individual outcome models in the presence of risk factors. Segregating the first 30 from the second 30 years of follow-up indicated that people dying earlier had lower arm circumference and vital capacity, whereas heart rate was higher for CVD and most of its major components (all p &lt; 0.0001). Conclusions: OPA was well related to the indicators of fitness involving muscular mass, cardio-circulatory and respiratory functions, thus adding predictive power for CVD events. The Fitscore derived from the above indicators represents another powerful long-term predictor of CHD, HDUE and stroke mortality.

The burden of premature coronary heart disease among adults with low socioeconomic status in Argentina: A modeling study.

The well-established inverse relationship between socioeconomic status (SES) and risk of developing coronary heart disease (CHD) cannot be explained solely by differences in traditional risk factors. To model the role SES plays in the burden of premature CHD in Argentina. We used the Cardiovascular Disease Policy Model-Argentina to project incident CHD events and mortality in low and high-SES Argentinean adults 35 to 64 years of age from 2015 to 2024. Using data from the 2018 National Risk Factor Survey, we defined low SES as not finishing high-school and/or reporting a household income in quintiles 1 or 2. We designed simulations to apportion CHD outcomes in low SES adults to: (1) differences in the prevalence of traditional risk factors between low and high SES adults; (2) nontraditional risk associated with low SES status; (3) preventable events if risk factors were improved to ideal levels; and (4) underlying age- and sex-based risk. 56% of Argentina´s 35- to 64-year-old population has low SES. Both high and low SES groups have poor control of traditional risk factors. Compared with high SES population, low SES population had nearly 2-fold higher rates of incident CHD and CHD deaths per 10 000 person-years (incident CHD: men 80.8 [95%CI 76.6-84.9] vs 42.9 [95%CI 37.4-48.1], women 39.0 [95%CI 36.-41.2] vs 18.6 [95%CI 16.3-20.9]; CHD deaths: men 10.0 [95%CI 9.5-10.5] vs 6.0 [95%CI 5.6-6.4], women 3.2 [95%CI 3.0-3.4] vs 1.8 [95%CI 1.7-1.9]). Nontraditional low SES risk accounts for 73.5% and 70.4% of the event rate gap between SES levels for incident CHD and CHD mortality rates, respectively. CHD prevention policies in Argentina should address contextual aspects linked to SES, such as access to education or healthcare, and should also aim to implement known clinical strategies to achieve better control of CHD risk factors in all socioeconomic levels.

Association of heavy menstrual bleeding with cardiovascular disease in US female hospitalizations

BackgroundHeavy menstrual bleeding (HMB) is a common menstrual disorder associated with multiple risk factors of cardiovascular disease (CVD) in women. In addition, HMB is often present with irregular menstruation (IM) which is a risk factor for CVD outcomes. However, the relationship between HMB and CVD outcomes is unexplored in the presence or absence of IM. We determined the association of HMB with multiple CVD outcomes using a nationally representative sample of female hospitalizations in the US.MethodsAll hospitalizations of females with HMB diagnosis and normal menstrual cycles from ages of 18 to 70 years were extracted from the National Inpatient Sample Database, 2017. The HMB was defined using the International Classification of Diseases (ICD)-10 for excessive and frequent menstruation bleeding and included any current or history of HMB diagnosis. Outcomes including major adverse cardiovascular events (MACE), coronary heart disease (CHD), stroke, heart failure (HF), atrial fibrillation (AF) or arrhythmia, myocardial infarction (MI), and diabetes (DM) were defined using ICD-10 codes. Adjusted logistic regression and prosperity scores-matched logistic regression analyses were conducted to summarize adjusted associations with an odds ratio (OR) and a 95% confidence interval (CI).ResultsAmong 2,430,851 hospitalizations, HMB was observed in 7762 (0.68%) females with age ≤ 40 years and 11,164 (0.86%) females with age > 40 years. Among hospitalizations with age ≤ 40 years, HMB was significantly associated with increased odds of CVD outcomes including MACE (OR = 1.61; 95% CI: 1.25, 2.08), CHD (OR = 1.72; 95% CI: 1.10, 2.71), stroke (OR = 1.95; 95% CI: 1.12, 3.40), HF (OR = 1.53; 95% CI: 1.15, 2.03), and AF/arrhythmia (OR = 1.84; 95% CI: 1.34, 2.54). These associations were confirmed in multiple sensitivity analyses. In contrast, HMB was not robustly associated with CVD events among hospitalizations of women with age > 40 years. HMB without IM was strongly associated with DM, HF, AF, and MACE outcomes while HMB with IM was strongly associated with CHD and AF outcomes in hospitalizations of young women.ConclusionsHMB is associated with CVD events among US hospitalizations of young women. A routine investigation and screening of menstrual disorders, especially HMB, is useful for CVD risk stratification and management in young women.

Association of Lipoprotein (a) and Standard Modifiable Cardiovascular Risk Factors With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry.

Lipoprotein (a) [Lp(a)] is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. We aimed to evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). This retrospective study used the Mass General Brigham Lp(a) Registry, which included patients aged ≥18 years with an Lp(a) measurement between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease. Diabetes, dyslipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as >90th percentile, and low Lp(a) was defined as <50th percentile. The primary outcome was fatal or nonfatal AMI. A combination of natural language processing algorithms, International Classification of Diseases (ICD) codes, and laboratory data was used to identify the outcome and covariates. A total of 6238 patients met the eligibility criteria. The median age was 54 (interquartile range, 43-65) years, and 45% were women. Overall, 23.7% had no SMuRFs, and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (interquartile range, 4.2-12.8) years, the incidence of AMI increased gradually, with higher number of SMuRFs among patients with high (log-rank P=0.031) and low Lp(a) (log-rank P<0.001). Across all SMuRF subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) versus low Lp(a). The risk of high Lp(a) was similar to having 2 SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained significantly associated with the primary outcome (hazard ratio, 2.9 [95% CI, 2.0-4.3]; P<0.001). Among patients with no prior atherosclerotic cardiovascular disease, high Lp(a) is associated with significantly higher risk for first AMI regardless of the number of SMuRFs.

The influence of thyroid status on long-term complications after stenting in patients with acute coronary syndrome without ST-segment elevation.

Backround. It is known that both subclinical hypothyroidism (SHT) and subclinical thyrotoxicosis (STT) can influence the outcome of coronary heart disease. The feasibility of routinely determining thyroid status in patients without obvious signs of thyroid dysfunction with acute coronary syndrome without ST-segment elevation (NSTEACS) to assess the effect on the status of implanted stents has not been determined.Objective. To evaluate the effect of subclinical hypothyroidism and subclinical thyrotoxicosis on lumen loss and the degree of endothelialization of drug-eluting stents after stenting for NSTE-ACS. Design and methods. The study included 173 patients who were urgently stented for NSTE-ACS, and who subsequently underwent repeat coronary angiography within a year on a planned or emergency basis with a targeted assessment of the condition of the installed stents. In 40 patients with everolimus-eluting stents, the condition of the coronary arteries was assessed 6.3 + 0.3 months after stenting using optical coherence tomography (OCT). All patients included in the study had their thyroid status assessed.Results. SHT was detected in 8 (21.6 %) patients with loss of lumen in the stent area and in 26 (19.1 %) patients without loss of lumen, p = 0.73. STT was detected in 2 (5.4 %) and 3 (2.2 %) patients, respectively, p = 0.30. A prognostic analysis performed by logistic regression with forced inclusion as predictors of lumen loss identified the parameters Syntax Score I, stent diameter, and the number of affected coronary arteries. No effect of thyroid status on lumen loss was found. In patients with subclinical hypothyroidism, OCT data revealed insufficient endothelialization of everolimus-eluting stents 6 months after stenting for NSTE-ACS. The percentage of uncovered stent struts depended on TSH levels (r = 0.42, p = 0.007). The higher the TSH level, the higher the healing index and the worse the stent endothelialization (r = 0.37, p = 0.016). Conclusion. Thus, routine determination of thyroid status indicators in patients with NSTE-ACS in order to identify subclinical thyroid dysfunction does not provide significant prognostic information regarding the risk of lumen loss of implanted stents. Considering the potential risk of thrombotic complications associated with insufficient endothelialization of everolimus-eluting stents in the presence of subclinical hypothyroidism, it seems advisable to identify it when deciding on de-escalation of antithrombotic therapy. The question remains open about the need to correct the parameters of subclinical thyroid dysfunction in order to modify the prognosis.

Predicted visceral adiposity index in relation to risk of coronary heart disease and all-cause mortality: insights from NHANES.

The Visceral Adiposity Index (VAI) is a straightforward and gender-specific marker that combines anthropometric measurements with lipid profiles. The objective of this study was to evaluate the relationship between VAI and coronary heart disease (CHD). The study examined data collected from adults during the NHANES 1999-2018 cycle. The analyses were weighted, and multivariable logistic regression models were employed to investigate the association between VAI and CHD. Additionally, subgroup analyses stratified by age were conducted. To evaluate the impact of VAI levels on survival outcomes, the study utilized the Kaplan-Meier method and performed the log-rank test to evaluate the survival outcome of participants with different VAI levels. The study findings revealed a significant association between VAI and CHD, indicating a non-linear relationship where an increase in VAI was associated with an elevated risk of CHD. High levels of VAI were linked to an increased prevalence of CHD (Q4 vs Q1, OR 1.50, 95% CI 1.12-2.01, P=0.01). Additionally, higher levels of VAI were associated with a poorer overall prognosis in terms of survival outcomes. There were no statistically significant differences in survival outcomes among the population with CHD. The results of this study highlighted a significant association between VAI and CHD, with a non-linear relationship observed. High VAI levels were associated with an increased risk of CHD and poor survival outcomes, emphasizing the importance of understanding and managing this risk factor, particularly in older age groups.

Vitamin D Deficiency, Inflammation, and Diminished Endogenous Regenerative Capacity in Coronary Heart Disease

BackgroundVitamin D deficiency (VDD) is associated with coronary heart disease (CHD) and poor outcomes, but supplementation does not improve prognosis. VDD has been implicated in and may promote greater risk through inflammation and impaired progenitor cell function. ObjectivesThe authors examined VDD, high-sensitivity C-reactive protein (hsCRP), circulating progenitor cell (CPC) counts, and outcomes in patients with CHD. They hypothesized that the higher risk with VDD is mediated by inflammation and impaired regenerative capacity. MethodsA total of 5,452 individuals with CHD in the Emory Cardiovascular Biobank had measurement of 25-hydroxyvitamin D, subsets of whom had hsCRP measurements and CPCs estimated as CD34-expressing mononuclear cell counts. Findings were validated in an independent cohort. 25-hydroxyvitamin D <20 ng/mL was considered VDD. Cox and Fine-Gray models determined associations between marker levels and: 1) all-cause mortality; 2) cardiovascular mortality; and 3) major adverse cardiovascular events, a composite of adverse CHD outcomes. ResultsVDD (43.6% of individuals) was associated with higher adjusted cardiovascular mortality (HR: 1.57, 95% CI: 1.09-2.28). There were significant interactions between VDD and hsCRP and CPC counts in predicting cardiovascular mortality. Individuals with both VDD and elevated hsCRP had the greatest risk (HR: 2.82, 95% CI: 2.16-3.67). Only individuals with both VDD and low CPC counts were at high risk (HR: 2.25, 95% CI: 1.46-3.46). These findings were reproduced in the validation cohort. ConclusionsVDD predicts adverse outcomes in CHD. Those with VDD, inflammation and/or diminished regenerative capacity are at a significantly greater risk of cardiovascular mortality. Whether targeted supplementation in these high-risk groups improves risk warrants further study.

Bridging the Gap: Assessing Public Awareness of Psychological Factors Influencing Coronary Heart Disease Outcomes in Makkah, Saudi Arabia.

Coronary heart disease (CHD) is a leading cause of death globally, and psychological factors are increasingly recognized as playing a significant role in its prognosis. This study aimed to assess the public's awareness of psychological factors affecting CHD prognosis in Makkah, Saudi Arabia. A cross-sectional online survey was conducted with 385 participants recruited randomly. The survey collected data on sociodemographic characteristics and respondents' opinions regarding the effects of negative and positive psychological factors on CHD prognosis, including differences based on age and gender. The majority of participants (96.9%) agreed that negative psychological factors, such as stress (80.5%), anxiety (76.9%), and depression (67.5%), influence CHD prognosis. Positive factors like satisfaction (79.2%) and happiness (75.6%) were also recognized as influential. Participants aged 30-50 and over 50 demonstrated higher awareness of the link between psychological factors and CHD compared to those under 30. No significant gender differences were observed in knowledge levels. This study suggests that the Makkah population has a good understanding of the impact of psychological factors on CHD prognosis. Integrating this knowledge into comprehensive health education programs could benefit CHD prevention, management, and prognosis in the region. Future research should explore broader populations and utilize diverse methodologies to refine and generalize these findings.

Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses

Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks. Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality. Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically predicted 25(OH)D with coronary heart disease (odds ratio [OR] per 10 nmol/L higher genetically-predicted 25(OH)D concentration 0·98, 95% CI 0·95-1·01), stroke (1·01, [0·97-1·05]), or all-cause mortality (0·99, 0·95-1·02). Null findings were also observed in genetic analyses for cause-specific mortality outcomes, and in stratified genetic analyses for all outcomes at all observed levels of 25(OH)D concentrations. Stratified Mendelian randomisation analyses suggest a lack of causal relationship for 25(OH)D concentrations with both cardiovascular and mortality outcomes for individuals at all levels of 25(OH)D. Our findings suggest that substantial reductions in mortality and cardiovascular morbidity due to long-term low-dose vitamin D supplementation are unlikely even if targeted at individuals with low vitamin D status. British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer.

Probiotic or probiotics add supplement interferes with coronary heart disease: A meta‐analysis of randomized controlled trials

AbstractThe effect of probiotics or probiotics add supplement on improving clinical outcomes of coronary heart disease (CHD) has produced conflicting results. This meta‐analysis aimed to evaluate the effect of probiotics supplementation or probiotics add supplement on blood glucose, lipids, blood pressure, inflammatory reaction, oxidative stress, and depress score in patients with CHD. Search PubMed, Web of Science, Embase, and Cochrane Library databases for relevant studies from February 1974 to September 2022. Pooled results were calculated using a fixed‐effect model to assess the effects of probiotics supplementation or probiotics add supplement in CHD. A total of 10 randomized controlled trials were included in this analysis. Overall, probiotics add supplement showed statistically significant reductions in triglycerides, insulin, homeostasis model of assessment‐insulin resistance (HOMA‐IR), high‐sensitivity C‐reactive protein (hs‐CRP), interleukin‐6, and Beck Depression Inventory (BDI) score, compared to the control group (standardized mean difference [SMD]: −0.35 mg/dL; SMD: −0.64 μIU/mL; SMD: −0.90; SMD: −0.57 mg/dL; SMD: −0.60 pg/mL; SMD: −0.52; respectively), but high‐density lipoprotein cholesterol, nitric oxide (NO) were statistically significant increased (SMD: 0.45 mg/dL; SMD: 1.01 μmol/L; respectively). Then, probiotics showed statistically significant reductions in hs‐CRP, and Beck Anxiety Inventory score BDI (SMD: −0.50 mg/dL; SMD: −0.67; SMD: −0.41; respectively). Moreover, subgroup analyses revealed that low‐density lipoprotein cholesterol, HOMA‐IR, diastolic blood pressure, NO indicators may influence by patients age, body mass index (BMI), duration of the supplement and dose of probiotics. Our analysis showed that probiotics supplementation or probiotics add supplement improved glucolipid metabolism, inflammatory response, oxidative stress, and depressive disorder, particularly the patients who ages ≥60, baseline BMI &lt;30 kg/m2, duration of intervention more than 12 weeks and the dose of probiotics ≥8 × 109 CFU/day. The PROSPERO ID was CRD42022357385.

Identification of genetic loci jointly influencing COVID-19 and coronary heart diseases

BackgroundComorbidities of coronavirus disease 2019 (COVID-19)/coronary heart disease (CHD) pose great threats to disease outcomes, yet little is known about their shared pathology. The study aimed to examine whether comorbidities of COVID-19/CHD involved shared genetic pathology, as well as to clarify the shared genetic variants predisposing risks common to COVID-19 severity and CHD risks.MethodsBy leveraging publicly available summary statistics, we assessed the genetically determined causality between COVID-19 and CHD with bidirectional Mendelian randomization. To further quantify the causality contributed by shared genetic variants, we interrogated their genetic correlation with the linkage disequilibrium score regression method. Bayesian colocalization analysis coupled with conditional/conjunctional false discovery rate analysis was applied to decipher the shared causal single nucleotide polymorphisms (SNPs).FindingsBriefly, we observed that the incident CHD risks post COVID-19 infection were partially determined by shared genetic variants. The shared genetic variants contributed to the causality at a proportion of 0.18 (95% CI 0.18–0.19) to 0.23 (95% CI 0.23–0.24). The SNP (rs10490770) located near LZTFL1 suggested direct causality (SNPs → COVID-19 → CHD), and SNPs in ABO (rs579459, rs495828), ILRUN(rs2744961), and CACFD1(rs4962153, rs3094379) may simultaneously influence COVID-19 severity and CHD risks.InterpretationFive SNPs located near LZTFL1 (rs10490770), ABO (rs579459, rs495828), ILRUN (rs2744961), and CACFD1 (rs4962153, rs3094379) may simultaneously influence their risks. The current study suggested that there may be shared mechanisms predisposing to both COVID-19 severity and CHD risks. Genetic predisposition to COVID-19 is a causal risk factor for CHD, supporting that reducing the COVID-19 infection risk or alleviating COVID-19 severity among those with specific genotypes might reduce their subsequent CHD adverse outcomes. Meanwhile, the shared genetic variants identified may be of clinical implications for identifying the target population who are more vulnerable to adverse CHD outcomes post COVID-19 and may also advance treatments of ‘Long COVID-19.’

Abstract 16773: The Association of Lp(a) and Standard Modifiable Cardiovascular Risk Factors (SMuRFs) With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry

Introduction: Lp(a) is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. However, there is a paucity of data regarding the risk of elevated Lp(a) in relation to other cardiovascular risk factors. Objective: To evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). Methods: This retrospective study utilized the MGB Lp(a) Registry which included patients ≥18 years with an Lp(a) measurement between 2000-2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease (ASCVD). Diabetes mellitus, hyperlipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as &gt;90 th percentile and low Lp(a) as &lt;50 th . The primary outcome was fatal or non-fatal AMI. A combination of natural language processing algorithms, ICD codes, and laboratory data were employed to identify the outcome and covariates. Results: A total of 6,238 patients met the eligibility criteria. The median age was 54 (IQR: 43-65) years and 45% were women. Overall, 23.7% had no SMuRFs and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (IQR: 4.2-12.8) years, the incidence of AMI increased in a stepwise manner with higher number of SMuRFs among patients with high (logrank p=0.031) and low Lp(a) (logrank p&lt;0.001). Across all SMuRFs subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) vs. low Lp(a) (Figure 1). The risk of high Lp(a) was higher than the risk imposed by any of the SMuRFs and was similar to having two SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained independently associated with the primary outcome (HR=2.9 (95%CI=2.0-4.3), p&lt;0.001). Conclusions: Among patients with no prior ASCVD, high Lp(a) is independently associated with increased risk for first AMI regardless of the number of SMuRFs.

Metabolic disorders mediate the relation of miscarriage with cardiovascular diseases.

The extent to which the contribution of pregnancy loss to cardiovascular diseases (CVDs) can be explained by metabolic disorders is poorly elucidated but holds insights for reducing long-term cardiovascular risk. The aim of this study is to investigate the mediating effects of hypertension, diabetes mellitus (DM), and lipoprotein metabolism disorders on the association of miscarriage and stillbirth with coronary heart disease (CHD), stroke, heart failure, atrial fibrillation, and composite outcomes. A total of 163 283 ever-gravid women (age 55.3 ± 7.9 years) from the UK Biobank cohort without established metabolic disorders and CVDs were included and followed from 2007 to 2010 baseline until December 2020. Causal mediation analyses were used to estimate the proportion mediated. Hypertension mediated 11.1% (95% confidence interval, 3.7-18.5%) of the association between a history of miscarriage and incident CHD. Approximately, 9.5% (4.1-14.8%) of the effect of recurrent miscarriages on incident CHD was via hypertension, 8.4% (2.5-14.3%) of the effect was via lipoprotein metabolism disorders, 1.7% (0.5-2.9%) of the effect was via DM, and 10.7% (0.2-21.1%) of the effect of recurrent miscarriages on incident stroke was via hypertension. Hypertension mediated the largest proportion of effect for the atherosclerotic cardiovascular event (15.5% for a history of miscarriage and 9.4% for recurrent miscarriages), followed by lipoprotein metabolism disorders and DM. Hypertension, DM, and lipoprotein metabolism disorders mediated the association between miscarriage and various cardiovascular outcomes in later life. In particular, hypertension mediated a large proportion of the relationship between miscarriage and atherosclerotic CVD.