Cardiovascular Disease Risk Research Articles

Association of P2Y12 inhibitor pretreatment strategy with short and long term ischemic and bleeding outcomes in NSTE-ACS patients

Abstract Background and Aims Oral P2Y12 inhibitors form the basis of both short and long term antiplatelet therapy in NSTE-ACS patients. While reducing thrombogenic activity and ischemic risk is the basis of routine P2Y12 inhibitor pretreatment in NSTE-ACS patients, timing of treatment became controversial as a result of studies showing routine P2Y12 inhibitor pretreatment is associated with an increased risk of bleeding. Even though routine pretreatment is no longer recommended in the ESC guidelines, the inadequacies in RCTs combining all treatment modalities have been noted. Our study aims to determine the relationship between P2Y12 inhibitor pretreatment strategy and short and long-term ischemic and bleeding events. Methods The study was designed as a single-center, prospective and observational study. 2602 patients, aged between 18 and 85, diagnosed with NSTE-ACS in accordance with ESC guidelines were included in the study. 2189 patients were administered with P2Y12 inhibitor pretreatment while 413 patients weren't. Demographic data, CVD risk factors, ECG, echocardiography and laboratory findings at the time of admission, interventional procedural details, type of antiplatelet and anticoagulant treatment and application time were recorded. Patients were divided into two groups as pretreatment and no-pretreatment according to the time of administration of P2Y12 inhibitor loading dose. In the no-pretreatment group choice of P2Y12 inhibitor was left to operator in the cath lab before proceeding to PCI. Post-procedural in-hospital and long term follow up (1 year) were obtained through hospital and national registry systems and patient survey. Results In the no-pretreatment group 91.3% of patients underwent coronary angiography and PCI was performed in 51.8%. In patients proceeding to PCI, 58.5% were given clopidogrel and 41.5% were given a potent P2Y12 inhibitor. In the pretreatment group, clopidogrel was the drug of choice in 93.8% of patients. In the pretreatment group, the primary composite endpoint (MACE and bleeding events) were more common during in-hospital follow-up and this difference was due to a significant increase in both BARC class I & II and class III, IV & V bleedings (Table 1). In the long-term follow up, statistically significant difference was only seen in BARC class I & II bleedings in the pretreatment group. There were no difference in MACE rates in neither in-hospital or long-term follow up (Table 2). Also in multivariate regression analysis, pretreatment with a P2Y12 inhibitor was found to be an independent predictor of short term primary composite endpoints and long-term all-cause mortality. Conclusion The results of our study investigating the effects of the P2Y12 inhibitor pretreatment strategy on ischemic and bleeding endpoints in NSTE-ACS patients showed that the pretreatment strategy did not lead to an improvement in MACE rates in in-hospital and long-term follow-up but caused on overall increase in bleeding events.Kaplan-Meier Survival Analysis

Air pollution and cerebrovascular diseases - retrospective analysis of 10,486 cases of acute ischemic stroke requiring intravenous thrombolysis. A report from the EP-PARTICLES study

Abstract Introduction Air pollution (AP) is becoming an increasingly important non-classical CVD risk factor. Recent years have brought us the introduction of new types of AP, such as ‘Polish smog’, rich in particulate matter (PM) and benzo(alpha)pyrene (B(a)P) - thus far overlooked in scientific research. Acute ischemic stroke (AIS) is an increasing healthcare challenge, with the ageing population and associated presence of atrial fibrillation worldwide. Intravenous thrombolysis (IVT), alongside thrombectomy, is the most effective AIS treatment method. Purpose To analyze the impact of AP on AIS requiring IVT incidence. To our knowledge this is the first study of its kind worldwide. Methods The study covered 500 municipalities inhabited by 5.7 million people in Poland in 2011-2020. AIS requiring IVT incidence data [hospitalizations with ICD-10 diagnosis (I63.X) and concomitant ICD-9 procedure (99.101/99.102/99.103)] and AP concentrations (PM2.5 and B(a)P) were obtained from the National Health Fund and Inspectorate for Environmental Protection, respectively. IVT was administered within 4.5 hours from the onset of AIS symptoms, ensuring accuracy in the timing of exposure. Using the GEM-AQ model we calculated AP levels for all 500 municipalities. To analyze the effects of AP we used quasi-Poisson generalized additive models with covariates such as weather conditions, day of the week, bank holidays, and seasonal trends. Results are presented as relative risks (RRs) and 95% confidence intervals (95% CI) per interquartile range increase in AP on the day of exposure (LAG 0) and the following days (LAG 1, etc). Results In the study period, we recorded 96,122 AIS with a slight predominance of females (52.6%) and median age 76 years old (y.o) [IQR 66-83]; 10,486 (10.9%) were treated with IVT (median age 74 y.o. IQR 65-82), females 51.3%. Mortality rates were lower in patients treated with IVT than overall AIS patients (13.3% vs 15.4%, p<0.001). Exposure to B(a)P was associated with the highest increase in AIS requiring IVT incidence on LAG 0 and this effect persisted for up to 3 days after exposure [Figure 1]. In the overall population, an increase in PM2.5 concentration was associated with an increased risk of AIS requiring IVT on LAG 0, LAG 1, and LAG 3 [Figure 1]. AP increased the risk of AIS requiring IVT in both young and older individuals, as well as in women and men. We recorded no differences between the effects of analyzed air pollutants and AIS requiring IVT depending on age and sex [Figure 2]. Conclusions AP acts as a trigger for AIS requiring IVT with a similar impact regardless of sex and age. Patients undergoing IVT are characterized by better survival. Public health changes should consider efforts to decrease levels of air pollutants. Highly polluted areas should have centers with rapid access to AIS treatments and our study could help to identify high risk areas that require adaptations in local infrastructure.Figure 1.Figure 2.

Clinical reality and challenges with familial hypercholesterolemia patients management. 2024 results from the Regional Center for Rare Diseases (RCRD) Registry in Poland

Abstract Background HeFH is one of the most prevalent genetic diseases significantly increasing the risk of CVD events and mortality. Despite new achievements with earlier diagnosis and new effective drugs, most of heFH patients do not achieve LDL-C goal and are still on residual CVD risk. Purpose We aimed to present the most recent data from the regional FH registry in Poland to show the challenges and reality of everyday clinical management with FH patients. Methods The registry is conducted at the RCRD in the 2nd largest, supraregional hospital in Poland. The main inclusion criteria were being phenotypically or genetically diagnosed with FH. Nonadherence was investigated based on detailed interview, monitoring the treatment’s effects and purchasing prescribed medications. For this analysis we investigated only adult FH patients from the registry. Due to small number of cases (n=5), patients treated with inclisiran were not included in this analysis. Results We included 142 consecutive heFH patients at mean age 45,8±14,9 years (min/max 18-75 years; 60% women). Mean BMI was 29.6±5.52 kg/m2, mean baseline TC was 282.9±80 mg/dl (the highest observed was 600 mg/dl), LDL-C 204.2±72.5 mg/dL (the highest observed -762 mg/dl), TG - 151.1±123.4 mg/dl, Lp(a) 37.6±41.5 mg/dl and HDL-C - 52.3±14.2 mg/dl. Most patients were diagnosed with LDLR (72%) or APOB (24%) mutations. High intensity statin therapy was used in 74.3% of patents, ezetimibe (mostly as a part of combination LLT) in 47.2%, and PCSK9 inhibitors in all those that met the reimbursement criteria – 25.6% of FH patients. Non-adherence to statin therapy and ezetimibe in the follow up of 2 years was 27%. In patients treated with statin therapy and ezetimibe mean achieved LDL-C was 153.6±82.82 mg/dl and on triple therapy - 64.5±43.73 mg/dl. Mean achieved LDL-C in the investigated population was 87.9±55.5 mg/dl. LDL-C goal was achieved in 39% of patients – in those treated with triple therapy with PCSK9 inhibitors it was 57.14%, and in those on statins and ezetimibe only 27.1%. Combination therapy of statins and ezetimibe did not significantly change baseline Lp(a) level (p=0.109), but when PCSK9 inhibitors were introduced the mean Lp(a) reduction by 34.2% (p=0.049) was observed. Based on the multivariable regression analysis, the following factors played the most important role for FH patients to be on LDL-C target: DLCN total score (OR 1.21, 95%CI: 1.04-1.40; p=0.013), DLCN category (10.39, 1.43-75.29; p=0.021), ezetimibe use (4.78, 1.15-19.92; p=0.031), and PCSK9 inhibitors use (4.56; 1.40-14.86; p=0.012). Conclusions FH patients in Poland are diagnosed definitely too late (45 years) and most of them are still not on LDL-C goal. Double and especially triple therapy significantly, even 5 times, increase the chance of achieving LDL-C goal, therefore PCSK9 inhibitors should be available for all FH patients, without the limitations existing currently e.g., within B101 drug program in Poland.

Long-term prognostic impact of fasting plasma glucose and myocardial flow reserve beyond other risk factors and heart disease phenotypes

Abstract Background Cardiometabolic risk factors, including high fasting plasma glucose (hFPG), are emerging determinants of residual mortality risk in patients with coronary artery disease (CAD) or heart failure (HF). Coronary microvascular dysfunction, encompassing a broad spectrum of traditional and emerging risk factors, might be a comprehensive risk predictor in these patients. Purpose To assess whether hFPG and global myocardial blood flow (MBF) reserve measured by positron emission tomography (PET), expressing global coronary function, may predict long-term prognosis beyond other risk factors and the presence of obstructive CAD or left ventricular (LV) dysfunction associated with HF. Methods Among 281 consecutive patients undergoing cardiac PET/CT because of stable chest pain or dyspnea we retrospectively collected long-term follow-up data in 103 patients (mean age 61±10 years, 74 males) in whom MBF measurements, coronary angiography and clinical data were available. Disease phenotypes included obstructive CAD (35%), LV dysfunction without obstructive CAD (43%) or none (22%). Results The mean age was 61±10 years (74 males, 72%). Among CVD risk factors, high LDL-cholesterol (hypercholesterolemia under treatment or LDL-C> 130 mg/dL) was present in 72%, high systemic blood pressure (hypertension under treatment or SBP>130/85 mmHg) in 51%, smoking habits in 49%, obesity (BMI>30 Kg/m2) in 22%, type 2 diabetes under treatment in 17%, low HDL-cholesterol (HDL-C< 40 mg/dL in males and <50 mg/dL in females) in 51%, high triglycerides (TG>150 mg/dL) in 27% and high fasting plasma glucose (FPG>100 mg/dL) in 33%. Global MBF reserve was <2 in 68% of patients. In a median follow-up of 10.9 years (7.8-13.9 IQR), 39 patients (37.8%) died (13.6% cardiac death). At multivariable Cox analyses including all risk factors and MBF reserve, age (HR 1.06, 95% CI 1.02-1.11), high FPG (HR 2.28, 95% CI 1.09-4.79) and depressed MBF reserve (HR 4.79, 95% CI 2.14-10.69) were the only independent predictors of death (Global χ2 36.74, P=0.0001). When disease phenotypes were added to the model, age (HR 1.07, 95% CI 1.02-1.12), high FPG (HR 2.18, 95% CI 1.02-4.63) and depressed MBF reserve (HR 4.47, 95% CI 1.96-10.18) remained independent predictors of death (Global χ2 37.41, P=0.0004) (Figure 1). Figure 2 plots the observed all cause death rate in patients with different disease phenotypes stratified for absence/presence of high FPG or MBF reserve <2. Death rate progressively increases according to disease phenotypes and is significantly associated with high FPG (P=0.049) or impaired MBF reserve (P=0.012) in each patient group. Conclusions These results suggest a strong long-term prognostic role of high FPG and depressed MBF reserve in a selected high-risk population of patients with high prevalence of obstructive CAD or HF.Figure 1 Figure 2

A sex-related analysis on the influence of lipoprotein(a) on primary cardiovascular disease prevention and its interplay with traditional lipid markers: results from a 20-year cohort study

Abstract Introduction Elevated lipoprotein(a) [Lp(a)] levels is an established risk factor mediating cardiovascular disease. Purpose The relationship between Lp(a) and the first fatal/non-fatal CVD incident over a 20-year period in males and females without CVD was assessed. Methods A longitudinal prospective study was conducted during 2002–2022. In 2002, a total of 3,042 CVD-free adults (1,514 males and 1,528 females) were enrolled. A follow-up was carried out after 20 years, in 2022, which included 2,169 participants. Out of these, 1,988 had comprehensive data for the occurrence of CVD. The recommended threshold of 50mg/dL was used to define abnormal Lp(a) status (≥50mg/dL). Results During the 2002-2022 period, 718 (i.e. 36%) of participants had a fatal or non-fatal CVD event. Twenty-year CVD-event rate was 35.8% and 40.0% in participants with normal and abnormal Lp(a) levels, respectively. For every mg/dL increase in Lp(a), the odds of having a CVD event within 20 years increases by approximately 0.36% (Hazard ratio (HR) = 1.0036, 95% confidence interval (CI) 1.001,1.007, p=0.048). When stratified by sex the relationship remained significant only in females (HR= 1.006, 95% confidence interval (CI) 1.001,1.011, p=0.023). In the multivariate analysis, significance was lost after adjusting for low- and high-density lipoprotein (LDL-C, HDL-C) and triglycerides (HR= 1.0017, 95% confidence interval (CI) 0.998,1.005, p=0.348). Conclusion Elevated Lp(a) levels are linked to higher CVD risk, particularly in females. Despite growing efforts to clarify Lp(a) as a risk-predicting marker in CVD, clinical guidelines still require definitive evidence, particularly from a sex-focused perspective.

Machine learning based prediction models for cardiovascular disease risk using electronic health records data: systematic review and meta-analysis

Abstract Background Cardiovascular disease (CVD) remains a major cause of mortality in the UK, prompting the need for improved risk predictive models for primary prevention. Machine learning (ML) models utilizing electronic health records (EHR) offer potential enhancements over traditional risk scores like QRISK3 and ASCVD. Objective To systematically evaluate and compare the efficacy of ML models against conventional CVD risk prediction algorithms using EHR data for medium to long-term (5-10 years) CVD risk prediction. Methods A systematic review and random-effect meta-analysis were conducted according to PRISMA guidelines, assessing studies from 2010 to 2024. We retrieved 32 ML models and 26 conventional statistical models from 20 selected studies, focusing on performance metrics such as Area Under the Curve (AUC) and heterogeneity across models. Results ML models, particularly random forest and deep learning, demonstrated superior performance, with the highest recorded pooled AUCs of 0.865 (95% CI: 0.812-0.917) and 0.847 (95% CI: 0.766-0.927), respectively. These significantly outperformed the conventional risk score of 0.765 (95% CI: 0.734-0.796). However, significant heterogeneity (I² > 99%) and potential publication bias were noted across the studies. Conclusion While ML models show enhanced calibration for CVD risk, substantial variability and methodological concerns limit their current clinical applicability. Future research should address these issues by enhancing methodological transparency and standardization to improve the reliability and utility of these models in clinical settings. Implications This study highlights the advanced capabilities of ML models in CVD risk prediction and emphasizes the need for rigorous validation to facilitate their integration into clinical practice. This review was registered with PROSPERO (CRD42021250058).

Office-based risk equation of Globorisk for prediction of ten-years cardiovascular risk among Iranian population: findings from Fasa PERSIAN cohort study

BackgroundGloborisk is one of the prediction tools for 10-year risk assessment of cardiovascular disease, featuring an office-based (non-laboratory-based) version. This version does not require laboratory tests for determining the CVD risk. The present study aims to determine the 10-year CVD risk using the office-based Globorisk model and factors associated with the 10-year CVD risk.MethodsIn this study, baseline data from 6810 individuals participating in the Fasa cohort study, with no history of CVD or stroke, were utilized. The risk equation of the office-based Globorisk model incorporates age, sex, systolic blood pressure (SBP), body mass index (BMI), and smoking status. The Globorisk model categorizes the risk into three groups: low risk (< 10%), moderate risk (10% to < 20%), and high risk (≥ 20%). To identify factors associated with the 10-year CVD risk, the predicted risk was categorized into two groups: <10% and ≥ 10%. Multivariable logistic regression analysis was employed to determine factors associated with an increased CVD risk.ResultsAccording to the 10-year CVD risk categorization, 78.3%, 16.4%, and 5.3% of men were in the low, moderate, and high risk groups, respectively, while 85.8%, 10.0%, and 4.2%, of women were in the respective risk groups. Multivariable logistic regression results indicated that in men, the 10-year CVD risk decreases with being an opium user, and increases with being illiterate, having abdominal obesity, and low or moderate physical activity compared to high physical activity. In women, being married, and higher fiber consumption decrease the 10-year CVD risk, while being illiterate, low or moderate physical activity compared to high physical activity, having abdominal obesity, opium use, and being in wealth quintiles 1 to 4 compared to quintile 5 increase the risk.ConclusionsConsidering the factors associated with increased CVD risk, there is a need to enhance awareness and modify lifestyle to mitigate and reduce the risk of CVD. Additionally, early identification of individuals at moderate to high risk is essential for preventing disease progression. The use of the office-based Globorisk model can be beneficial in settings where resources are limited for determining the 10-year CVD risk.

Usefulness of Atherogenic Indices for Predicting High Values of Avoidable Lost Life Years Heart Age in 139,634 Spanish Workers

Background: Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide, accounting for one-third of all global deaths. The World Health Organization (WHO) asserts that prevention is the most effective strategy to combat CVD, emphasizing the need for non-invasive, low-cost tools to identify individuals at high risk of CVD. Atherogenic indices and heart age (HA) are valuable tools for assessing cardiovascular risk (CVR). The aim of our study was to evaluate the association between atherogenic indices and HA. Methods: A cross-sectional study was conducted involving 139,634 Spanish workers to determine the association between three atherogenic indices and HA. ROC curves were employed to identify the cut-off values for the various atherogenic indices used to estimate high HA. The cut-off points, along with their sensitivity, specificity, and Youden index, were determined, and the area under the curve (AUC) was calculated. Results: As the values of the atherogenic indices increased, so did the risk of having elevated avoidable lost life years (ALLY) HA. In the ROC curve analysis, the AUC with the best results corresponded to the total cholesterol/HDL-c atherogenic index, with an AUC of 0.803 in females and 0.790 in males. The LDL-c/HDL-c atherogenic index showed an AUC of 0.780 in women and 0.750 in men, with Youden indices around 0.4. When analyzing the AUC of the atherogenic index for triglycerides/HDL-c, the results were 0.760 in women and 0.746 in men. Conclusions: Atherogenic indices and HA show a close relationship, with an increase in these indices leading to a rise in HA values. Raising patient awareness that as their CVR levels increase, so does their HA may be useful in achieving some benefit in reducing CVR.

Trends in prevalence of hypertension and high-normal blood pressure among US adults, 1999–2018

Hypertension and high-normal blood pressure (BP) increase the risk for cardiovascular diseases. Examining trends in hypertension and high-normal BP among US adults is crucial. Participants aged 20 years or older from the 1999–2018 National Health and Nutrition Examination Surveys, were included. Trend analyses were performed to assess temporal changes in prevalence of hypertension and high-normal BP among US adults. Among the 48,580 participants included in this analysis, the mean (SD) age was 47.2 years (18 years) and 50.9% were women. Age-adjusted prevalence of hypertension was stable from 1999 to 2000 (29.5% [95% CI 26.6–32.3%]) through 2017–2018 (31.9%, [95% CI 29.0–34.7%]) (P = 0.265 for linear trend). Age-adjusted prevalence of high-normal BP decreased from 10.9% (95% CI 9.4–12.5%) in 1999–2000 to 8.0% (95% CI 7.1–9.0%) in 2007–2008, then increased to 9.8% (95% CI 8.3–11.3%) in 2017–2018 (P = 0.002 for nonlinear trend). Compared with men, hypertension and high-normal BP was less likely among women (multivariable-adjusted prevalence ratio, 0.90 [95% CI 0.84–0.97]; 0.68 [95% CI 0.52–0.88], respectively). Compared with non-Hispanic Black, high-normal BP was less likely among Mexican American, non-Hispanic White, and other race (multivariable-adjusted prevalence ratio, 0.59 [95% CI 0.44–0.79]; 0.53 [95% CI 0.41–0.69]; 0.56 [95% CI 0.74 − 0.71], respectively). The same held for hypertension.

Persistent proteinuria is associated with the occurrence of cardiovascular disease: a nationwide population-based cohort study

Proteinuria is an important risk factor for cardiovascular disease (CVD) and acts as a surrogate marker of renal damage. This study aimed to determine the association between changes in proteinuria and the occurrence of CVD. In our study, 1,708,712 participants who consecutively underwent national health examinations from 2003−2004 (first period) to 2005−2006 (second period) were included. They were classified into four groups based on the presence of proteinuria at the two consecutive health examinations: (1) normal (0 → 0), (2) proteinuria-improved (participants who had improved proteinuria (+ 1 → 0, + 2 → ≤ +1 [0 or + 1], ≥ +3 → ≤ +2 [0, + 1 or + 2]), (3) proteinuria-progressed (0 → ≥ +1, + 1 → ≥ +2, + 2 → ≥ +3), and (4) proteinuria-persistent (+ 1 → +1, + 2 → +2, ≥ +3 → ≥ +3). We used a multivariate Cox proportional hazards model to assess the occurrence of CVD according to changes of presence and severity of proteinuria. During a median of 14.2 years of follow-up, 143,041 participants (event rate, 8.37%) with composite CVD were observed. Compared with the normal group, the risk of incident risk of CVD was increased according to the severity of proteinuria in each of the persistent, progressed, and improved groups (p for trend < 0.001). In a pairwise comparison, the risk of composite CVD in the improved (hazard ratio [HR]: 1.32, 95% confidence interval [CI]: 1.27–1.37), progressed (HR: 1.49, 95% CI: 1.44–1.54), and persistent groups (HR: 1.78, 95% CI: 1.64–1.94) were higher than that of the normal group. Furthermore, the improved group had a relatively lower risk of composite CVD compared to the persistent group (HR: 0.75, 95% CI: 0.69–0.83, p < 0.001). The incidence risk of composite CVD was associated with changes of presence and severity of proteinuria. Persistent proteinuria may be associated with increased risk of CVD, even compared with improved or progressed proteinuria status.

Kidney and cardiovascular outcomes in older population with mildly to moderately decreased kidney function - A nationwide cohort study.

Although the prevalence of chronic kidney disease (CKD) is increasing in the aging population, the clinical relevance of the CKD definition (glomerular filtration rate [GFR] &lt; 60 ml/min/1.73 m2) in older populations remains debatable. We investigated the clinical outcomes in older populations with mildly to moderately decreased GFR (45-59 ml/min/1.73 m2, CKD stage 3A). A total of 7,789,242 participants aged ≥ 40 years with estimated GFR (eGFR) ≥ 45 ml/min/1.73 m2 in national health screening examination from 2012 to 2017 were included in this retrospective cohort study using the Korean National Health Insurance Service database. The main outcomes included kidney failure, cardiovascular disease (CVD), and all-cause death. Cox regression hazard models were used to estimate the hazard ratios. The proportion of participants with eGFR 45-59 ml/min/1.73 m2 was 10.0% and 16.3% in the old (65-74 years) and very old (75 ≥ years) groups, respectively. Mildly to moderately decreased eGFR was associated with a higher risk of kidney failure, CVD, and all-cause death compared with eGFR 60-89 ml/min/1.73 m2 in the old and very old groups, regardless of proteinuria (adjusted hazard ratio [95% confidence interval] in the very old group without proteinuria: kidney failure 3.048 [2.495-3.722], CVD 1.103 [1.066-1.142], and all-cause death 1.172 [1.144-1.201]). Mildly to moderately decreased eGFR was associated with an increased risk of kidney failure, CVD, and all-cause death in the older population, regardless of proteinuria, suggesting the importance of appropriate monitoring and management in this population.

Gestational diabetes and future cardiovascular diseases: associations by sex-specific genetic data.

Observational studies have highlighted that gestational diabetes mellitus is associated with a higher risk of cardiovascular diseases, but the causality remains unclear. Herein, the causality between genetic predisposition to gestational diabetes mellitus and the risk of cardiovascular diseases was investigated using sex-specific Mendelian randomization analysis. Linkage disequilibrium score regression analysis and two-sample Mendelian randomization analysis were applied to infer the genetic correlation and causality, respectively. Mediation analysis was conducted using a two-step Mendelian randomization approach. Sensitivity analyses were performed to differentiate causality from pleiotropy. The genome-wide association study summary statistics for gestational diabetes mellitus were obtained from FinnGen consortium, while for cardiovascular diseases were generated based on individual-level genetic data from the UK Biobank. Linkage disequilibrium score regression analyses revealed that gestational diabetes mellitus had a significant genetic correlation with coronary artery disease and myocardial infarction after Benjamini-Hochberg correction in ever-pregnant women. In Mendelian randomization analyses, odds ratios (95% confidence interval) for coronary artery disease and myocardial infarction were 1.09 (1.01-1.17) and 1.12 (.96-1.31) per unit increase in the log-odds of genetic predisposition to gestational diabetes mellitus in ever-pregnant women, respectively. Further, Type 2 diabetes and hypertension were identified as mediators for the causality of genetic predisposition to gestational diabetes mellitus on coronary artery disease. In sensitivity analyses, the direction of odds ratio for the association between instrumental variables with gestational diabetes mellitus-predominant effects and the risk of coronary artery disease was consistent with the primary results in ever-pregnant women, although not statistically significant. This study demonstrated a suggestive causal relationship between genetic predisposition to gestational diabetes mellitus and the risk of coronary artery disease, which was mainly mediated by Type 2 diabetes and hypertension. These findings highlight targeting modifiable cardiometabolic risk factors may reduce the risk of coronary artery disease in women with a history of gestational diabetes mellitus.

Association between the triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular diseases in people living with HIV: Evidence from a retrospectively cohort study 2005-2022.

The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with HIV (PLWH) remain underexplored. We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People's Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects. At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) [95% confidence intervals (95% CI)] for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively (P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95%CI 3.35%-29.52, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence (P for non-linear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58, 21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88, 1.15, P = 0.880). Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Healthy Dietary Pattern Cycling Affects Gut Microbiota and Cardiovascular Disease Risk Factors: Results from a Randomized Controlled Feeding Trial with Young, Healthy Adults

Background: Previous research demonstrates that adopting, abandoning, and re-adopting (i.e., cycling) a healthy dietary pattern (HDP) improved, reverted, and re-improved cardiovascular disease (CVD) risk factors. In addition, changes in CVD risk factors are associated with dietary modifications of gut microbiota. Objective: We sought to assess the effects of cycling an HDP on gut microbiota and CVD risk factors. Methods: Retrospectively, we used data from a randomized controlled, crossover trial with three 3-week controlled dietary interventions, each separated by a 5-week period of participant-chosen, uncontrolled food intake. Seventeen participants (10 males, 7 females, age 26 ± 4 years old, BMI 23 ± 3 kg/m2) all consumed intervention diets that followed healthy U.S.-style dietary patterns. Gut microbiota composition and cardiovascular risk factors were measured before and after each HDP. Results: Repeatedly adopting and abandoning an HDP led to a cycling pattern of changes in the gut microbial community and taxonomic composition. During the HDP cycles, relative abundances of several bacterial taxa (e.g., Collinsella, Mediterraneibacter, Romboutsia, and Dorea) decreased and returned to baseline repeatedly. Similar HDP cycling occurred for multiple CVD risk factors (i.e., serum total cholesterol and LDL-C concentrations). Consistent negative associations were observed between changes in Mediterraneibacter or Collinsella and serum total cholesterol/HDL-C ratio. Conclusions: These results support previous findings that HDP cycling affected multiple CVD risk factors and expand the HDP cycling phenomenon to include several bacterial taxa. Young adults are encouraged to adopt and sustain a healthy dietary pattern to improve cardiovascular health, potentially through modifying gut microbiota composition.

Multi-Organ Phenotypes of Offspring Born Following Hypertensive Disorders of Pregnancy: A Systematic Review.

Hypertensive pregnancies are associated with an increased risk of cardiovascular and neurological diseases in the offspring during later life. However, less is known about the potential impact on multi-organ phenotypes in offspring before disease symptoms occur. The objective of this systematic review was to determine the associations of fetal exposure to maternal hypertensive pregnancy with multi-organ phenotypes across developmental stages. Ovid MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), WoS, Scopus, CINAHL, and ClinicalTrials.gov were systematically searched until February 2024. Records were independently screened by 2 authors. Studies reporting on the structure or function of the heart, blood vessels, brain, liver, and kidneys in offspring of hypertensive pregnancies compared with a normotensive control population were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. Extracted data were presented using harvest plots. Seventy-three studies including 7091 offspring of hypertensive pregnancies and 42 164 controls were identified that met the inclusion criteria. Thirty-two studies were investigations in fetuses, 24 in neonates and infants, 12 in children, 2 in adolescents, and 3 in adults. Offspring of hypertensive pregnancies had structural and functional changes in the heart compared with controls in some studies across developmental stages. Offspring of hypertensive pregnancies also had smaller occipital and parietal vessels, higher aortic intima-media thickness, and lower retinal arteriolar-to-venular ratio. Some conflicting evidence existed for other phenotypical alterations. There is still inconsistent evidence of multi-organ structural and functional differences in offspring of hypertensive pregnancies. The evidence base could therefore be further strengthened through well-designed and conducted prospective studies. www.crd.york.ac.uk. Unique Identifier: CRD42023387550.

Risk-enhancing factors and social determinants of health in risk assessment for atherosclerotic cardiovascular disease.

The Pooled Cohort Equations (PCEs) do not accurately estimate atherosclerotic cardiovascular disease (ASCVD) risk in certain populations. The 2018 AHA/ACC cholesterol guideline identified risk-enhancing factors as a supplement to PCEs-based risk assessment. However, the role of each risk-enhancing factor in ASCVD risk assessment has not been well quantified. Further, social determinants of health (SDOH) are not included in the PCEs nor considered as risk-enhancing factors in the US cholesterol guideline. We sought to evaluate ASCVD risk associated with each risk-enhancing factor and commonly collected SDOH including education, income, and employment status, and to assess if adding risk-enhancing factors and SDOH to the PCEs improve ASCVD risk prediction. We included individuals aged 40 to 75 years, without ASCVD or diabetes at baseline, and with low-density lipoprotein cholesterol 70-189 mg/dL from two contemporary prospective cohort studies (MESA and REGARDS) and from Kaiser Permanente Southern California (KPSC). The primary endpoint was incident ASCVD defined as nonfatal myocardial infarction, fatal coronary heart disease, or fatal or nonfatal stroke over a 10-year period (median follow-up 10 years). We used Cox proportional hazards models to estimate associations between risk-enhancing factors and SDOH with ASCVD. We also assessed changes in model performance after adding risk-enhancing factors and SDOH to the PCEs. We included 13,863 adults (mean age 60.7 years) from the prospective cohorts and 307,931 adults (mean age 54.8 years) from KPSC. Risk-enhancing factors including hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and chronic kidney disease were associated with a higher ASCVD risk, independent of 10-year risk estimated by the PCEs. Low education, low income, and unemployment were also associated with higher ASCVD risk. While adding individual risk-enhancing factors or SDOH to the PCEs had limited impact on model performance, adding multiple risk-enhancing factors and SDOH simultaneously led to modest improvements in discrimination (C-index increased by up to 0.07), calibration (integrated Brier score reduced by up to 2.3%), and net reclassification improvement up to 41.4%. These findings suggest including SDOH and risk-enhancing factors may improve ASCVD risk assessment.

Digital, Social Micro-Interventions to Promote Physical Activity Among Midlife Adults With Elevated Cardiovascular Risk: An Ambulatory Feasibility Study With Momentary Randomization.

Although regular physical activity (PA) mitigates the risk for cardiovascular disease (CVD) during midlife, existing PA interventions are minimally effective. Harnessing social influences in daily life shows promise: digital micro-interventions could effectively engage these influences on PA and require testing. This feasibility study employed ecological momentary assessment with embedded micro-randomization to activate two types of social influences (i.e., comparison, support; NCT04711512). Midlife adults (N = 30, MAge = 51, MBMI = 31.5kg/m2, 43% racial/ethnic minority) with ≥1 CVD risk conditions completed four mobile surveys per day for 7 days while wearing PA monitors. After 3 days of observation, participants were randomized at each survey to receive 1 of 3 comparison micro-interventions (days 4-5) or 1 of 3 support micro-interventions (days 6-7). Outcomes were indicators of feasibility (e.g., completion rate), acceptability (e.g., narrative feedback), and potential micro-intervention effects (on motivation and steps within-person). Feasibility and acceptability targets were met (e.g., 93% completion); ratings of micro-intervention helpfulness varied by intervention type and predicted PA motivation and behavior within-person (srs=0.16, 0.27). Participants liked the approach and were open to ongoing micro-intervention exposure. Within-person, PA motivation and behavior increased from baseline in response to specific micro-interventions (srs=0.23, 0.13), though responses were variable. Experimental manipulation of social influences in daily life is feasible and acceptable to midlife adults and shows potential effects on PA motivation and behavior. Findings support larger-scale testing of this approach to inform a digital, socially focused PA intervention for midlife adults.

Outcomes of ST-Elevation Myocardial Infarction in Patients with Adrenal Insufficiency

Abstract Background Patients with adrenal insufficiency (AI) have both increased risk of cardiovascular disease and adverse outcomes with many medical emergencies. However, limited data exist specifically regarding ST elevation myocardial infarction (STEMI) in the context of AI. Methods Admissions for STEMI were identified in the 2016-2019 National Inpatient Sample. In-hospital outcomes were compared between patients with and without AI. The primary outcome was in-hospital mortality. Secondary outcomes included percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) intervention, acute kidney injury (AKI), vasopressor use, mechanical circulatory support (MCS), mechanical ventilation, ventricular tachycardia (VT), hospital length of stay (LOS), and total charges. Multivariable regression models were used to adjust for potential confounders. Results Among 690,430 STEMI hospitalizations, 1,382 (0.2%) had a diagnosis of AI. AI was associated with higher odds of in-hospital mortality (adjusted OR [aOR] 1.51, 95% CI 1.03-2.2), lower odds of PCI (aOR 0.73, 95% CI 0.55-0.98), higher odds of CABG (aOR 2.8, 95% CI 1.89-4.2) and, AKI (aOR 2.38, 95% CI 1.72–3.3), VT (aOR 1.55, 95% CI 1.1-2.2), need for vasopressors (aOR 2.34, 95% CI 1.33-4.1), mechanical ventilation (aOR 2.11, 95% CI 1.54-2.89) and MCS (aOR 2.18, 95% CI 1.57–3.03). Patients with AI also had a longer LOS (10 days vs. 4.2 days, p&amp;lt;0.001) and higher charges ($258,475 vs. $115,505, p&amp;lt;0.001). Conclusion Patients with AI admitted for STEMI had higher in-hospital mortality, non-fatal adverse outcomes, and resource utilization compared to patients without AI.

Investigating the Role of Hub Calcification Proteins in Atherosclerosis via Integrated Transcriptomics and Network-Based Approach

Atherosclerosis (AS) is a chronic inflammatory condition of the arteries, characterized by plaque formation that can restrict blood flow and lead to potentially fatal cardiovascular events. Given that AS is responsible for a quarter of global deaths, this study aimed to develop a systematic bioinformatics approach to identify biomarkers and regulatory targets involved in plaque development, with the goal of reducing cardiovascular disease risk. AS-specific mRNA expression profiles were retrieved from a publicly accessible database, followed by differentially expressed genes (DEGs) identification and AS-specific weighted gene co-expression network (WGCN) construction. Thereafter, calcification and atherosclerosis-specific (CASS) DEGs were utilized for protein–protein interaction network (PPIN) formation, followed by gene ontology (GO) term and pathway enrichment analyses. Lastly, AS-specific 3-node miRNA feed-forward loop (FFL) construction and analysis was performed. Microarray datasets GSE43292 and GSE28829 were obtained from gene expression omnibus (GEO). A total of 3785 and 6176 DEGs were obtained in case of GSE28829 and GSE43292; 3256 and 5962 module DEGs corresponding to GSE28829 and GSE43292 were obtained from WGCN. From a total of 54 vascular calcification (VC) genes, 20 and 29 CASS-DEGs corresponding to GSE28829 and GSE43292 were overlapped. As observed from FFL centrality measures, the highest-order subnetwork motif comprised one TF (SOX7), one miRNA (miR-484), and one mRNA (SPARC) in the case of GSE28829. Also, in the case of GSE43292, the highest-order subnetwork motif comprised one TF (ESR2), one miRNA (miR-214-3p), and one mRNA (MEF2C). These findings have important implications for developing new therapeutic strategies for AS. The identified TFs and miRNAs may serve as potential therapeutic targets for treating atherosclerotic plaques, offering insights into the molecular mechanisms underlying the pathogenesis and highlighting new avenues for research and treatment.

An equation for estimating low-density lipoprotein-triglyceride content and its use for cardiovascular disease risk stratification

BackgroundThe triglyceride (TG) content of low-density lipoprotein (LDL-TG) has been shown to be more predictive of atherosclerotic cardiovascular disease (ASCVD) events than the cholesterol content of LDL (LDL-C). The goal of our study was to develop an equation for estimating LDL-TG (eLDL-TG) based on the standard lipid panel and to compare it to estimated LDL-C as an ASCVD risk biomarker.MethodsUsing least-square regression analysis, the following eLDL-TG equation was developed: eLDL-TG=TG38.5+NonHDL-C5.75+9.75TGNonHDL-C+244HDL-C−2.95. LDL-TG was measured by the β-quantification (BQ) reference method (N = 40,202). LDL-C was calculated by the Sampson-NIH equation. The association of LDL-C and eLDL-TG with ASCVD risk markers was performed in the National Heart and Nutrition Examination Survey (NHANES) (N = 37,053) and with ASCVD events in a primary prevention cohort from the UK Biobank (UKB) (N = 429,367) and the Atherosclerosis Risk in Communities (ARIC) study (N = 14,632).ResultseLDL-TG showed better ASCVD risk stratification of UKB participants than LDL-C (Wilcoxon Chi-Square: 2,099.6 vs. 418.7, respectively). Receiving-operating characteristics analysis revealed that eLDL-TG had a stronger association with ASCVD events than LDL-C (AUC: 0.596 vs. 0.542, respectively) and other conventional lipid markers. Similar findings were found in ARIC. Discordance analysis in UKB showed that the group with low LDL-C/high eLDL-TG had a similar risk as the high LDL-C/high eLDL-TG group. Furthermore, these same two groups with the highest eLDL-TG levels and the highest ASCVD event rate also had higher mean levels of systolic blood pressure, Body Mass Index, hemoglobin A1C, and C-reactive protein than the two lower eLDL-TG groups. Using eLDL-TG &amp;gt; 44.6 mg/dl (80th percentile) as a cut-point leads to a hazard ratio of 1.32 (95% CI, 1.29–1.36) for ASCVD events, which remained significant after adjustment for LDL-C and apoB. Furthemore, using eLDL-TG as a risk-enhancer test leads to reclassification of 50% more high-risk individuals than current lipid-enhancer test rules.ConclusionsLike LDL-C, LDL-TG can also be calculated from the results of the standard lipid panel. Compared to estimated LDL-C, eLDL-TG was a better risk marker for primary prevention and hence could improve initial ASCVD risk stratification.