Increased Risk Of Cardiovascular Disease Research Articles

Determinants of developing cardiovascular disease risk with emphasis on type-2 diabetes and predictive modeling utilizing machine learning algorithms.

This research aims to enhance our comprehensive understanding of the influence of type-2 diabetes on the development of cardiovascular diseases (CVD) risk, its underlying determinants, and to construct precise predictive models capable of accurately assessing CVD risk within the context of Bangladesh. This study combined data from the 2011 and 2017 to 2018 Bangladesh Demographic and Health Surveys, focusing on individuals with hypertension. CVD development followed World Health Organization (WHO) guidelines. Eight machine learning algorithms (Support Vector Machine, Logistic Regression, Decision Tree, Random Forest, Naïve Bayes, K-Nearest Neighbor, Light GBM, and XGBoost) were analyzed and compared using 6 evaluation metrics to assess model performance. The study reveals that individuals aged 35 to 54 years, 55 to 69 years, and ≥ 70 years face higher CVD risk with adjusted odds ratios (AOR) of 2.140, 3.015, and 3.963, respectively, compared to those aged 18 to 34 years. "Rich" respondents show increased CVD risk (AOR = 1.370, P < .01) compared to "poor" individuals. Also, "normal weight" (AOR = 1.489, P < .01) and "overweight/obese" (AOR = 1.871, P < .01) individuals exhibit higher CVD risk than "underweight" individuals. The predictive models achieve impressive performance, with 75.21% accuracy and an 80.79% AUC, with Random Forest (RF) excelling in specificity at 76.96%. This research holds practical implications for targeted interventions based on identified significant factors, utilizing ML models for early detection and risk assessment, enhancing awareness and education, addressing urbanization-related lifestyle changes, improving healthcare infrastructure in rural areas, and implementing workplace interventions to mitigate stress and promote physical activity.

Impact of short-term aircraft noise on cardiovascular disease risk in the area surrounding London Heathrow airport: the RISTANCO epidemiological study.

Long-term exposure to aircraft noise has been associated with small increases in cardiovascular disease risk, but there are almost no short-term exposure studies. Research questions were: Is there an association between short-term changes in exposure to aircraft noise and cardiovascular morbidity and mortality? What are the key effect modifiers? Is there variability in risk estimates between areas with consistent versus changing patterns of noise exposure? Do risk estimates differ when using different noise metrics? Descriptive analyses of noise levels and variability at different times of day, analyses of inequalities in noise exposure and case-crossover analyses of cardiovascular events in relation to aircraft noise exposure. Area surrounding London Heathrow airport. 2014-18. Whole population in study area. Cardiovascular disease hospitalisations and mortality. Aircraft noise levels modelled using a standard noise model for: (1) daily equivalent continuous sound levels at different times of day; (2) daily number of events above defined noise thresholds (2018 only). National Health Service digital hospital admission records and Office for National Statistics mortality records for 2014-18 for cardiovascular outcomes, plus individual-level confounders available from healthcare records. Confounder data including road traffic noise (Leicester modelled), rail noise and air pollution (Department for Environment, Food and Rural Affairs), area level deprivation and ethnicity (UK Census). The morning shoulder period (06.00-07.00 hours) was the noisiest of all eight bands (mean: 50.92 dB). The morning shoulder period also had the third highest number of noisy events (flights) > 60 dB per day, with three events across postcodes on average. However, the highest number of noisy events occurred in daytime (highest between 07.00 and 15.00 hours, second highest 15.00 and 19.00 hours). To identify areas with high variability in aircraft noise exposure (due to changes in flight paths because of wind direction and airport operations), we used coefficients of variation (CoV). The period 24.00-04.30 hours had the highest mean CoV (67.33-74.16), followed by 04.30-06.00 hours and 23.00-24.00 hours. Postcodes in the least deprived quintiles of Carstairs index or avoidable death rate had the lowest noise levels. In case-crossover analyses, we observed increased risk for cardiovascular disease hospital admissions for evening noise 19.00-23.00 hours (odds ratio 1.005, 95% confidence interval 1.000 to 1.010 per 5 dB), but not for other periods or mortality. Further analyses suggested that increased risks were occurring in postcodes with low CoV for noise. We found effect modification by age, sex, ethnicity, deprivation and season. The industry standard noise model, the Aviation Environmental Design Tool, used does not take account of wind direction, which may have led to some exposure misclassification. We developed a comprehensive dataset of daily aircraft noise variability. We found small associations between cardiovascular hospitalisations (but not deaths) and evening aircraft noise levels, particularly in areas with low variability of noise. More studies are needed to understand the effect of noise variation and respite/relief on cardiovascular disease. This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 15/192/13) and is published in full in Public Health Research; Vol. 12, No. 13. See the NIHR Funding and Awards website for further award information.

Lipoprotein(a) concentrations and cardiovascular disease in patients with chronic kidney disease: Results from the German Chronic Kidney Disease study.

Lipoprotein(a) (Lp(a)) is a causal, genetically determined risk factor for cardiovascular disease (CVD) in the general population. Patients with chronic kidney disease (CKD) have an increased CVD risk and elevated Lp(a) concentrations. Only a few studies on Lp(a) were performed in persons with mild-to-moderate CKD; none of them used genetic variants to explore potential causal associations. This study aims to investigate the association of measured and genetically predicted Lp(a) concentrations on prevalent and incident CVD events in the German Chronic Kidney Disease (GCKD) study. The study included 5043 participants of European ancestry with an estimated glomerular filtration rate (eGFR) between 30 and 60mL/min/1.73m2 or an eGFR >60mL/min/1.73m2 in the presence of overt albuminuria with a follow-up of 6.5 years. With each 10mg/dL higher Lp(a) concentration, odds for prevalent CVD (1290 events) increased 1.065-fold (95%CI: 1.042-1.088, p<0.001). The risk was significantly higher in patients with Lp(a) ≥50mg/dL but most pronounced in Lp(a) ≥70mg/dL (odds ratio=1.775 [1.409-2.231], p<0.001) compared to Lp(a) <30mg/dL. Each 10mg/dL higher Lp(a) concentration and Lp(a) ≥70mg/dL increased the risk for incident 3-point major adverse cardiovascular events (MACEs) (474 events): hazard ratio [HR]=1.037 [1.009-1.067], p=0.009 and HR=1.335 [1.001-1.781], p=0.050), respectively. Similar results were obtained for 4-point MACE (653 events). Analyses based on apo(a) isoforms and genetically predicted Lp(a) concentrations led to even stronger associations. In patients with mild-to-severe CKD, elevated Lp(a) concentrations and genetic determinants of Lp(a) concentrations are significantly associated with CVD at baseline and during follow-up, independent of traditional risk factors.

The relationship of cardiovascular disease risk, clozapine antipsychotic use and cognitive function in a large Chinese schizophrenia cohort

ObjectiveThis study explores the intricate relationship between clozapine use, cardiovascular disease (CVD) risk, and cognitive function in patients with schizophrenia (SCZ). MethodsA cohort comprising 765 patients was stratified based on clozapine usage. Data on demographics, clinical characteristics, and glycolipid metabolism were collected. The Framingham Risk Score and vascular age were calculated using gender-specific Cox regression calculators. Cognitive function was assessed with the Repeatable Battery for Assessment of Neuropsychological Status. ResultsAmong the patients, 34.6 % were clozapine users. Clozapine users exhibited lower systolic blood pressure, high-density lipoprotein cholesterol and total cholesterol (all ps < 0.05). Furthermore, clozapine users exhibited higher PANSS scores, along with lower scores in RBANS scores (all ps < 0.05). Correlation analysis revealed positive correlation between CVD risk in non-clozapine users and negative symptom scores (r = 0.074, p = 0.043), and negative correlation with positive symptom scores and RBANS scores (r = −0.121, p = 0.001; r = −0.091, p = 0.028). Multivariate stepwise regression analysis indicated that attention scores as predictive factors for increased CVD risk in clozapine users (B = −0.08, 95 %CI = −0.11 to −0.03, p = 0.003). ConclusionsPatients with SCZ using clozapine exhibit more severe clinical symptoms and cognitive impairments. Attention emerges as a predictor for increased CVD risk in clozapine users.

Atherogenic low-density lipoprotein and cardiovascular risk.

Despite reductions in low-density lipoprotein (LDL) cholesterol (LDLc), residual cardiovascular risk remains due to factors beyond lipoprotein levels, such as LDL particle count, size, electronegativity and modifications. Technological advances allow detailed profiling of LDL particles, offering potential biomarkers for diagnosis, prognosis, and treatment of cardiovascular disease (CVD). The aim of this review is to provide an updated overview of the state of knowledge in the field of LDL atherosclerotic role, which is evolving rapidly due to technological advances in biomarker measurement and applications. While small dense LDL has been linked to increased CVD risk, current approaches favor a comprehensive evaluation of all lipoprotein subtypes, as this is a more feasible and standardized method. The atherogenic potential of circulating oxidized LDL (oxLDL) may be the key factor in the onset and progression of atherosclerosis. Thus, elevated oxLDL levels are recognized as a marker of increased CVD risk in both general and high-risk populations, although further research is needed to clarify some conflicting findings. The oxidized LDL receptor 1 (LOX-1) has emerged as a promising target for immunotherapy and innovative drug delivery strategies to modulate atherosclerosis. A panel of biomarkers related to LDL atherogenicity may help predict future ischemic events. An atheroprotective diet and increased physical activity could improve LDL oxidation. OxLDL has become a target for immunomodulatory antiatherosclerosis therapy and delivering LDL-based nanocarriers holds promise for both imaging and therapeutics.

The prolonged impact of swapping non-fermented with fermented dairy products on cardiovascular disease: the ATTICA cohort study (2002-2022).

Scientific evidence suggests that substituting non-fermented with fermented dairy products may confer cardiovascular health benefits. The role of fermented in relation to non-fermented dairy products on 20-year fatal/non-fatal cardiovascular disease (CVD) incidence was examined. In 2001-2002, n = 3042 free-of-CVD men and women from Attica, Greece, were recruited. Dietary assessment was based on a validated semi-quantitative food frequency questionnaire. CVD evaluation was performed in three follow-up time points at 5, 10 and 20 years, in n = 1988 participants (718 cases). Participants reported >2 servings/day of fermented dairy products had 1.5 times lower risk to develop CVD compared with their lower level of consumption. Multi-adjusted analysis revealed similar cardioprotective properties per 1 serving increase in dairy consumption of fermented dairy products (Hazard Ratio (HR) = 0.82, 95% Confidence Interval (95%CI) (0.58, 0.95)) as well as when the ratios of fermented:total dairy products (0.90, (0.53, 0.95)) and fermented:non-fermented dairy products (0.74, (0.39, 0.92)) were ≥0.76 and ≥2.5, respectively. The associations were more evident in case of impaired inflammation status. Replacing 1 serving of non-fermented with 1 equivalent serving of fermented dairy products reduced CVD risk (0.74, (0.53, 0.92)). Substitution of low-fat with whole-fat yogurt increased CVD risk (1.35, (1.02, 1.58)). Replacing cheese (any kind) with low-fat yogurt reduced CVD risk (all HRs<1) while with whole-fat yogurt no significance was observed. Shift of guidelines to a daily pattern of dairy intake yet with an inclination towards emphasizing the consumption of fermented products is recommended.

Associations of baseline and changes in the triglyceride glucose-weight adjusted waist index and cardiovascular disease risk: evidence from middle-aged and older individuals

BackgroundExisting researches have predominantly focused on the implications of dynamic alterations in the triglyceride-glucose (TyG) index and traditional obesity measures for cardiovascular disease (CVD) risk. However, the application of the weight-adjusted waist index (WWI), which incorporates the dynamically changing body composition factors of weight and waist circumference, alongside the TyG index for predicting CVD risk, remains unexplored. This study explores the relationships between baseline TyG-WWI index and its dynamic changes with CVD risk.MethodsSubjects were drawn from the China Health and Retirement Longitudinal Study. Logistic regression analyses were conducted to determine the relationships between baseline and longitudinal changes in the TyG-WWI index and CVD risk, quantified through odds ratios (ORs) and 95% confidence intervals (CIs). The robustness of results was confirmed via subgroup analyses and E-values. Additionally, restricted cubic spline and quartile-based methods evaluated the relationships between baseline and cumulative TyG-WWI indices and CVD risk.ResultsOver two survey waves, 613 CVD events were recorded. Analysis using adjusted multivariable models demonstrated a significant relationship between the cumulative TyG-WWI index and increased CVD risk, with an adjusted OR (95% CI) of 1.005 (1.000, 1.009). Class 2 of the TyG-WWI index change showed greater risk of CVD compared to Class 1, with ORs of 1.270 (1.008, 1.605). However, no significant connection was observed between the baseline TyG-WWI index and CVD risk (OR = 1.007, 95% CI: 0.996, 1.019). These findings were corroborated through extensive sensitivity analyses.Graphical

Age-specific in the relationship between diastolic blood pressure and the risk of cardiovascular disease: A cohort study of the UK Biobank.

To investigate the effect of optimal diastolic blood pressure (DBP) level on cardiovascular disease (CVD) events, considering different age groups. And the nonlinear relationship between DBP and CVD events by age were evaluated. 358,734 participants of the UK biobank were included. Multivariable Cox regressions were performed to evaluate the relation between DBP and cardiovascular risk, and the natural cubic spline was applied to estimate the nonlinear relationship between the DBP measures and the hazard. In the UK Biobank, a total of 358,734 participants (mean [SD] age, 55.3 [8.1] years; 205,215 [57.2 %] female) were included in this analysis. The rate of CVD cases was 6.05 per 1000 person-years. For each SD increase, DBP was associated with elevated CVD events for both <50 year (HR, 1.19; 95 % CI, 1.12 to 1.26) and 50-59 year-old group (HR, 1.04; 95 % CI, 1.01 to 1.08). However, for every SD increment, a marginal protective effect against CVD events was observed between DBP and the CVD events in elder people (≥60 years old) and lower DBP (<70 mm Hg) may confer an increased CVD risks (HR, 1.10; 95 % CI, 1.03 to 1.17). For adults younger than 60 years old, the study seems to support the ACC/AHA blood pressure guidelines lowering the DBP threshold to 80 mm Hg. Conversely, it may be reasonable to rule out large effects of high DBP on CVD events and DBP <70 mm Hg may be cause for caution in older people aged 60-69.

Relationship between liver and cardiometabolic health in type 1 diabetes.

Type 1 diabetes (T1D) is a chronic condition marked by insulin deficiency and hyperglycemia, with an increasing global incidence, particularly among children. Despite improvements in diabetes management, individuals with T1D continue to experience higher rates of cardiovascular disease (CVD), the leading cause of mortality in this population. Traditional CVD risk factors such as dyslipidemia and poor glycemic control are insufficient to fully explain the elevated risk in T1D, prompting further investigation into additional factors. Emerging evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) plays a critical role in this heightened CVD risk. This narrative review aims to explore the relationship between MASLD and CVD in individuals with T1D. The review focuses on the prevalence of MASLD, its contributing risk factors, and the potential impact of liver dysfunction on cardiovascular outcomes in this population. A review of existing literature was conducted, focusing on observational studies, cohort studies, and meta-analyses that investigate the prevalence of MASLD in T1D populations and its association with CVD. The review also examines the physiological mechanisms linking MASLD and CVD, including insulin resistance, systemic inflammation, and hepatic dyslipidemia. Key studies were evaluated to identify patterns in MASLD prevalence based on diagnostic modalities and to assess the independent contribution of MASLD to cardiovascular risk in T1D patients. MASLD is increasingly recognized as a significant contributor to CVD in individuals with T1D, particularly in those with shared risk factors like obesity and insulin resistance. Evidence suggests that MASLD exacerbates hepatic and systemic metabolic dysfunction, increasing CVD risk through mechanisms such as chronic inflammation and atherogenic lipid profiles. Routine liver health assessments and tailored management strategies targeting MASLD should be incorporated into clinical care for individuals with T1D to mitigate long-term cardiovascular complications.

Linking Antibodies Against Apolipoprotein A-1 to Metabolic Dysfunction-Associated Steatohepatitis in Mice.

Metabolic dysfunction-associated fatty liver disease (MASLD) is a common liver and health issue associated with heightened cardiovascular disease (CVD) risk, with Cytokeratin 18 (CK-18) as a marker of liver injury across the MASLD to cirrhosis spectrum. Autoantibodies against apolipoprotein A-1 (AAA-1s) predict increased CVD risk, promoting atherosclerosis and liver steatosis in apoE-/- mice, though their impact on liver inflammation and fibrosis remains unclear. This study examined AAA-1s' impact on low-grade inflammation, liver steatosis, and fibrosis using a MASLD mouse model exposed to AAA-1s passive immunization (PI). Ten-week-old male C57BL/6J mice under a high-fat diet underwent PI with AAA-1s or control antibodies for ten days. Compared to controls, AAA-1-immunized mice showed higher plasma CK-18 (5.3 vs. 2.1 pg/mL, p = 0.031), IL-6 (13 vs. 6.9 pg/mL, p = 0.035), IL-10 (27.3 vs. 9.8 pg/mL, p = 0.007), TNF-α (32.1 vs. 24.2 pg/mL, p = 0.032), and liver steatosis (93.4% vs. 73.8%, p = 0.007). Transcriptomic analyses revealed hepatic upregulation of pro-fibrotic mRNAs in AAA-1-recipient mice, though histological changes were absent. In conclusion, short-term AAA-1 PI exacerbated liver steatosis, inflammation, and pro-fibrotic gene expression, suggesting that AAA-1s may play a role in MASLD progression. Further research with prolonged AAA-1 exposure is warranted to clarify their potential role in liver fibrosis and associated complications.

The impact of metabolic heterogeneity of obesity and transitions on cardiovascular disease incidence in Chinese middle-aged and elderly population: A nationwide prospective cohort study.

Previous studies indicated that metabolic heterogeneity of obesity would affect the risk of cardiovascular disease (CVD). However, the alterations in CVD risk associated with transitions between various metabolic health statuses influenced by obesity status remain unclear. We utilized data from the China Health and Retirement Longitudinal Study (CHARLS), a longitudinal cohort study involving Chinese residents aged 45 years and older. Baseline data were collected in 2011-2012, with follow-up surveys conducted up to 2020. Participants in the study were categorized into four body mass index-metabolic phenotypes: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obesity (MHOO), metabolically unhealthy normal weight (MUNW) and metabolically unhealthy overweight/obesity (MUOO). Transitions in these phenotypes over 4 years were analysed. Cox regression models were used to assess the associations of these phenotypes and their transitions with CVD incidence. Among 7721 participants, 1353 (17.5%) developed CVD during the follow-up period. Both overweight/obese and metabolically unhealthy statuses were associated with increased CVD risk. The highest risk was observed in the MUOO group (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.50-2.09, p < 0.0001), followed by the MUNW (HR 1.35, 95% CI: 1.13-1.66, p < 0.001) and MHOO (HR: 1.29, 95% CI: 1.08-1.56, p = 0.002) groups compared to the MHNW group. The deteriorations of obesity and metabolic health status elevated the incidence of CVD, whereas improvements in these statuses reduced the risk of CVD. Additionally, alterations in metabolic health status conferred greater benefits in overweight/obese individuals compared to those with normal weight. The study highlights the importance of maintaining and promoting metabolic health, particularly in overweight/obese individuals, to reduce CVD risk. Metabolic health status plays a more crucial role than obesity status in predicting CVD incidence.

Alterations of Some Apolipoprotein Levels and ApoE RNA Expression in Iraqi Patients with Chronic Hepatitis B Viral Infection

Abstract Background: The high prevalence of hepatitis B virus (HBV) makes it a significant health concern, especially in Iraq. Clinical studies have found that chronic HBV infection affects the occurrence of cardiovascular disease (CVD) by regulating cholesterol metabolism in liver cells. Objective: This study aimed to determine alterations in some serum lipoproteins (ApoA, ApoB, and apolipoprotein E [ApoE]) and oxidized low-density lipoprotein (OxLDL), as well as ApoE gene expression in Iraqi patients with chronic HBV infection, as potential markers for increased cardiovascular risk. Materials and Methods: This case-control study involved fifty patients with chronic HBV admitted to the Gastroenterology and Hepatology Teaching Hospital in Medical city, Baghdad, besides 40 individuals serving as a healthy control group. Results: The current study showed significantly higher levels of ApoA, ApoB, ApoE, and OxLDL among patients compared to the control group. Additionally, HBV patients demonstrated lower expression of ApoE gene in HBV patients. The receiver operating characteristic curve analysis for all parameters showed high sensitivity and specificity, with area under the curve affirming their potential as biomarkers for increased CVD risk in patients with chronic HBV infection. Conclusion: The study reveals significant disparities in plasma levels of ApoA, ApoB, ApoE, and OxLDL between HBV patients and controls, along with reduced ApoE gene expression in these patients, suggesting a potential role of HBV in apolipoproteins dysfunction. Thus, serum ApoA, ApoB, ApoE, and OxLDL in CHB patients may help identify high-risk patients for CVD, thereby preventing the development of CVD or early diagnosis of (CVD) in these patients.

Beyond the change: exploring age of menopause, lifestyle, and cardiovascular risk in women

Abstract Background Premature/early menopause increases the risk of future cardiovascular disease (CVD); however, whether lifestyle can offset this risk is unknown. Purpose Investigate the association between premature/early menopause and incident CVD and whether a healthy lifestyle modifies this association. Methods The 45 and Up Study prospectively recruited participants aged ≥45 years (n=267,357) between 2005-2009. Our study included women without prior CVD and those reporting menopausal age at baseline. Primary outcome was incident CVD (self-reported heart disease/stroke) based on survey data1 at Wave 2 (2012-2015) and/or Wave 3 (2018-2020). Logistic regression models assessed associations of premature (age &amp;lt;40 years) and early (age 40-44 years) menopause with CVD, compared to standard menopause (age 50-52 years), adjusting for sociodemographic and clinical variables. Healthy lifestyle adherence was assessed using a score of five factors: smoking, physical activity, sitting, sleep, and diet. Interaction effects were analysed between menopause and healthy lifestyle adherence on CVD. Results We included 46,273 women (mean age 62.1±8.2 years), with 5,425(11.7%) incident CVD over 15-year follow-up. After adjustment, the CVD risk was higher in women with premature menopause (odds ratio (OR): 1.36, 95% confidence intervals (CI), 1.17-1.59; p&amp;lt;0.0001) and early menopause (OR: 1.15, 95% CI, 1.03-1.28; p=0.013) compared to standard menopause. Among all menopausal women, high versus low healthy-lifestyle adherence led to 20% lower CVD risk (OR: 0.80, 95% CI, 0.71-0.90; p=0.0003). In the subset of high-risk women with premature menopause, high versus low healthy lifestyle adherence led to 50% lower risk of CVD (OR: 0.50, 95% CI, 0.31-0.80, p=0.0040). The healthy lifestyle effect was not significantly different across menopause groups (p=0.71). Conclusion Early and premature menopause were independently associated with increased CVD risk. Healthy versus unhealthy lifestyle significantly attenuated the risk of CVD in all menopausal women, particularly in the highest risk group of women with premature menopause, reducing this risk by 50%. 1 Secure data access was provided through the Sax Institute’s Secure Unified Research Environment (SURE).

Impact of addressing modifiable risk factors on the 10-year risk of cardiovascular disease in individuals with familial hypercholesterolemia: a causal analysis utilising UK biobank

Abstract Background Familial hypercholesterolemia (FH) is a prevalent autosomal dominant disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth. These elevated LDL-C levels significantly amplify the lifetime risk of cardiovascular disease (CVD). While the impact of early and effective initiation of lipid-lowering medication (LLM) on CVD risk is well documented in genetically confirmed FH, the additional impact of addressing modifiable lifestyle risk factors (MLRF) in that patient population remains largely unquantified. Methods This study quantified the potential effects of successfully managing 4 MLRF (smoking, obesity, alcohol consumption, and low physical activity) on the 10-year incidence of a first CVD diagnosis in adults with genetically confirmed FH treated with LLM within the UK Biobank. The synthesised causal estimates of these 4 MLF were obtained using two recent causal analysis frameworks, namely the doWhy causal calculus framework and the Causal Forest Double Machine Learning Method. Results In 660 FH individuals (mean age 56±8 years; 60.15% women), smoking cessation and reducing body mass index below 30 kg/m2 delivered the most substantial risk reductions (pooled estimates, adjusted for the 3 other MLRF: -6.5% and -3.2%, respectively; both p&amp;lt;0.001), followed by initiating moderate or high physical activity (-1.7%; p&amp;lt;0.001; Figure). Notably, cessation of alcohol consumption significantly increased CVD risk (+2.5%; p&amp;lt;0.001), aligning with existing literature. Conclusion In over 10 years, reductions in CVD risk ranging from 1.7% to 6.5% were achievable through smoking cessation, BMI reduction, and enhanced physical activity in FH individuals. Leveraging causal inference methodologies facilitates the discernment of which risk factors offer the most pronounced additional benefits beyond lipid-lowering interventions in this high-risk population.Forest Plot of Causal Effect Estimates

Cardiovascular events risk in office-masked nocturnal hypertension defined by home blood pressure monitoring: the J-HOP nocturnal blood pressure study

Abstract Background Elevated nocturnal home blood pressure (BP) has been reported to be associated with increased risk for cardiovascular disease (CVD). Masked hypertension defined by home BP monitoring is also a strong risk factor for adverse CVD outcomes. However, no study has investigated the association between office-masked nocturnal hypertension defined by home BP monitoring and CVD events risk. Purpose This study aimed to examine the association between office-masked nocturnal hypertension defined by home BP monitoring and CVD events risk in a clinical practice-based population. Methods This was a prospective observational study including Japanese participants with CVD or high risk of CVD. Three office BPs were taken on two different occasions. Nocturnal home BP was measured three times per night for two weeks. The association between office-masked nocturnal hypertension and incident total CVD events (including fatal and non-fatal stroke and coronary heart disease) was examined using Cox regression. Results 2,545 participants were followed for the mean of 7.1 years (18,116 person-years), during which 152 (6.0%) CVD events occurred. Mean age (standard deviation) was 63.3 (10.3) years; 49.0% were male; 82.6% took antihypertensive medications. The proportions of participants with normotension (office BP &amp;lt;140/90 mmHg and nocturnal home BP &amp;lt;120/70 mmHg), white-coat hypertension (office BP ≥140/90 mmHg and nocturnal home BP &amp;lt;120/70 mmHg), office-masked nocturnal hypertension (office BP &amp;lt;140/90 mmHg and nocturnal home BP ≥120/70 mmHg), and sustained hypertension (office BP ≥140/90 mmHg and nocturnal home BP ≥120/70 mmHg) were 25.3%, 14.4%, 23.2%, and 37.1%, respectively. The office-masked nocturnal hypertensive group and sustained hypertensive group had higher incidence rates of total CVD events compared with the normotensive group. Relative to normotension, those with both office-masked nocturnal hypertension (adjusted hazard ratio [aHR] 1.72, 95% confidence interval [CI] 1.01–2.92) and sustained hypertension (aHR 1.75, 95%CI 1.03–2.96) had similarly increased CVD risk, even after adjustment for daytime home BP values. Conclusions Screening for office-masked nocturnal hypertension with home BP monitoring identifies a potentially important group of patients with increased risk for incident CVD events for whom additional preventative measures may be appropriate.

Load-dependent mechanisms contribute to increased aortic stiffness among women with a history of preeclampsia: relation with cardiovagal baroreflex sensitivity.

Preeclampsia, a hypertensive disorder of pregnancy, results in increased lifetime cardiovascular disease (CVD) risk. Total aortic stiffness, a robust risk factor for CVD, is composed of load-dependent (blood pressure load on arterial wall) and structural (intrinsic changes in arterial wall) mechanisms. Total aortic stiffness is also associated with reduced cardiovagal baroreflex sensitivity (BRS). We sought to determine 1) whether elevated total aortic stiffness among women with a history of preeclampsia (hxPE) is attributed to load-dependent or structural stiffness, and 2) whether either mechanism is associated with lower BRS. Total aortic stiffness (carotid-femoral pulse wave velocity) and spontaneous cardiovagal BRS (sequence technique) were measured among women 1-5 yr postpartum (n = 115; age 34 ± 4 yr; hxPE n = 51; controls n = 64). Structural aortic stiffness was calculated from participant-specific exponential models by standardizing aortic stiffness to a "reference" blood pressure. Load-dependent stiffness was calculated as total minus structural stiffness. Total [+0.8 m/s, 95% confidence interval (CI) (-0.99, -0.23), P = 0.002] and load-dependent [+0.4 m/s, 95% CI (-0.56, -0.22), P < 0.001], but not structural [95% CI (-0.52, 0.08), P = 0.16] aortic stiffness were higher among women with a hxPE compared with controls. Women with a hxPE had lower BRS (P = 0.042) that was negatively associated with total [B = -3.24 ms/mmHg, 95% CI (-6.35, -0.13), P = 0.042] and load-dependent [B = -5.91 ms/mmHg, 95% CI (-11.31, -0.51), P = 0.033] aortic stiffness. Load-dependent, not structural, aortic stiffness mechanisms contribute to higher total aortic stiffness among women with a hxPE and are associated with lower cardiovagal BRS. Postpartum monitoring for high BP is critical to reduce increased CVD risk after preeclampsia.NEW & NOTEWORTHY The novel finding is that load-dependent stiffness, not structural stiffness, is the primary mechanism of aortic stiffness, and is associated with reduced baroreflex sensitivity in women with a history of preeclampsia. These findings may help tailor high blood pressure prevention and management strategies in this population to prevent structural aortic stiffening, altered baroreflex control, and increased lifetime cardiovascular disease (CVD) risk.

Assessing the relative importance of vitamin D deficiency in cardiovascular health.

Previous research has suggested a potential link between vitamin D (VD) deficiency and adverse cardiovascular health outcomes, although the findings have been inconsistent. This study investigates the association between VD deficiency and cardiovascular disease (CVD) within the context of established CVD risk factors. We utilized a Random Forest model to predict both CVD and VD deficiency risks, using a dataset of 1,078 observations from a rural Chinese population. Feature importance was evaluated using SHapley Additive exPlanations (SHAP) to discern the impact of various risk factors on the model's output. The results showed that the model for CVD prediction achieved a high accuracy of 87%, demonstrating robust performance across precision, recall, and F1 score metrics. Conversely, the VD deficiency prediction model exhibited suboptimal performance, with an accuracy of 52% and lower precision, recall, and F1 scores. Feature importance analysis indicated that traditional risk factors such as systolic blood pressure, diastolic blood pressure, age, body mass index, and waist-to-hip ratio significantly influenced CVD risk, collectively contributing to 70% of the model's predictive power. Although VD deficiency was associated with an increased risk of CVD, its importance in predicting CVD risk was notably low. Similarly, for VD deficiency prediction, CVD risk factors such as systolic blood pressure, glucose levels, diastolic blood pressure, and body mass index emerged as influential features. However, the overall predictive performance of the VD deficiency prediction model was weak (52%), indicating the absence of VD deficiency-related risk factors. Ablation experiments confirmed the relatively lower importance of VD deficiency in predicting CVD risk. Furthermore, the SHAP partial dependence plot revealed a nonlinear relationship between VD levels and CVD risk. In conclusion, while VD deficiency appears directly or indirectly associated with increased CVD risk, its relative importance within predictive models is considerably lower when compared to other risk factors. These findings suggest that VD deficiency may not warrant primary focus in CVD risk assessment and prevention strategies, however, further research is needed to explore the causal relationship between VD deficiency and CVD risk.

6870 Cardiac Imaging And Metabolomics Studies Suggest Differential Risk And Protective Biomarkers For Cardiovascular Disease In Renoprotected, Long-Duration Type 1 Diabetes

Abstract Disclosure: M. Yu: None. S. Jangolla: None. N. Ziemniak: None. E. Viebranz: None. T. Chokshi: None. K. Park: None. I. Wu: None. H. Shah: None. G.L. King: None. Cardiovascular disease (CVD) is a major cause of mortality in people with Type 1 diabetes (T1D), especially in those with nephropathy (DN). However, in long-duration T1D, a substantial proportion of individuals without DN still exhibit excessive CVD risks. The Joslin 50-Year “Medalist” Study (n=1043), composed of people with T1D≥50 years, are ideal for studying CVD in a renoprotected T1D cohort, as only 13% have DN, and yet 40% have CVD, despite excellent control of lipids and blood pressure. Stratifying the Medalists by DN revealed that exercise was cardioprotective in the group with DN (OR 0.60, p=0.04); while age at T1D diagnosis (OR 1.03, p=0.01), HbA1c (OR 1.25, p=0.01), C-reactive protein (OR 1.14, p=0.01), and interleukin-6 (OR 1.13, p=0.01) all increased CVD risk in Medalists without DN. A subset of Medalists also underwent coronary artery calcification scans (CAC; n=153) and cardiac magnetic resonance imaging of left ventricular (LV) structure and function (CMR; n=111). The majority of these Medalists (97.8%) had detectable CAC&amp;gt;0; furthermore, the median CAC score of 1000 was higher at any cutoff compared to similar age-matched T1D and Type 2 diabetes (T2D) populations with higher DN prevalence. In contrast, mean CMR values in this Medalist subset were comparable to other cohorts. Continuous glucose monitoring (CGM) metrics for hyperglycemia (mean glucose, β=0.002, p=0.03; glucose management indicator, β=0.09, p=0.03; and time above range&amp;gt;180 mg/dL, β=0.003, p=0.02), but not glucose variability or hypoglycemia, were associated with LV remodeling in the Medalists, even after adjusting for eGFR. Likewise, plasma levels of advanced glycation end-products (AGEs) N-carboxyethyl-lysine (CEL), N-carboxymethyl-lysine (CML), and methylglyoxal-derived hydroimidazolone (MGH1) were associated with CAC (β=16.22, p=0.05; β=15.21, p=0.01; and β=10.18, p=0.01, respectively) and LV remodeling (β=0.001, p=0.09; β=0.001, p=0.05; and β=0.001, p=0.04, respectively) in the Medalists. The association of CEL with CVD replicated in a separate Medalist subset (n=311) with self-reported CVD data (OR 1.26, p=0.01). Plasma global metabolomics studies (n=140) revealed that amino acid activation pathways, with lower levels of branched chain amino acids, were associated with CAC (FDR=0.002); while amino acid metabolism pathways were associated with less favorable LV volumes (FDR=0.03). In this comprehensive study of aging T1D people with no substantial DN, hyperlipidemia, or hypertension, cardiac imaging and metabolomics studies suggest disproportionate advanced CAC, as compared to subclinical LV remodeling or dysfunction, and highlight the importance of targeting hyperglycemia for CVD risk reduction. Plasma metabolites associated with CVD in T1D are different from those in T2D, and may provide novel information on potential therapeutic targets for CVD in T1D. Presentation: 6/1/2024

Death of a Parent, Racial Inequities, and Cardiovascular Disease Risk in Early to Mid-adulthood.

Black Americans experience the death of a parent much earlier in the life course than White Americans on average. However, studies have not considered whether the cardiovascular health consequences of early parental death vary by race. Using data from the National Longitudinal Study of Adolescent to Adult Health, we explore associations between early parental death and cardiovascular disease (CVD) risk in early to mid-adulthood (N = 4,193). We find that the death of a parent during childhood or adolescence (ages 0-17) or the transition to adulthood (ages 18-27) is associated with increased CVD risk for Black Americans, whereas parental death following the transition to adulthood (ages 28+) undermines cardiovascular health for both Black Americans and White Americans. These findings illustrate how a stress and life course perspective can help inform strategies aimed at addressing both the unequal burden of bereavement and high cardiovascular risk faced by Black Americans.

Differences in Emotion Expression, Suppression, and Cardiovascular Consequences Between Black and White Americans in the Midlife in the United States (MIDUS) Study.

Recent theoretical work suggests that the expression of emotions may differ among Black and White Americans, such that Black Americans engage more frequently in expressive suppression to regulate emotions and avoid conflict. Prior work has linked expressive suppression usage with increases in cardiovascular disease risk, suggesting that racialized differences in expressive suppression usage may be one mechanism by which racism "gets under the skin" and creates health disparities. To examine racialized differences in expressive suppression and blood pressure (a measure of cardiovascular disease risk), we used self-report and facial electromyography (fEMG) data from two cohorts of Black and White Americans from the Midlife in the United States (MIDUS) longitudinal study (MIDUS 2, n = 271, 34.7% Black, collected from 2004 to 2009; MIDUS Refresher 1, n = 114, 31.6% Black, collected from 2012 to 2016; total N = 385, 33.9% Black). Black Americans reported engaging in expressive suppression more frequently than White Americans ( t (260.95) = 2.18, p = .002) and showed less corrugator fEMG activity during negative images ( t (969) = 2.38, pFDR = .026). Less corrugator activity during negative images was associated with higher systolic blood pressure only for Black Americans ( b = -4.63, t (375) = 2.67, p = .008). Overall, results are consistent with theoretical accounts that Black Americans engage more frequently in expressive suppression, which in turn is related to higher cardiovascular risk. Additional research is needed to further test this claim, particularly in real-world contexts and self-reports of in-the-moment usage of expressive suppression.