Effect Of Cardiovascular Risk Factors Research Articles

Thrombospondin-1 associated with carotid intima-media thickness among individuals with hypertension.

In vivo and in vitro studies have demonstrated that thrombospondin-1 (TSP-1) is involved in atherosclerotic pathogenesis. However, the role of TSP-1 in clinical atherosclerosis remains unknown. This cross-sectional study investigated the relationship between TSP-1 and carotid intima-media thickness (IMT) and examined whether it interacts with conventional cardiovascular risk factors. A total of 587 participants were enrolled from February 2018 to December 2021. TSP-1 was dichotomized based on median value. Carotid IMT was measured bilaterally in each segment, and the average value was taken as the overall IMT variable. Analysis of covariance models were used to ascertain the main and interaction effects of cardiovascular risk factors and circulating TSP-1 levels on carotid IMT. Those with high TSP-1 (n = 294) had significantly higher carotid IMT than did those with low TSP-1 (n = 293; 0.74 ± 0.12 vs 0.72 ± 0.11 mm; p = 0.011). After the combined effects of TSP-1 and vascular risk factors on carotid IMT were evaluated, an interaction effect on IMT was observed between TSP-1 and hypertension (adjusted F = 8.760; p = 0.003). Stratification analysis revealed that individuals with hypertension and high TSP-1 had significantly higher IMT than did those with low TSP-1 (adjusted p = 0.007). However, this difference was not observed in normotensive individuals (adjusted p = 0.636). In conclusion, this is the first study to provide clinical data supporting the correlation between TSP-1 and atherosclerosis. TSP-1 may be a crucial marker of increased susceptibility to atherosclerosis in individuals with hypertension.

Effects of cardiovascular risk factors and pre-existing diseases on the short-term outcome of Takotsubo syndrome.

The effects of cardiovascular risk factors (CVRF) on the development of most acute cardiac conditions are well established; however, little is known about the frequency and effects of CVRF in Takotsubo syndrome (TTS) patients. The aim of our study was to compare the frequency of CVRF and pre-existing diseases (PD) of TTS patients to ST-elevation myocardial infarction (STEMI) patients and analyze their effects on short-term outcome. We analyzed the frequency of CVRF (hypertension, hyperlipidemia, type II diabetes mellitus, smoking, chronic kidney disease, family history) as well as somatic and psychiatric PD at admission in TTS patients and compared them with STEMI patients. Their effect on short-term outcome was calculated using acombined endpoint of cardiogenic shock, cardiopulmonary resuscitation, mechanical ventilation, and/or in-hospital death. In total, 150 TTS and 155 STEMI patients were included in our study. We observed ahigher frequency of psychiatric (30% vs. 7%, p < 0.001), neurological (5% vs. 0%, p = 0.01), and pulmonary (18% vs. 5%, p < 0.001) PD in TTS patients as compared to STEMI patients. There were less smokers (47% vs. 61%, p = 0.03) and patients with hyperlipidemia (24% vs. 51%, p < 0.001) in the TTS cohort than in the STEMI cohort. None of the CVRF or PD behaved as an independent predictor for adverse short-term outcome in TTS patients. Psychiatric, neurological, and pulmonary pre-existing diseases are more common in TTS than in STEMI patients. Interestingly, PD and CVRF do not seem to have any impact on the short-term outcome of TTS patients.

Update on sex specific risk factors in cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of death worldwide and accounts for roughly 1 in 5 deaths in the United States. Women in particular face significant disparities in their cardiovascular care when compared to men, both in the diagnosis and treatment of CVD. Sex differences exist in the prevalence and effect of cardiovascular risk factors. For example, women with history of traditional cardiovascular risk factors including hypertension, tobacco use, and diabetes carry a higher risk of major cardiovascular events and mortality when compared to men. These discrepancies in terms of the relative risk of CVD when traditional risk factors are present appear to explain some, but not all, of the observed differences among men and women. Sex-specific cardiovascular disease research-from identification, risk stratification, and treatment-has received increasing recognition in recent years, highlighting the current underestimated association between CVD and a woman's obstetric and reproductive history. In this comprehensive review, sex-specific risk factors unique to women including adverse pregnancy outcomes (APO), such as hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus, preterm delivery, and newborn size for gestational age, as well as premature menarche, menopause and vasomotor symptoms, polycystic ovarian syndrome (PCOS), and infertility will be discussed in full detail and their association with CVD risk. Additional entities including spontaneous coronary artery dissection (SCAD), coronary microvascular disease (CMD), systemic autoimmune disorders, and mental and behavioral health will also be discussed in terms of their prevalence among women and their association with CVD. In this comprehensive review, we will also provide clinicians with a guide to address current knowledge gaps including implementation of a sex-specific patient questionnaire to allow for appropriate risk assessment, stratification, and prevention of CVD in women.

Early insulin resistance in normoglycemic low-risk individuals is associated with subclinical atherosclerosis

BackgroundElevated glycated hemoglobin (HbA1c) is associated with a higher burden of subclinical atherosclerosis (SA). However, the association with SA of earlier insulin resistance markers is poorly understood. The study assessed the association between the homeostatic model assessment of insulin resistance index (HOMA-IR) and SA in addition to the effect of cardiovascular risk factors (CVRFs) in individuals with normal HbA1c.MethodsA cohort of 3,741 middle-aged individuals from the Progression of Early Subclinical Atherosclerosis (PESA) study with basal HbA1c < 6.0% (< 42 mmol/mol) and no known CV disease underwent extensive imaging (multiterritorial vascular ultrasound and coronary artery calcium score, CACS) to assess the presence, burden, and extent of SA.ResultsIndividuals with higher HOMA-IR values had higher rates of CVRFs. HOMA-IR showed a direct association with the multiterritorial extent of SA and CACS (p < 0.001) and with global plaque volume measured by 3-dimensional vascular ultrasound (p < 0.001). After adjusting for key CVRFs and HbA1c, HOMA-IR values ≥ 3 were associated with both the multiterritorial extent of SA (odds ratio 1.41; 95%CI: 1.01 to 1.95, p = 0.041) and CACS > 0 (odds ratio 1.74; 95%CI: 1.20 to 2.54, p = 0.004), as compared with the HOMA-IR < 2 (the reference HOMA-IR category). In a stratified analysis, this association remained significant in individuals with a low-to-moderate SCORE2 risk estimate (75.6% of the cohort) but not in high-risk individuals.ConclusionsThe use of HOMA-IR identified low-risk individuals with a higher burden of SA, after adjusting for the effects of key traditional CVRFs and HbA1c. HOMA-IR is a simple measure that could facilitate earlier implementation of primary CV prevention strategies in clinical practice.

Examining the Interactive Effect of Cardiovascular Risk Factors and APOE Genotype on Population Health Disparities in dementia risk

AbstractBackgroundThere is a need to better understand the role of modifiable risk factors in the development of racial/ethnic health disparities in Alzheimer’s disease (AD). In particular, research is lacking on how clinical risk scores may interact with genetic liability for dementia in diverse populations. Here, we examined the influence of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Score (CAIDE) and APOE genotype on MCI/Dementia risk in non‐Latinx White (NLW), Black, and Latinx populations.MethodParticipants were from the National Alzheimer’s Coordinating Center Uniform Dataset who self‐reported as NLW (n = 15,296), Black (n = 2,136), or Latinx (n = 955) who were either cognitively normal or had a clinical diagnosis of MCI/Dementia at baseline (Table 1). CAIDE is comprised of age, gender, years of education, hypertension, obesity, and hypercholesteremia with scores ranging from 0‐14. Logistic regression models stratified by race/ethnicity were used to examine the association between CAIDE, APOE genotype, or their combination (9 categories combining favorable, intermediate, and unfavorable CAIDE scores with APOE e3/e3, e2+, and e4+) on MCI/dementia (Fig. 1‐2). Population differences were determined using Fisher’s z‐score method.ResultsAPOE e2+ was associated with reduced odds of MCI/dementia in NLW participants, while APOE e4+ was associated with increased risk in Latinx, Black, and NLW participants. Higher CAIDE scores were associated with increased risk of MCI/dementia in Latinx and NLW but were non‐significant in Black participants. The association of CAIDE on MCI/dementia in Black participants was significantly different from that in NLW and Latinx participants. Similarly, the effect of APOE e4+ on the risk of MCI/dementia was weaker in Latinx compared to NLW participants. In NLW, increasingly unfavorable modifiable risk profiles attenuated the protective effect of APOE e2+ and accentuated the deleterious impact of APOE e4+ on MCI/dementia. In Black participants, modifiable risk factors did not significantly affect the relationship between APOE genotype and MCI/dementia; in Latinx participants, there was only a moderate effect.ConclusionThe risk associated with APOE on MCI/Dementia is moderated by modifiable risk factors with suggestive population‐specific effects. Addressing health disparities will require risk scores that combine clinical, genetic, and social determinants of health and are applicable across diverse populations.

The modifying effects of cardiovascular risk factors on the relationship between lifetime discrimination and cognitive function: Study of Healthy Aging in African Americans (STAR)

AbstractBackgroundDiscrimination is a root cause of health inequities contributing to the excess burden of cognitive impairment among Black Americans. Using the Study of Healthy Aging in African Americans (STAR) we examined whether the effect of lifetime discrimination on late‐life cognitive decline was magnified by early adulthood cardiovascular risk factors.MethodSTAR enrolled long‐term Kaiser Permanente Northern California members ages 50+ who identify as Black/African American. In early adulthood, participants completed Multiphasic Health Check‐ups (MHC; 1964‐1985) where systolic blood pressure (BP), total cholesterol, and body mass index (BMI) were assessed. A latent class analysis identified groups based on responses to the Major Experiences of Discrimination Scale and gender. Standardized z‐scores for executive function (EF) and verbal episodic memory (VEM) were measured over 3 waves (2018‐2022) using the Spanish and English Neuropsychological Assessment Scales. Linear mixed models with random intercepts and slopes associated latent class with cognitive decline adjusting for age at MHC, age at baseline cognitive assessment, education, and assessment mode (in‐person/telephone). Separate models tested class*cardiovascular risk factor interactions.ResultParticipants (n = 646) averaged 27.7(SD = 7.3) years of age at MHC and 68.5(SD = 8.8) at baseline cognitive assessment (Table 1). Four latent classes were identified: men reporting widespread discrimination (Class‐1men; 12%), women reporting widespread discrimination (Class‐2women; 22%), men and women reporting unfair police treatment (Class‐3police; 17%), and men and women reporting little/no discrimination (Class‐4no_discimination; 49%). Using Class‐4no_discimination as reference, those in Class‐2women had significantly higher baseline EF (β(95% CI):0.18(0.03,0.34)) while Class‐1men (β:0.04(‐0.15,0.23)) and Class‐3police (β:‐0.08(‐0.25,0.09)) did not differ (Figure 1). Class‐2women (β:0.17(0.00,0.33)) had higher baseline VEM compared to Class‐4no_discrimination while Class‐1men (β:‐0.40(‐0.60,‐0.19)) and Class‐3police (β:‐0.27(‐0.46,‐0.09)) had significantly lower (Figure 1). There were no differences in rate of decline. There was a systolic BP*class interaction (p = 0.04) where 5 mm Hg higher systolic BP in early adulthood was associated with worse EF for Class‐3police (β:‐0.07(‐0.12,‐0.02)) compared to Class‐4no_discrimination while Class‐1men and Class‐2women did not differ (Figure 2). This pattern was similar for VEM but non‐significant (interaction p = 0.07). We found no interactions with total cholesterol or BMI.ConclusionFor Black Americans, discriminatory experiences may differentially impact late‐life cognition, and elevated systolic BP in early adulthood may exacerbate this harm.

Prevention of cardiovascular diseases

Cardiovascular diseases (CVD) are socially significant diseases due to high morbidity and loss of people of working age. In Bulgaria, they are the leading cause of mortality among the population and are a consequence of the effect of cardiovascular risk factors. The draft of the National Health Strategy (NHS) 2021–2030 reports on their wide distribution, as well as on the insufficient knowledge, skills and motivation for their prevention and control. The purpose of this review is to address the prevention of cardiovascular disease, which is a significant problem worldwide. Prevention goals for patients with established cardiovascular disease and those at high risk include smoking cessation, healthy eating, physical activity, and lowering body mass index. There are various methods that are part of health promotion to reduce CVD risks. These methods include motivational interviewing, non-pharmacological means, the use of certain medications for CVD prevention, as well as physical activity. Strategies for effective primary prevention refer to engaging the patient to change their lifestyle and identifying risk factors, while secondary prevention is aimed at activities to detect the disease early and to slow down its progression. It is necessary to create a strategy for timely preventive actions with a view to preventing the negative influence of risk factors and improving people‘s heart health.

Accelerated DNA methylation age plays a role in the impact of cardiovascular risk factors on the human heart

BackgroundDNA methylation (DNAm) age acceleration (AgeAccel) and cardiac age by 12-lead advanced electrocardiography (A-ECG) are promising biomarkers of biological and cardiac aging, respectively. We aimed to explore the relationships between DNAm age and A-ECG heart age and to understand the extent to which DNAm AgeAccel relates to cardiovascular (CV) risk factors in a British birth cohort from 1946.ResultsWe studied four DNAm ages (AgeHannum, AgeHorvath, PhenoAge, and GrimAge) and their corresponding AgeAccel. Outcomes were the results from two publicly available ECG-based cardiac age scores: the Bayesian A-ECG-based heart age score of Lindow et al. 2022 and the deep neural network (DNN) ECG-based heart age score of Ribeiro et al. 2020. DNAm AgeAccel was also studied relative to results from two logistic regression-based A-ECG disease scores, one for left ventricular (LV) systolic dysfunction (LVSD), and one for LV electrical remodeling (LVER). Generalized linear models were used to explore the extent to which any associations between biological cardiometabolic risk factors (body mass index, hypertension, diabetes, high cholesterol, previous cardiovascular disease [CVD], and any CV risk factor) and the ECG-based outcomes are mediated by DNAm AgeAccel. We derived the total effects, average causal mediation effects (ACMEs), average direct effects (ADEs), and the proportion mediated [PM] with their 95% confidence intervals [CIs]. 498 participants (all 60–64 years) were included, with the youngest ECG heart age being 27 and the oldest 90. When exploring the associations between cardiometabolic risk factors and Bayesian A-ECG cardiac age, AgeAccelPheno appears to be a partial mediator, as ACME was 0.23 years [0.01, 0.52] p = 0.028 (i.e., PM≈18%) for diabetes, 0.34 [0.03, 0.74] p = 0.024 (i.e., PM≈15%) for high cholesterol, and 0.34 [0.03, 0.74] p = 0.024 (PM≈15%) for any CV risk factor. Similarly, AgeAccelGrim mediates ≈30% of the relationship between diabetes or high cholesterol and the DNN ECG-based heart age. When exploring the link between cardiometabolic risk factors and the A-ECG-based LVSD and LVER scores, it appears that AgeAccelPheno or AgeAccelGrim mediate 10–40% of these associations.ConclusionBy the age of 60, participants with accelerated DNA methylation appear to have older, weaker, and more electrically impaired hearts. We show that the harmful effects of CV risk factors on cardiac age and health, appear to be partially mediated by DNAm AgeAccelPheno and AgeAccelGrim. This highlights the need to further investigate the potential cardioprotective effects of selective DNA methyltransferases modulators.

Abstract P197: The Total And Direct Effects Of Cardiovascular Risk Factors On Target Organ Injury And The Indirect Effect Mediated Through Blood Pressure Severity: Modifying Effect Of Chronic Kidney Disease

Youth-onset chronic kidney disease (CKD) is associated with early development of increased cardiovascular (CV) disease risk. CV health factors (CVHF) such as obesity, dyslipidemia, and hyperglycemia contribute to CV risk, but their specific role in target organ injury (TOI) development in youth with CKD is not well understood. Our objective was to determine the modifying effect of CKD on the total and direct effects of CVHF on TOI and the indirect effect mediated through blood pressure (BP) severity in youth with HTN disorders, hypothesizing that CKD would increase the mediating role of BP. Interim cross-sectional analysis of baseline data from the SUPERHERO Registry, a multisite retrospective registry of EHR data from youth referred for HTN disorders. Diagnoses were defined by ICD-10 codes unless otherwise specified. Inclusion criteria were age &lt;19 years and HTN disorder from 1/1/2015-12/31/2022 at initial subspecialty clinic visit. Exclusion criteria were dialysis, kidney transplantation, or pregnancy. Presence of 0-3 CVHF defined our exposure: any combination of obesity (by BMI %ile), dyslipidemia, or hyperglycemia. Outcome was TOI (kidney and/or heart). Mediator was BP by HTN severity (defined by U.S. pediatric guidelines). Total and direct effects of CVHF on TOI and indirect effect mediated via HTN were analyzed using generalized linear models and causal mediation analysis adjusted for unmet social needs and participant home region, stratified by CKD. Of 11580 participants, 488 (4%) had a CKD diagnosis. Presence of only 1 CVHF was associated with lower odds of TOI overall in youth without CKD (OR 0.69, 95% CL 0.59, 0.81) but higher odds in youth with CKD (OR 1.7, 95% CL 0.98, 2.8), interaction term p &lt;0.05. Presence of 2 CVHF was associated with higher odds of overall TOI (OR 1.53; 95% CL 1.14, 2.04) and heart-/kidney-specific TOI (OR 1.45 to 1.92). We found low prevalence of 3 CVHF and heart-specific TOI. We found no evidence of BP mediation or interaction for overall or organ-specific TOI. Our findings may be due to differences in kidney TOI between youth with and without CKD, reliance on ICD-10 codes, or different practices for TOI surveillance in youth with CKD. Future ongoing steps include analyzing laboratory and echocardiogram results for precision.

Effect of Cardiovascular Risk Factors on 30-Day All-Cause Mortality in Cardiogenic Shock.

Although previous studies investigated the influence of cardiovascular risk (CVR) factors in patients with acute coronary syndrome, data concerning the effect of CVR factors on the prognosis of patients with cardiogenic shock (CS) is scarce. Consecutive patients with CS were prospectively included from 2019 to 2021. The prognosis of patients with "low CVR" (i.e., 0-1 CVR factors) was compared to patients with "high CVR" (i.e., 2-4 CVR factors) according to presence or absence of arterial hypertension, diabetes mellitus, hyperlipidaemia or smoking. The primary endpoint was 30-day all-cause mortality. Statistical analyses included Kaplan-Meier and Cox proportional regression analyses. 273 consecutive patients with CS were included. 28% presented with low CVR and 72% with high CVR. Within the entire study cohort, the risk of 30-day all-cause mortality did not differ between patients with high and low CVR (55% vs. 57%; log rank p = 0.727; HR = 0.942; 95% CI 0.663-1.338; p = 0.738). Even after multivariable adjustment, high CVR was not associated with an elevated risk of 30-day all-cause mortality (HR = 1.039; 95% CI 0.648-1.667; p = 0.873). The presence of arterial hypertension (55% vs. 58%; log rank p = 0.564; HR = 0.906; 95% CI 0.638-1.287; p = 0.582), diabetes mellitus (60% vs. 52%; log rank p = 0.215; HR = 1.213; 95% CI 0.881-1.671; p = 0.237) and a history of smoking (56% vs. 56%; log rank p = 0.725; HR = 0.945; 95% CI 0.679-1.315; p = 0.737) did not significantly influence short-term prognosis.. Only the absence of hyperlipidaemia significantly decreased the risk of all-cause mortality (65% vs. 51%; log rank p = 0.038; HR = 0.718; 95% CI 0.516-0.998; p = 0.049), which was no longer observed after multivariable adjustment (HR = 0.801; 95% CI 0.536-1.195; p = 0.277). In conclusion, neither the overall CVR nor individual CVR factors were associated with the risk of 30-day all-cause mortality in patients with CS.

Cardiac pericytes may contribute to heart disease

Cardiovascular diseases which are the leading cause of death worldwide are promoted by well-known risk factors that include high blood pressure, age, sex, diabetes and/or obesity. Pericytes are mural cells wrapped around microvessels in many organs. They are mostly described as essential for microvascular integrity in the brain and retina. While the detrimental effects of cardiovascular risk factors on endothelial cells have been extensively studied, little is known about their impact on the biology of pericytes, especially in the heart. To determine how cardiac pericytes are modified by some cardiovascular risk factors. To do so, we used mice that were exposed to a high-fat diet (HFD) only to recapitulate obesity, to a HFD together with low dose-streptozotocin injections to mimic type 2 diabetes or to a HFD and L-NAME to recapitulate obesity with a mild hypertension. Mice were sacrificed 3 or 6 months after establishing these risk factors for histological and gene expression analyses. In mice exposed to the HFD + L-NAME regimen for 3 months, the percentage of capillaries covered by pericytes was not modified. However their phenotype appeared to be modified. Indeed, we isolated pericytes (CD31–, CD146+ cells) in the heart of both HFD L-NAME fed mice and control mice using magnetic beads and performed a bulk RNA-sequencing analysis on these cells which identified 3 genes of which the expression was significantly different in the 2 groups. In particular, Angiopoietin-like 4 mRNA expression was increased in the pericytes of HFD + L-NAME fed mice. This protein plays an important role in the regulation of lipid metabolism which makes it attractive to explore. In mice exposed to either HFD alone of HFD + streptozotocin for 6 months, the percentage of capillaries covered by pericytes was significantly diminished suggesting pericyte death. Cardiovascular risk factors, such as obesity and diabetes, may change the phenotype and/or the number of pericytes in the heart suggesting that these cells, known to be critical for microvascular integrity, could contribute to the onset of cardiac diseases.

Evidence of causal effects of blood pressure on back pain and back pain on type II diabetes provided by a bidirectional Mendelian randomization study

Background contextCardiovascular risk factors (hypertension, dyslipidemia, and type II diabetes) have been proposed as risk factors for back pain. However, few longitudinal studies have found significant associations between cardiovascular risk factors and back pain, and these may be explained by confounding or reverse causation. PURPOSETo examine potential causal effects of cardiovascular risk factors on back pain, and vice versa. Study designBidirectional Mendelian randomization (MR) study. Patient samplesGenome-wide association studies (GWAS) with sample sizes between 173,082 and 1,028,947 participants. Outcome measuresOutcomes included (1) back pain associated with health care use (BP-HC) in the forward MR; and (2) seven cardiovascular phenotypes in the reverse MR, including 2 measurements used for the evaluation of hypertension (diastolic blood pressure and systolic blood pressure), 4 phenotypes related to dyslipidemia (LDL cholesterol, HDL cholesterol, total cholesterol, and triglycerides), and type II diabetes. MethodsWe used summary statistics from large, publicly available GWAS for BP-HC and the 7 cardiovascular phenotypes to obtain genetic instrumental variables. We examined MR evidence for causal associations using inverse-variance weighted (IVW) analysis, Causal Analysis Using Summary Effect (CAUSE), and sensitivity analyses. ResultsIn forward MR analyses of seven cardiovascular phenotypes, diastolic blood pressure was associated with BP-HC across all analyses (IVW estimate: OR = 1.10 per 10.5 mm Hg increase [1.04–1.17], p-value = .001), and significant associations of systolic blood pressure with BP-HC were also found (IVW estimate: OR = 1.09 per 19.3 mm Hg increase [1.04–1.15], p-value = .0006). In reverse MR analyses, only type II diabetes was associated with BP-HC across all analyses (IVW estimate: OR = 1.40 [1.13–1.73], p-value = .002). ConclusionsThese findings from analyses of large, population-based samples indicate that higher blood pressure increases the risk of BP-HC, and BP-HC itself increases the risk of type II diabetes.

The effect of cardiovascular risk on disease progression in de novo Parkinson's disease patients: An observational analysis.

Currently available treatment options for Parkinson's disease are symptomatic and do not alter the course of the disease. Recent studies have raised the possibility that cardiovascular risk management may slow the progression of the disease. We estimated the effect of baseline cardiovascular risk factors on the progression of Parkinson's disease, using measures for PD-specific motor signs and cognitive functions. We used data from 424 de novo Parkinson's disease patients and 199 age-matched controls from the observational, multicenter Parkinson's Progression Markers Initiative (PPMI) study, which included follow-up of up to 9 years. The primary outcome was the severity of PD-specific motor signs, assessed with the MDS-UPDRS part III in the "OFF"-state. The secondary outcome was cognitive function, measured with the Montreal Cognitive Assessment, Symbol Digit Modalities Test, and Letter-Number Sequencing task. Exposures of interest were diabetes mellitus, hypertension, body mass index, cardiovascular event history and hypercholesterolemia, and a modified Framingham risk score, measured at baseline. The effect of each of these exposures on disease progression was modeled using linear mixed models, including adjustment for identified confounders. A secondary analysis on the Tracking Parkinson's cohort including 1,841 patients was performed to validate our findings in an independent patient cohort. Mean age was 61.4 years, and the average follow-up was 5.5 years. We found no statistically significant effect of any individual cardiovascular risk factor on the MDS-UPDRS part III progression (all 95% confidence intervals (CIs) included zero), with one exception: in the PD group, the estimated effect of a one-point increase in body mass index was 0.059 points on the MDS-UPDRS part III per year (95% CI: 0.017 to 0.102). We found no evidence for an effect of any of the exposures on the rate of change in cognitive functioning in the PD group. Similar results were observed for the Tracking Parkinson's cohort (all 95% CIs overlapped with PPMI), but the 95% CI of the effect of body mass index on the MDS-UPDRS part III progression included zero. Based on this analysis of two large cohorts of de novo PD patients, we found no evidence to support clinically relevant effects of cardiovascular risk factors on the clinical progression of Parkinson's disease.

Impact of Fasting Blood Glucose Levels on Blood Pressure Parameters among Older Adults with Prediabetes.

Prediabetes mellitus (pre-DM) is defined as blood glucose levels higher than normal but lower than the threshold for diabetes mellitus (DM) diagnosis. Four-limb blood pressure (BP) differences can help identify a significant risk for cardiovascular diseases (CVDs). The current study aimed to determine the importance of BP and the ankle-brachial index (ABI) between two patient groups and the association between fasting blood glucose (FBG) levels and four-limb BP, ABI, interarm BP difference (IAD), and interleg BP difference (ILD). Moreover, the effect of cardiovascular risk factors on the development of pre-DM among older adults was evaluated. The participants were divided into the normal fasting glucose (NFG) and impaired fasting glucose (IFG) groups. Data on physical characteristics, lipid profiles, four-limb BP, ABI, IAD, ILD, and cardiovascular risk factors were assessed. The IFG group had a significantly higher systolic blood pressure (SBP) and pulse pressure than the NFG group (p < 0.05). SBP was significantly positively correlated with FBG levels (p < 0.05). The IFG group had a lower ABI than the NFG group (p < 0.05). However, there was no significant difference in terms of IAD and ILD between the two groups. Furthermore, hypertension (HT), metabolic syndrome (MetS), and dyslipidemia were significantly correlated with a high prevalence of prediabetes (p < 0.05). Individuals with prediabetes had a higher BP than those with normoglycemia. Prediabetes was correlated with HT, MetS, and dyslipidemia.

Causal Associations Between Cardiovascular Risk Factors and Venous Thromboembolism.

The aim of the study is to assess the causal effects of cardiovascular risk factors on venous thromboembolism (VTE) and its subtypes including deep vein thrombosis (DVT) and pulmonary embolism (PE). A summary-level Mendelian randomization (MR) analysis was performed by extracting data from public and large-scale genome-wide association studies for cardiovascular risk factors (hypertension, systolic blood pressure [SBP], diastolic blood pressure [DBP], total cholesterol, triglycerides, high-density lipoprotein [HDL], low-density lipoprotein [LDL], type 2 diabetes, fasting glucose, body mass index [BMI], smoking, alcohol, and physical activity), VTE, DVT, and PE to identify genetic instruments. BMI (per standard deviation [SD] increase; odds ratio [OR]: 1.39; 95% confidence interval [CI]: 1.25-1.54; p = 8.02 × 10-10) could increase the VTE risk, whereas SBP (per SD increase; OR: 0.99; 95% CI: 0.98-0.99; p = 0.0005) could decrease the VTE risk. For DVT, BMI (per SD increase; OR: 1.48; 95% CI: 1.28-1.72; p = 1.53 × 10-7) could increase the risk, whereas physical activity (per SD increase; OR: 0.05; 95% CI: 0.01-0.33; p = 0.0020) could decrease the risk. For PE, BMI (per SD increase; OR: 1.29; 95% CI: 1.12-1.49; p = 0.0005) could increase the risk, whereas SBP (per SD increase; OR: 0.99; 95% CI: 0.98-1.00; p = 0.0032) could decrease the risk. Suggestive evidence between smoking and higher risks of VTE and DVT was also observed. Our study supports that BMI is a causal risk factor for VTE, DVT, and PE. SBP is a protective factor for VTE and PE. Physical activity is a protective factor for DVT. However, the effects of other cardiovascular risk factors are not identified.

Cyclophilin A and D Levels in Acute Coronary Syndrome and Their Relationship with Cardiovascular Risk Factors.

Our objective was to evaluate cyclophilin levels in patients with acute coronary syndrome (ACS) and their association with the clinical characteristics of these patients. We enrolled 150 patients with ACS (n=75 ST-elevation myocardial infarction [STEMI], n = 75 non-ST-elevation myocardial infarction [NSTEMI]). For comparison, 25 healthy volunteers were included in the study. Levels of cyclophilin A, cyclophilin D, and C-reactive protein (CRP) were measured in both the acute myocardial infarction (AMI) groups and the healthy group. We examined the effects of cardiovascular risk factors, including diabetes mellitus, hypertension, dyslipidemia, age, gender, and smoking on these parameters. Cyclophilin A levels were significantly lower in the STEMI group, while cyclophilin D and CRP levels were significantly higher in all AMI groups (P < 0.05). A negative correlation existed between cyclophilin A and troponin T and CK-MB (respectively r = -0.287, P < 0.001; r = -0.231, P = 0.005). However, there was no correlation between cyclophilin D and the cardiac markers. A positive correlation was observed between cyclophilin D and CRP (r = 0.219, P = 0.004). Cyclophilin A was associated with hypertension, whereas cyclophilin D was associated with the female gender and dyslipidemia (P < 0.05). Our findings suggest that a decrease in cyclophilin A indicates a more severe disease in STEMI and an increase in cyclophilin D in both STEMI and NSTEMI may be valuable markers. Therefore, further detailed studies are warranted to monitor their changes and interactions in ACS patients.

121 RELEVANCE OF COMORBIDITIES ON INITIAL COMBINATION THERAPY IN PULMONARY ARTERIAL HYPERTENSION

Abstract Rationale Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. Methods The study enrolled 181 treatment-naive PAH patients with a 6- months (IQR 144-363 days) right heart catheterization and risk assessment after initial oral combination therapy. Results Group-A, 96 (53.0%) patients without cardiac comorbidities; Group-B, 54 (29.8%) patients with one cardiac comorbidity; Group-C, 31 (17.1%) patients with ≥2 cardiac comorbidities. Group-C patients were older with a balanced gender distribution. There was a significant difference in PVR reduction moving from the absence to one or ≥2 cardiac comorbidities, respectively, median -45.0%, -30.3%, -24.3%. A ERS/ESC low-risk status was present at first follow-up in 50 (52.0%) patients in Group-A, 19 (35.1%) in Group-B, and 9 (29.0%) in Group-C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group-A, 15 (27.7%) in Group-B, and 7 (22.6%) in Group-C. Group-A patients were 2.3 times more likely to achieve/maintain a low risk status compared with Group-B and -C (OR 2.27, 95% C.I. 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Conclusion Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment- induced decrease in PVR.

Abstract 11584: Systemic Inflammation and Coronary Plaque Among Asymptomatic US Adults - Insights From the Miami Heart Study at Baptist Health South Florida

Objective: We aimed to evaluate the association between inflammatory markers and coronary plaque as detected on coronary computed tomography angiography (CCTA) in an asymptomatic adult population. Methods: Data from Miami Heart Study — an ongoing prospective cohort study from the Greater Miami Area were used for this cross-sectional analysis. Exposures of interest were C-reactive protein (CRP; &lt;2 vs ≥ 2mg/L) and Interleukin-6 (IL-6; in tertiles). The outcomes of interest were CCTA-based plaque findings: any plaque, CAC&gt;0, CAC&gt;100, maximal stenosis &gt;50%, and high-risk plaque. Multivariable logistic regression models were constructed to evaluate the association between inflammatory markers and coronary plaque features. Results: We evaluated 2,359 patients (50.4% men), mean age 53.4±6.7 years. The largest racial/ethnic groups were Hispanics (47%) and non-Hispanic Whites (43.1%). Of the total cohort, 8.3% had diabetes, 56.2% were hypertensive, and 22.3% used statins. After adjusting for age, sex, race/ethnicity, CRP ≥2 mg/L was associated with increased odds of detection of any plaque on CCTA [odds ratio (OR), 1.31 (95% CI, 1.09-1.58)] and stenosis ≥ 50% [OR, 1.69 (95% CI, 1.18- 2.41)]. Likewise, IL-6 levels in 3 rd tertile had higher odds of detecting any plaque and ≥50% stenosis by 1.6 and 2.5 folds, respectively ( Figure ); and were also associated with a CAC &gt;100 [OR, 1.69 (95% CI, 1.09 - 2.61)]. Further adjustment for LDL-C, diabetes, and tobacco use attenuated these associations. In contrast, no significant associations were observed with having high-risk coronary plaque. Conclusions: Elevated levels of CRP and IL-6 are associated with presence of coronary plaque &amp; stenosis on CCTA adjusted for demographics. However, these associations are markedly attenuated when adjusted for additional cardiovascular risk factors. Our findings suggest a role of systemic inflammation as a mediator of the effect of cardiovascular risk factors on coronary plaque burden.

Relevance of comorbidities on initial combination therapy in pulmonary arterial hypertension.

Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. The study enrolled 181 treatment-naive PAH patients with a 6-month (IQR 144-363 days) right heart catheterisation and risk assessment after initial oral combination therapy. Group A included 96 (53.0%) patients without cardiac comorbidities; Group B included 54 (29.8%) patients with one cardiac comorbidity; Group C included 31 (17.1%) patients with two cardiac comorbidities or more. Group C patients were older with a balanced sex distribution. There was a significant difference in PVR reduction moving from the absence to one or at least two cardiac comorbidities, respectively: median -45.0%, -30.3%, -24.3%. A European Respiratory Society/European Society of Cardiology low-risk status was present at first follow-up in 50 (52.0%) patients in Group A, 19 (35.1%) in Group B and 9 (29.0%) in Group C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group A, 15 (27.7%) in Group B and 7 (22.6%) in Group C. Group A patients were 2.3 times more likely to achieve/maintain a low-risk status compared with Group B and C (OR 2.27, 95% CI 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment-induced decrease in PVR.

Differential Roles of Life-Course Cumulative Burden of Cardiovascular Risk Factors in Arterial Stiffness and Thickness.

Data are limited regarding differential and common effects of cardiovascular risk factors on subclinical changes in vascular structure and function. We aimed to examine the relationships of life-course cumulative burdens of cardiovascular risk factors with adult arterial pulse wave velocity (PWV) and carotid intima-media thickness (CIMT) in a longitudinal cohort of the Bogalusa Heart Study. The cohort consisted of 900 subjects who had aortic-femoral PWV and CIMT measurements. These participants were examined 5-16 times for body mass index (BMI), blood pressure, atherogenic index of plasma (AIP), and low-density lipoprotein cholesterol (LDLC) from childhood to adulthood. The area under the curve (AUC) was calculated as a measure of long-term burden of the risk factors. Adjusting for covariates, adult PWV was associated with AUCs of BMI, systolic blood pressure (SBP) and AIP (standardized regression coefficient [β]= 0.191, 0.321, 0.153, respectively; P < 0.001 for all). Adult CIMT was associated with AUCs of BMI, SBP, AIP and LDLC (β= 0.115, 0.202, 0.141, 0.152, respectively; P < 0.001 for all). Moreover, childhood BMI was associated with adult PWV and CIMT (β= 0.088 and 0.075, respectively; false discovery rate q values < 0.05 for both), and childhood LDLC with adult CIMT (β= 0.079; false discovery rate q value < 0.05). These associations did not differ significantly among race and sex groups. The life-course cumulative burden of BMI, SBP, and AIP has common effects on arterial wall stiffening and thickening, whereas LDLC is specifically associated with arterial wall thickness, and this effect starts in early life.