Established Cardiovascular Disease Risk Factors Research Articles

Fibrinogen to HDL-Cholesterol ratio as a predictor of mortality risk in patients with acute myocardial infarction

BackgroundAcute myocardial infarction (AMI) is characterized by inflammation, oxidative stress, and atherosclerosis, contributing to increased mortality risk. High-density lipoprotein (HDL) takes a crucial part in mitigating atherosclerosis and inflammation through its diverse functionalities. Conversely, fibrinogen is implicated in the development of atherosclerotic plaques. However, the mortality risk predictive capacity of fibrinogen to HDL-cholesterol ratio (FHR) in AMI patients remains unexplored. This research aimed to evaluate the effectiveness of FHR for mortality risk prediction in relation to AMI.MethodsA retrospective study involving 13,221 AMI patients from the Cardiorenal ImprovemeNt II cohort (NCT05050877) was conducted. Baseline FHR levels were used to categorize patients into quartiles. The assessment of survival disparities among various groups was conducted by employing Kaplan‒Meier diagram. Cox regression was performed for investigating the correlation between FHR and adverse clinical outcomes, while the Fine-Gray model was applied to evaluate the subdistribution hazard ratios for cardiovascular death.ResultsOver a median follow-up of 4.66 years, 2309 patients experienced all-cause death, with 1007 deaths attributed to cardiovascular disease (CVD). The hazard ratio (HR) and its 95% confidence interval (CI) for cardiac and all-cause death among individuals in the top quartile of FHR were 2.70 (1.99–3.65) and 1.48 (1.26–1.75), respectively, in comparison to ones in the first quartile, after covariate adjustment. Restricted cubic spline analysis revealed that FHR was linearly correlated with all-cause mortality, irrespective of whether models were adjusted or unadjusted (all P for nonlinearity > 0.05).ConclusionAMI patients with increased baseline FHR values had higher all-cause and cardiovascular mortality, regardless of established CVD risk factors. FHR holds promise as a valuable tool for evaluating mortality risk in AMI patients.Trial registrationThe Cardiorenal ImprovemeNt II registry NCT05050877.

Metabolic syndrome and cardiovascular disease in cancer survivors.

The risk of subsequent cardiovascular disease (CVD) is high in cancer survivors. Although metabolic syndrome is an established risk factor for CVD, its association with cancer survivors has not yet been established. This study aimed to clarify whether metabolic syndrome is associated with subsequent CVD risk in patients with cancer using a nationwide epidemiological dataset. We retrospectively analysed 53510 patients with a history of breast, colorectal, or stomach cancer, which is reportedly a major site for developing cancer in Japan. Study participants were categorized into two groups based on the presence of metabolic syndrome, defined using the Japanese criteria (high waist circumference and ≥2 metabolic parameters including elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, or elevated fasting plasma glucose). The clinical outcomes were collected between 2005 and 2021. The primary endpoint was defined as the composite CVD outcome, including myocardial infarction, angina pectoris, stroke, and heart failure. The median patient age was 54years, and 37.5% of the patients were men. Metabolic syndrome was observed in 5558 (10.4%) patients. Over a mean follow-up period of 973±791days, 3085 composite CVD outcomes were recorded. Multivariable Cox regression analyses showed that metabolic syndrome was associated with a greater risk of developing CVD events (HR=1.29, 95% CI=1.15-1.45). Metabolic syndrome was also associated with an increased risk of CVD in patients with a follow-up period ≥1year (HR=1.33, 95% CI=1.15-1.53). This relationship was also observed when metabolic syndrome was defined according to the International Diabetes Federation criteria (HR=1.34, 95% CI=1.21-1.49) and the National Cholesterol Education Program Adult Treatment Panel III criteria (HR=1.32, 95% CI=1.19-1.46). Subgroup analyses showed that the relationship between metabolic syndrome and incident CVD was more pronounced in the non-obese participants than in the obese participants. Metabolic syndrome is associated with a greater risk of developing CVD, even among cancer survivors.

Association Between Coexisting Hypertension, Dyslipidemia, and Elevated C-Reactive Protein with Cardiovascular Disease in the Health and Retirement Study

Background: Cardiovascular disease (CVD) is the leading cause of death globally. Hypertension and dyslipidemia are established CVD risk factors, but these diagnoses are often insufficient in predicting CVD individually. Inflammation has emerged as a contributor to CVD, but research on the combination of inflammation, hypertension, and dyslipidemia in CVD risk is limited. More thorough evaluations of CVD risk using all 3 aforementioned risk factors are crucial. Methods: This report analyzes data from the Health and Retirement Study, a representative cohort of US adults over 50 years of age (n = 1,527). Participants were classified as having prevalent CVD if they self-reported a healthcare provider’s diagnosis of either a heart condition or a stroke or transient ischemic attack (TIA). We developed a CVD risk score using three factors known to contribute to CVD: hypertension, dyslipidemia, and elevated C-reactive protein (CRP). Risk was categorized as low (0-1 factors), medium (2 factors), or high (all 3 factors). Weighted logistic regression models estimated the adjusted odds ratio (OR) of CVD for medium and high-risk groups versus the low-risk group. Results: CVD prevalence in medium risk participants was not significantly different from low risk participants (OR = 1.21, 95% CI: [0.86 - 1.70]). After adjusting for age, high risk participants had significantly higher odds of CVD prevalence compared to participants with 0 or 1 of the risk factors (OR = 1.86, 95% CI: [1.26 - 2.74]). This association was robust to additional demographic adjustment for sex, race/ethnicity, obesity status, smoking status, and diabetes mellitus or hyperglycemia. Conclusion: Co-occurrence of hypertension, dyslipidemia, and elevated CRP was associated with CVD prevalence in a representative sample of older US adults. Our findings emphasize the importance of multifactor screening for CVD risk in clinical settings.

Associations of overweight and obesity with the risk of cardiovascular disease according to metabolic risk factors among middle-aged Japanese workers: The Aichi Workers’ cohort study

BackgroundThe association between obesity and cardiovascular disease (CVD) remains unclear, particularly for those with established CVD risk factors. We analyzed follow-up data from the Aichi Workers’ Cohort Study. We studied the association between the degree of obesity and risk of CVD and its subtypes specifically among individuals with hypertension, hyper-low-density lipoprotein (LDL)-cholesterolemia, or diabetes. MethodsPooled data of 8972 adults (7076 men and 1896 women) who were recruited between 2002 and 2008 were used in the current analysis. We used multivariable Cox proportional hazard model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between the degree of obesity assessed with body mass index (BMI) and the risk of CVD and its subtypes, i.e., coronary heart disease (CHD) and stroke. ResultsDuring a median of 12 years, there were 197 CVDs (80 CHDs and 117 strokes). BMI ≥ 27.5 compared to 21.0–22.9 kg/m2 was positively and significantly associated with the risks of CVD, CHD, and total stroke. Hypertension, hyper-LDL-cholesterolemia, and diabetes mediated 15.9%, 5.8%, and 8.7% of obesity-CVD associations, respectively, and 28.3% by their combination. In the stratified analyses by the presence of risk factors, BMI ≥ 25.0 (overweight/obesity) compared to BMI < 25 kg/m2 was associated with a higher risk of CVD in those with and without hypertension, but only with hyper-LDL-cholesterolemia, and without diabetes. ConclusionsOverweight/obesity was associated with the risk of CVD and its subtypes. About 30% of the risk was explained by hypertension, hyper-LDL-cholesterolemia, and diabetes, of which hypertension accounted for approximately the half of the explained risk. However, overweight/obesity increased the risk of CVD even in those without hypertension. These findings highlight the importance of controlling and preventing overweight/obesity regardless of chronic disease status.

Pregnancy History at 40 Years of Age as a Marker of Cardiovascular Risk.

Individual pregnancy complications are associated with increased maternal risk of cardiovascular disease. We assessed the link between a woman's total pregnancy history at 40 years of age and her relative risk of dying from atherosclerotic cardiovascular disease (ASCVD). This population-based prospective study combined several Norwegian registries covering the period 1967 to 2020. We identified 854 442 women born after 1944 or registered with a pregnancy in 1967 or later, and surviving to 40 years of age. The main outcome was the time to ASCVD mortality through age 69 years. The exposure was a woman's number of recorded pregnancies (0, 1, 2, 3, or 4) and the number of those with complications (preterm delivery <35 gestational weeks, preeclampsia, placental abruption, perinatal death, and term or near-term birth weight <2700 g). Cox models provided estimates of hazard ratios across exposure categories. The group with the lowest ASCVD mortality was that with 3 pregnancies and no complications, which served as the reference group. Among women reaching 40 years of age, risk of ASCVD mortality through 69 years of age increased with the number of complicated pregnancies in a strong dose-response fashion, reaching 23-fold increased risk (95% CI, 10-51) for women with 4 complicated pregnancies. Based on pregnancy history alone, 19% of women at 40 years of age (including nulliparous women) had an increased ASCVD mortality risk in the range of 2.5- to 5-fold. Pregnancy history at 40 years of age is strongly associated with ASCVD mortality. Further research should explore how much pregnancy history at 40 years of age adds to established cardiovascular disease risk factors in predicting cardiovascular disease mortality.

Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis.

Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D). We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.

Comparison of Arterial Stiffness among Prehypertensive and Normotensive Subjects using Photo Pulse Plethysmography: A Pilot Study

Introduction: Increased arterial stiffness is a marker of Cardiovascular Disease (CVD), even before clinical signs and symptoms become evident. Hypertension is an established risk factor for CVD. However, recent studies have revealed increased arterial stiffness even among prehypertensives. Photo Pulse Plethysmography (PPG) is an efficient non-invasive, and cost-effective technique to measure arterial stiffness. Studying arterial stiffness using PPG can serve as a surrogate marker of Cardiovascular (CV) risk among prehypertensives. Aim: To compare arterial wall stiffness among prehypertensives and normotensives using PPG. Materials and Methods: This pilot study was conducted at the Sri Ramachandra Institute of Higher Education and Research, Chennai, TamilNadu, India from December 2022 to February 2023. The study population included 10 non diabetic prehypertensives and 10 normotensives, aged between 30- 50 years, with normal lipid profiles. The peripheral pulse was recorded using a PPG module and digitised using AUDACITY software. The Arterial Stiffness Index (SI) was calculated and compared between the two groups. The correlation between anthropometry and arterial SI was also determined. Pearson’s correlation test was used to assess the association using Statistical Package for Social Sciences (SPSS) version 24.0. Results: The SI was found to be higher in prehypertensives compared to normotensives, and this difference was statistically significant (p-value=0.04). SI showed a positive correlation with increasing Blood Pressure (BP) and anthropometric variables (Body Mass Index [BMI] and Waist-Hip Ratio [WHR]; r=0.2 and r=0.15, respectively); however, no significant relationship was observed among these variables. Conclusion: This study concludes that the SI, an important CV risk marker, shows a significant increase in prehypertensive subjects compared to normotensive subjects. However, SI showed mild positive correlation with BP and other anthropometric measurements, though not statistically significant.

Resting Heart Rate Independent of Cardiovascular Disease Risk Factors Is Associated With End-Stage Renal Disease: A Cohort Study Based on 476 347 Adults.

The relationship between resting heart rate (RHR) and the risk of end-stage renal disease (ESRD) among those without cardiovascular disease remains unclear. We aim to establish temporal consistency and elucidate the independent relationship between RHR and the risk of ESRD. This cohort enrolled participants from 476 347 individuals who had taken part in a screening program from 1996 to 2017. We identified 2504 participants who had ESRD, and the median follow-up was 13 years. RHR was extracted from electrocardiography results, and the study assessed the relationship between RHR and the risk of ESRD using the Cox proportional hazards model. Of the participants, 32.6% had an RHR of 60 to 69 beats per minute (bpm), and 22.2% had an RHR of ≥80 bpm. Participants with an RHR of ≥80 bpm had a higher stage of chronic kidney disease, lower estimated glomerular filtration rate, and more proteinuria than those with an RHR of 60 to 69 bpm. Participants with an RHR of 80 to 89 and ≥90 bpm had a 24% (hazard ratio [HR], 1.24 [95% CI, 1.09-1.42]) and 64% (HR, 1.64 [95% CI, 1.42-1.90]) higher risk of ESRD, respectively. The risk of ESRD remained significantly elevated (HR, 1.32 [95% CI, 1.10-1.58] per 10-beat increase from 60 bpm) after excluding participants who smoked; had hypertension, diabetes, or hyperlipidemia; or were overweight. An RHR of ≥80 bpm is significantly associated with an increased risk of ESRD. These results suggest that RHR may serve as a risk factor for kidney disease in individuals without established cardiovascular disease risk factors.

Abstract 18072: Multiple Sclerosis and Covid-19-Related Myocarditis: A Brain and Heart Affectation

Introduction: Myocarditis (MC) and multiple sclerosis (MS) are inflammatory affectations of the myocardium and the central nervous system, respectively. It has been suggested that MS and MC share similar immunological dysfunctions. MS and MC also have associations with viral infection, and SARS-CoV-2 specifically has been associated with MC, indicating that a viral infection may induce or enhance a dysfunctional immune response favored by individuals' genetic susceptibility. Hypothesis: We hypothesized that patients with preexisting MS may be more susceptible to COVID-19-related MC. Methods: A retrospective study was conducted using the PearlDiver database (PearlDiver Technologies, Fort Wayne, IN). Using ICD codes, a cohort of patients admitted for COVID-19 as the primary diagnosis (index event) was identified. The cohort then was divided into two groups based on the presence of MS upon admission. The records of both groups were compared by demographics and a panel of 16 comorbidities. Pearson's chi-square and t-test were used to compare the group's characteristics when appropriate. A Kaplan-Meier analysis was then used to compare the probability of the outcome (MC) 90 days following the index event. A p-value of &lt;0.05 was considered significant. Results: We found a total of 2,782,278 patients admitted for COVID-19, with 24,515 (0.88%) having a history of MS. Patients with MS were younger (mean age 58 vs. 60, p&lt;0.0001), predominantly female (73%), and had more comorbidities (Elixhauser Comorbidity Index 8.8 vs. 6.3, p&lt;0.0001). A history of hypertension, heart failure, obesity, cerebrovascular accident, drug abuse, smoking, asthma, cancer, diabetes, MC, and MI were significantly more prevalent in the MS group. No differences in rheumatoid arthritis, CKD, and HIV were identified. COVID-19 patients with pre-existing MS were significantly at higher risk of MC, 90 days after admission (Log-Rank p=0.04). Conclusions: Despite its striking analogies to MS, the precise mechanism by which SARS-CoV-2 induces MC is unknown. Our findings highlight the likelihood that SARS-CoV-2 can induce myocardial inflammation in patients with a dysfunctional immune response. Moreover, MS patients were more exposed to established cardiovascular disease risk factors.

A deep learning system for retinal vessel calibre improves cardiovascular risk prediction in Asians with chronic kidney disease.

Cardiovascular disease (CVD) and mortality is elevated in chronic kidney disease (CKD). Retinal vessel calibre in retinal photographs is associated with cardiovascular risk and automated measurements may aid CVD risk prediction. Retrospective cohort study of 860 Chinese, Malay and Indian participants aged 40-80 years with CKD [estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2] who attended the baseline visit (2004-2011) of the Singapore Epidemiology of Eye Diseases Study. Retinal vessel calibre measurements were obtained by a deep learning system (DLS). Incident CVD [non-fatal acute myocardial infarction (MI) and stroke, and death due to MI, stroke and other CVD] in those who were free of CVD at baseline was ascertained until 31 December 2019. Risk factors (established, kidney, and retinal features) were examined using Cox proportional hazards regression models. Model performance was assessed for discrimination, fit, and net reclassification improvement (NRI). Incident CVD occurred in 289 (33.6%) over mean follow-up of 9.3 (4.3)years. After adjusting for established cardiovascular risk factors, eGFR [adjusted HR 0.98 (95% CI: 0.97-0.99)] and retinal arteriolar narrowing [adjusted HR 1.40 (95% CI: 1.17-1.68)], but not venular dilation, were independent predictors for CVD in CKD. The addition of eGFR and retinal features to established cardiovascular risk factors improved model discrimination with significantly better fit and better risk prediction according to the low (<15%), intermediate (15-29.9%), and high (30% or more) risk categories (NRI 5.8%), and with higher risk thresholds (NRI 12.7%). Retinal vessel calibre measurements by DLS were significantly associated with incident CVD independent of established CVD risk factors. Addition of kidney function and retinal vessel calibre parameters may improve CVD risk prediction among Asians with CKD.

Abstract P148: Association Of Hypertension With Cardiovascular Disease In The United States

Background: Hypertension is strongly associated with cardiovascular disease (CVD). Nevertheless, its relative importance compared with other established CVD risk factors among U.S. adults is unclear. Objective: To determine the prevalence of CVD risk factors and compare their association with CVD in a large U.S. population. Methods: The 2017 and 2019 Behavioral Risk Factor Surveillance System queried a representative sample of U.S. adults about hypertension (HTN), diabetes, and high cholesterol based on health professional diagnosis, obesity (BMI ≥30 from self-reported weight and height), smoking, and physical inactivity. We used logistic regression to examine the association between risk factors and CVD (nonfatal stroke and/or nonfatal myocardial infarction). Coefficients were compared using Wald tests. Models were also examined across sex (male vs. female), race (Black vs. White), and age (≥ 65 and &lt;65), using interaction terms. Results: The weighted sample was 21.0% age ≥65 years, 51.3% female, 70.0% Non-Hispanic White, and 11.6% Non-Hispanic Black. While all risk factors were associated with CVD, HTN was most strongly associated with CVD in the fully adjusted model (OR = 2.26; P -values comparing to other coefficients were all &lt;0.001). There was no evidence of effect modification across sex and race (all P -interaction values &gt;0.05), the association between hypertension and CVD was stronger for age &lt;65 years ( P &lt;0.001). Nevertheless, hypertension was still the strongest risk factor among both age groups. Conclusion: In this large U.S. sample, hypertension was the most prevalent and strongest CVD risk factor and should be a primary focus of policy focused on CVD prevention.

The association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques assessed by near-infrared spectroscopy.

Lipid content in coronary atheromatous plaques, measured by near-infrared spectroscopy (NIRS), can predict the risk of future coronary events. Biomarkers that reflect lipid content in coronary plaques may therefore improve coronary artery disease (CAD) risk assessment. We aimed to investigate the association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques in statin-treated patients with stable CAD undergoing percutaneous coronary intervention. 56 patients with stable CAD underwent three-vessel imaging with NIRS when feasible. The coronary artery segment with the highest lipid content, defined as themaximum lipid core burden index within any4mmlength across the entire lesion (maxLCBI4mm), was defined as target segment. Lipoprotein subfractions and Lipoprotein a (Lp(a)) were analyzed in fasting serum samples by nuclear magnetic resonance spectroscopy and by standard in-hospital procedures, respectively. Penalized linear regression analyses were used to identify the best predictors of maxLCBI4mm. The uncertainty of the lasso estimates was assessed as the percentage presence of a variable in resampled datasets by bootstrapping. Only modest evidence was found for an association between lipoprotein subfractions and maxLCBI4mm. The lipoprotein subfractions with strongest potential as predictors according to the percentage presence in resampled datasets were Lp(a) (78.1 % presence) and free cholesterol in the smallest high-density lipoprotein (HDL) subfractions (74.3 % presence). When including established cardiovascular disease (CVD) risk factors in the regression model, none of the lipoprotein subfractions were considered potential predictors of maxLCBI4mm. In this study, serum levels of Lp(a) and free cholesterol in the smallest HDL subfractions showed the strongest potential as predictors for lipid content in coronary atheromatous plaques. Although the evidence is modest, our study suggests that measurement of lipoprotein subfractions may provide additional information with respect to coronary plaque composition compared to traditional lipid measurements, but not in addition to established risk factors. Further and larger studies are needed to assess the potential of circulating lipoprotein subfractions as meaningful biomarkers both for lipid content in coronary atheromatous plaques and as CVD risk markers.

Increased Adherence to a Mediterranean Diet Is Associated with Reduced Low-Grade Inflammation after a 12.7-Year Period: Results from the Moli-sani Study.

There is little knowledge on the association of changes over time in adherence to a Mediterranean diet (MD) with changes in modifiable cardiovascular disease (CVD) risk factors and of markers of low-grade inflammation. To evaluate the association between long-term changes in MD adherence and concurrent changes in established CVD risk factors and in markers of low-grade inflammation among adult Italians. A prospective cohort study was conducted. Dietary and health data were obtained both at baseline (2005-2010) and at follow-up (2017-2020). Adherence to the MD was estimated by a Mediterranean Diet Score ranging from zero to nine points, and the exposure was change in this score measured after a median 12.7-year period. This study included a subgroup of 897 men and 1,126 women aged ≥35 years at enrolment in the Moli-sani Study (n= 24,325). Changes in two composite z scores, including nine established CVD risk factors (eg, serum lipid levels and blood pressure) and four inflammatory markers (including C-reactive protein), respectively, were measured both at enrolment and after the same 12.7-year period. Multivariable-adjusted linear regression models were used. In a multivariable-adjusted analysis, an increased Mediterranean Diet Score over time was associated with decreased levels in the Inflammatory score (β= -0.372, 95% CI -0.720 to -0.025), but had little or no influence on the CVD risk score (β= -0.200, 95% CI -0.752 to 0.351), compared with individuals who had decreased their MD adherence. Among individual food groups/nutrients included in the Mediterranean Diet Score, an increased intake of monounsaturated over saturated fats over time was associated with lower CVD Risk Score, whereas increased consumption of cereals was inversely linked to the Inflammatory Score, compared with the reduced consumption group. An increased adherence to a traditional MD over time was associated with reduced low-grade inflammation. These findings suggest the potential of a traditional Mediterranean eating pattern to help reduce the long-term risk of inflammation-related chronic diseases in an ageing population.

Impact of perinatal factors on biomarkers of cardiovascular disease risk in preadolescent children.

This review aims to summarize associations of the perinatal environment with arterial biophysical properties in childhood, to elucidate possible perinatal origins of adult cardiovascular disease (CVD). A systematic search of PubMed database was performed (December 2020). Studies exploring associations of perinatal factors with arterial biophysical properties in children 12 years old or less were included. Properties studied included: pulse wave velocity; arterial stiffness or distensibility; augmentation index; intima-media thickness of aorta (aIMT) or carotids; endothelial function (laser flow Doppler, flow-mediated dilatation). Two reviewers independently performed study selection and data extraction. Fifty-two of 1084 identified records were included. Eleven studies explored associations with prematurity, 14 explored maternal factors during pregnancy, and 27 explored effects of low birth weight, small-for-gestational age and foetal growth restriction (LBW/SGA/FGR). aIMT was consistently higher in offspring affected by LBW/SGA/FGR in all six studies examining this variable. The cause of inconclusive or conflicting associations found with other arterial biophysical properties and perinatal factors may be multifactorial: in particular, measurements and analyses of related properties differed in technique, equipment, anatomical location, and covariates used. aIMT was consistently higher in LBW/SGA/FGR offspring, which may relate to increased long-term CVD risk. Larger and longer term cohort studies may help to elucidate clinical significance, particularly in relation to established CVD risk factors. Experimental studies may help to understand whether lifestyle or medical interventions can reverse perinatal changes aIMT. The field could be advanced by validation and standardization of techniques assessing arterial structure and function in children.

Isocaloric Substitution of Plant-Based Protein for Animal-Based Protein and Cardiometabolic Risk Factors in a Multiethnic Asian Population

BackgroundEvidence is accumulating that intake of animal-based and plant-based proteins has different effects on cardiometabolic health, but less is known about the health effect of isocaloric substitution of animal-based and plant-based proteins. Data from Asian populations are limited. ObjectivesThis study aimed to evaluate the effects of isocaloric substitution of total plant-based proteins for total and various animal-based protein food groups and to evaluate the effects of substituting protein from legumes and pulses for various animal-based protein food groups on cardiovascular disease (CVD) risk factors and predicted 10-y CVD risk. MethodsWe conducted a cross-sectional analysis using data collected from 9211 Singapore residents (aged 21–75 y) from the Singapore Multi-Ethnic Cohort. Data on sociodemographic and lifestyle factors were collected using questionnaires. Dietary intakes were assessed using a validated FFQ. BMI, waist circumference, and blood pressure were measured during a physical examination, and blood samples were collected to measure lipid profiles. Associations were assessed by substitution models using a multiple linear regression analysis. ResultsIsocaloric substitution of total plant-based proteins for total and all specific animal-based protein food groups were associated with lower BMI (β: −0.30; 95% CI: −0.38, −0.22), waist circumference (β: −0.85; 95% CI: −1.04, −0.66), and LDL cholesterol concentrations (β: −0.06; 95% CI: −0.08, −0.05) (P < 0.0056). Replacement of processed meat and processed seafood proteins with total plant-based proteins was associated with improvement in most CVD risk factors and predicted 10-y CVD risk. Replacement of oily fish with legume proteins was associated with lower HDL cholesterol and higher TG concentrations. ConclusionsThe substitution of plant-based proteins for animal-based proteins, especially from processed meat and processed seafood, was inversely associated with the established CVD risk factors such as BMI, waist circumference, and lipid concentrations and predicted 10-y CVD risk. These findings warrant further investigation in independent studies in other Asian populations.

Abstract P218: Quality of Plant-Based Diets is Differently Associated With Cardiovascular Mortality: A Longitudinal Analysis From the Moli-Sani Study

Introduction: Vegetarian diets are characterized by the absence of some animal foods (e.g. red and processed meats), and a high consumption of plant-based foods. However, plant-based foods can include foods with varying nutritional value and divergent health effects. Hypothesis: We assessed the hypothesis that three different pro-vegetarian (PVG) food patterns defined as general (gPVG), healthful (hPVG) and unhealthful (uPVG) are differently associated with the risk of cardiovascular disease (CVD) mortality in adult Italians. Established CVD risk factors ( e.g. blood lipids, inflammatory markers) were analyzed as potential biological mechanisms underpinning these associations. Methods: Longitudinal analysis on 22,895 women and men (mean age 55±12 y) from the Moli-sani Study (2005-2010). Food intake was assessed by a 188-item food frequency questionnaire. A pro-vegetarian food pattern was constructed by assigning positive scores to plant foods and reverse scores to animal foods. Both a healthful and an unhealthful pro-vegetarian food patterns, distinguishing between healthy ( e.g . fruits, vegetables, legumes) and less-healthy plant foods ( e.g . fruit juices, potatoes, sugary beverages), were built up. Cox proportional hazard regression models were used to estimate the association between dietary exposures (quarters of) and mortality. Hazard ratios (HRs) were calculated with their 95% confidence intervals (CIs) for each quarter, considering Q1 as the reference category. Results: After a median follow-up of 12.2 y (272,960 person/years), a total of 792 CVD deaths were ascertained. In multivariable-adjusted analyses controlled for common known risk factors, higher adherence to a gPVG was not associated with CVD mortality (HR=0.92; 0.75-1.13 for Q4 vs. Q1). Increasing adherence to a hPVG was linked to lower risk of CVD mortality (HR=0.78; 0.62-0.98 for Q4 vs. Q1), whereas a higher uPVG led to an increased risk (HR=1.28; 1.04-1.57). Altered levels of subclinical inflammation ( i.e. C-reactive protein) accounted for 13.4% (p=0.012) of the association of the hPVG with CVD mortality. Conclusions: In this large Italian general population, increasing adherence to a general pro-vegetarian food pattern was not associated with CVD mortality. Only participants preferring healthful vegetarian foods experienced a significant protection against CVD mortality risk, possibly through a favorable modulation of the inflammatory pathway. Consistently, a large dietary share of unhealthful vegetarian foods, mostly highly processed, was associated with increased risk of CVD mortality. We conclude that it is not sufficient to adopt a general vegetarian diet, since it is the quality of the plant food consumed that is critical to achieve vegetarian diet-related benefits on CVD mortality.

Adverse pregnancy outcomes and the development of short-term maternal cardiovascular disease risk factors

Adverse pregnancy outcomes (APOs) are linked to future maternal cardiovascular disease (CVD) risk factors and events. We sought to examine the association between APOs and short-term established CVD risk factors in a contemporary, high-risk, racially, and ethnically diverse hospital population in North Carolina.

769 EFFECT OF GLUCOSE LOWERING AGENTS ON CARDIAC AUTONOMIC FUNCTION AND STRUCTURE IN TYPE 2 DIABETES MELLITUS

Effects of novel glucose-lowering agents on cardiac autonomic function and structure in type 2 diabetes Ilaria Cavallari, Ernesto Maddaloni, Francesco Veneziano, Carla Indennidate, Maria Valeria Giaccari, Dario Tuccinardi, Silvia Pieralice, Nicola Napoli, Raffaella Buzzetti, Francesco Grigioni Background Novel glucose-lowering agents, such as sodium glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, have the potential to reduce major adverse cardiovascular events among people with type 2 diabetes. However, mechanisms behind their cardiovascular protection and the implications of positive chronotropic effects of GLP-1 receptor agonists are not fully understood. Purpose To elucidate and compare the effects of novel glucose-lowering agents on cardiac autonomic function and structure. Methods This prospective observational study included subjects with type 2 diabetes and either a history of established cardiovascular disease or multiple risk factors and early initiation (within 2 weeks) of a SGLT-2 inhibitor or a GLP-1 receptor agonist on top of standard of care. Patients were followed for a median of 2 months. As per study protocol, background medical therapy should have remained stable for the entire duration of the study. Cardiac autonomic reflex tests (heart rate response to a deep breathing and to standing) and echocardiography were performed in all patients at baseline and at the end of follow-up. Endpoints were changes from baseline of E/I ratio, 30:15 ratio and indices of cardiac structure and function. Results A total of 37 patients completed follow-up, of whom 20 were on SGLT-2 inhibitors and 17 on GLP-1 receptor agonists. Mean age was 69 years, mean disease duration was 14 years and mean HbA1c value was 7.5%. Cardiac autonomic dysfunction, defined as at least an abnormal test, was found in 19% of patients (n=7). At a median follow-up of 2 months, there were no differences from baseline in heart rate response to a deep breathing test (p=0.92) and to standing (p=0.86). No differences were found when patients were stratified according to drug class. Among echocardiographic parameters, significant reductions of left ventricular mass (300.5±73.3 vs 280.4±68.3 g/m2, p=0.048) and left atrial volume (61.3±29.4 vs 54.7±18.0 ml, p=0.034) were found with no interaction by drug class. Left ventricular end-diastolic and systolic volumes, ejection fraction, filling pressures and pulmonary artery pressure did not substantially change. Conclusions In a population of patients with type 2 diabetes, short-term treatment with novel glucose-lowering agents significantly reduced left ventricular mass and left atrial volume but did not affect cardiac autonomic function.

Podocyturia: an earlier biomarker of cardiovascular outcomes

Urinary podocin and nephrin mRNAs (podocyturia), as candidate biomarkers of endothelial/podocyte injury, were measured by quantitative PCR in Type II diabetics with normal albumin excretion rates (AER) at baseline, at 3–4 years, and at 7 years. Development of cardiovascular disease (CVD) was collected as outcome. Visit 1 podocyturia was significantly higher in subjects who subsequently developed CVD versus those who did not. Visit 1 AER terciles exhibited similar time to CVD, in contrast with stepwise and substantial increases in CVD events predicted by Visit 1 podocyturia terciles. Covariate-adjusted hazard ratios were highest for podocin, intermediate for nephrin mRNAs, and lowest for AER. Podocyturia was also measured in patients with and without significant coronary obstruction, and in 480 normoalbuminuric subjects at the enrolment visit to the Multi-Ethnic Study of Atherosclerosis (MESA). Podocyturia > 3 × 106 copies was associated with presence of obstructive coronary artery disease. In the MESA population, Visit 1 podocyturia was significantly higher in men, subjects with elevated BMI, and those with Type II DM. Conclusions: Podocyturia may be an earlier predictor of cardiovascular events than moderate albuminuria; it is significantly higher in patients with obstructive coronary artery disease, and in subjects with established risk factors for CVD.

Effects of lifestyle interventions on cardiovascular risk factors in South Asians: a systematic review and meta-analysis

BackgroundThe cardiovascular disease (CVD) burden among South Asians is high. Lifestyle interventions have been effective in the primary prevention of CVD, but this has not been replicated, through a synthesis...