Food Compass Score predicts incident cardiovascular disease: The ATTICA cohort study (2002-2022).

BACKGROUND: The Food Compass Score (FCS) is a novel nutrient profiling system, which evaluates food and diet quality. The present study aimed to prospectively assess the relationship of FCS with short-term (10 years) and long-term (20 years) cardiovascular disease (CVD) incidence and to explore whether this relationship is modified by long-term adherence to a Mediterranean type diet (MTD). METHODS: Volunteers of the ATTICA cohort study, with complete data for the calculation of FCS and incident CVD were included (n = 759). Development of CVD was determined at 10 and 20 years after baseline. Dietary intake was assessed through a validated food frequency questionnaire. The FCS was calculated for each participant based on the published algorithm. Long-term adherence to a MTD was evaluated through MedDietScore. RESULTS: FCS was inversely associated with CVD incidence (hazard ratio [HR] for 20-year follow-up = 0.97, 95% confidence interval [CI] = 0.95-0.99; HR for 10-year follow-up = 0.98, 95% CI = 0.96-1.01) in the total sample, as well as in those with a high baseline adherence to a MTD (HR for 20-year follow-up = 0.96, 95% CI = 0.93-0.99; HR for 10-year follow-up = 0.98, 95% CI = 0.95-1.02). FCS was also inversely associated with CVD risk in those who went away from the MTD (HR = 0.97, 95% CI = 0.96-0.99). CONCLUSIONS: FCS, a novel tool for assessing overall diet quality, was also found to be useful in identifying potential CVD candidates in a long-term period, even in populations with good background dietary habits, such as those following a MTD.

Timing and Predictors of Incident Cardiovascular Disease in Systemic Lupus Erythematosus: Risk Occurs Early and Highlights Racial Disparities.

OBJECTIVE: Systemic lupus erythematosus (SLE) affects Black people 2 to 3 times more frequently than non-Black people and is associated with higher morbidity and mortality. In total, 4 studies with predominantly non-Black SLE cohorts highlighted that cardiovascular disease (CVD) is no longer primarily a late complication of SLE. This study assessed the timing and predictors of incident CVD in a predominantly Black population-based SLE cohort. METHODS: Incident SLE cases from the population-based Georgia Lupus Registry were validated as having a CVD event through review of medical records and matching with the Georgia Hospital Discharge Database and the National Death Index. The surveillance period for an incident CVD event spanned a 15-year period, starting from 2 years prior to SLE diagnosis. RESULTS: Among 336 people with SLE, 253 (75%) were Black and 56 (17%) had an incident CVD event. The frequency of CVD events peaked in years 2 and 11 after SLE diagnosis. There was a 7-fold higher risk of incident CVD over the entire 15-year period; this risk was 19-fold higher in the first 12 years in Black people as compared to non-Black people with SLE. Black people with SLE (P < 0.001) and those with discoid rash (hazard ratio 3.2, 95% CI 1.4-7.1) had a higher risk of incident CVD events. CONCLUSION: The frequency of incident CVD events peaked in years 2 and 11 after SLE diagnosis. Being Black or having a discoid rash were strong predictors of an incident CVD event. Surveillance for CVD and preventive interventions, directed particularly toward Black people with recent SLE diagnoses, are needed to reduce racial disparities.

Prediction of cardiovascular disease by abdominal obesity measures is dependent on body weight and sex--results from two community based cohort studies.

AIM: To study waist-hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), and waist-hip-height ratio (WHHR) as predictors of CVD, in men and women stratified by BMI (cut-off ≥25). METHODS AND RESULTS: A cohort of n = 3741 (53% women) 60-year old individuals without CVD was followed for 11-years (375 CVD cases). To replicate the results, we also assessed another large independent cohort; The Malmö Diet and Cancer study - cardiovascular cohort (MDCC, (n = 5180, 60% women, 602 CVD cases during 16-years). After adjustment for established risk factors in normal-weight women, the hazard ratio (HR) per one standard deviation (SD) were; WHR; 1.91 (95% confidence interval (CI) 1.35-2.70), WC; 1.81 (95% CI 1.02-3.20), SAD; 1.25 (95% CI 0.74-2.11), and WHHR; 1.97 (95% CI 1.40-2.78). In men the association with WHR, WHHR and WC were not significant, whereas SAD was the only measure that significantly predicted CVD in men (HR 1.19 (95% CI 1.04-1.35). After adjustments for established risk factors in overweight/obese women, none of the measures were significantly associated with CVD risk. In men, however, all measures were significant predictors; WHR; 1.24 (955 CI 1.04-1.47), WC 1.19 (95% CI 1.00-1.42), SAD 1.21 (95% CI 1.00-1.46), and WHHR; 1.23 (95% CI 1.05-1.44). Only the findings in men with BMI ≥ 25 were verified in MDCC. CONCLUSION: In normal weight individuals, WHHR and WHR were the best predictors in women, whereas SAD was the only independent predictor in men. Among overweight/obese individuals all measures failed to predict CVD in women, whereas WHHR was the strongest predictor after adjustments for CVD risk factors in men.

Choline metabolites and incident cardiovascular disease in a prospective cohort of adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: The potential role for choline metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD) has garnered much attention, but there have been limited data from diverse population-based cohorts. Furthermore, few studies have included circulating choline and betaine, which can serve as precursors to TMAO and may independently influence CVD. OBJECTIVE: We quantified prospective associations between 3 choline metabolites and 19-y incident CVD in a population-based cohort and tested effect modification of metabolite-CVD associations by kidney function. METHODS: Data were from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a prospective cohort with recruitment from 4 US urban centers (year 0: 1985-1986, n = 5115, ages 18-30). The analytic sample included 3444 White and Black males and females, aged 33 to 45, who attended the year 15 follow-up exam and did not have prevalent CVD. TMAO, choline, and betaine were quantitated from stored plasma (-70°C) using liquid-chromatography mass-spectrometry. Nineteen-year incident CVD events (n = 221), including coronary heart disease and stroke, were identified through adjudicated hospitalization records and linkage with the National Death Register. RESULTS: Plasma choline was positively associated with CVD in Cox proportional hazards regression analysis adjusted for demographics, health behaviors, CVD risk factors, and metabolites (hazard ratio: 1.24; 95% CI: 1.09, 1.40 per standard deviation-unit choline). TMAO and betaine were not associated with CVD in an identically adjusted analysis. There was statistical evidence for effect modification by kidney function with CVD positively associated with TMAO and negatively associated with betaine at lower values of estimated glomerular filtration rate (interaction P values: 0.0046 and 0.020, respectively). CONCLUSIONS: Our findings are consistent with a positive association between plasma choline and incident CVD. Among participants with lower kidney function, TMAO was positively, and betaine negatively, associated with CVD. These results further our understanding of the potential role for choline metabolism on CVD risk.

High-Density Lipoprotein Particle Concentration and Size Predict Incident Coronary Artery Disease Events in a Cohort With Type 1 Diabetes.

BACKGROUND: The cholesterol efflux capacity of high density lipoprotein (HDL) is negatively associated with cardiovascular risk. Small HDL particles account almost quantitatively for cholesterol efflux capacity, perhaps mediated through efflux of cholesterol and outer leaflet plasma membrane phospholipids by ABCA1 (ATP binding cassette subfamily A member 1). People with type 1 diabetes are at increased coronary artery disease (CAD) risk despite normal HDL-cholesterol concentrations. We therefore tested the hypothesis that small HDL particles (HDL-P)-rather than HDL-cholesterol-predict incident CAD in type 1 diabetes. METHODS AND RESULTS: Incident CAD (CAD death, myocardial infarction, or coronary revascularization) was determined in 550 individuals with childhood-onset type 1 diabetes. HDL-P was quantified by calibrated ion mobility analysis and cholesterol efflux capacity was quantified with validated assays. During a median follow-up of 26 years, 36.5% of the participants developed incident CAD, for an incidence density of 181.3 per 10 000 person-years. In multivariable Cox models, neither HDL-cholesterol nor apolipoprotein A1 concentration was significantly associated with CAD risk. In contrast, higher extra-small HDL-P concentrations were significantly associated with decreased CAD risk (hazard ratio [HR], 0.26 [95% CI, 0.14-0.50]). Weaker associations were observed for total HDL-P (HR, 0.88 [95% CI, 0.83-0.93]), small HDL (HR, 0.83 [95% CI, 0.68-1.02]), medium HDL (HR, 0.79 [95% CI, 0.71-0.89]), and large HDL (HR, 0.72 [95% CI, 0.59-0.89]). Although cholesterol efflux capacity was negatively associated with incident CAD, this association was no longer significant after adjustment for total HDL-P. CONCLUSIONS: Lower concentrations of total HDL-P and HDL subpopulations were positively associated with incident CAD independently of HDL-cholesterol, apolipoprotein A1, and other common CVD risk factors. Extra-small HDL was a much stronger predictor of risk than the other HDLs. Our data are consistent with the proposal that extra-small HDL plays a critical role in cardioprotection in type 1 diabetes, mediated by macrophage cholesterol efflux by the ABCA1 pathway.

Novel Plasma Biomarkers Associated with Future Peripheral Atherosclerotic Disease and Abdominal Aortic Aneurysm-Insights from Contemporary Prospective Studies from the Malmö Diet and Cancer Study.

INTRODUCTION: The potential utility of inflammatory and hemodynamic plasma biomarkers for the prediction of incident lower extremity arterial disease (LEAD), carotid artery stenosis (CAS), isolated atherosclerotic disease without concomitant abdominal aortic aneurysm (AAA), and isolated AAA without concomitant atherosclerotic disease has not yet been integrated in clinical practice. The main objective of this prospective study was to find predictive plasma biomarkers for cardiovascular disease and to evaluate differences in plasma biomarker profiles between asymptomatic and symptomatic CAS, as well as between isolated atherosclerotic disease and isolated AAA. METHODS: Blood samples collected at baseline from participants in the prospective Malmö Diet and Cancer study (MDCS) cardiovascular cohort (n = 5550 middle-aged individuals; baseline 1991-1994) were used for plasma biomarker analysis. Validation of each incident cardiovascular diagnosis was performed by random sampling. Cox regression analysis was used to calculate hazard ratios (HRs) per one standard deviation increment of each respective log-transformed plasma biomarker with 95% confidence intervals (CI). RESULTS: Adjusted lipoprotein-associated phospholipase A2 (Lp-PLA2) activity (HR 1.33; CI 1.17-1.52) and mass (HR 1.20; CI 1.05-1.37), C-reactive protein (CRP) (HR 1.55; CI 1.36-1.76), copeptin (HR 1.46; CI 1.19-1.80), N-terminal pro-B-type natriuretic peptide (N-BNP) (HR 1.28; 1.11-1.48), and cystatin C (HR 1.19; 95% 1.10-1.29) were associated with incident symptomatic LEAD. Adjusted N-BNP (HR 1.59; CI 1.20-2.11), mid-regional proadrenomedullin (HR 1.40; CI 1.13-1.73), cystatin C (HR 1.21; CI 1.02-1.43), and CRP (HR 1.53; CI 1.13-1.73) were associated with incident symptomatic but not asymptomatic CAS. Adjusted HR was higher for Lp-PLA2 (mass) for incident isolated AAA compared to for isolated atherosclerotic disease. CONCLUSIONS: Plasma biomarker profile data support that subclinical vascular inflammation and cardiovascular stress seem to be relevant for the development of atherosclerotic disease and AAA.

Triglyceride/HDL cholesterol ratio and lipoprotein insulin resistance Score: Associations with subclinical atherosclerosis and incident cardiovascular disease.

BACKGROUND: The triglyceride/HDL cholesterol (TG/HDL-C) ratio and the Lipoprotein Insulin Resistance (LP-IR) score are lipid markers of insulin resistance. Their associations with carotid intima media thickness (cIMT; subclinical atherosclerosis) and incident cardiovascular disease (CVD) have not been thoroughly investigated. METHODS: In a cross-sectional cohort (89 subjects without type 2 diabetes (T2D) and 81 subjects with T2D we determined cIMT (ultrasound), homeostasis model assessment of insulin resistance (HOMA-IR) and the TG/HDL-C ratio. The LP-IR score, based on 6 lipoprotein characteristics determined by nuclear magnetic resonance spectroscopy, was measured in 123 participants. A prospective study was carried out among 6232 participants (Prevention of REnal and Vascular ENd-stage Disease study). RESULTS: Cross-sectionally, the adjusted associations of HOMA-IR, the TG/HDL-C ratio and the LP-IR score with cIMT were approximately similar (standardized ß = 0.34 (95 % CI 0.19-0.48), 0.24 (95 % CI 0.09-039) and 0.41 (95 % CI 0.23--0.59), respectively). Prospectively, 507 new cases of CVD were observed after a median follow-up of 8.2 (interquartile range 7.5-8.8) years. HOMA-IR, the TG/HDL-C ratio and LP-IR were each associated with incident CVD independent of potential confounders (HR 1.12, 95 % CI 1.02-1.24;1.22, 95 % CI 1.11-1.35 and 1.15. 95 % CI 1.01-1.31, respectively). The association of the TG/HDL-C ratio with incident CVD was somewhat stronger than that of HOMA-IR. CONCLUSION: Lipoprotein-based markers of insulin resistance are at least as strongly associated with subclinical atherosclerosis and clinical atherosclerosis development as HOMA-IR, obviating the need to measure insulin to determine the impact of insulin resistance. For practical purposes, the easily obtainable TG/HDL-C ratio may suffice.

HDL Particle Concentration and Size Predict Incident Coronary Artery Disease Events in People with Type 1 Diabetes.

Background: Cholesterol efflux capacity (CEC) negatively correlates with cardiovascular disease risk. Small HDL particles account almost quantitively for CEC, perhaps mediated through efflux of outer leaflet plasma membrane phospholipids by ABCA1. People with type 1 diabetes (T1D) are at increased risk of coronary artery disease (CAD) despite normal levels of HDL-cholesterol (HDL-C). We therefore tested the hypotheses that small HDL particles (HDL-P)-rather than HDL-C levels-predict incident CAD in T1D. Methods: Incident CAD (CAD death, myocardial infarction, and/or coronary revascularization) was determined in a cohort of 550 participants with childhood-onset T1D. HDL-P was quantified by calibrated ion mobility analysis. CEC and phospholipid efflux were quantified with validated assays. Results: During a median follow-up of 26 years, 36.5% of the participants developed incident CAD. In multivariable Cox models, levels of HDL-C and apolipoprotein A-I (APOA1) did not predict CAD risk. In contrast, extra-small HDL particle levels strongly and negatively predicted risk (hazard ratio [HR]=0.25, 95% confidence interval [CI]=0.13-0.49). An increased concentration of total HDL particles (T-HDL-P) (HR=0.87, CI=0.82-0.92) and three other HDL sizes were weaker predictors of risk: small HDL (HR=0.80, 0.65-0.98), medium HDL (HR=0.78, CI=0.70-0.87) and large HDL (HR=0.72, CI=0.59-0.89). Although CEC negatively associated with incident CAD, that association disappeared after the model was adjusted for T-HDL-P. Isolated small HDLs strongly promoted ABCA1-dependent efflux of membrane outer leaflet phospholipids. Conclusions: Low concentrations of T-HDL-P and all four sizes of HDL subpopulations predicted incident CAD independently of HDL-C, APOA1, and other common CVD risk factors. Extra-small HDL was a much stronger predictor of risk than the other HDLs. Our data are consistent with the proposal that small HDLs play a critical role in cardioprotection in T1D, which might be mediated by macrophage plasma membrane outer leaflet phospholipid export and cholesterol efflux by the ABCA1 pathway.

Sex differences in associations of comorbidities with incident cardiovascular disease: focus on absolute risk.

Aim: To examine sex differences in associations of obesity, type-2 diabetes, hypertension, and atrial fibrillation (AF) with incident cardiovascular disease (CVD), focusing on absolute risk measures. Methods and results: We included a total of 7994 individuals (mean age 49.1 years; 51.2% women) without prior CVD from the PREVEND (Prevention of Renal and Vascular End-stage Disease) cohort with a median follow-up of 12.5 years. Using Poisson regression, we calculated the increase in absolute as well as relative CVD risk associated with a comorbidity using incidence rate differences (IRD = IRcomorbidity-IRno-comorbidity) and incidence rate ratios (IRR = IRcomorbidity/IRno-comorbidity), respectively. Sex differences were presented as women-to-men differences (WMD = IRDwomen-IRDmen) and women-to-men ratios (WMR = IRRwomen/IRRmen). Absolute CVD risk was lower in women than in men (IRwomen: 6.73 vs. IRmen: 14.58 per 1000 person-years). While increase in absolute CVD risk associated with prevalent hypertension was lower in women than in men [WMD: -6.12, 95% confidence interval: (-9.84 to -2.40), P = 0.001], increase in absolute CVD risk associated with prevalent obesity [WMD: -4.25 (-9.11 to 0.61), P = 0.087], type-2 diabetes [WMD: -1.04 (-14.36 to 12.29), P = 0.879] and AF [WMD: 18.39 (-39.65 to 76.43), P = 0.535] did not significantly differ between the sexes. Using relative risk measures, prevalent hypertension [WMR: 1.49%, 95% confidence interval: (1.12-1.99), P = 0.006], type-2 diabetes [WMR: 1.73 (1.09-2.73), P = 0.019], and AF [WMR: 2.53 (1.12-5.70), P = 0.025] were all associated with higher CVD risk in women than in men. Conclusion: Increase in absolute risk of developing CVD is higher in hypertensive men than in hypertensive women, but no substantial sex-related differences were observed among individuals with obesity, type-2 diabetes and AF. On a relative risk scale, comorbidities, in general, confer a higher CVD risk in women than in men.

Circulating cardiac biomarkers improve risk stratification for incident cardiovascular disease in community dwelling populations.

BACKGROUND: Plasma cardiac markers may assist in prediction of incident cardiovascular disease. METHODS: The incremental value of cardiac Troponins (T and I) and NT-proBNP added to risk factors in the PREDICT score for incident cardiovascular disease (CVD) in primary care, was assessed in 4102 asymptomatic participants in a randomised controlled trial of Vitamin D (ViDA). Findings were corroborated in 2528 participants in a separate community-based observational registry of CVD-free volunteers (HVOLS). FINDINGS: Hazard ratios for first cardiovascular events adjusted for PREDICT risk factors, comparing fifth to first quintiles of marker plasma concentrations, were 2.57 (95% CI 1.47-4.49); 3.01 (1.66-5.48) and 3.38 (2.04-5.60) for hs-cTnI, hs-cTnT and NT-proBNP respectively. The C statistic for discrimination of the primary endpoint increased from 0.755 to 0.771 (+0.016, p = 0.01). Cardiac marker data correctly reclassified risk upwards in 6.7% of patients and downwards in 3.3%. These findings were corroborated by results from HVOLS. INTERPRETATION: Increments in plasma cardiac biomarkers robustly and reproducibly predicted increased hazard of incident CVD, independent of established risk factors, in two community-dwelling populations. Cardiac markers may augment risk assessment for onset of CVD in primary care. FUNDING: ViDA was funded by the Health Research Council of New Zealand (grant 10/400) and the Accident Compensation Corporation. HVOLS was funded by the Health Research Council of NZ Programme Grants (grants 02/152 and 08/070) and by grants from the Heart Foundation of NZ and the Christchurch Heart Institute Trust. Roche Diagnostics provided in-kind support for NT-proBNP and hs-cTnT assays and Abbott Laboratories for hs-cTnI assays.

Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population: Observations from the Dallas Heart Study.

BACKGROUND AND AIMS: Myeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline. METHODS: Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years. RESULTS: Adjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12-2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27-2.85). CONCLUSIONS: Increased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period.

Use of vitamin D receptor activator, incident cardiovascular disease and death in a cohort of hemodialysis patients.

The use of vitamin D receptor activators (VDRAs) is an independent predictor of a lower risk of death from cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). We examined whether the use of VDRAs and other CKD-mineral bone disorder (MBD)-related factors are associated with incident CVD or death after CVD in hemodialysis patients. This is a historical cohort study of 37 690 prevalent hemodialysis patients without previous history of CVD at the end of 2004 extracted from a nationwide registry in Japan. The key exposure was the use of VDRAs, and the outcomes were incident CVD (myocardial infarction, cerebral infarction, cerebral hemorrhage, and sudden death) and death after CVD during the 1-year follow-up. VDRAs were used in 57% of the subjects at baseline. We identified 2433 patients with incident CVD and 397 deaths after the events. In multivariate logistic regression models, independent predictors of incident CVD were non-use of VDRA, higher intact PTH, non-use of calcium-based phosphate-binder, and non-use of non-calcium-based phosphate binder. Risk of death after CVD was not significantly associated with VDRA, whereas it was lower in those with lower corrected calcium, and the risk was higher in those with higher phosphate and in non-users of calcium-based phosphate binders. The use of VDRAs was associated with a lower risk of incident CVD but not with death after CVD in this large cohort of hemodialysis patients. The CKD-MBD-related predictors of poor outcomes are associated with the risk of incident CVD, the risk of death after CVD, or both.