Objectives This study sought to evaluate the interrelation of atherosclerotic burden, as assessed by coronary artery calcium (CAC) score and coronary vascular function, as assessed by quantitative ...estimates of coronary flow reserve (CFR), with respect to prediction of clinical outcomes. Background The contribution of coronary vascular dysfunction, atherosclerotic burden, and the 2 combined to cardiac events is unknown. Method A total of 901 consecutive patients underwent82 Rubidium myocardial perfusion imaging (MPI) positron emission tomography (PET) and CAC scan. All patients had normal MPI. The primary endpoint was a composite of major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, late revascularization, and admission for heart failure. Results At baseline, CFR decreased (2.15 ± 0.72, 2.02 ± 0.65, and 1.88 ± 0.64, p < 0.0001) with increasing levels of CAC (0, 1 to 399, and ≥400). Over a median of 1.53 years (interquartile range: 0.77 to 2.44), there were 57 MACE. Annual risk-adjusted MACE rates were higher for patients with CFR <2.0 compared with ≥2.0 (1.9 vs. 5.5%/year, p = 0.0007) but were only borderline associated with CAC (3.1%, 3.4%, and 6.2%/year for CAC of 0, 1 to 399, and ≥400, respectively; p = 0.09). Annualized adjusted MACE was increased in the presence of impaired CFR even among patients with CAC = 0 (1.4% vs. 5.2%, p = 0.03). Cox proportional hazards analysis revealed that CFR improved model fit, risk discrimination, and risk reclassification over clinical risk, whereas CAC only modestly improved model fit without improving risk discrimination or reclassification. Conclusions In symptomatic patients with normal MPI, global CFR but not CAC provides significant incremental risk stratification over clinical risk score for prediction of major adverse cardiac events.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The cumulative exposure to apolipoprotein B (apoB)-containing lipoproteins in the blood during early adult life is a central determinant of atherosclerotic cardiovascular disease risk. To date, the ...patterns and rates of change in apoB through early adult life have not been described. Here, we used NMR to measure apoB concentrations in up to 3055 Coronary Artery Risk Development in Young Adults (CARDIA) Study participants who attended the years 2 (Y2), 7 (Y7), 15 (Y15), 20 (Y20), and 30 (Y30) exams. We examined individual-level spaghetti plots of apoB change, and we calculated average annualized rate of apoB concentration change during follow-up. We used multivariable linear regression models to assess the associations between CARDIA participant characteristics and annualized rates of apoB change. Male sex, higher measures of adiposity, lower HDL-C, lower Healthy Eating Index, and higher blood pressures were observed more commonly in individuals with higher apoB level at Y2 and Y20. Inter- and intra-individual variation in apoB concentration over time was substantial—while the mean (SD) rate of change was 0.52 (1.0) mg/dl/year, the range of annualized rates of change was −6.26 to +9.21 mg/dl/year. At baseline, lower first apoB measurement, female sex, White race, lower BMI, and current tobacco use were associated with apoB increase. We conclude that the significant variance in apoB level over time and the modest association between baseline measures and rates of apoB change suggest that the ability to predict an individual’s future apoB serum concentrations, and thus their cumulative apoB exposure, after a one-time assessment in young adulthood is low.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Aims
Coronary flow reserve (CFR) is an integrated measure of the entire coronary vasculature, and is a powerful prognostic marker in coronary artery disease (CAD). The extent to which ...coronary revascularization can improve CFR is unclear. This study aimed to evaluate the impact of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on CFR in patients with stable CAD.
Methods and results
In a prospective, multicentre observational study, CFR was measured by 15O-water positron emission tomography as the ratio of stress to rest myocardial blood flow at baseline and 6 months after optimal medical therapy (OMT) alone, PCI, or CABG. Changes in the SYNTAX and Leaman scores were angiographically evaluated as indicators of completeness of revascularization. Follow-up was completed by 75 (25 OMT alone, 28 PCI, and 22 CABG) out of 82 patients. The median SYNTAX and Leaman scores, and baseline CFR were 14.5 interquartile range (IQR): 8–24.5, 5.5 (IQR: 2.5–12.5), and 1.94 (IQR: 1.67–2.66), respectively. Baseline CFR was negatively correlated with the SYNTAX (ρ = −0.40, P < 0.001) and Leaman scores (ρ = −0.33, P = 0.004). Overall, only CABG was associated with a significant increase in CFR 1.67 (IQR: 1.14–1.96) vs. 1.98 (IQR: 1.60–2.39), P < 0.001. Among patients with CFR <2.0 (n = 41), CFR significantly increased in the PCI 1.70 (IQR: 1.42–1.79) vs. 2.21 (IQR: 1.78–2.49), P = 0.002, P < 0.001 for interaction between time and CFR and CABG groups 1.28 (IQR: 1.13–1.80) vs. 1.86 (IQR: 1.57–2.22), P < 0.001. The reduction in SYNTAX or Leaman scores after PCI or CABG was independently associated with the percent increase in CFR after adjusting for baseline characteristics (P = 0.012 and P = 0.011, respectively).
Conclusion
Coronary revascularization ameliorated reduced CFR in patients with obstructive CAD. The degree of improvement in angiographic CAD burden by revascularization was correlated with magnitude of improvement in CFR.
IMPORTANCE: Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less ...clear. OBJECTIVE: To examine whether CRF in young adults is associated with long-term clinical outcome and subclinical cardiovascular disease (CVD). DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 4872 US adults aged 18 to 30 years who underwent treadmill exercise testing at a baseline study visit from March 25, 1985, to June 7, 1986, and 2472 individuals who underwent a second treadmill test 7 years later. Median follow-up was 26.9 years, with assessment of obesity, left ventricular mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Follow-up was complete on August 31, 2011, and data were analyzed from recruitment through the end of follow-up. MAIN OUTCOMES AND MEASURES: The presence of CAC was assessed by computed tomography at years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011), and left ventricular mass was assessed at years 5 (1990-1991) and 25 (with global longitudinal strain). Incident CVD and all-cause mortality were adjudicated. RESULTS: Of the 4872 individuals, 273 (5.6%) died and 193 (4.0%) experienced CVD events during follow-up. After comprehensive adjustment, each additional minute of baseline exercise test duration was associated with a 15% lower hazard of death (hazard ratio HR, 0.85; 95% CI, 0.80-0.91; P < .001) and a 12% lower hazard of CVD (HR, 0.88; 95% CI, 0.81-0.96; P = .002). Higher levels of baseline CRF were associated with significantly lower left ventricular mass index (β = −0.24; 95% CI, −0.45 to −0.03; P = .02) and significantly better lobal longitudinal strain (β = −0.09; 95% CI, −0.14 to −0.05; P < .001) at year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by year 7 was associated with 21% and 20% increased hazards of death (HR, 1.21; 95% CI, 1.07-1.37; P = .002) and CVD (HR, 1.20; 95% CI, 1.06-1.37; P = .006), respectively, along with a more impaired strain (β = 0.15; 95% CI, 0.08-0.23; P < .001). No association between change in fitness and CAC was found. CONCLUSIONS AND RELEVANCE: Higher levels of fitness at baseline and improvement in fitness early in adulthood are favorably associated with lower risks for CVD and mortality. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.
The study sought to determine the associations between local (pericardial) fat and incident cardiovascular disease (CVD) events and cardiac remodeling independent of markers of overall adiposity.
The ...impact of pericardial fat-a local fat depot encasing the heart-on myocardial function and long-term CV prognosis independent of systemic consequences of adiposity or hepatic fat is an area of active debate.
We studied 4,234 participants enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) study with concomitant cardiac magnetic resonance imaging and computed tomography (CT) measurements for pericardial fat volume and hepatic attenuation (a measure of liver fat). Poisson and Cox regression were used to estimate the annualized risk of incident hard atherosclerotic CVD (ASCVD), all-cause death, heart failure, all-cause CVD, hard coronary heart disease, and stroke as a function of pericardial and hepatic fat. Generalized additive models were used to assess the association between cardiac magnetic resonance indices of left ventricular (LV) structure and function and pericardial fat. Models were adjusted for relevant clinical, demographic, and cardiometabolic covariates.
MESA study participants with higher pericardial and hepatic fat were more likely to be older, were more frequently men, and had a higher prevalence of cardiometabolic risk factors (including dysglycemia, dyslipidemia, hypertension), as well as adiposity-associated inflammation. Over a median 12.2-year follow-up (interquartile range: 11.6 to 12.8 years), pericardial fat was associated with a higher rate of incident hard ASCVD (standardized hazard ratio: 1.22; 95% confidence interval: 1.10 to 1.35; p = 0.0001). Hepatic fat by CT was not significantly associated with hard ASCVD (standardized hazard ratio: 0.96; 95% confidence interval: 0.86 to 1.08; p = 0.52). Higher pericardial fat was associated with greater indexed LV mass (37.8 g/m
vs. 33.9 g/m
, highest quartile vs. lowest quartile; p < 0.01), LV mass-to-volume ratio (1.2 vs. 1.1, highest quartile vs. lowest quartile; p < 0.01). In adjusted models, a higher pericardial fat volume was associated with greater LV mass (p < 0.0001) and concentricity (p < 0.0001).
Pericardial fat is associated with poorer CVD prognosis and LV remodeling, independent of insulin resistance, inflammation, and CT measures of hepatic fat.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The association of cardiovascular diseases (CVD) with liver fibrosis is poorly understood. We aim to assess the association of liver fibrosis by T1-mapping magnetic resonance imaging and CVD in MESA ...(Multi-Ethnic Study of Atherosclerosis).
MESA enrolled 6814 participants free of clinical CVD at baseline (2000-2002). A subsample of participants underwent T1-mapping magnetic resonance imaging 10 years after the baseline (Y10 MESA exam, 2010-2012). Liver T1 maps were generated avoiding vessels and biliary ducts from which native T1 (n=2087) and extracellular volume fraction (ECV, n=1234) were determined. Higher ECV and native T1 were indicators of liver fibrosis. Linear regression analysis evaluated the cross-sectional relationship between liver native T1 and ECV at Y10 MESA exam with a history of CVD events (atrial fibrillation, heart failure, and coronary heart disease CHD). Of the 2087 participants (68.7±9.1 years; 46% females), 153 had prior CVD events (78 atrial fibrillation, 25 heart failure, and 78 CHD). History of CVD events was associated with 18.5 ms higher liver native T1 (
<0.001) and 1.4% greater ECV (
=0.06). Prior atrial fibrillation was related to higher liver native T1 (β=21.1;
=0.001) and greater ECV (β=2.2;
=0.02), whereas previous heart failure was associated with greater liver ECV (β=4.1;
=0.02). There was also a relationship of prior CHD with liver native T1 (β=13;
=0.05) and ECV (β=1.9;
=0.05), which was attenuated by adjustment for coronary artery calcium score (β=7.1 and 1.6;
=0.37 and 0.13, respectively).
Liver fibrosis by T1-mapping magnetic resonance imaging is associated with history of heart failure, atrial fibrillation, and CHD in a multiethnic cohort. The association of liver fibrosis and CHD is at least in part mediated by atherosclerosis.
Observational studies of diet in cardiometabolic-cardiovascular disease (CM-CVD) focus on self-reported consumption of food or dietary pattern, with limited information on individual metabolic ...responses to dietary intake linked to CM-CVD. Here, machine learning approaches were used to identify individual metabolic patterns related to diet and relation to long-term CM-CVD in early adulthood.
In 2259 White and Black adults (age 32.1 ± 3.6 years, 45% women, 44% Black) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, multivariate models were employed to identify metabolite signatures of food group and composite dietary intake across 17 food groups, 2 nutrient groups, and healthy eating index-2015 (HEI2015) diet quality score. A broad array of metabolites associated with diet were uncovered, reflecting food-related components/catabolites (e.g. fish and long-chain unsaturated triacylglycerols), interactions with host features (microbiome), or pathways broadly implicated in CM-CVD (e.g. ceramide/sphingomyelin lipid metabolism). To integrate diet with metabolism, penalized machine learning models were used to define a metabolite signature linked to a putative CM-CVD-adverse diet (e.g. high in red/processed meat, refined grains), which was subsequently associated with long-term diabetes and CVD risk numerically more strongly than HEI2015 in CARDIA e.g. diabetes: standardized hazard ratio (HR): 1.62, 95% confidence interval (CI): 1.32-1.97, P < 0.0001; CVD: HR: 1.55, 95% CI: 1.12-2.14, P = 0.008, with associations replicated for diabetes (P < 0.0001) in the Framingham Heart Study.
Metabolic signatures of diet are associated with long-term CM-CVD independent of lifestyle and traditional risk factors. Metabolomics improves precision to identify adverse consequences and pathways of diet-related CM-CVD.
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