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BACKGROUND: Low endogenous estrogen concentrations after menopause may contribute to higher oxidative stress and greater cardiovascular disease (CVD) risk. However, differences in oxidative stress between similarly aged premenopausal and postmenopausal women are not well-characterized on a population level. We hypothesized that urinary isoprostane concentrations, a standard measure of systemic oxidative stress, are higher in women who have undergone menopause compared to premenopausal women. METHODS AND RESULTS: We examined differences in urinary 8-isoprostane (iPF(2α)-III) and 2,3-dinor-8-isoprostane (iPF(2α)-III-M) indexed to urinary creatinine between 279 postmenopausal and 196 premenopausal women in the Coronary Artery Risk Development in Young Adults (CARDIA) study, using linear regression with progressive adjustment for sociodemographic factors and traditional CVD risk factors. Unadjusted iPF(2α)-III-M concentrations were higher among postmenopausal compared to premenopausal women (Median [25th, 75th percentile]: 1762 [1178, 2974] vs. 1535 [1067, 2462] ng/g creatinine; p = 0.01). Menopause was associated with 25.5% higher iPF(2α)-III-M (95% confidence interval [6.5–47.9]) adjusted for age, race, college education, and field center. Further adjustments for tobacco use (21.2% [2.9–42.6]) and then CVD risk factors (18.8% [0.1–39.6]) led to additional partial attenuation. Menopause was associated with higher iPF(2α)-III in Black but not White women. CONCLUSIONS: We conclude that postmenopausal women had higher oxidative stress, which may contribute to greater CVD risk. ClinicalTrials.gov Identifier: NCT00005130.

Inflammation surrounding the coronary arteries can be non-invasively assessed using pericoronary adipose tissue attenuation (PCAT). While PCAT holds promise for further risk stratification of patients with low coronary artery disease (CAD) prevalence, its value in higher risk populations remains unknown.CORE320 enrolled patients referred for invasive coronary angiography with known or suspected CAD. Coronary computed tomography angiography (CCTA) images were collected for 381 patients for whom clinical outcomes were assessed 5 years after enrollment. Using semi-automated image analysis software, PCAT was obtained and normalized for the right coronary (RCA), left anterior descending (LAD), and left circumflex arteries (LCx). The association between PCAT and major adverse cardiovascular events (MACE) during follow up was assessed using Cox regression models.Thirty-seven patients were excluded due to technical failure. For the remaining 344 patients, median age was 62 (interquartile range, 55-68) with 59% having ≥1 coronary artery stenosis of ≥50% by quantitative coronary angiography. Mean attenuation values for PCAT in RCA, LAD, and LCx were -74.9, -74.2, and -71.2, respectively. Hazard ratios and 95% confidence intervals (CI) for normalized PCAT in the RCA, LAD, and LCx for MACE were 0.96 (CI: 0.75-1.22, p ​= ​0.71), 1.31 (95% CI: 0.96-1.78, p ​= ​0.09), and 0.98 (95% CI: 0.78-1.22, p ​= ​0.84), respectively. For death, stroke, or myocardial infarction only, hazard ratios were 0.68 (0.44-1.07), 0.85 (0.56-1.29), and 0.57 (0.41-0.80), respectively.In patients referred for invasive coronary angiography with suspected CAD, PCAT did not predict MACE during long term follow up. Further studies are needed to understand the relationship of PCAT with CAD risk.

RATIONALE: The effect of insulin resistance on left ventricular function is well documented; however, less is known regarding its effect on the right ventricle (RV). OBJECTIVES: To evaluate the association between insulin resistance and RV function by echocardiography in a cohort of adults without baseline cardiovascular disease. METHODS: We performed a retrospective cohort study in the MESA (Multi-Ethnic Study of Atherosclerosis). Linear regression was used to examine the association between overall insulin resistance measured by the mean triglyceride (TG) to high-density lipoprotein (HDL) cholesterol ratio (TG:HDL) and change in TG:HDL over time for each participant with echocardiographic RV function. Logistic regression was used to calculate the odds ratios (ORs) of RV systolic and diastolic dysfunction. RESULTS: Among 3,032 participants, higher mean TG:HDL was associated with lower (worse) absolute RV longitudinal strain (β, −0.38; 95% confidence interval [CI], −0.64 to −0.13; P

The effect of hepatic steatosis on the gradient-echo (GRE) based Modified Look-Locker Inversion Recovery (MOLLI) technique for T1 mapping has not been evaluated. The purpose of this study was to evaluate a GRE based MOLLI technique for hepatic T1 mapping and determine the relationship of T1 differences (ΔT1) on in-phase (IP) and out-of-phase (OP) to fat fraction (FF) measurement.3 T MRI included MOLLI T1 mapping with TE = 1.3 (OP), 2.4 (IP), and 1.8 ms, and chemical-shift-encoded sequence with spectral modeling of fat to generate FF map as a reference. Bloch simulations and oil/water phantoms were used to characterize the response of the MOLLI T1 in various FF 30% since MOLLI T1 estimation was erratic beyond this limit. Curve fit between ΔT1 and FF from simulation was applied to validate the phantom and the in-vivo results. Thirty-eight normal volunteers were included (16 women, Age 44 ± 12 years, BMI 27 ± 5.3 kg/mPhantom results were consistent with the Bloch simulations. The simulated relationship between FF (0-30%) and ΔT1 could be modeled precisely by a cubic equation with R2 = 1. In-vivo MOLLI ΔT1 and estimated FF were correlated to the reference FF (both R2 ≥ 0.96 and P 0.001). TE = 1.8 ms demonstrated less T1 bias (-1.34%) compared to TE = OP (5.32%) or IP (-3.8%, both P 0.001).At 3 T, TE of 1.8 ms can be used to reduce the T1 bias and deliver consistent T1 values when FF is30%.

Author(s): Shabani, Mahsima; Bakhshi, Hooman; Ostovaneh, Mohammad R; Ma, Xiaoyang; Wu, Colin O; Ambale-Venkatesh, Bharath; Blaha, Michael J; Allison, Matthew A; Budoff, Matthew J; Cushman, Mary; Tracy, Russell P; Herrington, David M; Szklo, Moyses; Cox, Christopher; Bluemke, David A; Lima, Joao AC | Abstract: AimsLittle is known about the association of temporal changes in inflammatory biomarkers and the risk of death and cardiovascular diseases. We aimed to evaluate the association between temporal changes in C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6) and risk of heart failure (HF), cardiovascular disease (CVD), and all-cause mortality in individuals without a history of prior CVD.Methods and resultsParticipants from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort with repeated measures of inflammatory biomarkers and no CVD event prior to the second measure were included. Quantitative measures, annual change, and biomarker change categories were used as main predictors in Cox proportional hazard models stratified based on sex and statin use. A total of 2258 subjects (50.6% female, mean age of 62nyears) were studied over an average of 8.1nyears of follow-up. The median annual decrease in CRP levels was 0.08nmg/L. Fibrinogen and IL-6 levels increased by a median of 30nmg/dL and 0.24npg/mL annually. Temporal changes in CRP were positively associated with HF risk among females (HR: 1.18 per each standard deviation increase, Pnln0.001) and other CVD in both female (HR: 1.12, Pn=n0.004) and male participants (HR: 1.24, Pn=n0.003). The association of CRP change with HF and other CVD was consistently observed in statin users (HR: 1.23 per SD increase, Pn=n0.001 for HF and HR: 1.19 per SD increase, Pnln0.001 for other CVD). There were no significant associations between temporal changes of fibrinogen or IL-6 with HF or other CVD. Men with sustained high values of IL-6 had a 2.3-fold higher risk of all-cause mortality (Pnln0.001) compared with those with sustained low values.ConclusionsTemporal change in CRP is associated with HF only in women and statin users, and other CVD in both women and men, and statin users. Annual changes in fibrinogen and IL-6 were not predictive of cardiovascular outcomes in either sex.

BackgroundThe association of physical activity with the development and progression of coronary artery calcium (CAC) scores has not been studied. This study aimed to evaluate the prospective association between physical activity and CAC scores in apparently healthy adults.MethodsProspective cohort study of men and women free of overt cardiovascular disease who underwent comprehensive health screening examinations between 1 March 2011 and 31 December 2017. Baseline physical activity was measured using the International Physical Activity Questionnaire Short Form (IPAQ-SF) and categorised into three groups (inactive, moderately active and health-enhancing physically active (HEPA)). The primary outcome was the difference in the 5-year change in CAC scores by physical activity category at baseline.ResultsWe analysed 25 485 participants with at least two CAC score measurements. The proportions of participants who were inactive, moderately active and HEPA were 46.8%, 38.0% and 15.2%, respectively. The estimated adjusted average baseline CAC scores (95% confidence intervals) in participants who were inactive, moderately active and HEPA were 9.45 (8.76, 10.14), 10.20 (9.40, 11.00) and 12.04 (10.81, 13.26). Compared with participants who were inactive, the estimated adjusted 5-year average increases in CAC in moderately active and HEPA participants were 3.20 (0.72, 5.69) and 8.16 (4.80, 11.53). Higher physical activity was association with faster progression of CAC scores both in participants with CAC=0 at baseline and in those with prevalent CAC.ConclusionWe found a positive, graded association between physical activity and the prevalence and the progression of CAC, regardless of baseline CAC scores.

Right ventricular function has prognostic significance in patients with pulmonary hypertension. We evaluated whether cardiac magnetic resonance-derived strain and strain rate parameters could reliably reflect right ventricular systolic and diastolic function in precapillary pulmonary hypertension. End-systolic elastance and the time constant of right ventricular relaxation tau, both derived from invasive high-fidelity micromanometer catheter measurements, were used as gold standards for assessing systolic and diastolic right ventricular function, respectively. Nineteen consecutive precapillary pulmonary hypertension patients underwent cardiac magnetic resonance and right heart catheterization prospectively. Cardiac magnetic resonance data were compared with those of 19 control subjects. In pulmonary hypertension patients, associations between strain- and strain rate-related parameters and invasive hemodynamic parameters were evaluated. Longitudinal peak systolic strain, strain rate, and early diastolic strain rate were lower in PAH patients than in controls; peak atrial-diastolic strain rate was higher in pulmonary hypertension patients. Similarly, circumferential peak systolic strain rate was lower and peak atrial-diastolic strain rate was higher in pulmonary hypertension. In pulmonary hypertension, no correlations existed between cardiac magnetic resonance-derived and hemodynamically derived measures of systolic right ventricular function. Regarding diastolic parameters, tau was significantly correlated with peak longitudinal atrial-diastolic strain rate ( r = −0.61), deceleration time ( r = 0.75), longitudinal systolic to diastolic time ratio ( r = 0.59), early diastolic strain rate ( r = −0.5), circumferential peak atrial-diastolic strain rate ( r = −0.52), and deceleration time ( r = 0.62). Strain analysis of the right ventricular diastolic phase is a reliable non-invasive method for detecting right ventricular diastolic dysfunction in PAH.

Both left atrial and left ventricular functional parameters influence the prognosis of patients with cardiovascular diseases. This study aimed to investigate the prognostic value of a novel left atrioventricular coupling index (LACI) in a population without history of cardiovascular diseases at baseline. Participants of the Multi-Ethnic Study of Atherosclerosis who underwent a baseline cardiovascular magnetic resonance study were analyzed. LACI was defined by the ratio of the left atrial end-diastolic volume divided by the left ventricular end-diastolic volume. Cox proportional hazard models were used to evaluate the association between LACI and atrial fibrillation, heart failure, coronary heart disease death, and hard cardiovascular disease defined by myocardial infarction, resuscitated cardiac arrest, fatal and nonfatal stroke, or coronary heart disease death. Among the 4124 participants (61.5±10.1 years, 47.4% men), 1074 cardiovascular events were observed (mean follow-up, 13.0±3.2 years). Greater LACI was independently associated with atrial fibrillation (hazard ratio, 1.86 [95% CI, 1.69–2.04]), heart failure (hazard ratio, 1.50 [95% CI, 1.38–1.62]), hard cardiovascular disease (1.23 [95% CI, 1.13–1.34]), and coronary heart disease death (hazard ratio, 1.29 [95% CI, 1.15–1.45]; all P

Aims Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD. Methods and results We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45–1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08–1.34). Similar results were shown when examining discordance across clinical cutpoints. Conclusions In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.

Background Quantification of non-ischemic myocardial scar remains a challenge due to the patchy diffuse nature of fibrosis. Extracellular volume (ECV) to guide late gadolinium enhancement (LGE) analysis may achieve a robust scar assessment. Methods Three cohorts of 80 non-ischemic-training, 20 non-ischemic-validation, and 10 ischemic-validation were prospectively enrolled and underwent 3.0 Tesla cardiac MRI. An ECV cutoff to differentiate LGE scar from non-scar was identified in the training cohort from the receiver-operating characteristic curve analysis, by comparing the ECV value against the visually-determined presence/absence of the LGE scar at the highest signal intensity (SI) area of the mid-left ventricle (LV) LGE. Based on the ECV cutoff, an LGE semi-automatic threshold of n-times of standard-deviation (n-SD) above the remote-myocardium SI was optimized in the individual cases ensuring correspondence between LGE and ECV images. The inter-method agreement of scar amount in comparison with manual (for non-ischemic) or full-width half-maximum (FWHM, for ischemic) was assessed. Intra- and inter-observer reproducibility were investigated in a randomly chosen subset of 40 non-ischemic and 10 ischemic cases. Results The non-ischemic groups were all female with the HIV positive rate of 73.8% (training) and 80% (validation). The ischemic group was all male with reduced LV function. An ECV cutoff of 31.5% achieved optimum performance (sensitivity: 90%, specificity: 86.7% in training; sensitivity: 100%, specificity: 81.8% in validation dataset). The identified n-SD threshold varied widely (range 3 SD–18 SD), and was independent of scar amount (β = −0.01, p = 0.92). In the non-ischemic cohorts, results suggested that the manual LGE assessment overestimated scar (%) in comparison to ECV-guided analysis [training: 4.5 (3.2–6.4) vs. 0.92 (0.1–2.1); validation: 2.5 (1.2–3.7) vs. 0.2 (0–1.6); P P Conclusions ECV-guided LGE analysis is a robust scar quantification method for a non-ischemic cohort. Trial registration ClinicalTrials.gov; NCT00000797, retrospectively-registered 2 November 1999; NCT02501811, registered 15 July 2015.

Background: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment–elevation myocardial infarction. Methods: REAL-TIMI 63B (A Randomized, Placebo‑controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment–elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012. Results: A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range [IQR], 103–221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6–24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3–13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79–16.38; placebo: 10.48%, [IQR, 4.92–16.61], 1-sided P =0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 [95% CI, NA–1.10], 1-sided P =0.30). There was no significant difference in treatment emergent serious adverse events. Conclusions: Administration of MEDI6012 in patients with acute ST-segment–elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03578809.

Background: Despite improvements in population health, marked racial and ethnic disparities in longevity and cardiovascular disease (CVD) mortality persist. This study aimed to describe risks for all-cause and CVD mortality by race and ethnicity, before and after accounting for socioeconomic status (SES) and other factors, in the MESA study (Multi-Ethnic Study of Atherosclerosis). Methods: MESA recruited 6814 US adults, 45 to 84 years of age, free of clinical CVD at baseline, including Black, White, Hispanic, and Chinese individuals (2000–2002). Using Cox proportional hazards modeling with time-updated covariates, we evaluated the association of self-reported race and ethnicity with all-cause and adjudicated CVD mortality, with progressive adjustments for age and sex, SES (neighborhood SES, income, education, and health insurance), lifestyle and psychosocial risk factors, clinical risk factors, and immigration history. Results: During a median of 15.8 years of follow-up, 22.8% of participants (n=1552) died, of which 5.3% (n=364) died of CVD. After adjusting for age and sex, Black participants had a 34% higher mortality hazard (hazard ratio [HR], 1.34 [95% CI, 1.19–1.51]), Chinese participants had a 21% lower mortality hazard (HR, 0.79 [95% CI, 0.66–0.95]), and there was no mortality difference in Hispanic participants (HR, 0.99 [95% CI, 0.86–1.14]) compared with White participants. After adjusting for SES, the mortality HR for Black participants compared with White participants was reduced (HR, 1.16 [95% CI, 1.01–1.34]) but still statistically significant. With adjustment for SES, the mortality hazards for Chinese and Hispanic participants also decreased in comparison with White participants. After further adjustment for additional risk factors and immigration history, Hispanic participants (HR, 0.77 [95% CI, 0.63–0.94]) had a lower mortality risk than White participants, and hazard ratios for Black participants (HR, 1.08 [95% CI, 0.92–1.26]) and Chinese participants (HR, 0.81 [95% CI, 0.60–1.08]) were not significantly different from those of White participants. Similar trends were seen for CVD mortality, although the age- and sex-adjusted HR for CVD mortality for Black participants compared with White participants was greater than all-cause mortality (HR, 1.72 [95% CI, 1.34–2.21] compared with HR, 1.34 [95% CI, 1.19–1.51]). Conclusions: These results highlight persistent racial and ethnic differences in overall and CVD mortality, largely attributable to social determinants of health, and support the need to identify and act on systemic factors that shape differences in health across racial and ethnic groups.

Heart failure with preserved ejection fraction (HFpEF) affects more women than men. Menopause may influence HFpEF development in women. We assessed cross-sectional and longitudinal associations between menopause and echocardiographic measures of left ventricular (LV) function and cardiac remodeling.We studied 1,723 women with available echo data from at least two of: year 5 (Y5) (1990-1991), Y25 (2010-2011), or Y30 (2015-2016) in the Coronary Artery Risk Development in Young Adults study. Cardiac structure and function were measured using 2D and Doppler echocardiography. Cross-sectional associations between menopausal status and repeated echo measures at Y25 and Y30 were analyzed using linear mixed models. Two-segmented models were used to compare longitudinal changes in echocardiographic measures in the premenopausal period to changes in the postmenopausal period.Mean ± SD age (years) at enrollment was 27 ± 3 in those with menopause by Y25, 25 ± 3 in those with menopause between Y25 and Y30, and 21 ± 3 in those premenopausal at Y30. There were no significant differences in race, body mass index, systolic blood pressure, or diabetes between the groups. Postmenopausal women had higher early diastolic mitral inflow (E) to annular (e') velocity ratio than premenopausal after adjusting for demographics and risk factors (P 0.05). Menopause was associated with relative increases in the rates of change in LV mass and left atrial volume, even after adjustment. Change in E/e' ratio was similar before and after menopause.Menopause is associated cross-sectionally with worse diastolic function and longitudinally with adverse LV and left atrial remodeling. This may contribute to the increased HFpEF risk in postmenopausal women.Video Summary:http://links.lww.com/MENO/A787.

Objectives This study sought to quantify and model conversion of a normal coronary artery calcium (CAC) scan to an abnormal CAC scan. Background Although the absence of CAC is associated with excellent prognosis, progression to CAC >0 confers increased risk. The time interval for repeated scanning remains poorly defined. Methods This study included 3,116 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with baseline CAC = 0 and follow-up scans over 10 years after baseline. Prevalence of incident CAC, defined by thresholds of CAC >0, CAC >10, or CAC >100, was calculated and time to progression was derived from a Weibull parametric survival model. Warranty periods were modeled as a function of sex, race/ethnicity, cardiovascular risk, and desired yield of repeated CAC testing. Further analysis was performed of the proportion of coronary events occurring in participants with baseline CAC = 0 that preceded and followed repeated CAC testing at different time intervals. Results Mean participants’ age was 58 ± 9 years, with 63% women, and mean 10-year cardiovascular risk of 14%. Prevalence of CAC >0, CAC >10, and CAC >100 was 53%, 36%, and 8%, respectively, at 10 years. Using a 25% testing yield (number needed to scan [NNS] = 4), the estimated warranty period of CAC >0 varied from 3 to 7 years depending on sex and race/ethnicity. Approximately 15% of participants progressed to CAC >10 in 5 to 8 years, whereas 10-year progression to CAC >100 was rare. Presence of diabetes was associated with significantly shorter warranty period, whereas family history and smoking had small effects. A total of 19% of all 10-year coronary events occurred in CAC = 0 prior to performance of a subsequent scan at 3 to 5 years, whereas detection of new CAC >0 preceded 55% of future events and identified individuals at 3-fold higher risk of coronary events. Conclusions In a large population of individuals with baseline CAC = 0, study data provide a robust estimation of the CAC = 0 warranty period, considering progression to CAC >0, CAC >10, and CAC >100 and its impact on missed versus detectable 10-year coronary heart disease events. Beyond age, sex, race/ethnicity, diabetes also has a significant impact on the warranty period. The study suggests that evidence-based guidance would be to consider rescanning in 3 to 7 years depending on individual demographics and risk profile.

We examined the longitudinal association between blood pressure (BP) and stroke incidence in young and middle-aged adults. BP measured during 9 examinations of the CARDIA study (Coronary Artery Risk Development in Young Adults) from 1985-1986 to 2015-2016 was used to classify participants (n=5079) according to the 2017 Hypertension Clinical Practice Guidelines. We used the highest BP obtained through the third examination (1990–1991) to define baseline BP categories; time-dependent categories (accounting for change in BP over time) were determined incorporating follow-up measurements. BP groups at ages 30 and 40 years were also defined. Stroke events were adjudicated until 2018. Mean age at baseline was 29.8 years. Stroke occurred in 100 participants. Stroke incidence (per 100 000 person-years) was higher ( P

BACKGROUND Early-onset hypertension has been established as a heritable trait and a risk factor for cardiovascular disease outcomes. However, the clinical correlates of early-onset hypertension remain unidentified. METHODS In this study, we assessed the demographic characteristics and lifestyle factors related to hypertension onset age in a sample of 3,286 Coronary Artery Risk Development in Young Adults (CARDIA) study participants (mean baseline age 25 ± 4 years, 57% women). We examined the association between the participants’ baseline characteristics and age of hypertension onset subgroups (, Graphical Abstract Graphical Abstract

AIMS CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy. METHODS AND RESULTS Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (-22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6-min walking distance, and peak oxygen consumption did not differ significantly among groups. CONCLUSIONS This is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline-directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients.

Background Little is known about the timing of preclinical heart failure (HF) development, particularly among blacks. The primary aims of this study were to delineate age-related left ventricular (LV) structure and function evolution in a biracial cohort and to test the hypothesis that young-adult LV parameters within normative ranges would be associated with incident stage B–defining LV abnormalities over 25 years, independent of cumulative risk factor burden. Methods Data from the Coronary Artery Risk Development in Young Adults study were analyzed. Participants (n = 2,833) had a mean baseline age of 30.1 years; 45% were black, and 56% were women. Generalized estimating equation logistic regression was used to estimate age-related probabilities of stage B LV abnormalities (remodeling, hypertrophy, or dysfunction) and logistic regression to examine risk factor–adjusted associations between baseline LV parameters and incident abnormalities. Cox regression was used to assess whether baseline LV parameters associated with incident stage B LV abnormalities were also associated with incident clinical (stage C/D) HF events over >25 years’ follow-up. Results Probabilities of stage B LV abnormalities at ages 25 and 60 years were 10.5% (95% CI, 9.4%–11.8%) and 45.0% (95% CI, 42.0%–48.1%), with significant race-sex disparities (e.g., at age 60, black men 52.7% [95% CI, 44.9%–60.3%], black women 59.4% [95% CI, 53.6%–65.0%], white men 39.1% [95% CI, 33.4%–45.0%], and white women 39.1% [95% CI, 33.9%–44.6%]). Over 25 years, baseline LV end-systolic dimension indexed to height was associated with incident systolic dysfunction (adjusted odds ratio per 1 SD higher, 2.56; 95% CI, 1.87–3.52), eccentric hypertrophy (1.34; 95% CI, 1.02–1.75), concentric hypertrophy (0.69; 95% CI, 0.51–0.91), and concentric remodeling (0.68; 95% CI, 0.58–0.79); baseline LV mass indexed to height2.7 was associated with incident eccentric hypertrophy (1.70; 95% CI, 1.25–2.32]), concentric hypertrophy (1.63; 95% CI, 1.19–2.24), and diastolic dysfunction (1.24; 95% CI, 1.01–1.52). Among the entire cohort with baseline echocardiographic data available (n = 4,097; 72 HF events), LV end-systolic dimension indexed to height and LV mass indexed to height2.7 were significantly associated with incident clinical HF (adjusted hazard ratios per 1 SD higher, 1.56 [95% CI, 1.26–1.93] and 1.42 [95% CI, 1.14–1.75], respectively). Conclusions Stage B LV abnormalities and related racial disparities were present in young adulthood, increased with age, and were associated with baseline variation in indexed LV end-systolic dimension and mass. Baseline indexed LV end-systolic dimension and mass were also associated with incident clinical HF. Efforts to prevent the LV abnormalities underlying clinical HF should start from a young age.

The prognostic value of traditional atherosclerotic cardiovascular disease (ASCVD) risk factors may decrease with age. We sought to determine whether the association between traditional ASCVD risk factors and incident coronary artery calcium (CAC) differs for younger versus older persons. We included 5,108 participants with baseline CAC = 0. Repeat CAC scoring occurred over 3 to 11 years of follow-up. Multivariable Cox proportional hazards regression assessed the association between traditional risk factors and incident CAC in young (32 to 45 years), middle-aged (46 to 64 years), and older adults (65 to 84 years). A total of 61% of the participants were women and 37% were Black. The proportion with incident CAC ranged from 22% among young adults, 34% for middle-aged adults, and 45% for older adults. In young adults, traditional risk factors were significantly associated with incident CAC except for diastolic blood pressure and high-density lipoprotein (HDL) cholesterol, whereas only total cholesterol/HDL cholesterol ≥3.5 (p = 0.04) was significantly associated with incident CAC in older persons. Non-HDL cholesterol (p = 0.02) was more strongly associated with incident CAC in young (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09 to 1.31) and middle aged (HR 1.14, 95% CI 1.07 to 1.23) compared to older adults (HR 1.11, 95% CI 0.99 to 1.23). When added to demographics, traditional risk factors provided a greater C-statistic improvement for incident CAC prediction in young (0.752, +0.070, p0.001) versus middle-aged (0.645, +0.054, p0.001) and older adults (0.597,+0.025, p = 0.08). In conclusion, traditional risk factors more strongly predict incident CAC in young compared to older adults, underlining the importance of primordial prevention through middle age while identifying the challenges of ASCVD risk assessment in older persons.

Rationale and objectives Left Atrial (LA) adverse remodeling is an important predictor of morbidity and mortality in several cardiovascular (CV) diseases. Our goals were to quantify and provide reference ranges for LA structure and function using feature tracking cine cardiac magnetic resonance. Materials and methods 2526 participants of the Multiethnic Study of Atherosclerosis study who had feature tracking cine cardiac magnetic resonance derived LA data and were free of atrial fibrillation/flutter and prior CV events at year five follow-up examination (2010–2012) were included in this study. LA phasic indexed volumes: maximum (LAVi max), minimum (LAVi min), and preatrial contraction (LAVi preA); LA empty fractions: total, passive, and active (LAtEF, LApEF, and LAaEF); LA longitudinal strain: maximum and preatrial contraction (S max and S preA); and LA longitudinal strain rate: systolic (SR max) and early/late diastolic (SR e and SR a) were measured. Age, gender, and race/ethnicity-specific reference ranges were identified. Also, reference values in a select subgroup of healthy participants free of traditional CV risk factors at the time of exam date were reported. Results The mean ± SD for LAVi max, LAVi min, LAVi preA, S max, SR e, and SR a were in the 45–65-year-old participants: (33.8 ± 10 mL/m2), (14.5 ± 6.4 mL/m2), (24.8 ± 8.2 mL/m2), (34.6 ± 13.8 %), (−1.4 ± 0.7 s−1), (−2.1 ± 1 s−1) and in the ≥ 65-year-old participants: (35 ± 11.5 mL/m2), (16.6 ± 8.3 mL/m2), (27.6 ± 9.9 mL/m2), (31.2 ± 14.3 %), (−1 ± 0.6 s−1), (−2.1 ± 1 s−1) respectively. Younger individuals had Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation smaller LA volumes and better LA function compared to their older counterparts. Similar findings were observed in Chinese-Americans as compared to Whites. Conclusion This study provides reference values of LA structure and function parameters from a healthy multiethnic community-based population aged 53–94 years evaluated by FTMRI.

Objective To assess the incidence of contrast-associated acute kidney injury (CAAKI) after repeated exposure to contrast material for computed tomography (CT) and conventional coronary angiography within short intervals. Methods We studied 651 patients enrolled in the CorE-64 (November 5, 2005–January 30, 2007) and CORE320 (October 21, 2009–August 17, 2011) multicenter studies. Participants with suspected obstructive coronary heart disease were referred for diagnostic cardiac catheterization and underwent coronary CT angiography for research before invasive angiography. Nonionic, low-osmolality iodinated contrast material was used for all imaging. Results The median age of the patients was 62 years, and 190 (29%) were women. Major risk factors for acute kidney injury were present in 277 of 651 (43%) patients. The median interval between CT imaging and invasive angiography was 3.1 days (interquartile range, 0.9-8.0 days). The median volume of contrast material was 100 mL for each test. In 16 (2.5%) of 651 patients, CAAKI developed. Of these cases, 1 occurred after the CT scan, whereas 6 were documented after invasive angiography (compared with post-CT creatinine concentration assessment). In 9 patients, CAAKI was found in comparing creatinine concentration after completion of both tests with baseline values (but not compared with post-CT imaging). Conclusion Acute kidney injury after repeated exposure to iodinated contrast media within a few days is uncommon even in a population of patients with highly prevalent risk factors. Withholding of clinically indicated contrast-enhanced imaging may therefore not be justified in this setting.

Aims Almost half of African American (AA) men and women have cardiovascular disease (CVD). Detection of prevalent CVD in community settings would facilitate secondary prevention of CVD. We sought to develop a tool for automated CVD detection. Methods and results Participants from the Jackson Heart Study (JHS) with analysable electrocardiograms (ECGs) (n = 3679; age, 62 ± 12 years; 36% men) were included. Vectorcardiographic (VCG) metrics QRS, T, and spatial ventricular gradient vectors’ magnitude and direction, and traditional ECG metrics were measured on 12-lead ECG. Random forests, convolutional neural network (CNN), lasso, adaptive lasso, plugin lasso, elastic net, ridge, and logistic regression models were developed in 80% and validated in 20% samples. We compared models with demographic, clinical, and VCG input (43 predictors) and those after the addition of ECG metrics (695 predictors). Prevalent CVD was diagnosed in 411 out of 3679 participants (11.2%). Machine learning models detected CVD with the area under the receiver operator curve (ROC AUC) 0.69–0.74. There was no difference in CVD detection accuracy between models with VCG and VCG + ECG input. Models with VCG input were better calibrated than models with ECG input. Plugin-based lasso model consisting of only two predictors (age and peak QRS-T angle) detected CVD with AUC 0.687 [95% confidence interval (CI) 0.625–0.749], which was similar (P = 0.394) to the CNN (0.660; 95% CI 0.597–0.722) and better (P Conclusions Simple model (age and QRS-T angle) can be used for prevalent CVD detection in limited-resources community settings, which opens an avenue for secondary prevention of CVD in underserved communities.

Impending major hardware advances in cardiac CT include three areas: ultra-high-resolution (UHR) CT, photon-counting CT, and phase-contrast CT. Cardiac CT is a particularly demanding CT application that requires a high degree of temporal resolution, spatial resolution, and soft-tissue contrast in a moving structure. In this review, cardiac CT is used to highlight the strengths of these technical advances. UHR CT improves visualization of calcified and stented vessels but may result in increased noise and radiation exposure. Photon-counting CT uses multiple photon energies to reduce artifacts, improve contrast resolution, and perform material decomposition. Finally, phase-contrast CT uses x-ray refraction properties to improve spatial and soft-tissue contrast. This review describes these hardware advances in CT and their relevance to cardiovascular imaging. © RSNA, 2020

Objectives The purpose of this study was to identify predictors of healthy arterial aging (long-term coronary artery calcification [CAC] of 0) among individuals with metabolic syndrome (Me...