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Supplemental digital content is available in the text. Background: Despite increasing minority enrollment in nursing programs, student attrition remains a persistent problem. Purpose: The purpose of this study was to describe the experiences of a diverse group of black alumni at a predominantly white institution in the United States. Method: In this qualitative descriptive study, researchers conducted focus group interviews with 16 recent graduates of accelerated baccalaureate and direct-entry nurse practitioner programs. Results: Four themes emerged as barriers to success: burden of exclusion and isolation, lack of diversity among students and faculty, struggling to find mentors, and cultural assumptions. Five themes captured the strategies alumni adopted to succeed: strength in numbers, helpful mentors, resilience, faith, and self-silencing. Conclusion: Participants experienced challenges but successfully navigated the program until they graduated. The study findings lay the groundwork for the development of programs that foster success for all students. [ABSTRACT FROM AUTHOR]

Background: Disability-adjusted life years (DALYs) are used to evaluate the relative burden of diseases in populations to help set prevention or treatment priorities. The impact of parental cardiovascular health (CVH) on healthy life years lost from cardiovascular disease (CVD) in adult offspring is unknown. We compared parent-offspring CVD DALYs trends over the life course and examined the association of parental CVH with offspring CVD DALYs. Methods: Using data from the Framingham Heart Study, 4814 offspring-mother-father trios were matched for age at selected baseline exams. CVH score was computed from the number of CVH metrics attained at recommended levels: poor (0–2), intermediate (3–4), and ideal (5–7). CVD DALYs were defined as the sum of years of life lost and years lived with CVD. Age-sex-standardized life expectancy and disability weights were derived from the actuarial life tables and Global Burden of Disease study, respectively. Multivariable-adjusted linear regression was used to investigate the association of parental CVH with offspring CVD DALYs. Results: Over an equal 47-year follow-up, parents lost nearly twice the number of CVD DALYs compared to their offspring (23 234 versus 12 217). However, age-adjusted CVD DALYs were higher at younger ages and similar along the life course for parents and offspring. One-unit increase in parental CVH was associated with 5 healthy life months saved in offspring. Offspring of mothers with ideal versus poor CVH had 3 healthy life years saved (β=−3.0 DALYs [95% CI, −5.6 to −0.3]). No statistically significant association was found between paternal CVH categories and offspring CVD DALYs. Conclusions: Higher maternal and paternal CVH were associated with increased healthy life years in offspring; however, the association was strongest between mothers and offspring. Investment in CVH promotion along the life course has the potential to reduce the burden of CVD in the current and future generation of adults. [ABSTRACT FROM AUTHOR]

Background: Matrix metalloproteinases (MMPs) play a key role in the pathogenesis of abdominal aortic aneurysm (AAA). Imaging aortic MMP activity, especially using positron emission tomography to access high sensitivity, quantitative data, could potentially improve AAA risk stratification. Here, we describe the design, synthesis, characterization, and evaluation in murine AAA and human aortic tissue of a first-in-class MMP-targeted positron emission tomography radioligand, 64Cu-RYM2. Methods: The broad spectrum MMP inhibitor, RYM2 was synthetized, and its potency as an MMP inhibitor was evaluated by a competitive inhibition assay. Toxicology studies were performed. Tracer biodistribution was evaluated in a murine model of AAA induced by angiotensin II infusion in Apolipoprotein E-deficient mice. 64Cu-RYM2 binding to normal and aneurysmal human aortic tissues was assessed by autoradiography. Results: RYM2 functioned as an MMP inhibitor with nanomolar affinities. Toxicology studies showed no adverse reaction in mice. Upon radiolabeling with Cu-64, the resulting tracer was stable in murine and human blood in vitro. Biodistribution and metabolite analysis in mice showed rapid renal clearance and acceptable in vivo stability. In vivo positron emission tomography/computed tomography in a murine model of AAA showed a specific aortic signal, which correlated with ex vivo measured MMP activity and Cd68 gene expression. 64Cu-RYM2 specifically bound to normal and aneurysmal human aortic tissues in correlation with MMP activity. Conclusions: 64Cu-RYM2 is a first-in-class MMP-targeted positron emission tomography tracer with favorable stability, biodistribution, performance in preclinical AAA, and importantly, specific binding to human tissues. These data set the stage for 64Cu-RYM2-based translational imaging studies of vessel wall MMP activity, and indirectly, inflammation, in AAA. [ABSTRACT FROM AUTHOR]

The evolution of antiretroviral therapies (ART) has redefined HIV infection from a life-threatening disease to a chronic manageable condition. Despite ART, HIV infection remains a serious health burden in Zimbabwe, particularly among women of reproductive age. In this interpretive phenomenology study, we interviewed 17 women with advanced HIV infection to uncover and understand their experiences of living with HIV infection in the ART era. Two themes (knowing the restorative power of ART and the heavy burden of being infected with HIV) reflected the women's experiences. ART brought physical and mental relief, but did not change the sobering reality of poverty or the challenges posed by the infective nature of HIV. The heavily donor-funded Zimbabwean ART program has been a success story, but there is uncertainty over its long-term sustainability. In resource-limited countries, clinicians and other stakeholders should continue to focus on HIV prevention as the cornerstone of HIV programming. [ABSTRACT FROM AUTHOR]

Background-Cardiac magnetic resonance is uniquely well suited for noninvasive imaging of the right ventricle. We sought to define normal cardiac magnetic resonance reference values and to identify the main determinants of right ventricular (RV) volumes and systolic function using a modern imaging sequence in a community-dwelling, longitudinally followed cohort free of clinical cardiovascular and pulmonary disease. Methods and Results-The Framingham Heart Study Offspring cohort has been followed since 1971. We scanned 1794 Offspring cohort members using steady-state free precession cardiac magnetic resonance and identified a reference group of 1336 adults (64±9 years, 576 men) free of prevalent cardiovascular and pulmonary disease. RV trabeculations and papillary muscles were considered cavity volume. Men had greater RV volumes and cardiac output before and after indexation to body size (all P<0.001). Women had higher RV ejection fraction than men (68±6% versus 64±7%; P<0.0001). RV volumes and cardiac output decreased with advancing age. There was an increase in raw and heightindexed RV measurements with increasing body mass index, but this trend was weakly inverted after indexation of RV volumes to body surface area. Sex, age, height, body mass index, and heart rate account for most of the variability in RV volumes and function in this community-dwelling population. Conclusions-We report sex-specific normative values for RV measurements among principally middle-aged and older adults. RV ejection fraction is greater in women. RV volumes increase with body size, are greater in men, and are smaller in older people. Body surface area seems to be appropriate for indexation of cardiac magnetic resonance-derived RV volumes. [ABSTRACT FROM AUTHOR]

Zimbabwean women are at high risk for HIV infection but often are not the focus of inquiry unless they are participants in controlled trials. In this phenomenological study, we interviewed 17 women living with advanced HIV infection to better understand their experiences and the aftermath of being diagnosed with HIV. Open-ended interviews were audiotaped, transcribed, translated into English, and analyzed. Two themes (living with suspicion of HIV infection and sensing the engulfing anguish of being HIV infected) emerged and were found to reflect the essence of the phenomena. Even though the women had suspected being HIV infected from internal and external cues, a confirmed diagnosis threw them into a state of anguish prompted by the possibility of dying from a disease they “did not deserve.” When designing prevention and treatment interventions, for the interventions to be effective, clinicians working with this population should consider the complexity of issues involved. [ABSTRACT FROM AUTHOR]

The article presents a study which investigated the effect of multiple comorbidities on mortality rate in heart failure (HF) patients, particularly the causes of death. By examining the incidence and predictors of cardiovascular and noncardiovascular death in HF patients, their results showed cardiovascular disease as the leading cause of death among HF patients. Noncardiovascular disease significantly contributes to mortality especially for individuals with preserved left ventricular ejection fraction.

The article discusses the results of a study which examined the influence of glycemic abnormalities and insulin resistance on cardiovascular magnetic resonance measures of cardiac function and structure. It was found that worsening glycemia and insulin resistance are independently and consistently associated with left ventricular mass (LVM)/LVM to end-diastolic volume ratio (LVM/LVEDV). The findings also suggest that insulin resistance and hyperglycemia may have a role in concentric left ventricular remodeling.

Aldosterone:renin ratio (ARR) is used to screen for hyperaldosteronism. Data regarding correlates of ambulatory ARR in the community and its relation to hypertension incidence are limited. We defined clinical correlates of ARR, determined its heritability, tested for association and linkage, and related ARR to blood pressure (BP) progression in nonhypertensive individuals among 3326 individuals from the Framingham Heart Study (53% women; mean age: 59 years). Ambulatory morning ARR (serum aldosterone and plasma renin concentrations) were related to clinical covariates, genetic variation across the REN locus, a 10-cM linkage map, and among nonhypertensive participants (n=1773) to progression of >or=1 Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure BP category (optimal: <120/80 mm Hg, normal: 120 to 129/80 to 84 mm Hg, high normal: 130 to 139/85 to 89 mm Hg, hypertension: >or=140/90 mm Hg), or incident hypertension (systolic BP: >or=140 mm Hg, diastolic BP: >or=90 mm Hg, or use of antihypertensive treatment). ARR was positively associated with age, female sex, untreated hypertension, total/high-density lipoprotein cholesterol ratio, hormone replacement therapy, and beta-blocker use, but negatively associated with angiotensin-converting enzyme inhibitor and diuretic use. ARR was heritable (h(2)=0.40), had modest linkage to chromosome 11p (logarithm of the odds: 1.89), but was not associated with 17 common variants in REN (n=1729). On follow-up (mean: 3 years), 607 nonhypertensive individuals (34.2%) developed BP progression, and 283 (16.0%) developed hypertension. Higher baseline logARR was associated with increased risk of BP progression (odds ratio per SD increment: 1.23; 95% CI: 1.11 to 1.37) and hypertension incidence (odds ratio per SD increment: 1.16; 95% CI: 1.00 to 1.33). ARR is a heritable trait influenced by clinical and genetic factors. There is a continuous gradient of increasing risk of BP progression across ARR levels in nonhypertensive individuals. [ABSTRACT FROM AUTHOR]

An understanding of mechanisms underlying the development of essential hypertension is critical for designing prevention and treatment strategies. Selected biomarkers may be elevated before the onset of hypertension, but previous studies are limited by cross-sectional designs or a focus on single biomarkers. We prospectively studied 1456 nonhypertensive individuals who had baseline measurement of 9 biomarkers: C-reactive protein (inflammation); fibrinogen (inflammation and thrombosis); plasminogen activator inhibitor-1 (fibrinolytic potential); aldosterone, renin, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptide (neurohormonal activity); homocysteine (renal function and oxidant stress); and urinary albumin/creatinine ratio (glomerular endothelial function). Incident hypertension, defined as blood pressure > or =140/90 mm Hg or antihypertensive therapy, developed in 232 participants over a mean follow-up of 3 years. After adjustment for clinical risk factors, the biomarker panel was significantly associated with incident hypertension (P=0.002). Three (of 9) biomarkers were significantly related to incident hypertension on backward elimination (multivariable-adjusted odds ratios, per SD increment in biomarker): C-reactive protein (1.26; 95% CI: 1.05 to 1.51), plasminogen activator inhibitor-1 (1.28; 95% CI: 1.05 to 1.57), and urinary albumin/creatinine ratio (1.21; 95% CI: 1.02 to 1.43). The incidence of hypertension was 4.5, 6.4, and 9.9 per 100 person years for participants with 0, 1, and > or=2 elevated biomarkers, respectively (elevation defined as > or =1 SD above the mean). The threshold of > or =2 elevated biomarkers for predicting hypertension was associated with high specificity (0.92) but low sensitivity (0.15). Biomarkers of inflammation, reduced fibrinolytic potential, and low-grade albuminuria are jointly associated with the incidence of hypertension. These data support the premise that abnormalities in multiple biological pathways antedate the onset of overt hypertension. [ABSTRACT FROM AUTHOR]

Background: Nonlaboratory-based (non-LB) algorithms have been developed to facilitate absolute cardiovascular risk assessment in resource-constrained settings. The non-LB Framingham algorithm, which substitute BMI for lipids in laboratory-based Framingham, exhibits best performance among non-LB algorithms. However, its external validity has not been evaluated., Aim: To examine the validity of non-LB Framingham algorithm in Atherosclerosis Risk in Communities dataset, and contrast performance with the laboratory-based Framingham algorithm., Methods: We developed Cox regression models including non-LB and laboratory-based Framingham covariates in Atherosclerosis Risk in Communities dataset. Discrimination was assessed via C-statistic, calibration via goodness-of-fit, and marginal discrimination value of BMI vis-à-vis lipids vis-à-vis waist-hip ratio via net reclassification improvement (NRI). Both models were compared via area under receiver operating characteristic., Results: Among 11 601 participants (mean age 54 years, 55% women, 23% black), non-LB vs. laboratory-based Framingham performed as follows: C-statistic 0.75 vs. 0.76 among women and 0.67 vs. 0.68 among men; goodness-of-fit 14.2 vs. 10.5 among women and 25.8 vs. 21.8 among men. Overall area under receiver operating characteristic was 0.706 vs. 0.710, respectively, with no racial differences in discrimination or calibration. BMI and total cholesterol had no impact on NRI. Incremental predictive value of HDL was comparable with waist-hip ratio (category-less NRI = 0.34 vs. 0.31; categorical NRI = 0.06 vs. 0.05, P < 0.01)., Conclusion: These results demonstrate the validity and limitations of the non-LB Framingham algorithm in a biracial cohort. Substituting BMI with a central adiposity metric such as waist-hip ratio or waist circumference could make the algorithm better or at par with the laboratory-based Framingham algorithm.

Objective: The objective of this study was to determine the prevalence and risk factor (RF) correlates of aortic plaque (AP) detected by cardiovascular magnetic resonance (CMR), which mainly shows noncalcified plaques, and by noncontrast computed tomography (CT), which best depicts calcified plaques, in community-dwelling adults., Approach and Results: A total of 1016 Framingham Heart Study Offspring cohort members (64 ± 9 years; 474 men) underwent CMR and CT of the aorta. Potential RFs for AP (age; sex; body mass index; blood pressure; low-density lipoprotein and high-density lipoprotein cholesterol; fasting glucose; C-reactive protein; prevalent hypertension, diabetes mellitus, smoking; use of antihypertensive, diabetes mellitus, or lipid-lowering drugs) were compared between participants, with zero versus nonzero AP by CMR and by CT. Candidate RFs attaining P<0.05 for difference with either imaging modality were entered into multivariable logistic regression models adjusting for age, sex, and other RFs. Odds ratios were calculated for modality-specific prevalence of AP. Associations between RFs and continuous measures of AP were assessed using Tobit regression. Prevalence of CMR and CT AP was 49% and 82%, respectively. AP burdens by CMR and CT were correlated, r=0.28, P<0.0001. Increasing age and smoking were associated with prevalent AP by both CMR and CT. Additionally, prevalent AP by CMR was associated with female sex and fasting glucose and prevalent AP by CT with hypertension treatment and adverse lipid profile., Conclusions: AP by CMR and CT are both associated with smoking and increasing age, but other RFs differ between calcified and noncalcified AP. The relative predictive value of AP detected by CMR versus by CT for incident cardiovascular events remains to be determined., (© 2014 American Heart Association, Inc.)

Objective: To evaluate if biomarkers reflecting left ventricular/vascular extracellular matrix remodeling are associated with cardiovascular disease (CVD) and death in the community., Methods and Results: In 922 Framingham Study participants (mean age, 58 years; 56% women), we related circulating concentrations of matrix metalloproteinase-9 (binary variable: detectable versus undetectable), log of tissue inhibitor of matrix metalloproteinase-1, and log of procollagen type III aminoterminal peptide (PIIINP) to incident CVD and death. On follow-up (mean, 9.9 years), 51 deaths and 81 CVD events occurred. Each SD increment of log of tissue inhibitor of matrix metalloproteinase-1 and log-PIIINP was associated with multivariable-adjusted hazards ratios of 1.72 (95% CI, 1.30 to 2.27) and 1.47 (95% CI, 1.11 to 1.96), respectively, for mortality risk. Log-PIIINP concentrations were also associated with CVD risk (hazard ratio [95% CI] per SD, 1.35 [1.05 to 1.74]). Death and CVD incidence rates were 2-fold higher in participants with both biomarkers higher than the median (corresponding hazard ratio [95% CI], 2.78 [1.43 to 5.40] and 1.77 [1.04 to 3.03], respectively) compared with those with either or both less than the median. The inclusion of both biomarkers improved the C-statistic (for predicting mortality) from 0.78 to 0.82 (P=0.03). Matrix metalloproteinase-9 was unrelated to either outcome., Conclusions: Higher circulating tissue inhibitor of matrix metalloproteinase-1 and PIIINP concentrations are associated with mortality, and higher PIIINP is associated with incident CVD, in the community.

Background: Several biological pathways are activated in ventricular remodeling and in overt heart failure (HF). There are no data, however, on the incremental utility of a parsimonious set of biomarkers (reflecting pathways implicated in HF) for predicting HF risk in the community., Methods and Results: We related a multibiomarker panel to the incidence of a first HF event in 2754 Framingham Heart Study participants (mean age, 58 years; 54 women) who were free of HF and underwent routine assays for 6 biomarkers (C-reactive protein, plasminogen activator inhibitor-1, homocysteine, aldosterone-to-renin ratio, B-type natriuretic peptide, and urinary albumin-to-creatinine ratio). We estimated model c statistic, calibration, and net reclassification improvement to assess the incremental predictive usefulness of biomarkers. We also related biomarkers to the incidence of nonischemic HF in participants without prevalent coronary heart disease. On follow-up (mean, 9.4 years), 95 first HF events occurred (54 in men). In multivariable-adjusted models, the biomarker panel was significantly related to HF risk (P=0.00005). On backward elimination, B-type natriuretic peptide and urinary albumin-to-creatinine ratio emerged as key biomarkers predicting HF risk; hazards ratios per 1-SD increment in log marker were 1.52 (95 confidence interval, 1.24 to 1.87) and 1.35 (95 confidence interval, 1.11 to 1.66), respectively. B-type natriuretic peptide and urinary albumin-to-creatinine ratio significantly improved the model c statistic from 0.84 (95 confidence interval, 0.80 to 0.88) in standard models to 0.86 (95 confidence interval, 0.83 to 0.90), enhanced risk reclassification (net reclassification improvement=0.13; P=0.002), and were independently associated with nonischemic HF risk., Conclusion: Using a multimarker strategy, we identified B-type natriuretic peptide and urinary albumin-to-creatinine ratio as key risk factors for new-onset HF with incremental predictive utility over standard risk factors.

Objective: To examine the association of serum gamma-glutamyltransferase (GGT) with incident heart failure., Methods and Results: We related serum GGT to the incidence of heart failure in 3544 (mean age, 44.5 years; 1833 women and 1711 men) Framingham Study participants who were free of heart failure and myocardial infarction. On follow-up (mean, 23.6 years), 188 participants (77 women) developed new-onset heart failure. In multivariable Cox proportional hazards regression models adjusting for standard risk factors and alcohol consumption as time-varying covariates (updated every 4 years), each SD increase in log-GGT was associated with a 1.39-fold risk of heart failure (95% CI, 1.20 to 1.62). The linearity of the association was confirmed by multivariable-adjusted splines, and the relations remained robust on additional adjustment for hepatic aminotransferases and C-reactive protein. Participants with a serum GGT level at the median or greater had a 1.71-fold risk of heart failure (95% CI, 1.21 to 2.41) compared with individuals with GGT concentrations less than the median. GGT marginally increased the model C-statistic from 0.85 to 0.86 but improved the risk reclassification modestly (net reclassification index, 5.7%; P=0.01)., Conclusions: In this prospective study of a large community-based sample, higher serum GGT concentrations within the "normal" range were associated with greater risk of heart failure and incrementally improved prediction of heart failure risk.

Objective: Experimental evidence identified the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB (RANK)/RANK ligand (RANKL) pathway as a candidate system modulating vascular remodeling and cardiovascular disease (CVD)., Methods and Results: Serum concentrations of OPG and RANKL were measured in 3250 Framingham Study participants (54% women, 61+/-9 years). During a mean follow-up of 4.6 years, 143 (of 3084 free of CVD at baseline) participants developed a first CVD event, and 235 died. In multivariable models, OPG was associated with increased hazards for incident CVD and mortality (hazard ratio, 1.27; 95% CI, 1.04 to 1.54; and hazard ratio, 1.25; 95% CI, 1.07 to 1.47, per 1-SD increment in log-OPG, respectively). Log-OPG was positively related to multiple CVD risk factors, including age, smoking, diabetes, systolic blood pressure, and prevalent CVD. In a subsample (n=1264), the prevalence of coronary artery calcification, measured by computed tomography, increased nonsignificantly with OPG quartiles. RANKL concentrations displayed inverse associations with multiple CVD risk factors, including smoking, diabetes, and antihypertensive treatment, and were not related to coronary artery calcification or incident CVD or mortality., Conclusions: Our prospective data reinforce OPG as marker for CVD risk factor burden and predictor for CVD and mortality in the community.

Background: Pericardial fat has been implicated in the pathogenesis of obesity-related cardiovascular disease. Whether the associations of pericardial fat and measures of cardiac structure and function are independent of the systemic effects of obesity and visceral adiposity has not been fully explored., Methods and Results: Participants from the Framingham Heart Study (n=997; 54.4% women) underwent chest and abdominal computed tomography and cardiovascular magnetic resonance imaging between 2002 and 2005. Pericardial fat, intrathoracic fat, and visceral adipose tissue quantified from multidetector computed tomography, along with body mass index and waist circumference, were examined in relation to cardiovascular magnetic resonance measures of left ventricular (LV) mass, LV end-diastolic volume, and left atrial dimension. In women, pericardial fat (r=0.20 to 0.35, P<0.001), intrathoracic fat (r=0.25 to 0.37, P<0.001), visceral adipose tissue (r=0.24 to 0.45, P<0.001), body mass index (r=0.36 to 0.53, P<0.001), and waist circumference (r=0.30 to 0.48, P<0.001) were directly correlated with LV mass, LV end-diastolic volume, and left atrial dimension. In men, pericardial fat (r=0.19 to 0.37, P<0.001), intrathoracic fat (r=0.17 to 0.31, P<0.001), visceral adipose tissue (r=0.19 to 0.36, P<0.001), body mass index (r=0.32 to 0.44, P<0.001), and waist circumference (r=0.34 to 0.44, P<0.001) were directly correlated with LV mass and left atrial dimension, but LV end-diastolic volume was not consistently associated with adiposity measures. Associations persisted after multivariable adjustment but not after additional adjustment for body weight and visceral adipose tissue, except for pericardial fat and left atrial dimension in men., Conclusions: Pericardial fat is correlated with cardiovascular magnetic resonance measures, but the association is not independent of or stronger than other ectopic fat stores or proxy measures of visceral adiposity. An important exception is left atrial dimension in men. These results suggest that the systemic effects of obesity on cardiac structure and function may outweigh the local pathogenic effects of pericardial fat.

Objective: The purpose of this study was to investigate the impact of age, sex, and hypertension (HTN) on aortic atherosclerotic burden using cardiovascular MRI (CMR) in a free-living longitudinally followed cohort., Methods and Results: 1763 participants (829 M and 934 F; 38 to 88 years of age) of the Framingham Heart Study Offspring cohort underwent CMR of the thoracoabdominal aorta using an ECG-gated 2D T2-weighted black-blood sequence. Of these, 1726 subjects (96%) with interpretable CMR were characterized by sex, age-quartile, and presence or absence of HTN and clinical cardiovascular disease (CVD). Aortic plaque prevalence and volume increased with increasing age in both sexes. For the nonhypertensive (no-HTN) group, plaque was identified in 702 (46%) with greater prevalence in women than in men (P<0.006). HTN was associated with greater aortic plaque burden (P<0.02). The 200 subjects with clinical CVD had greater plaque burden than subjects without CVD (P<0.0001)., Conclusions: In this free-living longitudinally followed cohort, subclinical aortic atherosclerosis was seen in nearly half of subjects and increased with advancing age. HTN was associated with increased aortic plaque burden. Among no-HTN subjects, women had greater plaque burden than men. These data suggest that subclinical atherosclerosis is more common in no-HTN women and emphasize the importance of focusing on preventive measures in both sexes.