Is It Time to Consider a "Time-Out" Before Primary Prevention Implantable Cardioverter-Defibrillator in Currently or Recently Hospitalized Older Patients with Heart Failure?

BACKGROUND: Trajectories of mortality after primary implantable cardioverter-defibrillator (ICD) placement for older heart failure (HF) patients during or soon after acute hospitalization have not been assessed. OBJECTIVES: To compare trajectories of mortality after primary ICD placement during or soon after acute cardiac or non-cardiac hospitalization. METHODS: We identified older HF patients with primary ICD using 20% Medicare data (2008-2018). Placement settings were: 1) 'current-H' during current hospitalization, 2) 'recent-H' within 90 days of hospitalization, or 3) 'chronic stable'. Hospitalization was categorized cardiac vs. non-cardiac. Interval mortality and hazard ratios (HRs) using Cox regression were estimated at 0-30 days, 31-90 days, and 91-365 days after ICD placement. RESULTS: Of 61,710 patients (mean age 76; 35% female; 85% White), 19%, 25%, and 56% had ICDs in 'current-H', 'recent-H', and 'chronic stable' settings. Mortality rates (per 100 person-years) were highest during 0-30 days with 38(34-42) and 22(19-24) for 'current-H' and 'recent-H', which declined to 21(20-22) and 16(15-17) during 91-365 days, respectively. Compared to 'chronic stable', HRs were greatest during 0-30 days post-ICD placement ('current-H' = 5.5[4.5-6.8], 'recent-H' = 3.4[2.8-4.2]) and decreased during 91-365 days ('current-H' = 2.0[1.8-2.1], 'recent-H' = 1.6[1.5-1.7]). HR pattens were similar for cardiac and non-cardiac hospitalization. CONCLUSION: Primary ICD placement during or soon after hospitalization for any reason was associated with worse mortality with diminishing risks after 90 days. Hospitalization likely identifies a sicker population in whom early mortality with or without ICD may be higher. Our results support careful consideration regarding ICD placement during the 90 days following hospitalization.

A Deep Patient-Similarity Learning Framework for the Assessment of Diastolic Dysfunction in Elderly Patients.

BACKGROUND AND AIMS: Age-related changes in cardiac structure and function are well recognized and make the clinical determination of abnormal LV diastolic function (LVDD) particularly challenging in the elderly. We investigated whether a deep neural network (DeepNN) model[70] of LVDD, previously validated in a younger cohort, can be implemented in an older population to predict incident heart failure (HF). METHODS: A previously developed DeepNN was tested on 5,596 older participants (66-90 years; 57% female; 20% black) from the Atherosclerosis Risk in Communities study. The association of DeepNN predictions with HF or all-cause death for the American College of Cardiology Foundation/American Heart Association Stage A/B (n = 4,054) and Stage C/D (n = 1,542) subgroups was assessed. RESULTS: The DeepNN-predicted High-Risk compared to the Low-Risk phenogroup demonstrated an increased incidence of HF and death for both Stage A/B and Stage C/D (log-rank p < 0.0001 for all). In multivariable analyses, the High-Risk phenogroup remained an independent predictor of HF and death in both Stages A/B (adjusted hazard ratio (HR) [95% confidence interval], 6.52[4.20-10.13] and 2.21(1.68-2.91), both p < 0.0001) and Stage C/D (6.51[4.06-10.44] and 1.03(1.00-1.06), both p < 0.0001) respectively. In addition, DeepNN showed incremental value over the 2016 ASE/EACVI guidelines (Net reclassification index, 0.5[CI:0.4-0.6], p < 0.001; C-statistic improvement, DeepNN [0.76] vs. ASE/EACVI [0.70], p < 0.001) overall and maintained across stage-groups. CONCLUSIONS: Despite training with a younger cohort, a deep patient-similarity-based learning framework for assessing LVDD provides a robust prediction of all-cause death and incident HF for older patients.

Racial differences in setting of implantable cardioverter-defibrillator placement in older adults with heart failure and association with disparate post-implant outcomes.

Background: Implantable cardioverter-defibrillator (ICD) placement in heart failure (HF) patients during or early after (≤90 days) unplanned cardiovascular hospitalizations has been associated with poor outcomes. Racial and ethnic differences in this "peri-hospitalization" ICD placement have not been well described. Methods: Using a 20% random sample of Medicare beneficiaries, we identified older (≥66 years) patients with HF who underwent ICD placement for primary prevention from 2008 to 2018. We investigated racial and ethnic differences in frequency of peri-hospitalization ICD placement using modified Poisson regression. We utilized Kaplan-Meier analyses and Cox regression to investigate the association of peri-hospitalization ICD placement with differences in all-cause mortality and hospitalization (HF, cardiovascular and all-cause) within and between race and ethnicity groups for up to 5-year follow-up. Results: Among the 61,710 beneficiaries receiving ICDs (35% female, 82% White, 10% Black, 6% Hispanic), 44% were implanted peri-hospitalization. Black [adjusted rate ratio (RR) 95% Confidence Interval (95% CI): 1.16 (1.12, 1.20)] and Hispanic [RR (95% CI): 1.10 (1.06, 1.14)] beneficiaries were more likely than White beneficiaries to have ICD placement peri-hospitalization. Peri-hospitalization ICD placement was associated with an at least 1.5× increased risk of death, 1.5× increased risk of re-hospitalization and 1.7× increased risk of HF hospitalization during 3-year follow-up in fully adjusted models. Although beneficiaries with peri-hospitalization placement had the highest mortality and readmission rates 1- and 3-year post-implant (log-rank p < 0.0001), the magnitude of the associated risk did not differ significantly by race and ethnicity (p = NS for interaction). Conclusions: ICD implantation occurring during the peri-hospitalization period was associated with worse prognosis and occurred at higher rates among Black and Hispanic compared to White Medicare beneficiaries with HF during the period under study. The risk associated with peri-hospitalization ICD placement did not differ by race and ethnicity. Future paradigms aimed at enhancing real-world effectiveness of ICD therapy and addressing disparate outcomes should consider timing and setting of ICD placement in HFrEF patients who otherwise meet guideline eligibility.

The role of aldosterone and ideal cardiovascular health in incident cardiovascular disease: The Jackson heart study.

Background: Higher levels of ideal cardiovascular health (ICH) are associated with lower levels of aldosterone and incidence of cardiovascular disease (CVD). However, the degree to which aldosterone mediates the association between ICH and CVD incidence has not been explored. Thus, we investigated the mediational role of aldosterone in the association of 5 components of ICH (cholesterol, body mass index (BMI), physical activity, diet and smoking) with incident CVD and the mediational role of blood pressure (BP) and glucose in the association of aldosterone with incident CVD in a cohort of African Americans (AA). Methods: The Jackson Heart Study is a prospective cohort of AAs adults with data on CVD outcomes. Aldosterone, ICH metrics and baseline characteristics were collected at exam 1 (2000-2004). ICH score was developed by summing 5 ICH metrics (smoking, dietary intake, physical activity, BMI, and total cholesterol) and grouped into two categories (0-2 and ≥3 metrics). Incident CVD was defined as stroke, coronary heart disease, or heart failure. Cox proportional hazard regression models were used to model the association of categorical ICH score with incident CVD. The R Package Mediation was utilized to examine: 1) The mediational role of aldosterone in the association of ICH with incident CVD and 2) The mediational role of blood pressure and glucose in the association of aldosterone with incident CVD. Results: Among 3,274 individuals (mean age: 54±12.4 years, 65% female), there were 368 cases of incident CVD over a median of 12.7 years. The risk of incident CVD was 46% lower (HR: 0.54; 95%CI 0.36, 0.80) in those with ≥3 ICH metrics at baseline compared to 0-2. Aldosterone mediated 5.4% (p = 0.006) of the effect of ICH on incident CVD. A 1-unit increase in log-aldosterone was associated with a 38% higher risk of incident CVD (HR 1.38, 95%CI: 1.19, 1.61) with BP and glucose mediating 25.6% (p<0.001) and 4.8% (p = 0.048), respectively. Conclusion: Aldosterone partially mediates the association of ICH with incident CVD and both blood pressure and glucose partially mediate the association of aldosterone with incident CVD, emphasizing the potential importance of aldosterone and ICH in risk of CVD among AAs.

The role of aldosterone and ideal cardiovascular health in incident diabetes: The Jackson Heart Study.

Background: Greater attainment of ideal cardiovascular health (ICH) and lower serum aldosterone are associated with lower diabetes risk. Higher levels of ICH are associated with lower aldosterone. The mediational role of aldosterone in the association of ICH with incident diabetes remains unexplored. Thus, we examined the mediational role of aldosterone in the association of 5 ICH components (smoking, diet, physical activity, body mass index [BMI], and cholesterol) with incident diabetes. Additionally, we investigated the mediational role of glucose and blood pressure (BP) in the association of aldosterone with incident diabetes in an African American (AA) cohort. Methods: We conducted a prospective cohort analysis among AA adults, aged 21-94 years, in the Jackson Heart Study. Data on ICH, aldosterone, and cardiometabolic risk factors were collected at exam 1 (2000-2004). Diabetes (fasting glucose ≥ 126 mg/dL, physician diagnosis, use of diabetes drugs, or glycated hemoglobin ≥ 6.5%) was assessed at exams 1 through 3 (2009-2012). ICH metrics were defined by American Heart Association 2020 goals for smoking, dietary intake, physical activity, BMI, total cholesterol, BP and glucose. The number of ICH metrics attained at exam 1, excluding BP and fasting glucose, were summed (0-2, vs. 3+). R Package Mediation was used to examine: 1) The mediational role of aldosterone in the association of ICH with incident diabetes; and 2) the mediational role of BP and glucose in the association of aldosterone with incident diabetes. Results: Among 2,791 participants (mean age: 53±12, 65% female) over a median of 7.5 years, there were 497 incident diabetes cases. Risk of incident diabetes was 37% (HR: 0.63, 95%CI: 0.47, 0.84) lower in 3+ ICH category compared to 0-2 ICH category. Aldosterone mediated 6.98% (95% CI: 1.8%, 18.0%) of the direct effect of ICH on incident diabetes. A 1-unit increase in log-aldosterone was associated with a 44% higher risk of diabetes (HR 1.44, 95%CI 1.25-1.64). BP and glucose mediated 16.3% (95% CI: 7.0%, 31.0%) and 19.7% (95% CI: 6.5%, 34.0%) of the association of aldosterone with incident diabetes, respectively. Conclusion: Aldosterone is a mediator of the association of ICH with incident diabetes, whereas BP and glucose are mediators of the association of aldosterone with incident diabetes, emphasizing the importance of the renin-angiotensin-aldosterone system and ICH in lowering risk of diabetes in AA populations.

Validity of International Classification of Diseases (ICD)-10 Diagnosis Codes for Identification of Acute Heart Failure Hospitalization and Heart Failure with Reduced Versus Preserved Ejection Fraction in a National Medicare Sample.

BACKGROUND: Heart failure (HF) is a leading cause of hospitalization in older adults. Medicare data have been used to assess HF outcomes. However, the validity of ICD-10 diagnosis codes (used since 2015) to identify acute HF hospitalization or distinguish reduced (heart failure with reduced ejection fraction) versus preserved ejection fraction (HFpEF) is unknown in Medicare data. METHODS: Using Medicare data (2015-2017), we randomly sampled 200 HF hospitalizations with ICD-10 diagnosis codes for HF in the first/second claim position in a 1:1:2 ratio for systolic HF (I50.2), diastolic HF (I50.3), and other HF (I50.X). The primary gold standards included recorded HF diagnosis by a treating physician for HF hospitalization, ejection fraction (EF)≤50 for heart failure with reduced ejection fraction, and EF>50 for HFpEF. If the quantitative EF was not present, then qualitative descriptions of EF were used for heart failure with reduced ejection fraction/HFpEF gold standards. Multiple secondary gold standards were also tested. Gold standard data were extracted from medical records using standardized forms and adjudicated by cardiology fellows/staff. We calculated positive predictive values with 95% CIs. RESULTS: The 200-chart validation sample included 50 systolic, 50 diastolic, 47 combined dysfunction, and 53 unspecified HF patients. The positive predictive values of acute HF hospitalization was 98% [95% CI, 95-100] for first-position ICD-10 HF diagnosis and 66% [95% CI, 58-74] for first/second-position diagnosis. Quantitative EF was available for ≥80% of patients with systolic, diastolic, or combined dysfunction ICD-10 codes. The positive predictive value of systolic HF codes was 90% [95% CI, 82-98] for EFs≤50% and 72% [95% CI, 60-85] for EFs≤40%. The positive predictive value was 92% [95% CI, 85-100] for HFpEF for EFs>50%. The ICD-10 codes for combined or unspecified HF poorly predicted heart failure with reduced ejection fraction or HFpEF. CONCLUSIONS: ICD-10 principal diagnosis identified acute HF hospitalization with a high positive predictive value. Systolic and diastolic ICD-10 diagnoses reliably identified heart failure with reduced ejection fraction and HFpEF when EF 50% was used as the cutoff.

Disparate Cardiovascular Hospitalization Trends Among Young and Middle-Aged Adults Within and Across Race and Ethnicity Groups in Four States in the United States.

Background Inpatient hospitalizations for cardiovascular disease (CVD) decreased nationally in the past decade. However, data are lacking on whether national declines represent trends within and across race and ethnicity populations from different US regions. Methods and Results Using State Inpatient Databases, Census Bureau and Behavioral Risk Factor Surveillance System data for Florida, Kentucky, New Jersey, and North Carolina, we identified all CVD hospitalizations and population characteristics for adults aged 18 to 64 years between January 1, 2009 and December 31, 2018. We calculated yearly CVD hospitalization rates for each state for the overall population, by sex, race, and ethnicity. We modeled yearly trends in age-adjusted CVD hospitalization rate in each state using negative binomial regression. State base populations were similar by age (mean age: 40-42 years) and sex (50%-51% female) throughout the study period. There were 314 973 and 288 843 total CVD hospitalizations among the 4 states in 2009 and 2018, respectively. Crude hospitalization rates declined in all states (age 18-44 years NJ: -33.4%; KY: -17.0%; FL: -11.9%; NC: -11.2%; age 45-64 years NJ: -29.8%; KY: -20.3%; FL: -12.2%; NC: -11.6%) over the study period. In age-adjusted models, overall hospitalization rates declined significantly in NJ -2.5%/y (95% CI, -2.9 to -2.1) and in KY -1.6%/y (-1.9 to -1.2) with no significant declining trend in FL and NC. Similar findings were present by sex. Among non-Hispanic White populations, mean yearly decline in hospitalization rate was significant in all states except FL, with the greatest declines in NJ (-3.8%/y [-4.4 to -3.2], P values for state-year interaction <0.0001). By contrast, a significant declining trend was present for non-Hispanic Black and Hispanic populations only in NJ (P values for state-year interaction <0.001). We found similar differences in trend between states in sensitivity analyses incorporating additional demographic and comorbid characteristics. Conclusions Decreases in CVD hospitalization rates in the past decade among nonelderly adults varied considerably by state and appeared largely driven by declines among non-Hispanic White populations. Overall declines did not represent divergent trends between states within non-Hispanic Black and Hispanic populations. Recognition of differences not just between but also within race and ethnicity populations should inform national and local policy initiatives aimed at reducing disparities in CVD outcomes.

Relation of Sociodemographic Factors With Primary Cause of Hospitalization Among Patients With Left Ventricular Assist Devices (from the National Inpatient Sample 2012 to 2017).

Left ventricular assist devices (LVADs) are an established intervention for end-stage heart failure (HF). Rehospitalization for serious complications remains common during the continuous-flow LVAD era. Whether sociodemographic factors are associated with differences in the frequency of severe complications leading to hospitalization remains unclear. Using data from the National Inpatient Sample, we identified all hospitalizations from 2012 to 2017 of adults aged ≥18 years with previous LVAD placement. We categorized the primary cause of hospitalizations into key adverse diagnoses, including bleeding, HF, arrhythmias, LVAD complications, stroke, and a composite of device-related infection or sepsis. We assessed the association of sociodemographic markers with primary diagnoses using modified Poisson regression. We identified 62,630 hospitalizations during the study period (41% aged ≥65, 77% men, 26% Black, 5% Hispanic). Bleeding (18%), infections (15%), and HF (15%) were the most common primary diagnoses. In the multivariable analyses, gastrointestinal bleeding was more likely among older adults (relative risk [RR] 95% confidence interval [CI] 4.69 [3.57 to 6.16]; age ≥65 vs 18 to 44 years), among Black than White patients (RR 95% CI 1.17 [1.04 to 1.32]), and less likely for the highest income quartile than the lowest (RR 95% CI 0.79 [0.69 to 0.91]). Device-related infection/sepsis was also less likely for patients with higher income (RR 95% CI 0.80 [0.67 to 0.96]). Ventricular arrhythmias were less frequent diagnoses for women than men (RR 95% CI 0.59 [0.46 to 0.75]). LVADs complications were less likely in older adults than younger adults (RR 95% CI 0.70 [0.50 to 0.98]). In conclusion, after LVAD implantation, the frequency in which specific adverse events are the primary cause of rehospitalization varies significantly by sociodemographic factors. Further study is needed to determine if there are opportunities for targeted preventive measures based on sociodemographic markers.

Thirty-Year Trends in Graft Survival After Heart Transplant: Modeled Analyses of a Transplant Registry.

BACKGROUND: Heart failure is an epidemic in the United States, and transplantation remains the most definitive therapy. We describe multidecade trends in posttransplant graft survival, adjusted for concurrent changes in the population, over the 30 years antecedent to the most recent heart allocation policy change. METHODS: Scientific Registry of Transplant Recipients data were used to identify all primary adult heart recipients from 1989 to 2017. We described temporal changes in population characteristics (recipient and donor demographics and comorbidities, pretransplant interventions, clinical transplant measures, and providers). The primary outcome was graft survival, defined as freedom from all-cause death and graft failure, within 6 months posttransplant. Modified Poisson logistic regression estimated relative changes in risk of outcomes compared with 1989, with and without adjustment for changing population characteristics. We identified risk factors, quantified by associated risk ratios. RESULTS: Among 56,488 primary adult heart recipients, we observed 5529 (9.8%) all-cause deaths and 1933 (3.4%) graft failure events within 6 months posttransplant. Prevalence of known recipient risk factors increased over time. Unadjusted modeling demonstrated a significant 30-year improvement in graft survival, averaging 2.6% per year (95% confidence interval, 2.4-2.9; P for trend < .001). After adjusting for population changes the 30-year trend remained significant and graft survival improved on average 3.0% per year (95% confidence interval, 2.6-3.3). Regression modeling identified multiple predictors of graft survival. Modeling 2 additional outcomes of 6-month mortality and 6-month graft failure produced similar results. CONCLUSIONS: Short-term graft survival after heart transplantation has improved significantly leading up to the 2018 heart allocation policy change, despite concurrent increase in prevalence of higher risk population characteristics.

Fibroblast growth factor-23 and subclinical markers of cardiac dysfunction: The coronary artery risk development in young adults (CARDIA) study.

BACKGROUND: Elevated Fibroblast Growth Factor-23 (FGF23) levels have been associated with greater left ventricular mass (LVM) and heart failure. Whether higher FGF23 is associated with higher LVH prevalence and longitudinal changes in LVM and myocardial strain in middle-aged adults without cardiovascular disease (CVD) or chronic kidney disease (CKD) is unknown. METHODS: We studied 3,113 adults without CVD at baseline participating in the Year 25 (2010-2011) follow-up exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study. We studied the association of Year 25 c-terminal FGF23 concentrations with indexed LVM (LVMI=LVM/height2.7), LVH and myocardial strain as assessed by speckle tracking strain echocardiography. Among the 2,758 (88.6%) participants who returned for the Year 30 examination, we also investigated the association of Year 25 FGF23 with 5 Year change in LVMI, strain parameters and incident LVH. RESULTS: The mean age was 50.0 (±3.6) years, 56.8% were female, 45.7% were Black and 6.4% had CKD. There was 6.0% LVH prevalence at Year 25. Mean 5 Year change in LVMI was 5.3 (±7.7) grams/meter. In multivariable models, FGF23 in the highest quartile was associated with greater odds of LVH at Year 25 compared to lower quartiles. [Odds Ratio 95% CI: 1.81 (1.28, 2.58)] with similar findings after exclusion of participants with CKD. There was no interaction between FGF23 and race (P = .18) or sex (P = .80). There was no association between FGF23 and global longitudinal strain. There was no association between FGF23 and 5 Year change in LVMI. There was no association between higher FGF23 and 5 year incident LVH. CONCLUSIONS: In a middle-aged adult population without known CVD or CKD, higher FGF23 was associated with greater odds of LVH, but not with greater increases in LVM over time. Further study is needed to elucidate whether FGF23 is a risk marker for underlying LVH or a mechanism for increased LVM over time in younger and middle-aged adult populations without CKD.

Fibroblast Growth Factor 23 and Incident Cardiovascular Disease and Mortality in Middle-Aged Adults.

Background Higher circulating fibroblast growth factor 23 (FGF23) associates with greater risk of cardiovascular disease (CVD) and mortality in older adults. The association of FGF23 with cardiovascular outcomes in younger populations has been incompletely explored. Methods and Results We measured C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) in 3151 middle-aged adults (mean age, 45±4) who participated in the year 20 examination of the CARDIA (Coronary Artery Risk Development in Young Adults) study. We used separate Cox proportional hazards models to examine the associations of cFGF23 and iFGF23 with incident CVD and mortality, adjusting models sequentially for sociodemographic, clinical, and laboratory factors. A total of 157 incident CVD events and 135 deaths occurred over a median 7.6 years of follow-up (interquartile range, 4.1-9.9). In fully adjusted models, there were no statistically significant associations of FGF23 with incident CVD events (hazard ratio per doubling of cFGF23: 1.14, 95%CI 0.97,1.34; iFGF23: 0.76, 95%CI 0.57,1.02) or all-cause mortality (hazard ratio per doubling of cFGF23, 1.17; 95% CI, 1.00-1.38; iFGF23, 0.86; 95% CI, 0.64-1.17). In analyses stratified by CVD subtypes, higher cFGF23 was associated with greater risk of heart failure hospitalization (hazard ratio per doubling of cFGF23, 1.52; 95% CI, 1.18-1.96) but not coronary heart disease or stroke, whereas iFGF23 was not associated with CVD subtypes in any model. Conclusions In middle-aged adults with few comorbidities, higher cFGF23 and iFGF23 were not independently associated with greater risk of CVD events or death. Higher cFGF23 was independently associated with greater risk of heart failure hospitalization.

Disparities in Elevated Body Mass Index in Youth Receiving Care at Community Health Centers.

Childhood obesity has increased significantly in the United States. Racial subgroups are often grouped into categories in research, limiting our understanding of disparities. This study describes the prevalence of obesity among youth of diverse racial and ethnic backgrounds receiving care at community health centers (CHCs). This cross-sectional study describes the prevalence of elevated body mass index (BMI) (≥85th percentile) and obesity (≥95th percentile) in youth aged 9 to 19 years receiving care in CHCs in 2014. Multilevel logistic regression estimated the prevalence of elevated BMI and obesity by age, race/ethnicity, and sex. Among 64 925 youth, 40% had elevated BMI and 22% were obese. By race, obesity was lowest in the combined Asian/Pacific Islander category (13%); however, when subgroups were separated, the highest prevalence was among Native Hawaiians (33%) and Other Pacific Islanders (42%) and the lowest in Asians. By sex, Black females and Hispanic and Asian males were more likely to be obese. By age, the highest prevalence of obesity was among those aged 9 to 10 years (25%). Youth served by CHCs have a high prevalence of obesity, with significant differences observed by race, sex, and age. Combining race categories obscures disparities. The heterogeneity of communities warrants research that describes different populations to address obesity.

Surge in Delayed Myocardial Infarction Presentations: An Inadvertent Consequence of Social Distancing During the COVID-19 Pandemic.

This case series summarizes our experience of delayed acute myocardial infarction presentations during the coronavirus disease-2019 pandemic predominantly driven by patient fear of contracting the virus in the hospital. Many presented with complications rarely seen in the primary percutaneous coronary intervention era including ventricular septal rupture, left ventricular pseudoaneurysm, and right ventricular infarction. (Level of Difficulty: Beginner.).

Sex differences in cardiovascular risk factors before and after the development of type 2 diabetes and risk for incident cardiovascular disease.

AIMS: To assess sex differences in cardiovascular (CVD) risk factor changes before and after the development of type 2 diabetes, and, the association between incident diabetes with incident CVD in mid-life. METHODS: We included 4893 Coronary Artery Risk Development in Young Adults Study participants, age 18-30 years at enrollment (1985-86). We ascertained incident diabetes and assessed sex differences in annual change in body mass index, blood pressure, and lipids before and after the ascertainment of diabetes using piecewise linear regression. We examined sex differences in the association between incident diabetes with incident CVD over 31 years of median follow-up. RESULTS: Progression in most CVD risk factors did not differ by sex before diabetes. Women had better CVD profiles at the time of diabetes compared to men, and after diabetes, women had worse annual changes in blood pressure and lipids. Incident diabetes was associated with a higher hazard for incident CVD (Hazard Ratio [HR]: 1.45, 95% confidence limits: 1.07, 1.96) and we did not observe effect modification by sex (p for interaction = 0.8). CONCLUSIONS: CVD risk factors worsened more rapidly after the development of type 2 diabetes for women than men. However, diabetes was not a stronger risk factor for incident CVD for women than men.

The Association of Life's Simple 7 with Aldosterone among African Americans in the Jackson Heart Study.

BACKGROUND: Among African Americans (AAs), attaining higher levels of American Heart Association (AHA) ideal cardiovascular health (Life's Simple 7 [LS7]) is associated with lower risk of diabetes and cardiovascular disease (CVD). We previously showed that aldosterone is associated with higher risk of diabetes and CVD in AAs. Thus, we investigated the association of LS7 metrics with aldosterone in the Jackson Heart Study (JHS). METHODS: Ideal metrics were defined by AHA 2020 goals for health behaviors (smoking, dietary intake, physical activity, and body mass index) and health factors (total cholesterol, blood pressure, and fasting glucose). The number of ideal LS7 metrics attained at baseline were summed into a continuous score (0-7) and categorical groups (Poor: 0-1, Intermediate: 2-3, and Ideal: ≥4 ideal LS7 metrics). Multivariable linear regression was used. RESULTS: Among 4,095 JHS participants (mean age 55 ± 13 years, 65% female), median serum aldosterone was 4.90, 4.30, and 3.70 ng/dL in the poor (n = 1132), intermediate (n = 2288) and ideal (n = 675) categories respectively. Aldosterone was 15% [0.85 (0.80, 0.90)] and 33% [0.67 (0.61, 0.75)] lower in the intermediate and ideal LS7 categories compared to the poor LS7 category. Each additional LS7 metric attained on continuous LS7 score (0-7) was associated with an 11% [0.89 (0.86, 0.91)] lower aldosterone level with variation by sex with women having a 15% lower aldosterone vs. 5% in men. CONCLUSIONS: Higher attainment of ideal LS7 metrics was associated with lower serum aldosterone among AAs with a greater magnitude of association among women compared to men.

Fibroblast Growth Factor-23, Heart Failure Risk, and Renin-Angiotensin-Aldosterone-System Blockade in Hypertension: The MESA Study.

BACKGROUND: Higher fibroblast growth factor-23 (FGF23) concentrations have been found to be associated with incident heart failure (HF). Experimental data suggest FGF23 directly stimulates myocardial hypertrophy. FGF23 may also enhance renin-angiotensin-aldosterone system activity. Whether FGF23 is associated with increased HF risk in populations with hypertension and whether this association is weaker in the presence of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy is unknown. METHODS: We studied 2,858 adults with hypertension free of cardiovascular disease at baseline (65.6 ± 9.5 years, 46.2% male) participating in the Multi-Ethnic Study of Atherosclerosis (MESA). We investigated the association of baseline serum intact FGF23 with incident HF over a 14-year median follow-up and whether ACEI/ARB therapy modified this risk. We also investigated the relationship of FGF23 with aldosterone and plasma renin activity in a random subgroup of the entire MESA cohort with available assays (N = 1,642). RESULTS: In adjusted Cox regression models, higher FGF23 was associated with a 63% greater hazard of incident HF (hazard ratio: 1.63, 95% confidence interval: [1.13-2.36] per 1-unit increase in log-transformed FGF23), which persisted after exclusion of participants with chronic kidney disease (hazard ratio: 1.94 [1.10-3.43]). There was no heterogeneity by ACEI/ARB use (Pinteraction = 0.438). FGF23 improved model fit over covariables (likelihood ratio χ2 = 6.67, P = 0.010). In multivariable linear regression models, there was no association between FGF23 and aldosterone or plasma renin activity. CONCLUSIONS: Higher FGF23 concentrations are associated with a significantly increased risk of HF in hypertension but this risk did not differ by ACEI/ARB treatment status. FGF23 may be a useful biomarker for HF risk in hypertensive populations.

Racial Differences in Rates of Change of Childhood Body Mass Index and Blood Pressure Percentiles.

OBJECTIVE: To assess whether racial differences in rates of change in body mass index (BMI) and blood pressure (BP) percentiles emerge during distinct periods of childhood. STUDY DESIGN: In this retrospective cohort study, we included children aged 5-20 years who received regular outpatient care at a large academic medical center between January 1996 and April 2016. BMI was expressed as age- and sex-specific percentiles and BP as age-, sex-, and height-specific percentiles. Linear mixed models incorporating linear spline functions with 2 breakpoints at 9 and 12 years of age were used to estimate the changes in BMI and BP percentiles over time during age periods: <9, 9-<12, and >12 years of age. RESULTS: Among 5703 children (24.8% black, 10.1% Hispanic), Hispanic females had an increased rate of change in BMI percentile per year relative to white females during ages 5-9 years (+2.94%; 95% CI, 0.24-5.64; P = .033). Black and Hispanic males also had an increased rate of change in BMI percentile per year relative to white males that occurred from ages 5-9 (+2.35% [95% CI, 0.76-3.94; P = .004]; +2.63% [95% CI, 0.31-4.95; P = .026], respectively). There were no significant racial differences in the rate of change of BP percentiles, although black females had higher hypertension rates compared with white females (10.0% vs 5.7%; P < .001). CONCLUSIONS: Childhood patterns in BMI percentiles differ by race. Racial differences in rates of change in BMI percentile emerge early in childhood. Further study of early patterns could help to identify critical periods during childhood where disparities begin to emerge.

A Prospective Pilot Study of Pocket-Carried Ultrasound Pre- and Postdischarge Inferior Vena Cava Assessment for Prediction of Heart Failure Rehospitalization.

BACKGROUND: Rehospitalization for heart failure (HF) is common, and subclinical congestion may be present at discharge. Larger inferior vena cava (IVC) size and lower collapsibility at discharge assessed via bedside ultrasound are predictive of rehospitalization; however, the utility of IVC assessment with the use of pocket-carried ultrasound (PCUS) during the transition from discharge to the posthospitalization follow-up visit (FU) has not been investigated. METHODS AND RESULTS: IVCmax and IVCmin were measured with the use of PCUS, and the collapsibility index (IVCCI = [IVCmax - IVCmin]/IVCmax) was determined. The primary outcome was 90-day rehospitalization or death. We prospectively enrolled 49 adults (71 ± 13 years of age, 51% male, 47% black, 43% preserved ejection fraction) hospitalized for HF. Nineteen patients (39%) experienced the outcome. Within the rehospitalized group, discharge and FU mean IVCmax were both >2.1 cm (2.2 ± 0.5 and 2.2 ± 0.7) and IVCCIs <50% (44 ± 20% and 45 ± 24%). Within those not rehospitalized, FU IVCmax was ≤2.1 cm (2.1 ± 0.6 and 1.9 ± 0.6; P = .038) and IVCCI >50% at both time points (55 ± 25% and 62 ± 19%; P = NS). FU IVCCI below an optimal cutoff of 42% had modest discrimination alone (c-statistic = 0.73). FU IVCCI <42% was associated with a greater hazard of the outcome independent of admission log B-type natriuretic peptide (adjusted hazard ratio = 6.8; 95% confidence interval 2.4-19.0; P < .001). CONCLUSIONS: Posthospitalization IVCCI assessment with PCUS predicts HF rehospitalization and may identify patients in need of intervention.

FGF23 (Fibroblast Growth Factor-23) and Incident Hypertension in Young and Middle-Aged Adults: The CARDIA Study.

Blacks have the highest prevalence of hypertension in the United States. Higher levels of FGF23 (fibroblast growth factor-23) have been associated with worse cardiovascular outcomes. Whether FGF23 is associated with rising blood pressure (BP) and racial differences in incident hypertension is unclear. We studied 1758 adults (45.0±3.7 years; 57.8% female; 36.9% black) without hypertension or cardiovascular disease who participated in the year 20 (2005-2006) follow-up examination of the CARDIA study (Coronary Artery Risk Development in Young Adults). We investigated the associations of baseline (year 20) cFGF23 (C-terminal FGF23) levels with longitudinal BP patterns and incident hypertension (defined as being on antihypertensive medication, systolic BP ≥130 or diastolic BP ≥80 mm Hg) during 2 follow-up visits (years 25 and 30). During follow-up, 35.2% of participants developed hypertension. In multivariable linear mixed models, there were greater increases in systolic BP from year 20 to 25 and year 25 to 30 in the highest FGF23 quartile relative to the lowest quartile (+2.1 mm Hg, P=0.0057 and +2.2 mm Hg, P=0.0108, respectively for each time period), whereas there were greater increases in diastolic BP from year 20 to 25 in the highest quartile relative to the lowest (+1.6 mm Hg; P=0.0024). In multivariable modified Poisson regression analyses, the highest FGF23 quartile was associated with a 45% greater risk of developing hypertension during follow-up compared with the lowest quartile (relative risk, 1.45 [1.18-1.77]). Results did not vary by race (Pinteraction=0.1523). Higher FGF23 levels are independently associated with rising BP over time and an increased risk of incident hypertension but not racial differences in hypertension.