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1.
Circulation ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134326

RESUMO

Background: Type 2 diabetes mellitus (T2DM) is associated with higher risk for heart failure (HF). The impact of a lifestyle intervention and changes in cardiorespiratory fitness (CRF), and body mass index (BMI) on risk for HF is not well-established. Methods: Participants from the Look AHEAD (Action for Health in Diabetes) trial without prevalent HF were included. Time to event analyses were used to compare the risk of incident HF between the intensive lifestyle intervention (ILI) vs. diabetes support and education (DSE) groups. The associations of baseline measures of CRF estimated from a maximal treadmill test, BMI, and longitudinal changes in these parameters with risk of HF were evaluated using multivariable adjusted Cox models. Results: Among the 5,109 trial participants, there was no significant difference in the risk of incident HF (n = 257) between the ILI vs. DSE groups [HR (95% CI) = 0.96 (0.75 to 1.23)] over a median follow-up of 12.4 years. In the most adjusted Cox models, the risk of HF was 39% and 62% lower among moderate fit [Tertile 2: HR (95% CI) = 0.61 (0.44 to 0.83)] and high fit [Tertile 3: HR (95% CI) = 0.38 (0.24 to 0.59)] groups, respectively (referent group: low fit, Tertile 1). Among HF subtypes, after adjustment for traditional CV risk factors and interval incidence of MI, baseline CRF was not significantly associated with risk of incident HFrEF. In contrast, the risk of incident HFpEF was 40% lower in moderate fit and 77% lower in the high fit groups. Baseline BMI was also not associated with risk of incident HF, HFpEF, or HFrEF after adjustment for CRF and traditional CV risk factors. Among participants with repeat CRF assessments (n = 3,902), improvements in CRF and weight loss over 4-year follow-up was significantly associated with lower risk of HF [HR (95% CI) per 10% increase in CRF = 0.90 (0.82 to 0.99), per 10% decrease in BMI = 0.80 (0.69 to 0.94)]. Conclusions: Among participants with T2DM in the Look AHEAD trial, the ILI did not appear to modify the risk of HF. Higher baseline CRF and sustained improvements in CRF and weight loss were associated with lower risk of HF. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT00017953.

2.
JAMA Netw Open ; 3(2): e200181, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32108893

RESUMO

Importance: The United States spends more money on medications than any other country. Most extended-release drugs have not consistently shown therapeutic or adherence superiority, and switching these medications to less expensive, generic, immediate-release formulations may offer an opportunity to reduce health care spending. Objective: To evaluate Medicare Part D and Medicaid spending on extended-release drug formulations and the potential savings associated with switching to generic immediate-release formulations. Design, Setting, and Participants: This cross-sectional study used the 2012 to 2017 Medicare Part D Drug Event and Medicaid Spending and Utilization data sets to analyze 20 extended-release drugs with 37 Medicare formulations and 36 Medicaid formulations. Only cardiovascular, diabetes, neurologic, and psychiatric extended-release drugs saving at most 1 additional daily dose compared with their immediate-release counterparts were included. Extended-release drugs with therapeutic superiority were excluded. Analyses were conducted from January to December 2019. Main Outcomes and Measures: Estimated Medicare Part D and Medicaid savings from switching extended-release to immediate-release drug formulations between 2012 and 2017. Results: Of the 6252 drugs screened for eligibility from the 2017 Medicaid Drug Utilization database and the 2017 Medicare Part D database, 67 drugs with extended-release formulations that were identified in the Medicare data set (20 distinct drugs with 37 formulations [19 brand, 18 generic]) were included in the analysis. In 2017, Medicare Part D spent $2.2 billion and Medicaid spent $952 million (a combined $3.1 billion) on 20 extended-release drugs. Between 2012 and 2017, Medicare Part D and Medicaid spent $12 billion and $5.9 billion, respectively, on extended-release formulations. Switching from brand-name to generic extended-release formulations was estimated to be associated with a $247 million reduction in Medicare spending and $299 million reduction in Medicaid spending in 2017, whereas switching all brand-name and generic extended-release formulations to immediate-release formulations in both Medicare and Medicaid was estimated to reduce spending by $2.6 billion ($1.8 billion for Medicare and $836 million for Medicaid) in 2017. During the study period, the estimated spending reduction associated with switching all patients receiving extended-release formulations (brand name extended-release and generic extended-release) to generic immediate-release formulations was $13.7 billion ($8.5 billion from Medicare and $5.2 billion from Medicaid). Conclusions and Relevance: The findings suggest that switching from extended-release drug formulations to therapeutically equivalent immediate-release formulations when available represents a potential option to reduce Medicare and Medicaid spending.

4.
JAMA Cardiol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913411

RESUMO

Importance: The association of the Hospital Readmission Reduction Program (HRRP) with reductions in racial disparities in 30-day outcomes for myocardial infarction (MI), is unknown, including whether this varies by HRRP hospital penalty status. Objective: To assess temporal trends in 30-day readmission and mortality rates among black and nonblack patients discharged after hospitalization for acute MI at low-performing and high-performing hospitals, as defined by readmission penalty status after HRRP implementation. Design, Setting, and Participants: This observational cohort analysis used data from the multicenter National Cardiovascular Data Registry Chest Pain-MI Registry centers that were subject to the first cycle of HRRP, between January 1, 2008, and November 30, 2016. All patients hospitalized with MI who were included in National Cardiovascular Data Registry Chest Pain-MI Registry were included in the analysis. Data were analyzed from April 2018 to September 2019. Exposures: Hospital performance category and race (black compared with nonblack patients). Centers were classified as high performing or low performing based on the excess readmission ratio (predicted to expected 30-day risk adjusted readmission rate) for MI during the first HRRP cycle (in October 2012). Main Outcomes and Measures: Thirty-day all-cause readmission and mortality rates. Results: Among 753 hospitals that treated 155 397 patients with acute MI (of whom 11 280 [7.3%] were black), 399 hospitals (53.0%) were high performing. Thirty-day readmission rates declined over time in both black and nonblack patients (annualized 30-day readmission rate: 17.9% vs 20.8%). Black (compared with nonblack) race was associated with higher unadjusted odds of 30-day readmission in both low-performing and high-performing centers (odds ratios: before HRRP: low-performing hospitals, 1.14 [95% CI, 1.03-1.26]; P = .01; high-performing hospitals, 1.17 [95% CI, 1.04-1.32]; P = .01; after HRRP: low-performing hospitals, 1.23 [95% CI, 1.13-1.34]; P < .001; high-performing hospitals, 1.25 [95% CI, 1.12-1.39]; P < .001). However, these racial differences were not significant after adjustment for patient characteristics. The 30-day mortality rates declined significantly over time in nonblack patients, with stable (nonsignificant) temporal trends among black patients. Adjusted associations between race and 30-day mortality showed that 30-day mortality rates were significantly lower among black (compared with nonblack) patients in the low-performing hospitals (odds ratios: pre-HRRP, 0.79 [95% CI, 0.63-0.97]; P = .03; post-HRRP, 0.80 [95% CI, 0.68-0.95]; P = .01) but not in high-performing hospitals. Finally, the association between race and 30-day outcomes did not vary after the HRRP period began in either high-performing or low-performing hospitals. Conclusions and Relevance: In this analysis, 30-day readmission rates among patients with MI declined over time for both black and nonblack patients. Differences in race-specific 30-day readmission rates persisted but appeared to be attributable to patient-level factors. The 30-day mortality rates have declined for nonblack patients and remained stable among black patients. Implementation of the HRRP was not associated with improvement or worsening of racial disparities in readmission and mortality rates.

5.
Circulation ; 141(12): 957-967, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-31931608

RESUMO

BACKGROUND: A malignant subphenotype of left ventricular hypertrophy (LVH) has been described, in which minimal elevations in cardiac biomarkers identify individuals with LVH at high risk for developing heart failure (HF). We tested the hypothesis that a higher prevalence of malignant LVH among blacks may contribute to racial disparities in HF risk. METHODS: Participants (n=15 710) without prevalent cardiovascular disease were pooled from 3 population-based cohort studies, the ARIC Study (Atherosclerosis Risk in Communities), the DHS (Dallas Heart Study), and the MESA (Multi-Ethnic Study of Atherosclerosis). Participants were classified into 3 groups: those without ECG-LVH, those with ECG-LVH and normal biomarkers (hs-cTnT (high sensitivity cardiac troponin-T) <6 ng/L and NT-proBNP (N-terminal pro-B-type natriuretic peptide) <100 pg/mL), and those with ECG-LVH and abnormal levels of either biomarker (malignant LVH). The outcome was incident HF. RESULTS: Over the 10-year follow-up period, HF occurred in 512 (3.3%) participants, with 5.2% in black men, 3.8% in white men, 3.2% in black women, and 2.2% in white women. The prevalence of malignant LVH was 3-fold higher among black men and women versus white men and women. Compared with participants without LVH, the adjusted hazard ratio for HF was 2.8 (95% CI, 2.1-3.5) in those with malignant LVH and 0.9 (95% CI, 0.6-1.5) in those with LVH and normal biomarkers, with similar findings in each race/sex subgroup. Mediation analyses indicated that 33% of excess hazard for HF among black men and 11% of the excess hazard among black women was explained by the higher prevalence of malignant LVH in blacks. Of black men who developed HF, 30.8% had malignant LVH at baseline, with a corresponding population attributable fraction of 0.21. The proportion of HF cases occurring among those with malignant LVH, and the corresponding population attributable fraction, were intermediate and similar among black women and white men and lowest among white women. CONCLUSIONS: A higher prevalence of malignant LVH may in part explain the higher risk of HF among blacks versus whites. Strategies to prevent development or attenuate risk associated with malignant LVH should be investigated as a strategy to lower HF risk and mitigate racial disparities.

6.
JACC Heart Fail ; 8(2): 111-121, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31706837

RESUMO

OBJECTIVES: The aim of this study was to evaluate the association between age and invasive cardiovascular hemodynamics during upright exercise among healthy adults. BACKGROUND: The marked age-related decline in maximal exercise oxygen uptake (peak VO2) may contribute to the high burden of heart failure among older individuals and their greater severity of exertional symptoms. However, the mechanisms underlying this decline are not well understood. METHODS: A total of 104 healthy community-dwelling volunteers age 20 to 76 years well screened for cardiovascular disease underwent exhaustive upright exercise with brachial and pulmonary artery catheters; radionuclide ventriculography; and expired gas analysis for the measurement of peak VO2, cardiac output, left ventricular stroke volume, end-diastolic volume, end-systolic volume, ejection fraction, pulmonary capillary wedge pressure, and arteriovenous oxygen difference. RESULTS: Over a 5.5-decade age range, there was a 40% decline in peak VO2 due primarily to reduced peak exercise cardiac output; peak arteriovenous oxygen difference was unaffected by age. The lower age-related exercise cardiac output was related to lower peak exercise heart rate and stroke volume. Aging was also associated with lower peak exercise ejection fraction, indicating reduced inotropic reserve. Peak exercise end-diastolic volume was lower with aging despite similar left ventricular filling pressure, suggesting age-related reduced diastolic compliance limiting the use of the Frank-Starling mechanism to compensate for reduced chronotropic and inotropic reserves. These age relationships were unaffected by sex. CONCLUSIONS: The age-related decline in exercise capacity among healthy persons is due predominantly to cardiac mechanisms, including reduced chronotropic and inotropic reserve and possibly reduced Frank-Starling reserve. Peak exercise left ventricular filling pressure and arteriovenous oxygen difference are unchanged with healthy aging.

7.
Eur J Heart Fail ; 22(1): 148-158, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31637815

RESUMO

AIM: To identify distinct phenotypic subgroups in a highly-dimensional, mixed-data cohort of individuals with heart failure (HF) with preserved ejection fraction (HFpEF) using unsupervised clustering analysis. METHODS AND RESULTS: The study included all Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) participants from the Americas (n = 1767). In the subset of participants with available echocardiographic data (derivation cohort, n = 654), we characterized three mutually exclusive phenogroups of HFpEF participants using penalized finite mixture model-based clustering analysis on 61 mixed-data phenotypic variables. Phenogroup 1 had higher burden of co-morbidities, natriuretic peptides, and abnormalities in left ventricular structure and function; phenogroup 2 had lower prevalence of cardiovascular and non-cardiac co-morbidities but higher burden of diastolic dysfunction; and phenogroup 3 had lower natriuretic peptide levels, intermediate co-morbidity burden, and the most favourable diastolic function profile. In adjusted Cox models, participants in phenogroup 1 (vs. phenogroup 3) had significantly higher risk for all adverse clinical events including the primary composite endpoint, all-cause mortality, and HF hospitalization. Phenogroup 2 (vs. phenogroup 3) was significantly associated with higher risk of HF hospitalization but a lower risk of atherosclerotic event (myocardial infarction, stroke, or cardiovascular death), and comparable risk of mortality. Similar patterns of association were also observed in the non-echocardiographic TOPCAT cohort (internal validation cohort, n = 1113) and an external cohort of patients with HFpEF [Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial cohort, n = 198], with the highest risk of adverse outcome noted in phenogroup 1 participants. CONCLUSIONS: Machine learning-based cluster analysis can identify phenogroups of patients with HFpEF with distinct clinical characteristics and long-term outcomes.

8.
Eur Heart J Qual Care Clin Outcomes ; 6(1): 62-71, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31124567

RESUMO

AIMS: Thirty-day risk standardized readmission and mortality rates (RSRR, RSMR) are key determinants for hospital performance for cardiovascular conditions such as acute myocardial infarction (AMI) and heart failure (HF). We evaluated whether individual hospitals in the USA perform similarly for HF and AMI over time based on readmission and mortality metrics. METHODS AND RESULTS: A total of 1950 hospitals in the USA with continuous participation in the Centers for Medicare and Medicaid Services (CMS) public reporting programme between 2010 and 2016 were identified. Latent mixture modelling was used to define performance trajectory groups. Overall, there were consistent declines in the RSMR (16.1-14.0%) and RSRR (20.3-16.6%) for AMI from 2010 to 2016. For HF, RSRR declined over time (25.1-21.7%), while there was a modest increase in RSMR (11.3-12.0%); parallel findings were observed across performance trajectory groups. The proportion of best performing centres for HF care that were also best performers for AMI care based on the 30-day RSMR and 30-day RSRR metric was 54% and 35%, respectively. Furthermore, the discordance rate between the best and worst performers for both conditions was low (<2% for both 30-day outcomes). CONCLUSION: In the USA, despite variation in baseline hospital-level outcomes, hospitals had consistent longitudinal trajectories (worsening or improvement) across conditions and metrics. Hospitals identified as high performing were frequently similar across target conditions and over time, suggesting that performance may be driven by systems of care influencing different disease states in a comparable manner.

10.
Prog Cardiovasc Dis ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31863785

RESUMO

The updated scientific statement by the American Heart Association has defined resistant hypertension (HTN;RH) as uncontrolled blood pressure (BP) ≥ 130/80 mmHg, despite concurrent use of 3 anti-HTN drug classes comprising a calcium channel blocker, a blocker of renin-angiotensin system, and a thiazide diuretic, preferably chlorthalidone. Using the updated BP criteria, the prevalence of RH in the United States is found to be modestly increased by approximately 3-4% among treated population. Meta-analysis of observational studies have demonstrated that pseudo-RH from white coat HTN or medication nonadherence is as much common as the truly RH. Thus, screening for pseudo-resistance in the evaluation of all apparent RH is of utmost importance as diagnosis of white-coat HTN requires no treatment, while medication nonadherence would benefit from identifying and targeting barriers to adherence.

11.
Circulation ; 140(25): 2076-2088, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31707797

RESUMO

BACKGROUND: Risk for atherosclerotic cardiovascular disease was a novel consideration for antihypertensive medication initiation in the 2017 American College of Cardiology/American Heart Association Blood Pressure (BP) guideline. Whether biomarkers of chronic myocardial injury (high-sensitivity cardiac troponin T ≥6 ng/L] and stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥100 pg/mL) can inform cardiovascular (CV) risk stratification and treatment decisions among adults with elevated BP and hypertension is unclear. METHODS: Participant-level data from 3 cohort studies (Atherosclerosis Risk in Communities Study, Dallas Heart Study, and Multiethnic Study of Atherosclerosis) were pooled, excluding individuals with prevalent CV disease and those taking antihypertensive medication at baseline. Participants were analyzed according to BP treatment group from the 2017 American College of Cardiology/American Heart Association BP guideline and those with high BP (120 to 159/<100 mm Hg) were further stratified by biomarker status. Cumulative incidence rates for CV event (atherosclerotic cardiovascular disease or heart failure), and the corresponding 10-year number needed to treat to prevent 1 event with intensive BP lowering (to target systolic BP <120 mm Hg), were estimated for BP and biomarker-based subgroups. RESULTS: The study included 12 987 participants (mean age, 55 years; 55% women; 21.5% with elevated high-sensitivity cardiac troponin T; 17.7% with elevated NT-proBNP) with 825 incident CV events over 10-year follow-up. Participants with elevated BP or hypertension not recommended for antihypertensive medication with versus without either elevated high-sensitivity cardiac troponin T or NT-proBNP had a 10-year CV incidence rate of 11.0% and 4.6%, with a 10-year number needed to treat to prevent 1 event for intensive BP lowering of 36 and 85, respectively. Among participants with stage 1 or stage 2 hypertension recommended for antihypertensive medication with BP <160/100 mm Hg, those with versus without an elevated biomarker had a 10-year CV incidence rate of 15.1% and 7.9%, with a 10-year number needed to treat to prevent 1 event of 26 and 49, respectively. CONCLUSIONS: Elevations in high-sensitivity cardiac troponin T or NT-proBNP identify individuals with elevated BP or hypertension not currently recommended for antihypertensive medication who are at high risk for CV events. The presence of nonelevated biomarkers, even in the setting of stage 1 or stage 2 hypertension, was associated with lower risk. Incorporation of biomarkers into risk assessment algorithms may lead to more appropriate matching of intensive BP control with patient risk.

12.
JAMA Cardiol ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31738371

RESUMO

Importance: In 2015, the US Food and Drug Administration approved 2 new medications for treatment of heart failure with reduced ejection fraction, sacubitril/valsartan and ivabradine. However, few national data are available examining their contemporary use and associated costs. Objective: To evaluate national patterns of use of sacubitril/valsartan and ivabradine and associated therapeutic spending in Medicare Part D and Medicaid. Design, Setting, and Participants: In this US nationwide claims-based study, we analyzed data from the Medicare Part D Prescription Drug Event and Medicaid Utilization and Spending data sets to compare national patterns of use of sacubitril/valsartan and ivabradine between 2016 and 2017. Main Outcomes and Measures: Changes in total spending, per-beneficiary/claim spending, number of beneficiaries, and number of claims between 2016 and 2017 for sacubitril/valsartan and ivabradine. Results: The number of Medicare beneficiaries prescribed sacubitril/valsartan increased from 35 423 to 90 606 (156% increase from 2016 to 2017). Medicare beneficiaries prescribed ivabradine increased from 15 856 to 23 213 (46% increase). In 2017, Medicare Part D spent $227 million and $7.3 million on sacubitril/valsartan and ivabradine, respectively. This represented increases of 241% and 59% compared with 2016 spending, respectively. The annual Medicare per-beneficiary spending on sacubitril/valsartan and ivabradine was $2512 and $2400. Parallel trends in use patterns and spending were observed among Medicaid beneficiaries. Conclusions and Relevance: Although initial experiences suggested slow uptake after regulatory approval, these national data demonstrate an increase in use of sacubitril/valsartan and, to a lesser degree, ivabradine in the United States. Current annual per-beneficiary expenditures remain less than spending thresholds that have been reported to be cost-effective. Ongoing efforts are needed to promote high-value care while improving affordability and access to established and emerging heart failure therapies.

13.
JACC Heart Fail ; 7(12): 1001-1011, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31779921

RESUMO

Frailty, a syndrome characterized by an exaggerated decline in function and reserve of multiple physiological systems, is common in older patients with heart failure (HF) and is associated with worse clinical and patient-reported outcomes. Although several detailed assessment tools have been developed and validated in the geriatric population, they are cumbersome, not validated in patients with HF, and not commonly used in routine management of patients with HF. More recently, there has been an increasing interest in developing simple frailty screening tools that could efficiently and quickly identify frail patients with HF in routine clinical settings. As the burden and recognition of frailty in older patients with HF increase, a more comprehensive approach to management is needed that targets deficits across multiple domains, including physical function and medical, cognitive, and social domains. Such a multidomain approach is critical to address the unique, multidimensional challenges to the care of these high-risk patients and to improve their functional status, quality of life, and long-term clinical outcomes. This review discusses the burden of frailty, the conceptual underpinnings of frailty in older patients with HF, and potential strategies for the assessment, screening, and management of frailty in this vulnerable patient population.

14.
JACC Heart Fail ; 7(12): 1079-1088, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31779931

RESUMO

OBJECTIVES: This study sought to assess the prevalence of frailty, its associations with physical function, quality of life (QoL), cognition, and depression and to investigate more efficient methods of detection in older patients hospitalized with acute decompensated heart failure (ADHF). BACKGROUND: In contrast to the outpatient population with chronic HF, much less is known regarding frailty in older, hospitalized patients with ADHF. METHODS: Older hospitalized patients (N = 202) with ADHF underwent assessment of frailty (using Fried criteria), short physical performance battery (SPPB), 6-min walk test (6-MWT) distance, quality of life (QoL using the Kansas City Cardiomyopathy Questionnaire), cognition (using the Montreal Cognition Assessment), and depression (using the Geriatric Depression Screen [GDS]). The associations of frailty with these patient-centered outcomes were assessed by using adjusted linear regression models. Novel strategies to identify frailty were examined. RESULTS: A total of 50% of older, hospitalized patients with ADHF were frail, 48% were pre-frail, and 2% were non-frail. Female sex, burden of comorbidity, and prior HF hospitalization were significantly associated with higher likelihood of frailty. Frailty (vs. pre-frail status) was associated with a significantly worse SPPB score (5 ± 2.2 vs. 7 ± 2.4, respectively), 6-MWT distance (143 ± 79 m vs. 221 ± 99 m, respectively), QoL (35 ± 19 vs. 46 ± 21, respectively), and more depression (GDS score: 5.5 ± 3.5 vs. 4.2 ± 3.3, respectively) but similar cognition. These associations were unchanged after adjustment for age, sex, race, total comorbidities, and body mass index. Slow gait speed plus low physical activity signaled frailty status as well (C-statistic = 0.85). CONCLUSIONS: Ninety-eight percent of older, hospitalized patients with ADHF are frail or pre-frail. Frailty (vs. pre-frail status) is associated with worse physical function, QoL, comorbidity, and depression. The simple 4-m walk test combined with self-reported physical activity may quickly and efficiently identify frailty in older patients with ADHF.

16.
J Am Heart Assoc ; 8(20): e012876, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31597504

RESUMO

Background Substantial heterogeneity exists in the cardiorespiratory fitness (CRF) change in response to exercise training, and its long-term prognostic implication is not well understood. We evaluated the association between the short-term supervised training-related changes in CRF and CRF levels 10 years later. Methods and Results STRRIDE (Studies of a Targeted Risk Reduction Intervention Through Defined Exercise) trial participants who were originally randomized to exercise training for 8 months and participated in the 10-year follow-up visit were included. CRF levels were measured at baseline, after training (8 months), and at 10-year follow-up as peak oxygen uptake (vo2, mL/kg per min) using the maximal treadmill test. Participants were stratified into low, moderate, and high CRF response groups according to the training regimen-specific tertiles of CRF change. The study included 80 participants (age: 52 years; 35% female). At 10-year follow-up, the high-response CRF group had the least decline in CRF compared with the moderate- and low-response CRF groups (-0.35 versus -2.20 and -4.25 mL/kg per minute, respectively; P=0.02). This result was largely related to the differential age-related changes in peak oxygen pulse across the 3 groups (0.58, -0.23, and -0.86 mL/beat, respectively; P=0.03) with no difference in the peak heart rate change. In adjusted linear regression analysis, high response was significantly associated with greater CRF at follow-up independent of other baseline characteristics (high versus low [reference] CRF response: standard ß=0.25; P=0.004). Conclusions Greater CRF improvement in response to short-term training is associated with higher CRF levels 10 years later. Lack of CRF improvements in response to short-term training may identify individuals at risk for exaggerated CRF decline with aging.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31529024

RESUMO

AIMS: The 2018 ESC/ESH guidelines for hypertension recommend differential management of patients who are <65, 65-79, and ≥80 years of age. However, it is unclear whether intensive blood pressure lowering is well-tolerated and modifies risk uniformly across the age spectrum. METHODS AND RESULTS: SPRINT randomized 9,361 high-risk adults without diabetes and age ≥50 years with systolic blood pressure 130-180 mmHg to either intensive or standard antihypertensive treatment. The primary efficacy endpoint was the composite of acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. The primary safety endpoint was composite serious adverse events. We assessed whether age modified the efficacy and safety of intensive versus standard blood pressure lowering using Cox proportional-hazards regression and restricted cubic splines. In all, 3,805 (41%), 4,390 (47%), and 1,166 (12%) were <65, 65-79, and ≥80 years. Mean age was similar between the two study groups (intensive group 67.9±9.4 years versus standard group 67.9±9.5 years; P = 0.94). Median follow-up was 3.3 years. In multivariable models, age was linearly associated with the risk of stroke (P < 0.001) and non-linearly associated with the risk of primary efficacy events, death from cardiovascular causes, death from any cause, heart failure, and serious adverse events (P < 0.001). The safety and efficacy of intensive blood pressure lowering was not modified by age, whether tested continuously or categorically (P > 0.05). CONCLUSION: In SPRINT, the benefits and risks of intensive blood pressure lowering did not differ according to the age categories proposed by the ESC/ESH guidelines for hypertension.

18.
Circ Cardiovasc Imaging ; 12(9): e009226, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31522549

RESUMO

BACKGROUND: Absence of cardiovascular risk factors (RF) in young adulthood is associated with a lower risk for cardiovascular disease. However, it is unclear if low RF burden in young adulthood decreases the quantitative burden and qualitative features of atherosclerosis. METHODS: Multi-contrast carotid magnetic resonance imaging was performed on 440 Chicago Healthy Aging Study participants in 2009 to 2011, whose RF (total cholesterol, blood pressure, diabetes mellitus, and smoking) were measured in 1967 to 1973. Participants were divided into 4 groups: low-risk (with total cholesterol <200 mg/dL and no treatment, blood pressure <120/80 mm Hg and no treatment, no smoking, and no diabetes mellitus), 0 high RF but some RF unfavorable (≥1 RF above low-risk threshold but below high-risk threshold), 1 high RF (total cholesterol ≥240 mg/dL or treated, blood pressure ≥140/90 or treated, diabetes mellitus, or smoking), and 2 or more high RF. Association of baseline RF status with carotid atherosclerosis (overall mean carotid wall thickness and lipid-rich necrotic core) at follow-up was assessed. RESULTS: Among 424 participants with evaluable carotid magnetic resonance images, the mean age was 32 years at baseline and 73 years at follow-up; 67% were male, 86% white, and 36% were low-risk at baseline. Two or more high RF status was associated with higher carotid wall thickness (0.99±0.11 mm) and lipid-rich necrotic core prevalence (30%), as compared with low-risk group (0.94±0.09 mm and 17%, respectively). Each increment in baseline RF status was associated with higher carotid wall thickness (ß-coefficient, 0.015; 95% CI, 0.004-0.026) and with higher lipid-rich necrotic core prevalence at older age (odds ratio, 1.26; 95% CI, 1.00-1.58) in models adjusted for baseline RF and demographics. CONCLUSIONS: RF status in young adulthood is associated with the burden and quality of carotid atherosclerosis in older age suggesting that the decades-long protective effect of low-risk status might be mediated through a lower burden of quantitative and qualitative features of atherosclerotic plaque.

19.
Diabetes Care ; 42(12): 2298-2306, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31519694

RESUMO

OBJECTIVE: To develop and validate a novel, machine learning-derived model to predict the risk of heart failure (HF) among patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Using data from 8,756 patients free at baseline of HF, with <10% missing data, and enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, we used random survival forest (RSF) methods, a nonparametric decision tree machine learning approach, to identify predictors of incident HF. The RSF model was externally validated in a cohort of individuals with T2DM using the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). RESULTS: Over a median follow-up of 4.9 years, 319 patients (3.6%) developed incident HF. The RSF models demonstrated better discrimination than the best performing Cox-based method (C-index 0.77 [95% CI 0.75-0.80] vs. 0.73 [0.70-0.76] respectively) and had acceptable calibration (Hosmer-Lemeshow statistic χ2 = 9.63, P = 0.29) in the internal validation data set. From the identified predictors, an integer-based risk score for 5-year HF incidence was created: the WATCH-DM (Weight [BMI], Age, hyperTension, Creatinine, HDL-C, Diabetes control [fasting plasma glucose], QRS Duration, MI, and CABG) risk score. Each 1-unit increment in the risk score was associated with a 24% higher relative risk of HF within 5 years. The cumulative 5-year incidence of HF increased in a graded fashion from 1.1% in quintile 1 (WATCH-DM score ≤7) to 17.4% in quintile 5 (WATCH-DM score ≥14). In the external validation cohort, the RSF-based risk prediction model and the WATCH-DM risk score performed well with good discrimination (C-index = 0.74 and 0.70, respectively), acceptable calibration (P ≥0.20 for both), and broad risk stratification (5-year HF risk range from 2.5 to 18.7% across quintiles 1-5). CONCLUSIONS: We developed and validated a novel, machine learning-derived risk score that integrates readily available clinical, laboratory, and electrocardiographic variables to predict the risk of HF among outpatients with T2DM.

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