Kidney Function and Physical Performance Decline: The Brain in Kidney Disease (BRINK) Cohort Study.

Rationale & Objective: Patients with kidney failure have poor physical performance, but its trajectory is less clear. We examined physical function over the course of kidney disease, including the transition to dialysis. Study Design: Observational cohort. Setting & Participants: Community-dwelling adults aged ≥45 years in the Brain in Kidney Disease (BRINK) cohort study. Predictors: Estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). Outcomes: Change in physical performance using the Short Physical Performance Battery (SPPB) (primary) and gait speed (secondary). Analytical Approach: Linear mixed effects regression models. Results: The analytical cohort included 562 participants with mean age of 69.3 (SD, 9.8) years followed for up to 63 months. In total, 49.8% were women. In addition, 79.9% self-identified as White, and 15.3% self-identified as Black. In total, 48.8% had diabetes. Mean eGFR at baseline was 48.1 (SD, 24.3) mL/min/1.73 m2. In unadjusted analysis, lower eGFR was associated with greater decline in SPPB score (P trend < 0.001). The decline in SPPB score was larger among participants with lower eGFR, with a gradient from -0.15 (95% CI, -0.23 to -0.07) points per year for participants with eGFR ≥60 mL/min/1.73 m2 to -0.56 (95% CI, -0.84 to -0.27) for participants with eGFR <15 mL/min/1.73 m2 and -0.61 (95% CI, -0.90 to -0.33) after dialysis initiation. In covariate-adjusted models, SPPB did not continue to decline after dialysis initiation. In secondary analyses evaluating change in gait speed, gait speed continued to decline after dialysis initiation. Higher UACR was also associated with a greater decline in SPPB score and gait speed in unadjusted and adjusted models. Limitations: Small number of participants started dialysis. Conclusions: We found a graded association of chronic kidney disease stage and albuminuria with decline in physical performance. The decline in SPPB was not accelerated after dialysis initiation in covariate-adjusted models, whereas gait speed continued to decline.

Physical function is an important patient-centered outcome in chronic kidney disease (CKD), but whether physical performance changes as kidney disease progresses or when patients start dialysis is not well understood. We found that measures of physical performance, like strength and walking speed, worsened as kidney disease worsened. However, 1 combination of physical performance tests appeared stable (rather than getting worse) after starting dialysis compared to those with very advanced CKD who had not yet started dialysis, while gait speed continued to get worse. This information may help counsel patients who are learning about CKD and considering treatment options. It may also help guide research on interventions to improve physical function in patients with CKD.

Development and validation of a risk model for hospital-acquired venous thrombosis: the Medical Inpatients Thrombosis and Hemostasis study.

BACKGROUND: Regulatory organizations recommend assessing hospital-acquired (HA) venous thromboembolism (VTE) risk for medical inpatients. OBJECTIVES: To develop and validate a risk assessment model (RAM) for HA-VTE in medical inpatients using objective and assessable risk factors knowable at admission. METHODS: The development cohort included people admitted to medical services at the University of Vermont Medical Center (Burlington, Vermont) between 2010 and 2019, and the validation cohorts included people admitted to Hennepin County Medical Center (Minneapolis, Minnesota), University of Michigan Medical Center (Ann Arbor, Michigan), and Harris Health Systems (Houston, Texas). Individuals with VTE at admission, aged <18 years, and admitted for <1 midnight were excluded. We used a Bayesian penalized regression technique to select candidate HA-VTE risk factors for final inclusion in the RAM. RESULTS: The development cohort included 60 633 admissions and 227 HA-VTE, and the validation cohorts included 111 269 admissions and 651 HA-VTE. Seven HA-VTE risk factors with t statistics ≥1.5 were included in the RAM: history of VTE, low hemoglobin level, elevated creatinine level, active cancer, hyponatremia, increased red cell distribution width, and malnutrition. The areas under the receiver operating characteristic curve and calibration slope were 0.72 and 1.10, respectively. The areas under the receiver operating characteristic curve and calibration slope were 0.70 and 0.93 at Hennepin County Medical Center, 0.70 and 0.87 at the University of Michigan Medical Center, and 0.71 and 1.00 at Harris Health Systems, respectively. The RAM performed well stratified by age, sex, and race. CONCLUSION: We developed and validated a RAM for HA-VTE in medical inpatients. By quantifying risk, clinicians can determine the potential benefits of measures to reduce HA-VTE.

Prospective Study of Endogenous Hormones and Incidence of Venous Thromboembolism: The Atherosclerosis Risk in Communities Study.

Exogenous hormone treatments in women (oral contraceptives and hormone replacement therapy [HRT]) are established risk factors for venous thromboembolism (VTE), but less is known about associations between plasma levels of endogenous hormones and VTE risk. We examined the association of baseline dehydroepiandrosterone sulphate (DHEAS), testosterone and sex hormone-binding globulin (SHBG) with risk of future VTE in men and post-menopausal women in the Atherosclerosis Risk in Communities Study. Testosterone, DHEAS and SHBG were measured in plasma samples collected in 1996 to 1998. Cox proportional hazards models were used to estimate hazard ratios for incident VTE adjusting for age, race/ethnicity, body mass index, height, smoking, estimated glomerular filtration rate and C-reactive protein. All analyses were stratified by sex and by current HRT use in women. Among 3,051 non-HRT-using women, 1,414 HRT-using women and 3,925 men at risk at baseline, 184, 62 and 206 experienced incident VTE after a median follow-up of 17.6 years. Plasma hormones were not associated with incidence of VTE among men and non-HRT-using women, although lower plasma DHEAS, when modelled using quartiles or restricted cubic splines, was associated with higher risk of VTE among HRT-using women. This study does not support the existence of an important association between plasma concentrations of endogenous testosterone, DHEAS or SHBG with risk of VTE in middle-aged to older men or post-menopausal women not using HRT.

Physical Activity and Lifetime Risk of Cardiovascular Disease and Cancer.

PURPOSE: Although the World Health Organization has recommended moderate- to vigorous-intensity physical activity (MVPA) to prevent cardiovascular disease (CVD) and some cancers, there are no estimates of lifetime risk of these noncommunicable diseases according to PA levels. We aimed to estimate the lifetime risk of CVD and cancers according to PA levels. METHODS: We followed 5807 men and 7252 women in the United States, 45-64 yr old, initially free of CVD and cancer from 1987 through 2012, and used a life table approach to estimate lifetime risks of CVD (coronary heart disease, heart failure, and stroke) and total cancer according to PA levels: poor (0 min·wk of MVPA), intermediate (1-74 min·wk of VPA or 1-149 min·wk of MVPA), or recommended (≥75 min·wk of VPA or ≥150 min·wk of MVPA). RESULTS: During the 246,886 person-years of follow-up, we documented 4065 CVD and 3509 cancer events and 2062 non-CVD and 2326 noncancer deaths. In men, the lifetime risks of CVD from 45 through 85 yr were 52.7% (95% confidence interval = 49.4-55.5) for poor PA and 45.7% (42.7-48.3) for recommended PA. In women, the respective lifetime risks of CVD were 42.4% (39.5-44.9) and 30.5% (27.5-33.1). Lifetime risks of total cancer were 40.1% (36.9-42.7) for poor PA and 42.6% (39.7-45.2) for recommended activity in men and 31.4% (28.7-33.8) and 30.4% (27.7-32.9), respectively, in women. CONCLUSIONS: Compared with a poor PA level, the PA recommended by the World Health Organization was associated with lower lifetime risk of CVD, but not total cancer, in both men and women.

Lifetime Risk and Risk Factors for Abdominal Aortic Aneurysm in a 24-Year Prospective Study: The ARIC Study (Atherosclerosis Risk in Communities).

OBJECTIVE: Abdominal aortic aneurysm (AAA) is an important vascular disease in older adults, but data on lifetime risk of AAA are sparse. We examined lifetime risk of AAA in a community-based cohort and prospectively assessed the association between midlife cardiovascular risk factors and AAAs. APPROACH AND RESULTS: In ARIC study (Atherosclerosis Risk in Communities), 15 792 participants were recruited at visit 1 in 1987 to 1989 and followed up through 2013. Longitudinal smoking status was defined using smoking behavior ascertained from visit 1 (1987-1989) to visit 4 (1996-1998). We followed up participants for incident, clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through 2011 and identified 590 incident AAAs. An abdominal ultrasound was conducted in 2011 to 2013 in 5911 surviving participants, and 75 asymptomatic AAAs were identified. We estimated the lifetime risk of AAA from the index age 45 years through 85 years of age. At age 45, the lifetime risk for AAA was 5.6% (95% confidence interval, 4.8-6.1) and was higher in men (8.2%) and current smokers (10.5%). Smokers who quit smoking between visit 1 and visit 4 had a 29% lower AAA lifetime risk compared with continuous smokers but had a higher risk than pre-visit 1 quitters. The lifetime risk of rupture or medical intervention was 1.6% (95% confidence interval, 1.2-1.8). Smoking, white race, male sex, greater height, and greater low-density lipoprotein or total cholesterol were associated with an increased risk of clinical AAA and asymptomatic AAA. CONCLUSIONS: At least 1 in 9 middle-aged current smokers developed AAA in their lifetime. Smoking cessation reduced the lifetime risk of AAA.

Carotid Intima-Media Thickness and Arterial Stiffness and the Risk of Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study, Multi-Ethnic Study of Atherosclerosis (MESA), and the Rotterdam Study.

BACKGROUND: We evaluated the association of carotid intima-media thickness (cIMT), carotid plaque, carotid distensibility coefficient (DC), and aortic pulse wave velocity (PWV) with incident atrial fibrillation (AF) and their role in improving AF risk prediction beyond the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF risk score. METHODS AND RESULTS: We analyzed data from 3 population-based cohort studies: Atherosclerosis Risk in Communities (ARIC) Study (n=13 907); Multi-Ethnic Study of Atherosclerosis (MESA; n=6640), and the Rotterdam Study (RS; n=5220). We evaluated the association of arterial indices with incident AF and computed the C-statistic, category-based net reclassification improvement (NRI), and relative integrated discrimination improvement (IDI) of incorporating arterial indices into the CHARGE-AF risk score (age, race, height weight, systolic and diastolic blood pressure, antihypertensive medication use, smoking, diabetes, previous myocardial infarction, and previous heart failure). Higher cIMT (meta-analyzed hazard ratio [95% CI] per 1-SD increment, 1.12 [1.08-1.16]) and presence of carotid plaque (1.30 [1.19-1.42]) were associated with higher AF incidence after adjustment for CHARGE-AF risk-score variables. Lower DC and higher PWV were associated with higher AF incidence only after adjustment for the CHARGE-AF risk-score variables excepting height, weight, and systolic and diastolic blood pressure. Addition of cIMT or carotid plaque marginally improved CHARGE-AF score prediction as assessed by the relative IDI (estimates, 0.025-0.051), but not when assessed with the C-statistic and NRI. CONCLUSIONS: Higher cIMT, presence of carotid plaque, and greater arterial stiffness are associated with higher AF incidence, indicating that atherosclerosis and arterial stiffness play a role in AF etiopathogenesis. However, arterial indices only modestly improve AF risk prediction.

American Heart Association's Life's Simple 7: Avoiding Heart Failure and Preserving Cardiac Structure and Function.

BACKGROUND: Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association's Life's Simple 7 guidelines­on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose­is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. METHODS: We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults ages 45-64 years in 1987-1989. From the 1987-1989 risk factor measurements, we created a Life's Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4855 participants free of clinical cardiovascular disease in 2011-2013, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. RESULTS: One in four participants (25.5%) developed heart failure through age 85 years. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life's Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life's Simple 7 score, compared with an inadequate score. CONCLUSIONS: Greater achievement of American Heart Association's Life's Simple 7 in middle age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function.

Hypothalamic-pituitary-gonadal axis homeostasis predicts longevity.

The reproductive-cell cycle theory of aging posits that reproductive hormone changes associated with menopause and andropause drive senescence via altered cell cycle signaling. Using data from the Wisconsin Longitudinal Study (n = 5,034), we analyzed the relationship between longevity and menopause, including other factors that impact "ovarian lifespan" such as births, oophorectomy, and hormone replacement therapy. We found that later onset of menopause was associated with lower mortality, with and without adjusting for additional factors (years of education, smoking status, body mass index, and marital status). Each year of delayed menopause resulted in a 2.9% reduction in mortality; after including a number of additional controls, the effect was attenuated modestly but remained statistically significant (2.6% reduction in mortality). We also found that no other reproductive parameters assessed added to the prediction of longevity, suggesting that reproductive factors shown to affect longevity elsewhere may be mediated by age of menopause. Thus, surgical and natural menopause at age 40, for example, resulted in identical survival probabilities. These results support the maintenance of the hypothalamic-pituitary-gonadal axis in homeostasis in prolonging human longevity, which provides a coherent framework for understanding the relationship between reproduction and longevity.