We examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with ...glucose metabolism and incident type 2 diabetes in older adults.
Between 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants ≥65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 1989-1994. In 1989-1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989-1990 and again in 1992-1993, 1994-1995, 1996-1997, and 1998-1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history.
Observed apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio HR 1.84 95% CI 1.19-2.86), snoring (HR 1.27 95% CI 0.95-1.71), and daytime sleepiness (HR 1.54 95% CI 1.13-2.12). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes.
Easily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may prove useful in identifying candidates for lifestyle or pharmacological therapy. Further studies are needed to determine whether insomnia symptoms affect the risk of diabetes in younger adults.
To develop and validate a patient-specific multivariable prediction model that uses variables readily available in the electronic medical record to predict 12-month mobility at the time of initial ...post-amputation prosthetic prescription. The prediction model is designed for patients who have undergone their initial transtibial (TT) or transfemoral (TF) amputation because of complications of diabetes and/or peripheral artery disease.
Multi-methodology cohort study that identified patients retrospectively through a large Veteran's Affairs (VA) dataset then prospectively collected their patient-reported mobility.
The VA Corporate Data Warehouse, the National Prosthetics Patient Database, participant mailings, and phone calls.
Three-hundred fifty-seven veterans who underwent an incident dysvascular TT or TF amputation and received a qualifying lower limb prosthesis between March 1, 2018, and November 30, 2020 (N=357).
Not applicable.
The Amputee Single Item Mobility Measure (AMPSIMM) was divided into a 4-category outcome to predict wheelchair mobility (0-2), and household (3), basic community (4), or advanced community ambulation (5-6).
Multinomial logistic lasso regression, a machine learning methodology designed to select variables that most contribute to prediction while controlling for overfitting, led to a final model including 23 predictors of the 4-category AMPSIMM outcome that effectively discriminates household ambulation from basic community ambulation and from advanced community ambulation-levels of key clinical importance when estimating future prosthetic demands. The overall model performance was modest as it did not discriminate wheelchair from household mobility as effectively.
The AMPREDICT PROsthetics model can assist providers in estimating individual patients' future mobility at the time of prosthetic prescription, thereby aiding in the formulation of appropriate mobility goals, as well as facilitating the prescription of a prosthetic device that is most appropriate for anticipated functional goals.
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Introduction:
Circulating androgen levels in men decline with advancing age and have been linked to diabetes and atherosclerotic cardiovascular disease (ASCVD). A similar relationship ...has been reported for low total testosterone (T) and incident heart failure (HF), but whether this differs for free T or the more potent androgen, dihydrotestosterone (DHT), remains unknown.
Methods:
We hypothesized that total and free T are inversely related and SHBG positively related to incident HF in older men, whereas, based on earlier data on ASCVD in CHS, total DHT bears a U-shaped relationship with this outcome. In a male sample from CHS without prevalent ASCVD or HF, serum T and DHT concentration were measured by liquid chromatography tandem mass spectrometry, and sex hormone-binding globulin (SHBG) by immunoassay. Free T was calculated from total T, SHBG and albumin. We used Cox regression to estimate relative risks of HF, adjusting for age, race, BMI, smoking, alcohol, physical activity, systolic BP, antihypertensive use, total and HDL cholesterol, and eGFR.
Results:
In 1061 men (age 76±5) followed for a median of 9.6 years, there were 368 HF events. Restricted cubic splines showed no meaningful departure from linearity, and relationships were expressed per SD decrement in androgen levels. After adjustment, lower free T was significantly associated with higher risk of HF (HR 1.14 95% CI 1.01, 1.28), p=0.03). Risk estimates for total T (HR 1.12 0.99, 1.26, p=0.07), DHT (HR 1.10 0.97, 1.24, p=0.14) and SHBG (HR 1.07 0.95, 1.21, p=0.25) were directionally similar, but not statistically significant. The association of lower free T and HF was not altered after further adjustment for diabetes or atrial fibrillation. In a sensitivity analysis excluding participants with history of prostate cancer, findings were similar.
Conclusion:
Total T, free T, DHT and SHBG were inversely associated with incident HF, but only the association of free T was statistically significant. These findings suggest a contribution of androgen deficiency to HF incidence among men late in life, the segment of the population at highest risk of both conditions. Additional research is needed to determine whether androgen replacement therapy is an effective strategy to lower HF risk in older men.
BackgroundSubclinical aortic valve calcification is common among older adults, but the incidence and prevalence of clinically significant aortic stenosis (AS) in the general population is not well ...characterized. We leveraged the Cardiovascular Health Study (CHS), a population-based investigation of older adults with up to 25 years of follow up, to study AS at an epidemiologic level.MethodsWe used a case capture methodology involving ICD-9 diagnosis and procedure codes and CHS echo data to ascertain probable or definite cases of AS at baseline and during longitudinal follow up. Using targeted procedure- and diagnosis-code screening, review of CHF hospitalizations and CHS echo data, along with systematic review of longitudinal hospital records, we identified CHS subjects who developed at least moderate AS, had AS-related hospitalizations, or had AS-related valve interventions.ResultsThere were 5888 participants in CHS (mean age 72.9, 42% male). Of these, 958 were identified for review based on screening methods. Among those with an echo at baseline (1989-1990 for the first cohort and 1994-1995 for the second cohort) and without AS at that time, there were 275 (4.7%) incident probable or definite cases of moderate or greater AS and 169 (2.9%) incident probable or definite cases of severe AS. The median time to moderate or greater AS was 11.3 (range 0.3-24.9) years following baseline echo. Among these subjects, 248 (90%) had an AS-related hospitalization, while only 98 (36%) underwent an aortic valve procedure in this largely pre-TAVR era. Sensitivity analyses were performed, showing that clinically significant AS among the non-reviewed subjects was uncommon (<1%).ConclusionsTo our knowledge, this is the first study to evaluate the long-term incidence of clinical AS in the general elderly U.S. population. Starting at age 65, moderate to severe AS affects about 1 in 20 individuals late in life, and is associated with high rate of morbidity leading to hospitalization.
Age-related clonal hematopoiesis of indeterminate potential (CHIP), defined as clonally expanded leukemogenic sequence variations (particularly in DNMT3A, TET2, ASXL1, and JAK2) in asymptomatic ...individuals, is associated with cardiovascular events, including recurrent heart failure (HF).
This study sought to evaluate whether CHIP is associated with incident HF.
CHIP status was obtained from whole exome or genome sequencing of blood DNA in participants without prevalent HF or hematological malignancy from 5 cohorts. Cox proportional hazards models were performed within each cohort, adjusting for demographic and clinical risk factors, followed by fixed-effect meta-analyses. Large CHIP clones (defined as variant allele frequency >10%), HF with or without baseline coronary heart disease, and left ventricular ejection fraction were evaluated in secondary analyses.
Of 56,597 individuals (59% women, mean age 58 years at baseline), 3,406 (6%) had CHIP, and 4,694 developed HF (8.3%) over up to 20 years of follow-up. CHIP was prospectively associated with a 25% increased risk of HF in meta-analysis (hazard ratio: 1.25; 95% confidence interval: 1.13-1.38) with consistent associations across cohorts. ASXL1, TET2, and JAK2 sequence variations were each associated with an increased risk of HF, whereas DNMT3A sequence variations were not associated with HF. Secondary analyses suggested large CHIP was associated with a greater risk of HF (hazard ratio: 1.29; 95% confidence interval: 1.15-1.44), and the associations for CHIP on HF with and without prior coronary heart disease were homogenous. ASXL1 sequence variations were associated with reduced left ventricular ejection fraction.
CHIP, particularly sequence variations in ASXL1, TET2, and JAK2, represents a new risk factor for HF.
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Introduction:
Cardiovascular disease is the leading cause of mortality in old age, yet there is limited research on the patterns of cardiovascular risk factors that predict survival to ...90 years.
Hypothesis:
The patterns of cardiovascular risk factors that portend longevity will differ from those that confer low cardiovascular risk.
Methods:
We examined repeated measures of blood pressure, LDL-cholesterol, and BMI from age 67 and survival to 90 years in the Cardiovascular Health Study (CHS). CHS is a prospective study of 5,888 black and white adults in two waves (1989-90 and 1992-93) from Medicare eligibility lists in four counties in the U.S. We restricted to participants aged 67 to 75 years at baseline to control for birth cohort effects and examined repeated measures of cardiovascular risk factors throughout the late-life course. We fit logistic regression models to predict survival to age 90 using generalized estimating equations, and modeled the risk factors as linear, a linear spline, and clinically relevant categories. Models were adjusted for demographics and medication use, and we also examined whether the association of each risk factor with longevity varied by the age of risk factor measurement. Best fit models are presented.
Results:
Among 3,645 participants in the birth cohort, 1,160 (31.8%) survived to 90 by June 16
th
, 2015. Higher systolic blood pressure in early old age was associated with reduced odds for longevity, but there was an interaction with age such that the association crossed the null at 80 years. (Table) Among those with LDL-cholesterol <130 mg/dL, higher LDL-cholesterol was associated with greater longevity; at levels above 130 mg/dL there was no association between LDL-cholesterol and longevity. BMI had a u-shaped association with longevity.
Conclusions:
In summary, the patterns of risk factors that predict longevity differ from that considered to predict low cardiovascular risk. The risk of high systolic blood pressure appears to depend on the age of blood pressure measurement.
De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human ...evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains <1% of variation. While we are underpowered to see small differences, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, we did find significantly fewer DNMs in Amish individuals, even when compared with other Europeans, and even after accounting for parental age and sequencing center. Specifically, we found significant reductions in the number of C→A and T→C mutations in the Amish, which seem to underpin their overall reduction in DNMs. Finally, we calculated near-zero estimates of narrow sense heritability (h²), which suggest that variation in DNM rate is significantly shaped by nonadditive genetic effects and the environment.
Studies in Taiwan and Argentina suggest that ingestion of inorganic arsenic from drinking water results in increased risks of internal cancers, particularly bladder and lung cancer. The authors ...investigated cancer mortality in a population of around 400,000 people in a region of Northern Chile (Region II) exposed to high arsenic levels in drinking water in past years. Arsenic concentrations from 1950 to the present were obtained. Population-weighted average arsenic levels reached 570 μg/liter between 1955 to 1969, and decreased to less than 100 μg/liter by 1980. Standardized mortality ratios (SMRs) were calculated for the years 1989 to 1993. Increased mortality was found for bladder, lung, kidney, and skin cancer. Bladder cancer mortality was markedly elevated (men, SMR = 6.0 (95% confidence interval (CI) 4.8–7.4); women, SMR = 8.2 (95% CI 6.3–10.5)) as was lung cancer mortality (men, SMR = 3.8 (95% CI 3.5–4.1); women, SMR = 3.1 (95% CI 2.7–3.7)). Smoking survey data and mortality rates from chronic obstructive pulmonary disease provided evidence that smoking did not contribute to the increased mortality from these cancers. The findings provide additional evidence that ingestion of inorganic arsenic in drinking water is indeed a cause of bladder and lung cancer. It was estimated that arsenic might account for 7% of all deaths among those aged 30 years and over. If so, the impact of arsenic on the population mortality in Region II of Chile is greater than that reported anywhere to date from environmental exposure to a carcinogen in a major population. Am J Epidemiol 1998; 147: 660–9.
Objective: We examined the relationship between race/ethnicity and testis cancer survival in a population-based setting. Methods: We analyzed 16,086 cases of primary testis cancer diagnosed during ...1973-1999 and reported to 12 cancer registries participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. We compared testis cancer-specific survival between patients from different racial/ethnic groups by use of the hazard ratio (HR) and 95% confidence intervals (CI) calculated from Cox proportional hazards models, adjusting for stage, histology, and period of diagnosis. Results: Relative to non-Hispanic whites, a greater proportion of African American, Native American, Hawaiian, and Hispanic patients were diagnosed at late stages. There were 886 deaths among 16,086 testis cancer patients and overall 5-year survival was 95%. After adjustment for stage, histology, and period of diagnosis, the risk of dying from testis cancer was increased among African Americans (HR = 2.3; CI: 1.6-3.2), Native Americans (HR = 2.1; CI: 1.1-3.9), Filipinos (HR = 3.6; CI: 1.3-9.5), Hawaiians (HR = 2.4; CI: 1.4-4.1), and Hispanics (HR = 1.4; CI: 1.1-1.8), compared to non-Hispanic whites. Conclusion: These findings are consistent with previous reports of race/ethnic disparities in stage at diagnosis and survival in testis cancer patients as well as other cancer patients. Further research is needed to understand the reasons underlying these disparities.
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