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Background Hearing loss is associated with restricted physical activity (PA) and impaired physical functioning, yet the relationship between severity of hearing impairment (HI) and novel PA measures in older adults with untreated HI is not well understood. Methods Analyses included 845 participants aged ≥70 years (mean = 76.6 years) with a better-hearing ear pure-tone average (PTA) ≥30 and <70 dB in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study who wore an ActiGraph accelerometer for 7 days. Physical functioning measures included grip strength and the Short Physical Performance Battery (SPPB). Linear regression models estimated the association by HI level (moderate or greater [PTA ≥ 40 dB] vs mild [PTA < 40 dB]) and continuous hearing with total daily activity counts, active minutes/day, activity fragmentation, grip strength, and gait speed. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of poor performance on the SPPB (≤6) and its subtests (≤2). Mixed-effects models estimated differences by HI level in activity by time of day. Results Participants with moderate or greater HI had poorer physical functioning, particularly balance (OR = 2.17, 95% CI = 1.29–3.67), versus those with mild impairment. There was no association of HI level with activity quantities or fragmentation. For diurnal patterns of activity, participants with moderate or greater HI had fewer activity counts in the afternoon (12:00 pm –05:59 pm). Conclusions Older adults with worse hearing had shifted diurnal patterns and poorer balance performance. Exercise programs should be tailored to older adults with different levels of HI to maintain PA and physical functioning, particularly balance control. [ABSTRACT FROM AUTHOR]

Background Streptococcus pneumoniae vaccination effectiveness (VE) in individuals with reduced kidney function is unknown. We estimated pneumococcal conjugate vaccine (PCV13), pneumococcal polysaccharide vaccine (PPSV23), and combined PCV13 and PPSV23 effectiveness against pneumococcal disease in individuals with and without reduced estimated glomerular filtration rate (eGFR). Methods All eligible individuals (case and controls) were adults (aged ≥18 years) hospitalized within the Geisinger Health System and required to have S. pneumoniae urinary antigen testing (i.e. test-negative design). Vaccination records were obtained from the electronic health record and statewide vaccination registry. After controlling for the probability of receiving a pneumococcal vaccine, we used multivariable logistic regression models to estimate the odds ratios (ORs) of vaccination between those who did and did not meet the S. pneumoniae case definition. VE was calculated as (1 – OR) × 100%. Results There were 180 cases and 3889 controls (mean age 69 years, female 48%, white 97%, mean eGFR 71 mL/min/1.73 m2). The adjusted population PCV13 VE was 39% (95% CI 13%–58%), and combination PCV13 and PPSV23 was 39% (95% CI 12%–58%). PPSV23 VE was –3.7% (95% CI –57% to 32%). Stratified by eGFR, adjusted PCV13 VE was consistent in eGFR ≥60 [VE 38% (95% CI 2.9%–61%)] and 30–59 [VE 61% (95% CI 24%–80%)] without significant interaction. VE was not calculable for eGFR <30 due to small sample size. Conclusion PCV13 vaccination was associated with reduced risk of S. pneumoniae hospitalization in individuals with a reduced eGFR (30–59 mL/min/1.73 m2). [ABSTRACT FROM AUTHOR]

Background There is interest in identifying novel filtration markers that lead to more accurate GFR estimates than current markers (creatinine and cystatin C) and are more consistent across demographic groups. We hypothesize that large-scale metabolomics can identify serum metabolites that are strongly influenced by glomerular filtration rate (GFR) and are more consistent across demographic variables than creatinine, which would be promising filtration markers for future investigation. Methods We evaluated the consistency of associations between measured GFR (mGFR) and 887 common, known metabolites quantified by an untargeted chromatography- and spectroscopy-based metabolomics platform (Metabolon) performed on frozen blood samples from 580 participants in Chronic Kidney Disease in Children (CKiD), 674 participants in Modification of Diet in Renal Disease (MDRD) Study and 962 participants in African American Study of Kidney Disease and Hypertension (AASK). We evaluated metabolite–mGFR correlation association with metabolite class, molecular weight, assay platform and measurement coefficient of variation (CV). Among metabolites with strong negative correlations with mGFR (r < −0.5), we assessed additional variation by age (height in children), sex, race and body mass index (BMI). Results A total of 561 metabolites (63%) were negatively correlated with mGFR. Correlations with mGFR were highly consistent across study, sex, race and BMI categories (correlation of metabolite–mGFR correlations between 0.88 and 0.95). Amino acids, carbohydrates and nucleotides were more often negatively correlated with mGFR compared with lipids, but there was no association with metabolite molecular weight, liquid chromatography/mass spectrometry platform and measurement CV. Among 114 metabolites with strong negative associations with mGFR (r < −0.5), 27 were consistently not associated with age (height in children), sex or race. Conclusions The majority of metabolite–mGFR correlations were negative and consistent across sex, race, BMI and study. Metabolites with consistent strong negative correlations with mGFR and non-association with demographic variables may represent candidate markers to improve estimation of GFR. [ABSTRACT FROM AUTHOR]

Background New equations to estimate glomerular filtration rate based on creatinine (eGFRcr), cystatin C (eGFRcys) or both (eGFRcr-cys) have been developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the European Kidney Function Consortium (EKFC). There is a need to evaluate the performance of these equations in diverse European settings to inform implementation decisions, especially among people with key comorbid conditions. Methods We performed a cross-sectional study including 6174 adults referred for single-point plasma clearance of iohexol in Stockholm, Sweden, with 9579 concurrent measurements of creatinine and cystatin C. We assessed the performance of the CKD-EPI 2009/2012/2021, EKFC 2021/2023, revised Lund-Malmö (RLM) 2011 and Caucasian, Asian, Pediatric and Adult (CAPA) 2014 equations against measured GFR (mGFR). Results Mean age was 56 years, median mGFR was 62 mL/min/1.73 m2 and 40% were female. Comorbid conditions were common: cardiovascular disease (30%), liver disease (28%), diabetes (26%) and cancer (26%). All eGFRcr-cys equations had small bias and P30 (the percentage of estimated values within 30% of mGFR) close to 90%, and performed better than eGFRcr or eGFRcys equations. Among eGFRcr equations, CKD-EPI 2009 and CKD-EPI 2021 showed larger bias and lower P30 than EKFC 2021 and RLM. There were no meaningful differences in performance across eGFRcys equations. Findings were consistent across comorbid conditions, and eGFRcr-cys equations showed good performance in patients with liver disease, cancer and heart failure. Conclusions In conclusion, eGFRcr-cys equations performed best, with minimal variation among equations in this Swedish cohort. The lower performance of CKD-EPI eGFRcr equations compared with EKFC and RLM may reflect differences in population characteristics and mGFR methods. Implementing eGFRcr equations will require a trade-off between accuracy and uniformity across regions. [ABSTRACT FROM AUTHOR]

Background Physical function and its decline in older age may be connected to treatable vascular risk factors in mid-life. This study aimed to evaluate whether these factors affect the underlying rate of decline. Methods This prospective cohort included 5 481 older adults aged 67–91 in the Atherosclerosis Risk in Communities Study (mean [standard deviation { SD }] age = 75.8 [5.0], 58% women, 21% Black race) without a history of stroke. The main outcome was the rate of Short Physical Performance Battery (SPPB) decline over a median late-life follow-up of 4.8 years. Primary mid-life (aged 45–64) exposures were Visit 1 hypertension (>140/90 mm Hg or treatment), diabetes (>126 mg/dL or treatment), high cholesterol (>240 mg/dL or treatment), and smoking, and number of decades of vascular risk exposure across Visits 1–4. Results The average adjusted rate of SPPB decline (points per 5 years) for older adults was −0.79 (confidence interval [CI]: −0.87, 0.71) and was accelerated by mid-life hypertension (+57% decline vs normotension: additional decline of −0.47, 95% CI: −0.64, −0.30), diabetes (+73% decline vs no diabetes: additional decline of −0.67, 95% CI: −1.09, −0.24), elevated systolic blood pressure (+17% decline per SD : −0.16, 95% CI: −0.23, −0.10), and elevated fasting blood glucose (+16% decline per SD : −0.015, 95% CI: −0.24, −0.06). Each decade greater mid-life exposure to hypertension (+32% decline: −0.93, 95% CI: −1.25, −0.61) and diabetes (+35% decline: −1.03, 95% CI: −1.68, −0.38) was associated with faster SPPB decline. Conclusions Mid-life control of blood pressure and diabetes may offset aging-related functional decline. [ABSTRACT FROM AUTHOR]

Background Hearing loss is linked to loneliness and social isolation, but evidence is typically based on self-reported hearing. This study quantifies the associations of objective and subjective hearing loss with loneliness and social network characteristics among older adults with untreated hearing loss. Methods This study uses baseline data (N  = 933) from the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study. Hearing loss was quantified by the better ear, speech-frequency pure tone average (PTA), Quick Speech-in-Noise test, and hearing-related quality of life. Outcomes were validated measures of loneliness and social network characteristics. Associations were assessed by Poisson, negative binomial, and linear regression adjusted for demographic, health, and study design characteristics. Results Participants were mean of 76.8 (4.0) years, 54.0% female, and 87.6% White. Prevalence of loneliness was 38%. Worse PTA was associated with a 19% greater prevalence of moderate or greater loneliness (prevalence ration [PR]: 1.19.95% CI: 1.06, 1.33). Better speech-in-noise recognition was associated with greater social network characteristics (eg, larger social network size [IRR: 1.04, 95% CI: 1.00, 1.07]). Worse hearing-related quality of life was associated with a 29% greater prevalence of moderate or greater loneliness (PR: 1.29, 95% CI: 1.19, 1.39) and worse social network characteristics (eg, more constricted social network size [IRR: 0.96, 95% CI: 0.91, 1.00]). Conclusions Results suggest the importance of multiple dimensions of hearing to loneliness and social connectedness. Hearing-related quality of life may be a potentially useful, easily administered clinical tool for identifying older adults with hearing loss associated with greater loneliness and social isolation. [ABSTRACT FROM AUTHOR]

BACKGROUND ACC/AHA guidelines caution against the use of antihypertensive therapy in the setting of low standing systolic BP (SBP) < 110 mm Hg due to unclear benefits. METHODS The Atherosclerosis Risk in Communities (ARIC) Study measured supine and standing SBP in adults aged 45–64 years between 1987 and 1989. We used Cox regression to evaluate the associations of low standing SBP (<110 mm Hg) with risk of falls, syncope, coronary heart disease (CHD), and mortality through December 31, 2019. Falls and syncope were ascertained by hospitalization and outpatient claims; CHD events were adjudicated. Associations were examined overall and in strata of hypertension stage, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and sex. RESULTS Among 12,467 adults followed a median of 24 years (mean age at enrollment 54.1 ± 5.8 years, 55% women, 26% Black adults), 3,000 (24%) had a standing SBP < 110 mm Hg. A standing SBP < 110 mm Hg compared to standing SBP ≥ 110 mm Hg was not significantly associated with falls or syncope, and was associated with a lower risk of CHD events and mortality with HRs of 1.02 (95% CI 0.94, 1.11), 1.02 (0.93, 1.11), 0.88 (0.80, 0.97), and 0.91 (0.86, 0.97), respectively. There were no clinically meaningful differences when stratified by hypertension stage, 10-year ASCVD risk, age, and sex. CONCLUSIONS In this community-based population, low standing SBP was common and not significantly associated with falls or syncope, but was associated with a lower risk of CHD and mortality. These findings do not support screening for low standing BP as a risk factor for adverse events. [ABSTRACT FROM AUTHOR]

Aims Cardiac troponin T and I can be measured using a number of high-sensitivity (hs) assays. This study aimed to characterize correlations between four such assays and test their comparative associations with mortality. Methods and results Among adults without cardiovascular disease in the 1999–2004 National Health and Nutrition Examination Survey, hs-troponin T was measured using one assay (Roche) and hs-troponin I using three assays (Abbott, Siemens, and Ortho). Cox regression was used to estimate associations with all-cause and cardiovascular mortality. Pearson's correlation coefficients comparing concentrations from each assay ranged from 0.53 to 0.77. There were 2188 deaths (488 cardiovascular) among 9810 participants. Each hs-troponin assay [log-transformed, per 1 standard deviation (SD)] was independently associated with all-cause mortality: hazard ratio (HR) 1.20 [95% confidence interval (CI) 1.13–1.28] for Abbott hs-troponin I; HR 1.10 (95% CI 1.02–1.18) for Siemens hs-troponin I; HR 1.23 (95% CI 1.14–1.33) for Ortho hs-troponin I; and HR 1.31 (95% CI 1.21–1.42) for Roche hs-troponin T. Each hs-troponin assay was also independently associated with cardiovascular mortality (HR 1.44 to 1.65 per 1 SD). Associations of hs-troponin T and all-cause and cardiovascular mortality remained significant after adjusting for hs-troponin I. Furthermore, associations of hs-troponin I remained significant after mutually adjusting for hs-troponin I from the other individual assays: e.g. cardiovascular mortality HR 1.46 (95% CI 1.19–1.79) for Abbott after adjustment for the Siemens assay and HR 1.29 (95% CI 1.09–1.53) for Abbott after adjustment for the Ortho assay. Conclusion This study demonstrates only modest correlations between hs-troponin T and three hs-troponin I assays and that hs-troponin I assays can provide distinct risk information for mortality in the general population. [ABSTRACT FROM AUTHOR]

Background Hearing loss is highly prevalent in older ages and has several health consequences. Some cardiovascular risk factors are associated with worse hearing at older ages. Still, the role of midlife leisure-time physical activity (PA) as a risk factor for hearing loss is yet to be investigated. Methods Among 3 198 participants of the Atherosclerosis Risk in Communities study, we investigated the associations of midlife and change from mid- to late-life PA (assessed via modified Baecke questionnaire) with hearing loss (audiometric battery [worse-ear pure-tone average, and speech-in-noise test]) at older ages. We used regression analyses, adjusted for demographics, medical conditions, and noise exposure, to estimate differences in hearing between those who met and did not meet PA recommendations at midlife and at late life. Results A total of 1 386 (43.3%) participants met PA recommendations at midlife. These participants, compared to those who did not meet recommendations, had lower (better) pure-tone average by 1.51 (0.46, 2.55) decibels, identified 0.37 (0.01, 0.74) more words (better score) in the speech-in-noise test, and had a lower relative risk of having hearing loss at older ages (eg, relative risk ratio for severe hearing loss vs normal hearing = 0.70 [0.52, 0.95]). Similarly, those who persistently met PA recommendations from mid- to late life had, compared with those who did not, a better hearing at older ages. Conclusions Meeting PA public health recommendations in midlife and mid- to late life was associated with better hearing at older ages and reduced risk of hearing loss. Promoting adequate levels of PA may be an essential component of hearing care. [ABSTRACT FROM AUTHOR]

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a cardiac biomarker used in the clinical management of heart failure. We sought to create updated reference intervals for NT-proBNP for healthy US children, adolescents, and adults. Methods: We identified a population of healthy individuals using the 1999 to 2004 cycles of the National Health and Nutrition Examination Survey (NHANES). We measured serum NT-proBNP in 12 346 adults and 15 752 children and adolescents with the Elecsys NT-proBNP assay on the Roche e601 autoanalyzer. We compared 4 methods for reference interval calculation, and presented the final reference intervals using the robust method partitioned by age and sex categories. Results: NT-proBNP values were available for 1949 healthy adults and 5250 healthy children and adolescents. NT-proBNP concentrations in males and females varied according to age, being higher in early childhood, relatively lower in late adolescence, and highest through middle age and older age. Females tended to have higher NT-proBNP concentrations compared to men from late adolescence until middle age. The upper reference limit, or 97.5th percentile, for 50 to 59 year-old men was 225 ng/L (90% CI: 158 to 236), and for 50 to 59 year-old women, 292 ng/L (90% CI: 242 to 348). Conclusions: Among healthy individuals, NT-proBNP concentrations varied greatly according age and sex. The reference intervals presented here should inform future clinical decision limits and suggest that age- and sex-specific intervals may be necessary to more precisely characterize risk. [ABSTRACT FROM AUTHOR]

Aims Chronic kidney disease (CKD) is widely prevalent and independently increases cardiovascular risk. Cardiovascular risk prediction tools derived in the general population perform poorly in CKD. Through large-scale proteomics discovery, this study aimed to create more accurate cardiovascular risk models. Methods and results Elastic net regression was used to derive a proteomic risk model for incident cardiovascular risk in 2182 participants from the Chronic Renal Insufficiency Cohort. The model was then validated in 485 participants from the Atherosclerosis Risk in Communities cohort. All participants had CKD and no history of cardiovascular disease at study baseline when ∼5000 proteins were measured. The proteomic risk model, which consisted of 32 proteins, was superior to both the 2013 ACC/AHA Pooled Cohort Equation and a modified Pooled Cohort Equation that included estimated glomerular filtrate rate. The Chronic Renal Insufficiency Cohort internal validation set demonstrated annualized receiver operating characteristic area under the curve values from 1 to 10 years ranging between 0.84 and 0.89 for the protein and 0.70 and 0.73 for the clinical models. Similar findings were observed in the Atherosclerosis Risk in Communities validation cohort. For nearly half of the individual proteins independently associated with cardiovascular risk, Mendelian randomization suggested a causal link to cardiovascular events or risk factors. Pathway analyses revealed enrichment of proteins involved in immunologic function, vascular and neuronal development, and hepatic fibrosis. Conclusion In two sizeable populations with CKD, a proteomic risk model for incident cardiovascular disease surpassed clinical risk models recommended in clinical practice, even after including estimated glomerular filtration rate. New biological insights may prioritize the development of therapeutic strategies for cardiovascular risk reduction in the CKD population. [ABSTRACT FROM AUTHOR]

Aims Chronic kidney disease (CKD) increases risk of cardiovascular disease (CVD). Less is known about how CVD associates with future risk of kidney failure with replacement therapy (KFRT). Methods and results The study included 25 903 761 individuals from the CKD Prognosis Consortium with known baseline estimated glomerular filtration rate (eGFR) and evaluated the impact of prevalent and incident coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) events as time-varying exposures on KFRT outcomes. Mean age was 53 (standard deviation 17) years and mean eGFR was 89 mL/min/1.73 m2, 15% had diabetes and 8.4% had urinary albumin-to-creatinine ratio (ACR) available (median 13 mg/g); 9.5% had prevalent CHD, 3.2% prior stroke, 3.3% HF, and 4.4% prior AF. During follow-up, there were 269 142 CHD, 311 021 stroke, 712 556 HF, and 605 596 AF incident events and 101 044 (0.4%) patients experienced KFRT. Both prevalent and incident CVD were associated with subsequent KFRT with adjusted hazard ratios (HRs) of 3.1 [95% confidence interval (CI): 2.9–3.3], 2.0 (1.9–2.1), 4.5 (4.2–4.9), 2.8 (2.7–3.1) after incident CHD, stroke, HF and AF, respectively. HRs were highest in first 3 months post-CVD incidence declining to baseline after 3 years. Incident HF hospitalizations showed the strongest association with KFRT [HR 46 (95% CI: 43–50) within 3 months] after adjustment for other CVD subtype incidence. Conclusion Incident CVD events strongly and independently associate with future KFRT risk, most notably after HF, then CHD, stroke, and AF. Optimal strategies for addressing the dramatic risk of KFRT following CVD events are needed. [ABSTRACT FROM AUTHOR]

Background While American nephrology societies recommend using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) equation without a Black race coefficient, it is unknown how this would impact disease distribution, prognosis and kidney failure risk prediction in predominantly White non-US populations. Methods We studied 1.6 million Stockholm adults with serum/plasma creatinine measurements between 2007 and 2019. We calculated changes in eGFR and reclassification across KDIGO GFR categories when changing from the 2009 to 2021 CKD-EPI equation; estimated associations between eGFR and the clinical outcomes kidney failure with replacement therapy (KFRT), (cardiovascular) mortality and major adverse cardiovascular events using Cox regression; and investigated prognostic accuracy (discrimination and calibration) of both equations within the Kidney Failure Risk Equation. Results Compared with the 2009 equation, the 2021 equation yielded a higher eGFR by a median [interquartile range (IQR)] of 3.9 (2.9–4.8) mL/min/1.73 m2, which was larger at older age and for men. Consequently, 9.9% of the total population and 36.2% of the population with CKD G3a–G5 was reclassified to a higher eGFR category. Reclassified individuals exhibited a lower risk of KFRT, but higher risks of all-cause/cardiovascular death and major adverse cardiovascular events, compared with non-reclassified participants of similar eGFR. eGFR by both equations strongly predicted study outcomes, with equal discrimination and calibration for the Kidney Failure Risk Equation. Conclusions Implementing the 2021 CKD-EPI equation in predominantly White European populations would raise eGFR by a modest amount (larger at older age and in men) and shift a major proportion of CKD patients to a higher eGFR category. eGFR by both equations strongly predicted outcomes. [ABSTRACT FROM AUTHOR]

Background The association of renin with adverse kidney outcomes is largely unknown, and renin measurement strategies vary. We aimed to measure the clinical correlates of different renin measurements and the association between renin and incident chronic kidney disease (CKD), end-stage kidney disease (ESKD), and mortality. Methods We performed a prospective cohort analysis of 9,420 participants in the Atherosclerosis Risk in Communities study followed from 1996 to 1998 through 2019. We estimated longitudinal associations of renin measured using SomaScan modified nucleotide aptamer assay with incident CKD, ESKD, and death using Cox proportional hazards models. Using samples from a subsequent study visit, we compared SomaScan renin with plasma renin activity (PRA) and renin level from Olink, and estimated associations with covariates using univariate and multivariable regression. Results Higher SomaScan renin levels were associated with a higher risk of incident CKD (hazard ratio per two-fold higher [HR], 1.14; 95% confidence interval [CI], 1.09 to 1.20), ESKD (HR, 1.20; 95% CI, 1.03 to 1.41), and mortality (HR, 1.08; 95% CI, 1.04 to 1.13) in analyses adjusted for demographic, clinical, and socioeconomic covariates. SomaScan renin was moderately correlated with PRA (r  = 0.61) and highly correlated with Olink renin (r  = 0.94). SomaScan renin and PRA had similar clinical correlates except for divergent associations with age and beta-blocker use, both of which correlated positively with SomaScan renin but negatively with PRA. Conclusions SomaScan aptamer-based renin level was associated with a higher risk of CKD, ESKD, and mortality. It was moderately correlated with PRA, sharing generally similar clinical covariate associations. [ABSTRACT FROM AUTHOR]

Background: Although a few studies reported an association between varicose veins and physical function, this potentially bidirectional association has not been systematically evaluated in the general population.Method: In 5 580 participants (aged 71-90 years) from the Atherosclerosis Risk in Communities study, varicose veins were identified in outpatient and inpatient administrative data prior to (prevalent cases) and after (incident cases) visit 5 (2011-2013). Physical function was evaluated by the Short Physical Performance Battery (SPPB, score ranging from 0 to 12). We evaluated (i) cross-sectional association between prevalent varicose veins and physical function, (ii) association of prevalent varicose veins with subsequent changes in physical function from visit 5 to visits 6 (2016-2017) and 7 (2018-2019), and (iii) association of physical function at visit 5 with incident varicose veins during a median follow-up of 3.6 years (105 incident varicose veins among 5 350 participants without prevalent cases at baseline).Results: At baseline, varicose veins were recognized in 230 (4.1%) participants and cross-sectionally associated with reduced physical function. Longitudinally, prevalent varicose veins were not significantly associated with a decline in SPPB over time. In contrast, a low SPPB ≤6 was associated with a greater incidence of varicose veins compared to SPPB ≥10 (adjusted hazard ratio 2.13 [95% confidence interval = 1.19, 3.81]).Conclusion: In community-dwelling older adults, varicose veins and low physical function were associated cross-sectionally. Longitudinally, low physical function was a risk factor for incident varicose veins, but not vice versa. Our findings suggest an etiological contribution of low physical function to incident varicose veins. [ABSTRACT FROM AUTHOR]

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre–coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18–108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories. [ABSTRACT FROM AUTHOR]

Background: Glycated albumin is cleared by the Food and Drug Administration (FDA) for clinical use in diabetes care. To understand its performance in the general US population, we conducted measurements in >19 000 samples from the National Health and Nutrition Examination Survey (NHANES). Of these samples, 5.7% had previously undergone at least 2 freeze–thaw cycles and were considered "non-pristine." Methods: We measured glycated albumin and albumin using the Lucica GA-L (Asahi Kasei) assay in stored serum samples from NHANES 1999–2004. Serum albumin (Roche/Beckman) was previously measured. We examined the correlations of percent glycated albumin with hemoglobin A1C (HbA1c)and fasting glucose in the pristine and non-pristine samples. We also measured cystatin C (Siemens) and compared these to cystatin C (Dade Behring) previously obtained in a subsample. Results: Glycated albumin (%) was significantly lower in pristine vs non-pristine samples (13.8% vs 23.4%, P < 0.0001). The results from the Asahi Kasei albumin assay (g/dL) were highly correlated with albumin originally measured in NHANES (Pearson's correlation coefficient, r = 0.76) but values were systematically higher (+0.25 g/dL, P < 0.0001). Cystatin C (Siemens) was similar to previous cystatin C measurements (r = 0.98) and did not differ by pristine status (P = 0.119). Glycated albumin (%) was highly correlated with HbA1c and fasting glucose in pristine samples (r = 0.78 and r = 0.71, respectively) but not in non-pristine samples (r = 0.11 and r = 0.12, respectively). Conclusions: The performance of the glycated albumin assay in the pristine samples was excellent. Performance in non-pristine samples was highly problematic. Analyses of glycated albumin in NHANES 1999–2004 should be limited to pristine samples only. These results have major implications for the use of these public data. [ABSTRACT FROM AUTHOR]

Background: Glycated albumin may provide complementary information to hemoglobin A1c (HbA1c). We compared cross-sectional associations of HbA1c and glycated albumin with chronic kidney disease (CKD) in US adults. Methods: We included 10 923 adults (9955 without diagnosed diabetes, 968 with a diabetes diagnosis) from the National Health and Nutrition Examination Survey 1999–2004. We examined continuous associations and clinical cut points for HbA1c among those without diabetes (<5.0%, 5.0%–5.6% (reference), 5.7%–6.4%, ≥6.5%) and among those with diagnosed diabetes (<7.0%, 7.0%–8.9%, ≥9.0%) and percentile equivalents for glycated albumin. We used logistic regression to compare associations with prevalent CKD, adjusting for traditional risk factors. We used likelihood ratio tests to assess whether adding glycated albumin improved the model with HbA1c. Results: There were J-shaped associations for both glycated albumin and HbA1c with CKD. Persons without a history of diabetes and very low glycated albumin or HbA1c were more likely to have CKD compared to those without diabetes and normoglycemia. The odds ratios (ORs) for CKD were 1.32 (95% CI, 1.12–1.55) for HbA1c 5.7% to 6.4% and 2.04 (95% CI, 1.28–3.25) for HbA1c ≥6.5%. The ORs for glycated albumin were 1.27 (95% CI, 1.06–1.51) and 2.48 (95% CI, 1.50–4.08) for glycated albumin 14.4% to 17.8% and ≥17.9%, respectively. The inclusion of glycated albumin in the model with HbA1c and traditional risk factors modestly but significantly improved the model fit (P value = 0.006). Conclusions: Glycated albumin and HbA1c were similarly associated with prevalent CKD. Glycated albumin provides complementary information to HbA1c for prevalent CKD. [ABSTRACT FROM AUTHOR]

Objective: Fibroblast growth factor 23 (FGF23) concentration increases in response to declining kidney function to preserve normal phosphate concentrations. However, the etiological association of change in FGF23 concentration with mortality has not been examined in the general population. Design and methods: We analyzed 5458 participants of the Atherosclerosis Risk in C ommunities Study who had intact FGF23 and estimated glomerular filtration rate (eGFR) assessed d uring midlife (visit 3, 1993-1995, mean age: 58 years) and late life (visit 5, 2011-2013, 76 years) to examine the ass ociation of FGF23 change over 18 years from mid-life to late life with the subsequent risk of mortality in late life us ing Cox regression models. Results: The median 18-year change in intact FGF23 was +17.3 pg/mL. Dur ing a median follow-up of 7.2 years following visit 5, 1176 participants died. In multivariable Cox models, e levated mortality was seen in the highest quartile of FGF23 change (ΔFGF23: =31.3 pg/mL) (adjusted hazard ratio (aHR): 1.61 (95%CI: 1.36-1.9 0), or 1.37 (1.15-1.64) after additionally adjusting for eGFR change, compared with the lowes t quartile (=6.4 pg/mL)). When both FGF23 change and FGF23 in late life were simultaneously entered into the Cox model, FGF23 in late life, but not FGF23 change, was an independent predictor of mortality; however, we observed a high correlation between FGF23 change from midlife to late life and FGF23 in late life (r = 0.77). Conclusions: Serum intact FGF23 change from midlife to late life was associ ated with subsequent risk of mortality independent of decline in kidney function. Our findings further support the implications of FGF23 beyond its association with kidney function. [ABSTRACT FROM AUTHOR]

In the article, the authors present their study which assessed the stability of serum bone-mineral, kidney and cardiac biomarkers following a freeze-thaw cycle using data from the Atherosclerosis Risk in Communities (ARIC) Study. Topics include the calculation of Pearson coefficients and intraclass correlation coefficients (ICC) and the biomarkers for parathyroid hormone (PTH), phosphorus, and bone-mineral metabolism.

Aims  Heart failure increases the risk of kidney disease progression. However, whether cardiac function and structure are associated with the risk of incident chronic kidney disease (CKD) is not well characterized in a community setting. Methods and results  Among 4188 participants (mean age 75 years and 22% blacks) of the Atherosclerosis Risk in Communities Study without prevalent CKD in 2011–13, we examined the association of echocardiographic measures of left ventricular (LV) mass index, ejection fraction, left atrial volume index (LAVi), right ventricular (RV) fractional area change, and peak RV-right atrium (RA) gradient, with the subsequent risk of incident CKD, as defined by >25% decline to estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, hospitalization with CKD diagnosis, or incident end-stage kidney disease. Multivariable Cox regression models were used to estimate hazard ratios (HRs). The risk of incident CKD was monotonically increased with each of higher LV mass index [adjusted HR 2.61 (1.92–3.55) for highest quartile (Q4) vs. lowest (Q1)], lower ejection fraction [1.54 (1.17–2.04) for Q1 vs. Q4], higher LAVi [2.12 (1.56–2.89) for Q4 vs. Q1], and higher peak RV-RA gradient [2.17 (1.45–3.25) for Q4 vs. Q1] but not with RV function. The associations were consistent between subgroups by sex and race. Conclusion  Among community-dwelling older individuals, LV mass index, ejection fraction, LAVi, and peak RV-RA gradient were independently associated with the risk of incident CKD. Our results further support that heart disease is associated with the risk of kidney disease progression and suggest the value of echocardiography for assessing cardiac and kidney health in older populations. [ABSTRACT FROM AUTHOR]

BACKGROUND 2014 hypertension guidelines raised treatment goals in older adults. The objective was to examine changes in blood pressure (BP) control (<140/90 mm Hg) from 2011–2013 to 2016–2017 among Black and white older adults with treated hypertension. METHODS Participants were 1,600 white and 650 Black adults aged 71–90 years in the Atherosclerosis Risk in Communities (ARIC) Study with treated hypertension in 2011–2013 (baseline) who had BP measured in 2016–2017 (follow-up). Predictors of changes in BP control were examined by race. RESULTS BP was controlled among 75.3% of white and 65.7% of Black participants at baseline and 59.0% of white and 56.5% of Black participants at follow-up. Among those with baseline BP control, risk factors for incident uncontrolled BP included age (relative risk [RR] 1.15 per 5 years, 95% confidence interval [CI] 1.07–1.25), female sex (RR 1.36, 95% CI 1.16–1.60), and chronic kidney disease (RR 1.19, 95% CI 1.01–1.40) among white participants, and hypertension duration (RR 1.14 per 5 years, 95% CI 1.03–1.27) and diabetes (RR 1.48, 95% CI 1.15–1.91) among Black participants. Among those with uncontrolled BP at baseline, white females vs. males (RR 0.60, 95% CI 0.46–0.78) and Black participants with chronic kidney disease vs. without (RR 0.58, 95% CI 0.36–0.93) were less likely to have incident controlled BP. CONCLUSIONS BP control decreased among white and Black older adults. Black individuals with diabetes or chronic kidney disease were less likely to have controlled BP at follow-up. Higher treatment goals may have contributed to these findings and unintended differences by race. [ABSTRACT FROM AUTHOR]

BACKGROUND Blood pressure (BP) measurement error may lead to under- or overtreatment of hypertension. One common source of error is terminal digit preference, most often a terminal digit of "0." The objective was to evaluate national trends in terminal digit preference in office BP measurements among adults with treated hypertension. METHODS Data were from IQVIA's National Disease and Therapeutic Index, a nationally representative, serial cross-sectional survey of office-based physicians. The analysis included office visits from 2015 to 2019 among adults aged ≥18 years receiving antihypertensive treatment. Annual trends were examined in the percent of systolic and diastolic BP measurements ending in zero by patient sex, age, and race/ethnicity, physician specialty, and first or subsequent hypertension treatment visit. RESULTS From 2015 to 2019, there were ~60 million hypertension treatment visits annually (unweighted N : 5,585–9,085). There was a decrease in the percent of visits with systolic (41.7%–37.7%) or diastolic (42.7%–37.8%) BP recordings ending in zero. Trends were similar by patient characteristics. However, a greater proportion of measurements ended in zero among patients aged ≥80 (vs. 15–59 or 60–79) years, first (vs. subsequent) treatment visits, visits to cardiologists (vs. primary care physicians), and visits with systolic BP ≥140 or diastolic BP ≥90 (vs. <140/90) mm Hg. CONCLUSIONS Despite modest improvement, terminal digit preference remains a common problem in office BP measurement in the United States. Without bias, 10%–20% of measurements are expected to end in zero. Reducing digit preference is a priority for improving BP measurement accuracy and hypertension management. [ABSTRACT FROM AUTHOR]

Background Few studies have investigated the association of magnesium levels with incident peripheral artery disease (PAD) despite emerging evidence of magnesium contributing to vascular calcification. Moreover, no data are available on whether the magnesium–PAD relationship is independent of or modified by kidney function. Methods A cohort of 11 839 participants free of PAD in the Atherosclerosis Risk in Communities Study at Visit 2 (1990–92) was studied. We investigated the association of serum magnesium and other bone–mineral metabolism markers [calcium, phosphorus, intact parathyroid hormone (iPTH) and intact fibroblast growth factor-23] with incident PAD using multivariable Cox proportional hazards regression. Results Over a median of 23 years, there were 471 cases of incident PAD. The hazard ratio for incident PAD in Quartile 1 (<1.5 mEq/L) versus Quartile 4 (>1.7 mEq/L) of magnesium was 1.96 (95% confidence interval 1.40–2.74) after adjustment for potential confounders. Lower magnesium levels were associated with greater incidence of PAD, particularly in those with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n  = 11 606). In contrast, the association was largely flat in those with eGFR <60 mL/min/1.73 m2 (n  = 233) with P-for-interaction 0.03. Among bone–mineral metabolism markers, only higher iPTH showed an interaction with kidney function (P-for-interaction 0.01) and iPTH >65 pg/mL was significantly related to PAD only in those with eGFR <60 mL/min/1.73 m2. Conclusions Lower magnesium was independently associated with incident PAD, but this association was significantly weaker in those with reduced kidney function. In contrast, higher iPTH levels were particularly related to PAD risk in this clinical population. [ABSTRACT FROM AUTHOR]

Few studies have comprehensively investigated the association of 2 key kidney disease measures, estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR), with cancer incidence. In 8,935 participants at the baseline (1996–1998) from the Atherosclerosis Risk in Communities study, we quantified the associations of eGFR (based on creatinine and cystatin C) and ACR with cancer risk using Cox regression models adjusted for potential confounders. Due to changing guidelines for prostate cancer screening during the follow-up period, we investigated overall cancer, overall nonprostate cancer, and site-specific cancer. During a median follow-up of 14.7 years, 2,030 incident cancer cases occurred. In demographically adjusted models, low eGFR and high ACR were associated with cancer incidence (both overall and overall nonprostate cancer). These associations were attenuated after adjusting for other shared risk factors, with a significant association remaining only for ACR (≥103 compared with 5 mg/g) and overall nonprostate cancer. For site-specific cancer, only high ACR showed a significant association with lung and urinary tract cancers. Of these, the association between ACR and lung cancer appeared most robust in several sensitivity analyses. Kidney disease measures, particularly high ACR, were independently associated with cancer risk. The association between ACR and lung cancer was uniquely robust, warranting future studies to explore potential mechanisms. [ABSTRACT FROM AUTHOR]

Background Residual kidney function (RKF) is thought to exert beneficial effects through clearance of uremic toxins. However, the level of native kidney function where clearance becomes negligible is not known. Methods We aimed to assess whether levels of nonurea solutes differed among patients with 'clinically negligible' RKF compared with those with no RKF. The hemodialysis study excluded patients with urinary urea clearance >1.5 mL/min, below which RKF was considered to be 'clinically negligible'. We measured eight nonurea solutes from 1280 patients participating in this study and calculated the relative difference in solute levels among patients with and without RKF based on measured urinary urea clearance. Results The mean age of the participants was 57 years and 57% were female. At baseline, 34% of the included participants had clinically negligible RKF (mean 0.7 ± 0.4 mL/min) and 66% had no RKF. Seven of the eight nonurea solute levels measured were significantly lower in patients with RKF than in those without RKF, ranging from −24% [95% confidence interval (CI) −31 to −16] for hippurate, −7% (−14 to −1) for trimethylamine- N -oxide and −4% (−6 to −1) for asymmetric dimethylarginine. The effect of RKF on plasma levels was comparable or more pronounced than that achieved with a 31% higher dialysis dose (sp Kt/V urea 1.7 versus 1.3). Preserved RKF at 1-year follow-up was associated with a lower risk of cardiac death and first cardiovascular event. Conclusions Even at very low levels, RKF is not 'negligible', as it continues to provide nonurea solute clearance. Management of patients with RKF should consider these differences. [ABSTRACT FROM AUTHOR]

Whether persons without prevalent cardiovascular disease (CVD) but elevated levels of high-sensitivity cardiac troponin T (hs-cTnT) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) are at high risk of infection is unknown. Using 1996–2013 data from the Atherosclerosis Risk in Communities Study, we estimated hazard ratios for incident hospitalization with infection in relation to plasma hs-cTnT and NT-proBNP concentrations among participants without prevalent CVD and contrasted them with hazard ratios for persons with prevalent CVD (coronary heart disease, heart failure, or stroke). In a multivariable Cox model, prevalent CVD was significantly associated with risk of hospitalization with infection (hazard ratio (HR) = 1.31, 95% confidence interval (CI): 1.19, 1.45). Among participants without prevalent CVD, hs-cTnT and NT-proBNP were independently associated with infection risk in a graded fashion (e.g., HR = 1.44 (95% CI: 1.24, 1.69) for hs-cTnT ≥14 ng/L and HR = 1.28 (95% CI: 1.14, 1.44) for hs-cTnT 9–13 ng/L vs. <3 ng/L; HR = 1.57 (95% CI: 1.35, 1.81) for NT-proBNP ≥248.1 pg/mL and HR = 1.19 (95% CI: 1.06, 1.34) for NT-proBNP 137.2–248.0 pg/mL vs. <48.1 pg/mL). The 15-year cumulative incidences of hospitalization with infection were similar for participants with prevalent CVD and participants who did not have prevalent CVD but had hs-cTnT ≥14 ng/L or NT-proBNP ≥248.1 pg/mL. Thus, hs-cTnT and NT-proBNP were independently associated with infection risk. Persons without CVD but with elevated hs-cTnT or NT-proBNP levels should be recognized to have similar infection risks as persons with prevalent CVD. [ABSTRACT FROM AUTHOR]

Background There is strong evidence of an association between socioeconomic status (SES) and end-stage renal disease (ESRD). However, the association of SES with the risk of chronic kidney disease (CKD) and the rate of change in kidney function is unclear. Methods A cohort of 14 086 participants with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at baseline in the Atherosclerosis Risk in Communities study (1987–89) were studied. The association of annual household income, educational attainment and neighborhood deprivation with incident ESRD, incident CKD and change in eGFR using four measurements over ∼23 years was assessed. Results A total of 432 participants developed ESRD and 3510 developed CKD over a median follow-up time of ∼23 years. After adjustment for demographics and baseline eGFR, the hazard ratio (HR) for incident ESRD compared with the high-income group was 1.56 [95% confidence interval (CI) 1.22–1.99 in the medium-income group and 2.30 (95% CI 1.75–3.02) in the low-income group (P-trend < 0.001), and for CKD was 1.10 (95% CI 1.01–1.20) in the medium-income group and 1.30 (95% CI 1.17–1.44) in the low-income group (P-trend < 0.001). After full adjustments, the HR for ESRD was 1.33 (95% CI 1.03–1.70) in the medium-income group and 1.50 (95% CI 1.14–1.98) in the low-income group (P-trend = 0.003) and for CKD was 1.01 (95% CI 0.92–1.10) in the medium-income group and 1.04 (95% CI 0.93–1.16) in the low-income group (P-trend = 0.50). The eGFR decline was 5% and 15% steeper in the medium- and low-income groups, respectively, after full adjustment (P-trend < 0.001). Results were similar, with lower educational attainment and higher neighborhood deprivation being associated with adverse outcomes. Conclusions SES (annual household income, educational attainment or neighborhood deprivation) was associated not only with ESRD risk but also with eGFR decline, although the association with CKD appeared weaker. [ABSTRACT FROM AUTHOR]

Background: There is growing interest in the use of multiplexed aptamer-based assays for large-scale proteomic studies. However, the analytic, short- and long-term variation of the measured proteins is largely uncharacterized. Methods: We quantified 4001 plasma protein analytes from 42 participants in the Atherosclerosis Risk in Communities (ARIC) Study in split samples and at multiple visits using a multiplexed modified aptamer assay. We calculated the CV, Spearman correlation, and intraclass correlation (ICC) between split samples and evaluated the short-term (4-9 weeks) and long-term (approximately 20 years) variability using paired t-tests with logtransformed protein concentrations and Bonferroni-corrected significance thresholds. We performed principal component (PC) analysis of protein analyte concentrations and evaluated their associations with age, sex, race, and estimated glomerular filtration rate (eGFR). Results: The mean baseline age was 57 years at the first visit, 43% of participants were male and 57% were white. Among 3693 protein analytes that passed quality control, half (n = 1846) had CVs < 5.0%, Spearman correlations > 0.89, and ICCs > 0.96 among the split samples. Over the short term, only 1 analyte had a statistically significant difference between the 2 time points, whereas, over approximately 20 years, 866 analytes (23.4%) had statistically significant differences (P < 1.4 x 10-5, 681 increased, 185 decreased). PC1 had high correlations with age (-0.73) and eGFR (0.60). PC2 had moderate correlation with male sex (0.18) and white race (0.31). Conclusions: Multiplexed modified aptamer technology can assay thousands of proteins with excellent precision. Our results support the potential for large-scale studies of the plasma proteome over the lifespan. [ABSTRACT FROM AUTHOR]

Background: Accurate assessment of the burden of stroke, a major cause of disability and death, is crucial. We aimed to estimate rates of validated ischaemic stroke hospitalizations in the USA during 1998-2011.Methods: We used the Atherosclerosis Risk in Communities (ARIC) study cohort's adjudicated stroke data for participants aged ≥55 years, to construct validation models for each International Classification of Diseases (ICD)-code group and patient covariates. These models were applied to the Nationwide Inpatient Sample (NIS) data to estimate the probability of validated ischaemic stroke for each eligible hospitalization. Rates and trends in NIS using ICD codes vs estimates of validated ischaemic stroke were compared.Results: After applying validation models, the estimated annual average rate of validated ischaemic stroke hospitalizations in the USA during 1998-2011 was 3.37 [95% confidence interval (CI): 3.31, 3.43) per 1000 person-years. Validated rates declined during 1998-2011 from 4.7/1000 to 2.9/1000; however, the decline was limited to 1998-2007, with no further decline subsequently through 2011. Validation models showed that the false-positive (∼23% of strokes) and false-negative rates of ICD-9-CM codes in primary position for ischaemic stroke approximately cancel. Therefore, estimates of ischaemic stroke hospitalizations did not substantially change after applying validation models.Conclusions: Overall, ischaemic stroke hospitalization rates in the USA have declined during 1998-2007, but no further decline was observed from 2007 to 2011. Validated ischaemic stroke hospitalizations estimates were similar to published estimates of hospitalizations with ischaemic stroke ICD codes in primary position. Validation of national discharge data using prospective chart review data is important to estimate the accuracy of reported burden of stroke. [ABSTRACT FROM AUTHOR]

Background Estimation of glomerular filtration rate (GFR) using estimated glomerular filtration rate creatinine (eGFRcr) is central to clinical practice but has limitations. We tested the hypothesis that serum metabolomic profiling can identify novel markers that in combination can provide more accurate GFR estimates. Methods We performed a cross-sectional study of 200 African American Study of Kidney Disease and Hypertension (AASK) and 265 Multi-Ethnic Study of Atherosclerosis (MESA) participants with measured GFR (mGFR). Untargeted gas chromatography/dual mass spectrometry– and liquid chromatography/dual mass spectrometry–based quantification was followed by the development of targeted assays for 15 metabolites. On the log scale, GFR was estimated from single- and multiple-metabolite panels and compared with eGFR using the Chronic Kidney Disease Epidemiology equations with creatinine and/or cystatin C using established metrics, including the proportion of errors >30% of mGFR (1-P30), before and after bias correction. Results Of untargeted metabolites in the AASK and MESA, 283 of 780 (36%) and 387 of 1447 (27%), respectively, were significantly correlated (P ≤ 0.001) with mGFR. A targeted metabolite panel eGFR developed in the AASK and validated in the MESA was more accurate (1-P30 3.7 and 1.9%, respectively) than eGFRcr [11.2 and 18.5%, respectively (P < 0.001 for both)] and estimating GFR using cystatin C (eGFRcys) [10.6% (P = 0.02) and 9.1% (P < 0.05), respectively] but was not consistently better than eGFR using both creatinine and cystatin C [3.7% (P > 0.05) and 9.1% (P < 0.05), respectively]. A panel excluding creatinine and demographics still performed well [1-P30 6.4% (P = 0.11) and 3.4% (P < 0.001) in the AASK and MESA] versus eGFRcr. Conclusions Multimetabolite panels can enable accurate GFR estimation. Metabolomic equations, preferably excluding creatinine and demographic characteristics, should be tested for robustness and generalizability as a potential confirmatory test when eGFRcr is unreliable. [ABSTRACT FROM AUTHOR]

Background. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are recommended for glomerular filtration rate (GFR) estimation in the general population. They have not been evaluated in community-based populations, including Blacks at higher levels of GFR, but are commonly applied in such populations. Methods. In an ancillary study of Multi-Ethnic Study of Atherosclerosis conducted at one site, we evaluated the performance of the CKD-EPI equations for creatinine (eGFRcr), cystatin C (eGFRcys) or the combination (eGFRcr-cys) compared with GFR measured as plasma clearance of iohexol. Results. Among 294 participants, the mean age was 71 (SD 9) years, 47% were Black, 48% were women and themean measured GFR (mGFR) was 72.6 (SD 18.8) mL/min/1.73 m2. The CKDEPI equations overestimated mGFR with a larger median bias for eGFRcr and eGFRcr-cys than eGFRcys [-8.3 (95% confidence interval -9.7, -6.5), -7.8 (-9.2, -6.2) and -3.7 (-5.0, -1.8) mL/min/1.73 m2, respectively], with smaller bias for those with lower compared with higher eGFR and by race compared with sex. Conclusion. The small differential bias of the CKD-EPI equation between races suggests that they can be used in Blacks as well as Whites in older community-based adults. The large differential bias in women versus men in all equations is in contrast to other studies and is unexplained. Further studies are required in multiracial and multiethnic community-based cohorts, taking into account differences in GFR measurement methods. [ABSTRACT FROM AUTHOR]

Aims Sudden cardiac death (SCD) is a major public health burden. Mitochondrial dysfunction has been implicated in a wide range of cardiovascular diseases including cardiomyopathy, heart failure, and arrhythmias, but it is unknown if it also contributes to SCD risk. We sought to examine the prospective association between mtDNA copy number (mtDNA-CN), a surrogate marker of mitochondrial function, and SCD risk. Methods and results We measured baseline mtDNA-CN in 11 093 participants from the Atherosclerosis Risk in Communities (ARIC) study. mtDNA copy number was calculated from probe intensities of mitochondrial single nucleotide polymorphisms (SNP) on the Affymetrix Genome-Wide Human SNP Array 6.0. Sudden cardiac death was defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual without evidence of a non-cardiac cause of cardiac arrest. Sudden cardiac death cases were reviewed and adjudicated by an expert committee. During a median follow-up of 20.4 years, we observed 361 SCD cases. After adjusting for age, race, sex, and centre, the hazard ratio for SCD comparing the 1st to the 5th quintiles of mtDNA-CN was 2.24 (95% confidence interval 1.58-3.19; P-trend <0.001). When further adjusting for traditional cardiovascular disease risk factors, prevalent coronary heart disease, heart rate, QT interval, and QRS duration, the association remained statistically significant. Spline regression models showed that the association was approximately linear over the range of mtDNA-CN values. No apparent interaction by race or by sex was detected. Conclusion In this community-based prospective study, mtDNA-CN in peripheral blood was inversely associated with the risk of SCD. [ABSTRACT FROM AUTHOR]