Faculty Bibliography

INTRODUCTION/BACKGROUND:Varicose veins are common in older adults and are associated with adverse clinical outcomes such as deep venous thrombosis. Established risk factors for varicose veins include female sex, height, and obesity, but other risk factors are relatively uncharacterized. METHODS:This was a prospective cohort analysis of 6241 participants aged 66-70 years from the Atherosclerosis Risk in Communities (ARIC) Study. Incident varicose veins were defined as two outpatient encounters (at least a week apart) or inpatient diagnoses through 2018 with ICD 9 code 454 or ICD 10 code I83. Participants with a history of clinically-recognized varicose veins at baseline were excluded. Cox regression was used to evaluate established (e.g., female, height, body mass index) and potential demographic and clinical risk factors. RESULTS:During a median follow-up of 13 years, 349 (6%) of participants developed clinically-recognized varicose veins. Consistent with prior research, female sex, taller height, and higher body mass index were associated with varicose veins. After accounting for these, White race, prevalent heart failure, loop diuretic use, higher cardiac troponin T, and higher natriuretic peptide were independently associated with incident varicose veins. CONCLUSIONS:In this community-based cohort study of older adults, known and newly identified risk factors, including cardiac function and heart failure, were independently associated with incidence of clinically-recognized varicose veins. The potential usefulness of cardiac biomarkers for prevention and screening of varicose veins requires further investigations.

BACKGROUND/UNASSIGNED:Physical activity fragmentation represents the frequency of transitioning from an active to sedentary state. The prognostic information of physical activity fragmentation is unclear in Hispanics/Latinos. This study examined the association of PA fragmentation with all-cause mortality in Hispanic/Latino adults. METHODS/UNASSIGNED:We investigated 11,992 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (18-74 yr; 52.2% women), from four United States urban communities (Bronx, New York; Chicago, Illinois; Miami, Florida; San Diego, California), that wore an accelerometer for one week. Physical activity fragmentation was calculated using the active-to-sedentary transition probability (ASTP) as the reciprocal of the average active bout duration. Daily total log-transformed activity count (TLAC) was used as a measure of total physical activity. The residual of ASTP regressed on TLAC (TLAC-adjusted ASTP) was explored to investigate the association of ASTP independent of total physical activity. Deaths were identified from annual follow-up interviews, obituary searches, or matches to the National Death Index through December 31, 2021. Cox regression models were fitted according to physical activity fragmentation. FINDINGS/UNASSIGNED:There were 745 deaths (6.2%) over a mean follow-up of 11.2 (SD 2.2) years. The highest compared to the lowest tertile of ASTP showed a HR of 1.45 (95% CI 1.10-1.92) of all-cause mortality after accounting for confounders. The mortality risk also increased for each 0.10-unit increase of ASTP, as a continuous variable, by 22% (HR 1.22; 95% CI 1.07-1.39). The results were similar considering TLAC-adjusted ASTP. INTERPRETATION/UNASSIGNED:Among Hispanic/Latino adults, more fragmented physical activity was associated with elevated all-cause mortality, independent of total physical activity volume. FUNDING/UNASSIGNED:HCHS/SOL was supported by the National Institutes of Health.

BACKGROUND AND AIMS/OBJECTIVE:The association of physical activity (PA) with coronary artery calcification (CAC), one of the strongest predictors of cardiovascular disease, is unclear. Moreover, different domains of PA (e.g., exercise/sports vs. work) and extra-coronary calcification (ECC) have not been extensively studied. We comprehensively evaluated the association of PA with CAC and ECC. METHODS:We investigated 2025 ARIC participants (age 73-95 years) without coronary heart disease at visit 7 (2018-19). Mid-life total and domain-specific (sport, leisure, and work) PA scores were estimated using a modified Baecke questionnaire. We modeled the averaged PA scores at visit 1 (1987-89; age 44-65 years) and visit 3 (1993-95; age 49-70 years). We explored continuous CAC and ECC (log-transformed [Agatston score+1]) or the presence of any CAC and ECC (Agatston score >0 vs. 0) as dependent variables using multivariable linear regression and logistic regression models, as appropriate. RESULTS:Total PA scores showed a U-shaped association with both continuous and any vs. no CAC. Higher total PA scores were associated inversely with ECC and most pronounced for the descending aorta calcification. The associations were generally consistent across demographic subgroups. When specific PA domains were examined, higher sport and work PA scores were significantly associated with lower descending aorta calcification. CONCLUSIONS:Mid-life PA showed a U-shaped association with late-life CAC. Among ECC, the association of higher PA with lower calcification of the descending aorta was the most consistent. Our results further corroborate a complex interplay between PA and vascular health and unique pathological processes across different vascular beds.

PURPOSE OF REVIEW/OBJECTIVE:Serum creatinine reflects both muscle mass and kidney function. Serum cystatin C has recently been recommended as an additional marker for estimating kidney function, and use of both markers together may provide an index of muscle mass. This review aims to describe the biological basis for and recent research examining the relationship of these markers to muscle mass in a range of adult populations and settings. RECENT FINDINGS/RESULTS:This review identified 67 studies, 50 of which had direct measures of muscle mass, and almost all found relationships between serum creatinine and cystatin C and muscle mass and related outcomes. Most studies have been performed in older adults, but similar associations were found in general populations as well as in subgroups with cancer, chronic kidney disease (CKD), and other morbid conditions. Creatinine to cystatin C ratio was the measure examined the most often, but other measures showed similar associations across studies. SUMMARY/CONCLUSIONS:Measures of serum creatinine and cystatin C together can be an index of muscle mass. They are simple and reliable measures that can be used in clinical practice and research. Further study is needed to determine actionable threshold values for each measure and clinical utility of testing and intervention.

BACKGROUND/UNASSIGNED:The prevalence of hypertension and uncontrolled hypertension may differ by age and sex. METHODS/UNASSIGNED:We included participants in the Atherosclerosis Risk in Communities study at seven study visits over 33 years (visit 1: 15 636 participants; mean age, 54 years; 55% women), estimating sex differences in prevalence of hypertension (systolic blood pressure ≥130 mm Hg; diastolic blood pressure ≥80 mm Hg; or self-reported antihypertension medication use) and uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) using unadjusted and comorbidity-adjusted models. RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:Sex differences in the prevalence of hypertension and uncontrolled hypertension vary by age, with the latter having implications for health throughout the life course.

RATIONALE & OBJECTIVE/UNASSIGNED:The prevalence of chronic kidney disease (CKD) is known to increase with age; however, creatinine may be a less reliable filtration marker in older adults. Few studies have investigated the prevalence and progression of CKD using different filtration markers for estimating glomerular filtration rate (GFR). STUDY DESIGN/UNASSIGNED:A prospective observational cohort study. SETTING & PARTICIPANTS/UNASSIGNED:6,393 White and African American participants aged 65-100 years from the Atherosclerosis Risk in Communities Study (ARIC) at Visit 5, followed longitudinally at Visits 6 and 7. EXPOSURE AND OUTCOME/UNASSIGNED:The eGFR was estimated either by creatinine (eGFRcr), cystatin C (eGFRcys), creatinine and cystatin C (eGFRcr-cys), or using creatinine, cystatin C, and β-2-microglobulin (eGFRcr-cys-b2m). CKD progression was defined as 30% decline in eGFR at follow-up visits. ANALYTICAL APPROACH/UNASSIGNED:Logistic regression models, adjusted for sex, race and study center, diabetes, blood pressure, body mass index, prevalent cardiovascular disease, and heart failure. RESULTS/UNASSIGNED:when using eGFRcys (33%) compared with eGFRcr-cys (12%) or eGFRcr-cys-b2m (18%). The proportion with 30% eGFR decline was lowest with eGFRcr and highest with eGFRcys, with greater incidence in older age groups for all markers. LIMITATIONS/UNASSIGNED:No direct measurement of GFR. Not all participants survived or attended subsequent follow-up visits. CONCLUSIONS/UNASSIGNED:The prevalence and progression of CKD increase with age, but estimates vary with the filtration marker used. The eGFRcr gave the lowest estimate of CKD at 15% for people aged 65-69 years at Visit 5 while eGFRcys gave the highest estimates of CKD at 26% for that same population.

BACKGROUND AND AIMS:The potential impact of peripheral artery disease (PAD) on kidney outcomes is not well understood. The aim of this study was to explore the association between PAD and end-stage kidney disease (ESKD) and chronic kidney disease (CKD). METHODS:with a ≥25 % decline from the baseline) using multivariable Cox proportional hazards models. RESULTS:Over ∼30 years of follow-up, there were 598 cases of incident ESKD and 4686 cases of incident CKD. After adjusting for potential confounders, both symptomatic PAD and asymptomatic PAD conferred a significantly elevated risk of ESKD (hazard ratio 2.28 [95 % confidence interval 1.23-4.22] and 1.75 [1.19-2.57], respectively). Corresponding estimates for CKD were 1.54 (1.14-2.09) and 1.63 (1.38-1.93). Borderline low ABI 0.91-1.00 also showed elevated risk of adverse kidney outcomes after adjustment for demographic variables. Largely consistent results were observed across demographic and clinical subgroups. CONCLUSIONS:Symptomatic PAD and asymptomatic PAD were independently associated with an elevated risk of ESKD and CKD. These results highlight the importance of monitoring kidney function in persons with PAD, even when symptoms are absent.