Faculty Bibliography

AIMS/OBJECTIVE:Carotid-femoral pulse wave velocity (cfPWV) is a representative measure of central arterial stiffness and an independent predictor of cardiovascular disease (CVD). Femoral-ankle PWV (faPWV) represents peripheral arterial stiffness, but its association with CVD has not been specifically investigated. METHODS:We analyzed 3,402 ARIC participants without prior coronary heart disease (CHD), heart failure (HF), or stroke at Visit 5 (2011-13) (mean age 74.8 [4.9] years, 36.1% male, 22.0% Black). faPWV and cfPWV were measured by Omron VP-1000 Plus. The primary outcome was CVD (CHD, HF, and stroke). We used multivariable Cox proportional hazards models. RESULTS:During a median 9.0-year follow-up, 607 CVD events occurred. Overall, faPWV showed an inverse association with CVD, with hazard ratio (HR) for top vs. bottom quartile 0.80 (95%CI 0.64-1.01) and p-for-trend 0.017 in Model 1 (demographically adjusted) and HR 0.86 (0.68-1.09) and p-for-trend 0.096 in Model 2 (further adjusted for CVD risk factors). In contrast, cfPWV was positively associated with CVD in both Models (HR for top vs. bottom quartile 1.22 [0.95-1.56], p-for-trend=0.043 in Model 2). The ratio of cfPWV to faPWV ("cf-fa ratio") showed a stronger association with CVD (HR 1.37 [1.07-1.74], p-for-trend=0.005) than cfPWV. Examining CVD subtypes, the significant contrast in Model 2 was cf-fa ratio and HF. CONCLUSIONS:faPWV showed a borderline significant inverse association with CVD, and cf-fa ratio appeared more strongly associated with CVD than cfPWV. Our findings indicate distinct prognostic implications of central vs. peripheral arterial stiffness and support cf-fa ratio as an alternative measure for CVD risk assessment.

BACKGROUND:Few studies have comprehensively examined health outcomes among older caregivers. We aimed to describe older caregivers and characterize risks for mortality and hospitalization compared to non-caregivers. METHODS:Caregiving status and characteristics were determined for Atherosclerosis Risk in Communities (ARIC) Study participants via a one-time telephone assessment in 2015. All-cause mortality was identified from active surveillance, state records, and linkage to the National Death Index through December 31, 2021. Hospitalizations were identified from active cohort surveillance. Cox proportional hazard models assessed risks of mortality and hospitalization. RESULTS:Among 5,239 ARIC participants [mean age: 75.4 (SD 5.1) years; female: 60.0%; Black: 18.9%], 427 (8.2%) reported caregiving. Caregivers were generally female and younger as compared to non-caregivers. Most caregivers provided care for their spouse (55.0%) and 28.3% reported spending >40 hours/week on caregiving activities. Caregivers had modestly better cognitive scores but were similar to non-caregivers in the number of comorbidities and self-rated health. During a mean 5.4 (SD 1.3) years of follow-up, caregivers had a lower risk of mortality than non-caregivers (18.7% vs. 23.8%), although not statistically significant in fully adjusted time-to-event models (hazard ratio [HR]=0.84; 95%CI:0.67-1.06). Caregivers and non-caregivers had similar risk of hospitalization (63.5% vs. 64.9%; HR = 1.00; 95%CI:0.89-1.14). CONCLUSIONS:Older caregivers provide substantial care while facing their own health challenges. Despite similar baseline comorbidity burdens as non-caregivers, caregivers had a lower risk of all-cause mortality over the 6 years of follow-up. Future studies should examine the potential protective factors of caregiving in older age to inform caregiver support initiatives for older adults providing care.

IMPORTANCE/UNASSIGNED:Characterizing population-level changes in type 1 diabetes (T1D) management can inform public health policies and interventions. OBJECTIVE/UNASSIGNED:To characterize trends and disparities in glycemic control and use of diabetes technology among US youths and adults with T1D. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This serial, cross-sectional analysis used the Optum Labs Data Warehouse, a national, deidentified database of electronic health records, to identify US youths (aged <18 years) and adults (aged ≥18 years) with T1D. Data were obtained from records from January 1, 2009, to December 31, 2023. EXPOSURES/UNASSIGNED:Calendar years divided into 3-year study periods from 2009 to 2011 to 2021 to 2023. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Glycemic control (mean hemoglobin A1c level, <7%) and use of diabetes technology (continuous glucose monitoring systems and/or insulin pumps) were defined using laboratory data and prescriptions, procedures, and diagnoses codes from electronic health records. RESULTS/UNASSIGNED:A total of 186 590 participants with T1D was identified (mean [SD] age, 40 [19] years; 96 766 [52%] male; 12 493 [7%] Hispanic, 2819 [2%] non-Hispanic Asian, 21 459 [12%] non-Hispanic Black, and 141 847 [76%] non-Hispanic White). Of these, 26 853 participants were youths (mean [SD] age, 12 [4] years; 14 060 [52%] male; 19 822 [74%] non-Hispanic White) and 159 737 were adults (mean [SD] age, 45 [16] years; 82 706 [52%] male; 122 025 [76%] non-Hispanic White). From the 2009-2011 to 2021-2023 study periods, the prevalence of glycemic control (mean hemoglobin A1c level <7%) increased from 7% (95% CI, 7%-8%) to 19% (95% CI, 19%-20%) in youths (P < .001 for trend) and 21% (95% CI, 21%-22%) to 28% (95% CI, 28%-29%) in adults (P < .001 for trend). During this same period, there was a substantial increase in the percentage of patients using continuous glucose monitoring (4% to 82% for youths; 5% to 57% for adults), insulin pumps (16% to 50% for youths; 11% to 29% for adults), and both devices concurrently (1% to 47% for youths; 1% to 22% for adults) (P < .001 for trend for all). The prevalence of glycemic control and use of diabetes technology were lowest in Hispanic, non-Hispanic Black, and Medicaid-insured youths and adults, and differences persisted or increased over time. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cross-sectional study, there was a rapid increase in the use of diabetes technology and notable improvements in glycemic control among youths and adults with T1D during the past 15 years. Nonetheless, the prevalence of glycemic control remained low, and racial, ethnic, and socioeconomic differences grew over time.

BACKGROUND/UNASSIGNED:Infections are a major cause of hospitalization in people with chronic kidney disease (CKD), with incidence similar to cardiovascular disease, yet the risk of infection has not been systematically studied across stages of CKD. METHODS/UNASSIGNED:We conducted a meta-analysis of individual participant data including 1,246,912 individuals across 47 cohorts in the CKD Prognosis Consortium, with information on estimated glomerular filtration rate based on serum creatinine (eGFRcr) and urinary albuminuria (ACR) (or proteinuria converted to ACR), to examine the association of eGFR and ACR with the risk of hospitalization with infection. Outcomes were ascertained through diagnostic codes on hospital discharge records relevant to acute infections (i.e., upper and lower respiratory tract, urinary tract, skin and soft tissue, musculoskeletal, gastrointestinal tract, genital, nervous system, and cardiovascular system infections, and sepsis). Follow-up was censored on December 31, 2019 or on the last date of cohort follow-up, whichever was earlier. Multivariable Cox models were used to estimate hazard ratios (HRs). FINDINGS/UNASSIGNED:in eGFR and 1.48 [1.44-1.53] per 8-fold increase in ACR). INTERPRETATION/UNASSIGNED:Lower kidney function and higher albuminuria were independently associated with higher risk of infection. The risk was elevated even in mild to moderate CKD, with the highest risk seen in the most advanced stage of CKD. Infection prevention measures should target individuals across all CKD stages. FUNDING/UNASSIGNED:US National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases.

RATIONALE & OBJECTIVE/OBJECTIVE:Arterial stiffness is associated with prevalent chronic kidney disease (CKD). Whether arterial stiffness is prospectively associated with incident CKD is inconclusive. STUDY DESIGN/METHODS:Longitudinal cohort study. SETTING & PARTICIPANTS/METHODS:Using data from the Atherosclerosis Risk in Communities (ARIC) Study, the primary analysis included 3,161 participants without prevalent CKD at visit 5; a secondary analysis studied 4,341 participants with any estimated glomerular filtration rate (eGFR) record across visits 5 to 7. EXPOSURE/METHODS:Carotid-femoral pulse wave velocity (cfPWV), heart-femoral PWV (hfPWV), heart-ankle PWV (haPWV), brachial-ankle PWV (baPWV), heart-carotid PWV (hcPWV), and femoral-ankle PWV (faPWV). OUTCOMES/RESULTS:accompanied by >25% decline eGFR or CKD hospitalization. Secondary analysis - eGFR slope. ANALYTICAL APPROACH/METHODS:Primary analysis - Cox regression models to calculate hazard ratio (HR). Secondary analysis - multilevel mixed effects models to estimate the eGFR slope across visits. RESULTS:/year [95% CI, -0.56 to -0.33] in Q4 versus -0.37 [95% CI, -0.48 to -0.26] in Q1). All p-value <0.05. faPWV was not associated with incident CKD or eGFR slope. LIMITATIONS/CONCLUSIONS:Residual confounding. CONCLUSIONS:Greater arterial stiffness, especially higher cfPWV, hfPWV, and haPWV, was prospectively associated with a higher risk of incident CKD and faster decline in eGFR among community-dwelling older adults, supporting a pathophysiological contribution of arterial stiffness to the development of CKD.

BACKGROUND:Our understanding of traditional atherosclerotic risk factors is based predominantly on one-time measurements and associations with adverse cardiovascular outcomes. OBJECTIVES/OBJECTIVE:The aim of this study was to evaluate the contribution of mid- to late-life cumulative risk factor exposure to healthy arterial aging, represented by a persistent coronary artery calcium (CAC) score of zero. METHODS:Among 2,044 community-dwelling, participants free of coronary heart disease from the ARIC (Atherosclerosis Risk in Communities) study, the associations of ∼30-year time-weighted average mid- to late-life (starting at a median age of 49 years in 1987-1989) traditional atherosclerotic risk factors (cholesterol, systolic blood pressure, fasting glucose, and smoking) with late-life (median age 80 years in 2018-2019) CAC 0 were evaluated. RESULTS:A total of 204 participants (10.0%) had CAC 0, and they tended to have more favorable mid- to late-life average risk factor profiles than those with CAC: lower total cholesterol, especially <160 mg/dL; lower systolic blood pressure, especially <125 mm Hg; and higher high-density lipoprotein cholesterol, especially >45 mg/dL. The association was less evident for fasting glucose, with no increased probability of CAC 0 at <95 mg/dL. Never smoking was associated with a 5.7 (95% CI: 2.3-16.7) times greater odds of CAC 0 vs smoking throughout mid- to late-life. Within sex-race groups, average modifiable risk factors predicted substantial differences in CAC 0 probability (eg, for a Black woman, 53% vs 0.4% for a low vs high risk factor profile, respectively). CONCLUSIONS:Favorable average risk factor profiles at mid- to late-life were associated with a greater probability of CAC 0 at older age. These results highlight the importance of maintaining a healthy risk factor profile from mid- to late-life, with implications for public health promotion and policy.

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.