Lucia Kwak

Six-Year Changes in Physical Activity and the Risk of Incident Heart Failure: The Atherosclerosis Risk in Communities (ARIC) Study

Background —Higher physical activity (PA) is associated with lower heart failure (HF) risk. However, the impact of changes in PA on HF risk is unknown. Methods —We evaluated 11,351 ARIC participants (mean age 60 years) who attended Visit 3 (1993-95) and did not have a history of cardiovascular disease. Exercise PA was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines as recommended, intermediate, or poor. We used Cox regression models to characterize the association of 6-year changes in PA between the first (1987-1989) and third ARIC visits and HF risk. Results —During a median of 19 years of follow-up, there were 1,750 HF events. Compared to those with poor activity at both visits, the lowest HF risk was seen for those with persistently recommended activity (HR 0.69; 95% CI: 0.60, 0.80). However, those whose PA increased from poor to recommended also had reduced HF risk (HR 0.77; 95% CI: 0.63, 0.93). Among participants with poor baseline activity, each 1-SD higher PA at 6 years (512.5 METS*minutes/week; corresponding to approximately 30 minutes of brisk walking 4 times per week) was associated with significantly lower future HF risk (HR: 0.89, 95% CI: 0.82, 0.96). Conclusions —While maintaining recommended activity levels is associated with the lowest HF risk, initiating and increasing PA, even in late middle age, are also linked to lower HF risk. Augmenting PA may be an important component of strategies to prevent HF.Background: Higher physical activity (PA) is associated with lower heart failure (HF) risk; however, the effect of changes in PA on HF risk is unknown. Methods: We evaluated 11 351 ARIC study (Atherosclerosis Risk in Communities) participants (mean age 60 years) who attended visit 3 (1993–1995) and did not have a history of cardiovascular disease. Exercise PA was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines as recommended, intermediate, or poor. We used Cox regression models to characterize the association of 6-year changes in PA between the first (1987–1989) and third ARIC visits and HF risk. Results: During a median of 19 years of follow-up, 1750 HF events occurred. Compared with those with poor activity at both visits, the lowest HF risk was seen for those with persistently recommended activity (hazard ratio, 0.69; 95% confidence interval, 0.60–0.80). However, those whose PA increased from poor to recommended also had reduced HF risk (hazard ratio, 0.77; 95% confidence interval 0.63–0.93). Among participants with poor baseline activity, each 1 SD higher PA at 6 years (512.5 METS*minutes/week, corresponding to ≈30 minutes of brisk walking 4 times per week) was associated with significantly lower future HF risk (hazard ratio, 0.89, 95% confidence interval, 0.82–0.96). Conclusions: Although maintaining recommended activity levels is associated with the lowest HF risk, initiating and increasing PA, even in late middle age, are also linked to lower HF risk. Augmenting PA may be an important component of strategies to prevent HF.

High-sensitivity cardiac troponin and natriuretic peptide with risk of lower-extremity peripheral artery disease: the Atherosclerosis Risk in Communities (ARIC) Study

Aims Cardiac troponin T (cTnT) is suggested as a predictor of amputation in patients with peripheral artery disease (PAD). However, cTnT-PAD association has not been systematically studied in a large study. This study evaluated the association of high-sensitivity cTnT (hs-cTnT) with PAD incidence and also explored whether natriuretic peptide (NT-proBNP), another representative cardiac marker, predicts PAD risk. Methods and results Among 12 288 middle-aged adults, the associations of hs-cTnT and NT-proBNP with incident PAD (hospitalizations with PAD diagnosis or leg revascularization [cases with rest pain or tissue loss considered as critical limb ischaemia (CLI)]) were quantified with multivariable Cox regression models. The risk discrimination was assessed by c-statistic. During a follow-up over 22 years, 454 participants developed PAD (164 CLI cases). In demographically adjusted models, the highest category of hs-cTnT (≥14 vs. <3 ng/L) and NT-proBNP (≥258.3 vs. <51.5 pg/mL) showed ∼8- and 10-20-fold higher risk of PAD and CLI, respectively. Even after adjusting for potential confounders and each other, hazard ratios were greater for CLI than for PAD (7.74 95% confidence interval [95% CI 4.43-13.55] vs. 2.84 [2.02-4.00] for the highest vs. reference hs-cTnT category and 4.63 [2.61-8.23] vs. 3.16 [2.23-4.49] for the highest vs. reference NT-proBNP category). The addition of these cardiac markers improved c-statistics for CLI. Conclusion High-sensitivity cTnT and NT-proBNP were independently associated with incident PAD, particularly its severe form, CLI. Although future studies are warranted to investigate pathophysiological mechanisms behind these associations, our study suggests the usefulness of cardiac markers to identify individuals at high risk of CLI.

Socioeconomic Status and Incidence of Hospitalization With Lower‐Extremity Peripheral Artery Disease: Atherosclerosis Risk in Communities Study

Background Compared to coronary heart disease, heart failure, and stroke, the relationship between low socioeconomic status (SES) and peripheral artery disease (PAD) is less well established. We examined the association between SES and incidence of hospitalization with PAD and explored whether this association can be explained by traditional cardiovascular risk factors and healthcare access. Methods and Results A total of 12 517 participants in the Atherosclerosis Risk in Communities (ARIC) Study (1987‐1989) with no prior PAD were examined. Individual‐level SES was assessed from household income (low <

Kidney Disease Measures and Left Ventricular Structure and Function: The Atherosclerosis Risk in Communities Study

12 000/year, medium

Traditional and nontraditional glycemic markers and risk of peripheral artery disease: The Atherosclerosis Risk in Communities (ARIC) study

12 000 to

Chronic kidney disease measures and the risk of abdominal aortic aneurysm

24 999/year, and high ≥

Community burden and prognostic impact of reduced kidney function among patients hospitalized with acute decompensated heart failure: The Atherosclerosis Risk in Communities (ARIC) Study Community Surveillance

25 000/year [double to approximate to values in 2016]) and educational attainment (high school), and area‐level SES from area deprivation index (quintiles). During a median follow‐up of 23.6 (Interquartile range 19.6‐24.5) years, 433 participants had a hospitalization with PAD. In Cox proportional hazards regression analysis, the demographically adjusted hazard ratio was 2.42 (1.81‐3.23) for low household income, 2.08 (1.60‐2.69) for low educational attainment, and 2.18 (1.35‐3.53) for most deprived neighborhoods, compared to their high‐SES counterparts. After adjustment for traditional cardiovascular risk factors and heath care access, the associations were attenuated but remained significant, particularly for income and education. Results were consistent when stratified by race (P‐values for interaction >0.2 for all SES parameters). Conclusions Low individual‐ and area‐level SES are strong predictors of hospitalization with PAD, in part due to increased prevalence of cardiovascular risk factors and poor access to care in these groups. Additional risk factors may also need to be identified and acted on to eliminate SES disparities in PAD hospitalization.

Counterclockwise and clockwise rotation of QRS transitional zone: Prospective correlates of change and time-varying associations with cardiovascular outcomes

Background Heart failure is one of the most important complications of chronic kidney disease (CKD). However, few studies comprehensively investigated left ventricular (LV) structure and function in relation to 2 key CKD measures, estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR). Methods and Results Among 4175 ARIC (Atherosclerosis Risk in Communities) participants (aged 66–90 years during 2011–2013), we quantified the association of eGFR and ACR with echocardiogram parameters of LV mass, size, systolic function, and diastolic function. Adjusting for demographic variables, both CKD measures were significantly associated with most echocardiogram parameters. Additionally accounting for other potential confounders, we observed significantly higher LV mass index according to reduced eGFR (82.3 [95% confidence interval (CI), 77.6–87.0] g/m2 for eGFR <30 mL/min per 1.73 m2, 80.9 [95% CI, 77.3–84.6] g/m2 for eGFR 30–44 mL/min per 1.73 m2, and 80.1 [95% CI, 76.7–83.5] g/m2 for eGFR 45–59 mL/min per 1.73 m2 compared with 78.7 [95% CI, 75.3–82.1] g/m2 for eGFR 75–89 mL/min per 1.73 m2; trend P<0.001). Regarding LV size and function, significant differences were observed for some parameters, particularly at eGFR <30 mL/min per 1.73 m2. For ACR, the associations remained significant for most parameters (eg, LV mass index, 91.5 [95% CI, 86.6–96.5] g/m2 for ACR ≥300 mg/g and 82.9 [95% CI, 79.4–86.3] g/m2 for ACR 30–299 mg/g compared with 77.7 [95% CI, 74.4–81.1] g/m2 for ACR <10 mg/g [trend P<0.001]; left arterial volume index, 24.9 [95% CI, 22.9–26.8] and 24.7 [95% CI, 23.4–26.1] mL/m2 compared with 23.4 [95% CI, 22.1–24.7] mL/m2, respectively [trend P=0.010]). Dichotomizing echo parameters with clinical thresholds, the stronger relationships of ACR over eGFR were further evident. Conclusions LV mass was related to both CKD measures, whereas LV size and function were robustly associated with albuminuria. These results have implications for pathophysiological processes behind cardiorenal syndrome and targeted cardiac assessment in patients with CKD.

Physical Activity, Obesity, and Subclinical Myocardial Damage

BACKGROUND AND AIMS Traditional glycemic markers, fasting glucose and hemoglobin A1c (HbA1c), predict incident peripheral artery disease (PAD). However, it is unknown whether nontraditional glycemic markers, fructosamine, glycated albumin, and 1,5-anhydroglucitol, are associated with PAD and whether these glycemic markers demonstrate particularly strong associations with severe PAD, critical limb ischemia (CLI). METHODS We quantified the associations of these five glycemic markers with incident PAD (hospitalizations with PAD diagnosis or leg revascularization) in 11,634 ARIC participants using Cox regression models. Participants were categorized according to diabetes diagnosis and clinical cut-points of glycemic markers (nontraditional glycemic markers were categorized according to percentiles corresponding to the HbA1c cut-points). RESULTS Over a median follow-up of 20.7 years, there were 392 cases of PAD (133 were CLI with tissue loss). HbA1c was more strongly associated with incident PAD than fasting glucose, with adjusted hazard ratios (HR) 6.00 (95% CI, 3.73-9.66) for diagnosed diabetes with HbA1c ≥ 7% and 3.53 (2.39-5.22) for no diagnosed diabetes with HbA1c ≥ 6.5% compared to no diagnosed diabetes with HbA1c <5.7%. Three nontraditional glycemic markers demonstrated risk gradients intermediate between HbA1c and fasting glucose and their risk gradients were substantially attenuated after adjusting for HbA1c. All glycemic markers consistently demonstrated stronger associations with CLI than PAD without CLI (p for difference <0.02 for all glycemic markers). CONCLUSIONS Nontraditional glycemic markers were associated with incident PAD independent of fasting glucose but not necessarily HbA1c. Our results also support the importance of glucose metabolism in the progression to CLI.

Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease

BACKGROUND AND AIMS Despite its strong link to cardiovascular outcomes, the association of chronic kidney disease (CKD) with abdominal aortic aneurysm (AAA) has not been explicitly and comprehensively investigated. METHODS In 10,724 participants in the Atherosclerosis Risk in Communities Study (aged 53-75 years during 1996-1998), we evaluated the associations of two key CKD measures - estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) - with incident AAA (AAA diagnosis in outpatient, hospitalization discharge, or death records). Additionally, we performed a cross-sectional analysis for the CKD measures and ultrasound-based abdominal aortic diameter in 4258 participants during 2011-2013. RESULTS During a median follow-up of 13.9 years, 347 participants developed AAA. The demographically-adjusted hazard ratio (HR) was 4.44 (95% CI 1.58-12.49) for eGFR <30, 3.29 (1.89-5.72) for 30-44, 2.03 (1.29-3.19) for 45-59, and 1.62 (1.11-2.35) for 60-74 compared to eGFR ≥90 mL/min/1.73 m2 and was 2.49 (1.28-4.87) for ACR ≥300, 1.99 (1.40-2.83) for 30-299, and 1.46 (1.08-1.97) for 10-29 compared to ACR <10 mg/g. The associations were generally similar after accounting for additional confounders, such as smoking (although attenuated), or after stratifying by subgroups, including diabetes. The cross-sectional analysis also showed continuous positive associations of these CKD measures with aortic diameter, particularly at the distal aortic segment assessed. CONCLUSIONS Reduced eGFR and elevated albuminuria were independently associated with greater incidence of AAA and greater abdominal aortic diameter. Our results suggest the potential usefulness of CKD measures to identify persons at high risk of AAA and the need to investigate pathophysiological pathways linking CKD to AAA.