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Insulin resistance and reduced cardiac autonomic function in older adults: the Atherosclerosis Risk in Communities study.

ABSTRACT: BACKGROUND:Prior studies have shown insulin resistance is associated with reduced cardiac autonomic function measured at rest, but few studies have determined whether insulin resistance is associated with reduced cardiac autonomic function measured during daily activities. METHODS:We examined older adults without diabetes with 48-h ambulatory electrocardiography (n?=?759) in an ancillary study of the Atherosclerosis Risk in Communities Study. Insulin resistance, the exposure, was defined by quartiles for three indexes: 1) the homeostatic model assessment of insulin resistance (HOMA-IR), 2) the triglyceride and glucose index (TyG), and 3) the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Low heart rate variability, the outcome, was defined by <25th percentile for four measures: 1) standard deviation of normal-to-normal R-R intervals (SDNN), a measure of total variability; 2) root mean square of successive differences in normal-to-normal R-R intervals (RMSSD), a measure of vagal activity; 3) low frequency spectral component (LF), a measure of sympathetic and vagal activity; and 4) high frequency spectral component (HF), a measure of vagal activity. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals weighted for sampling/non-response, adjusted for age at ancillary visit, sex, and race/study-site. Insulin resistance quartiles 4, 3, and 2 were compared to quartile 1; high indexes refer to quartile 4 versus quartile 1. RESULTS:The average age was 78?years, 66% (n?=?497) were women, and 58% (n?=?438) were African American. Estimates of association were not robust at all levels of HOMA-IR, TyG, and TG/HDL-C, but suggest that high indexes were associated consistently with indicators of vagal activity. High HOMA-IR, high TyG, and high TG/HDL-C were consistently associated with low RMSSD (OR: 1.68 (1.00, 2.81), OR: 2.03 (1.21, 3.39), and OR: 1.73 (1.01, 2.91), respectively). High HOMA-IR, high TyG, and high TG/HDL-C were consistently associated with low HF (OR: 1.90 (1.14, 3.18), OR: 1.98 (1.21, 3.25), and OR: 1.76 (1.07, 2.90), respectively). CONCLUSIONS:In older adults without diabetes, insulin resistance was associated with reduced cardiac autonomic function - specifically and consistently for indicators of vagal activity - measured during daily activities. Primary prevention of insulin resistance may reduce the related risk of cardiac autonomic dysfunction.

SUBMITTER: Poon AK

PROVIDER: S-EPMC7216367 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Insulin resistance and reduced cardiac autonomic function in older adults: the Atherosclerosis Risk in Communities study.

Poon Anna K AK Whitsel Eric A EA Heiss Gerardo G Soliman Elsayed Z EZ Wagenknecht Lynne E LE Suzuki Takeki T Loehr Laura L

BMC cardiovascular disorders 20200511 1

<h4>Background</h4>Prior studies have shown insulin resistance is associated with reduced cardiac autonomic function measured at rest, but few studies have determined whether insulin resistance is associated with reduced cardiac autonomic function measured during daily activities.<h4>Methods</h4>We examined older adults without diabetes with 48-h ambulatory electrocardiography (n = 759) in an ancillary study of the Atherosclerosis Risk in Communities Study. Insulin resistance, the exposure, was ...[more]

PMID: 32393179

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Project description:BackgroundAlthough age-associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident heart failure (HF), as well as their associations with circulating biomarkers of HF risk.MethodsAmong 5801 elderly participants in the ARIC study (Atherosclerosis Risk in Communities; age range, 67-90 years; mean age, 76±5 years; 42% male; 21% black), we determined the continuous association of diastolic measures (tissue Doppler imaging [TDI] e', E/e', and left atrial size) with concomitant N-terminal pro-brain natriuretic peptide and subsequent HF hospitalization or death. We also determined sex-specific 10th and 90th percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors.ResultsEach measure of diastolic function was robustly associated with N-terminal pro-brain natriuretic peptide and incident HF or death. ARIC-based reference limits for TDI e' (4.6 and 5.2 cm/s for septal and lateral TDI e', respectively) were substantially lower than guideline cut points (7 and 10 cm/s, respectively), whereas E/e' and left atrial size demonstrated good agreement with guideline cut points. TDI e' was nonlinearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cut points based on the integrated discrimination improvement (P<0.001) and continuous net reclassification improvement (P<0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. With these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/y over a mean 1.7-year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/y), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/y).ConclusionsOur findings suggest that left ventricular longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death.

Project description:Rationale & objectiveRecent literature suggests improvement in kidney function after percutaneous valvular replacement therapies, implying a pathophysiological contribution of valvular heart disease to chronic kidney disease (CKD). However, this association has not been investigated epidemiologically. We aimed to assess the association of valvular abnormality with prevalent and incident CKD.Study designCross-sectional and prospective analyses.Setting & participantsCommunity-dwelling participants (mean age 75.5 [standard deviation 5.1] years) from the Atherosclerosis Risk in Communities study (2011-2013).ExposureValvular abnormality defined as echocardiography-based aortic stenosis, aortic regurgitation, and mitral regurgitation.OutcomesPrevalent CKD was defined as estimated glomerular filtration rate (eGFR]) <60 mL/min/1.73 m2. Incident CKD was defined as progression to eGFR <60 mL/min/1.73 m2 with ≥25% decline or hospitalization/deaths with CKD diagnosis.Analytical approachWe cross-sectionally evaluated the association between valvular abnormality and prevalent CKD with logistic regression in 5,216 participants. Then, 3,752 participants without prevalent CKD were analyzed for incident CKD using Cox models.ResultsThere were 1.4% (n = 74) with any aortic stenosis, 10.6% (n = 555) with any aortic regurgitation, and 43.1% (n = 2,249) with any mitral regurgitation. After adjustment for potential confounders, any mitral regurgitation and moderate/severe aortic regurgitation showed significant associations with prevalent CKD (adjusted OR, 1.17 [95% CI, 1.03-1.34] and 2.82 [95% CI, 1.12-7.10]), as did any aortic stenosis in a sensitivity analysis with prevalent CKD defined including albuminuria ≥30 mg/g (1.83 [95% CI, 1.10-3.05]). Only any aortic stenosis showed an independent association with incident CKD (adjusted HR, 2.12 [95% CI, 1.13-4.00]).LimitationsDespite a relatively large study population, some subgroups had small numbers. Although we minimized reverse causation, we cannot completely rule it out.ConclusionsDifferent valvular abnormality types were associated with prevalent CKD. Only aortic stenosis was robustly associated with incident CKD. These findings suggest an etiological link between valvular abnormality and CKD, highlighting the importance of clinical attention to kidney function in individuals with aortic stenosis.

Project description:BackgroundThe aim of this study was to assess the association of high-sensitivity cardiac troponin (hs-cTnT) and other cardiac, kidney, hyperglycemia, and inflammatory biomarkers with peripheral neuropathy (PN) in a community-based population.MethodsWe conducted a cross-sectional analysis of 3056 black and white participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent standardized monofilament PN testing and had measures of cardiac function (hs-cTnT, N-terminal pro-B-type natriuretic peptide [NT-proBNP], and growth differentiation factor 15 [GDF15]), kidney function (serum creatinine, cystatin C, β-2 microglobulin, urine albumin-to-creatinine ratio), hyperglycemia (fasting glucose, hemoglobin A1c [Hb A1c], fructosamine, glycated albumin, 1,5-anhydroglucitol), and inflammation (C-reactive protein) assessed at visit 6 (2016-2017; age 71-94 years). We used logistic regression to assess the associations of these biomarkers (modeled in diabetes-specific tertiles) with PN in older adults with and without diabetes after adjusting for traditional risk factors.ResultsIn total, 33.5% of participants had PN (37.3% with diabetes and 31.9% without diabetes). There was an independent association of hs-cTnT with PN regardless of diabetes status (diabetes T3 vs. T1: odds ratio [OR], 2.15 [95% CI, 1.44-3.22]; no diabetes: OR, 2.31 [95%CI, 1.76-3.03]; P = 0.72 for interaction). Among participants without diabetes, there were also significant associations of NT-proBNP (OR, 1.40 [95% CI, 1.08-1.81]) and urine albumin-to-creatinine ratio (OR, 1.55 [95% CI, 1.22-1.97]) with PN. Associations of hyperglycemia biomarkers including Hb A1c (OR, 1.76 [95% CI, 1.22-2.54]), fructosamine (OR, 1.71 [95% CI, 1.19-2.46]), and glycated albumin (OR, 1.45 [95% CI, 1.03-2.03]) with PN were significant only among participants with diabetes.ConclusionsOverall, hs-cTnT appears to be a global marker of end organ damage, including PN. Laboratory biomarkers may be able to help us identify those individuals with PN.

Project description:AimsHigher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established.MethodsN-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance.ResultsLower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P < 0.001 for all four indices). Although the genetic score was strongly related to measured NT-proBNP levels amongst European Americans (F statistic = 71.08), we observed no association of genetically determined NT-proBNP with insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP).ConclusionsIn older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study.

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Insulin resistance and reduced cardiac autonomic function in older adults: the Atherosclerosis Risk in Communities study.

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Insulin resistance and reduced cardiac autonomic function in older adults: the Atherosclerosis Risk in Communities study.

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