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

ABSTRACT: 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.

SUBMITTER: Matsushita K

PROVIDER: S-EPMC6031056 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveCardiovascular disease (CVD) is the major cause of morbidity and mortality in diabetes; yet, heterogeneity in CVD risk has been suggested in diabetes, providing a compelling rationale for improving diabetes risk stratification. We hypothesized that N-terminal prohormone brain natriuretic peptide (NTproBNP) and high-sensitivity troponin T may enhance CVD risk stratification beyond commonly used markers of risk and that CVD risk is heterogeneous in diabetes.Research design and methodsAmong 8,402 participants without prevalent CVD at visit 4 (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) study there were 1,510 subjects with diabetes (mean age 63 years, 52% women, 31% African American, and 60% hypertensive).ResultsOver a median follow-up of 13.1 years, there were 540 incident fatal/nonfatal CVD events (coronary heart disease, heart failure, and stroke). Both troponin T ≥14 ng/L (hazard ratio [HR] 1.96 [95% CI 1.57-2.46]) and NTproBNP >125 pg/mL (1.61 [1.29-1.99]) were independent predictors of incident CVD events at multivariable Cox proportional hazard models. Addition of circulating cardiac biomarkers to traditional risk factors, abnormal electrocardiogram (ECG), and conventional markers of diabetes complications including retinopathy, nephropathy, and peripheral arterial disease significantly improved CVD risk prediction (net reclassification index 0.16 [95% CI 0.07-0.22]). Compared with individuals without diabetes, subjects with diabetes had 1.6-fold higher adjusted risk of incident CVD. However, participants with diabetes with normal cardiac biomarkers and no conventional complications/abnormal ECG (n = 725 [48%]) were at low risk (HR 1.12 [95% CI 0.95-1.31]), while those with abnormal cardiac biomarkers, alone (n = 186 [12%]) or in combination with conventional complications/abnormal ECG (n = 243 [16%]), were at greater risk (1.99 [1.59-2.50] and 2.80 [2.34-3.35], respectively).ConclusionsAbnormal levels of NTproBNP and troponin T may help to distinguish individuals with high diabetes risk from those with low diabetes risk, providing incremental risk prediction beyond commonly used markers of risk.

Project description:Epidemiologic data for cardiac abnormality predating decreased kidney function are sparse. We investigated the associations of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) with end-stage renal disease (ESRD) risk in a community-based cohort.A prospective cohort study.10,749 white and black participants at the fourth visit (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) Study with follow-up through 2010.hs-cTnT (3, 6, 9, and 14ng/L) and NT-proBNP (41.6, 81.0, 142.5, and 272.5pg/mL) levels were divided into 5 categories at the same percentiles (32th, 57th, 77th, and 91th; corresponding to ordinary thresholds of hs-cTnT), with the lowest category as a reference.Incident ESRD defined as initiation of dialysis therapy, transplantation, or death due to kidney disease.Relative risk and risk prediction of ESRD according to hs-cTnT and NT-proBNP levels based on Cox proportional hazards models.During a median follow-up of 13.1 years, 235 participants developed ESRD (1.8 cases/1,000 person-years). hs-cTnT and NT-proBNP levels were associated with ESRD risk independently of each other and of potential confounders, including kidney function and albuminuria (adjusted HRs for highest category, 4.43 [95% CI, 2.43-8.09] and 2.28 [95% CI, 1.44-3.60], respectively). For hs-cTnT level, the association was significant even at the third category (HR for 6-8ng/L of hs-cTnT, 2.74 [95% CI, 1.54-4.88]). Their associations were largely consistent even among persons without decreased kidney function or history of cardiovascular disease. hs-cTnT and NT-proBNP levels both significantly improved ESRD prediction (C statistic differences of 0.0084 [95% CI, 0.0005-0.0164] and 0.0045 [95% CI, 0.0004-0.0087], respectively, from 0.884 with conventional risk factors).Relatively small number of ESRD cases and single measurement of hs-cTnT and NT-proBNP.hs-cTnT and NT-proBNP levels independently predicted ESRD risk in the general population, with more evident results for hs-cTnT. These results suggest the involvement of cardiac abnormality, particularly cardiac injury, in the progression of reduced kidney function and/or may reflect the useful property of hs-cTnT as an end-organ damage marker.

Project description:BackgroundIt remains unclear whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, is prospectively associated with incident peripheral arterial disease (PAD).MethodsWe included 12,320 Atherosclerosis Risk in Communities Study participants (aged 54.3 ± 5.7 years) free of a history of PAD at baseline (visit 1: 1987-1989). The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and measured at 5 visits between 1987 and 2013. Incident PAD was defined as the first hospitalization with PAD diagnosis or a new onset of measured ABI < 0.90 during follow-up visits. We quantified the association of both baseline and trajectories of TyG index with incident PAD using Cox regression and logistic regression analysis, respectively.ResultsOver a median follow-up of 23 years, 1300 participants developed PAD. After adjustment for traditional PAD risk factors, each 1-SD (0.58) increase in TyG index was associated with an 11.9% higher risk of incident PAD [hazard ratio, 1.119 (95% CI, 1.049-1.195)]. Results were similar when individuals were categorized by TyG index quartiles [hazard ratio, 1.239 (95% CI, 1.028-1.492); comparing extreme quartiles]. Four distinct trajectories of stable TyG indexes at various levels along the follow-up duration were identified [low (22.2%), moderate (43.2%), high (27.5%), and very high (7.1%) trajectory groups]. Compared with those with a TyG index trajectory at a low level, those participants with TyG index trajectories at high and very high levels had an even greater risk of future incident PAD [odds ratio (95%CI): 1.404 (1.132-1.740) and 1.742 (1.294-2.344), respectively] after multivariate adjustments for traditional PAD risk factors.ConclusionsHigher TyG index is independently associated with an increased risk of incident PAD. Long-term trajectories of TyG index help identify individuals at a higher risk of PAD who deserve specific preventive and therapeutic approaches.Trial registrationClinical trial registration number: The ARIC trial was registered at clinicaltrials.gov as NCT00005131.

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

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