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Cardiovascular biomarkers and subclinical brain disease in the atherosclerosis risk in communities study.

ABSTRACT: Cerebrovascular and cardiovascular disease share common risk factors. Our goal was to determine whether levels of N-terminal brain natriuretic peptide (NT-proBNP) and cardiac troponin T measured with a highly sensitive assay (hs-cTnT) are associated with silent brain infarcts (BIs) and white matter lesions (WMLs) on MRI in the Atherosclerosis Risk in Communities (ARIC) study.At ARIC visit 3 (1993-1995), 1920 participants had brain MRI. NT-proBNP and hs-cTnT were measured in all individuals at ARIC visit 4 (1996-1998). Of 1920 individuals, 1112 had a follow-up MRI [2004-2006]). We analyzed the association of NT-proBNP and hs-cTnT with MRI-defined BI and WML on the initial MRI and incident BI and WML progression on the follow-up MRI in participants without heart failure, coronary heart disease, or stroke.In the adjusted model, individuals in the highest NT-proBNP quartile had significantly more BI (odds ratio, 3.50; 95% confidence interval, 2.03-6.20), and WML (?-coefficient, 0.09; SE, 0.03) on the baseline MRI and more incident BI (odds ratio, 2.18; 95% confidence interval, 1.38-3.47) and WML progression (?-coefficient, 0.22; SE, 0.10) on the follow-up MRI. Individuals in the highest hs-cTnT category had more BI (odds ratio, 3.03; 95% confidence interval, 1.57-5.82) and WML (?-coefficient, 0.11; SE, 0.04) on the initial MRI and more WML progression (?-coefficient, 0.43; SE, 0.17) on the follow-up MRI.NT-proBNP and hs-cTnT are independently associated with silent MRI-defined BI and WML, suggesting that cardiovascular biomarkers may be useful to identify individuals with subclinical cerebral injury.

SUBMITTER: Dadu RT

PROVIDER: S-EPMC4334904 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Cardiovascular biomarkers and subclinical brain disease in the atherosclerosis risk in communities study.

Dadu Razvan T RT Fornage Myriam M Virani Salim S SS Nambi Vijay V Hoogeveen Ron C RC Boerwinkle Eric E Alonso Alvaro A Gottesman Rebecca F RF Mosley Thomas H TH Ballantyne Christie M CM

Stroke 20130509 7

<h4>Background and purpose</h4>Cerebrovascular and cardiovascular disease share common risk factors. Our goal was to determine whether levels of N-terminal brain natriuretic peptide (NT-proBNP) and cardiac troponin T measured with a highly sensitive assay (hs-cTnT) are associated with silent brain infarcts (BIs) and white matter lesions (WMLs) on MRI in the Atherosclerosis Risk in Communities (ARIC) study.<h4>Methods</h4>At ARIC visit 3 (1993-1995), 1920 participants had brain MRI. NT-proBNP and ...[more]

PMID: 23660848

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Project description:BACKGROUND/OBJECTIVES:Falls are frequent and often devastating events among older adults. Cardiovascular disease (CVD) is associated with greater fall risk; however, it is unknown if pathways that contribute to CVD, such as subclinical myocardial damage or wall strain, are related to future falls. We hypothesized that elevations in high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), measured in older adults, would be associated with greater fall risk. DESIGN:Prospective cohort study. SETTING AND PARTICIPANTS:Atherosclerosis Risk in Communities Study participants without known coronary heart disease, heart failure, or stroke. MEASUREMENTS:We measured hs-cTnT or NT-proBNP in 2011 to 2013. Falls were identified from hospital discharge International Classification of Diseases, Ninth Revision (ICD-9), codes or Centers for Medicare and Medicaid Services claims. We used Poisson models adjusted for age, sex, and race/study center to quantify fall rates across approximate quartiles of hs-cTnT (less than 8, 8-10, 11-16, and 17?or greater ng/L) and NT-proBNP (less than 75, 75-124, 125-274, and 275?or greater pg/mL). We used Cox models to determine the association of cardiac markers with fall risk, adjusted for age, sex, race/center, and multiple fall risk factors. RESULTS:Among 3973 participants (mean age = 76?±?5 years, 62% women, 22% black), 457 had a subsequent fall during a median follow-up of 4.5 years. Incidence rates across quartiles of hs-cTnT and NT-proBNP were 17.1, 20.0, 26.2, and 36.4 per 1000 person-years and 12.8, 22.2, 28.7, and 48.4 per 1000 person-years, respectively. Comparing highest vs lowest quartiles of either hs-cTnT or NT-proBNP demonstrated a greater than two-fold higher fall risk, with hazard ratios of 2.17 (95% confidence interval {CI} = 1.60-2.95) and 2.34 (95% CI = 1.73-3.16), respectively. In a joint model, the relationships of hs-cTnT and NT-proBNP with falls were significant and independent. CONCLUSION:Subclinical elevations of cardiac damage and wall strain were each associated with a higher fall risk in older adults. Further research is needed to determine whether interventions that lower hs-cTnT or NT-proBNP also lower fall risk. J Am Geriatr Soc 67:1795-1802, 2019.

Project description:IMPORTANCE:Vitamin D deficiency has been associated with hypertension, diabetes mellitus, and incident stroke. Little is known about the association between vitamin D and subclinical cerebrovascular disease. OBJECTIVE:To examine the relationship of 25-hydroxyvitamin D (25[OH]D) levels with cerebrovascular abnormalities as assessed on brain magnetic resonance imaging (MRI) among participants of the Atherosclerosis Risk in Communities (ARIC) Brain MRI study. DESIGN, SETTING, AND PARTICIPANTS:Participants were white and black adults aged 55 to 72 years with no history of clinical stroke who underwent a cerebral MRI at ARIC visit 3 (n?=?1622) and a second cerebral MRI approximately 10 years later (n?=?888). EXPOSURES:The 25(OH)D level was measured by mass spectrometry at visit 3, with levels adjusted for calendar month and categorized using race-specific quartiles. MAIN OUTCOMES AND MEASURES:The cross-sectional and prospective associations of 25(OH)D levels with white matter hyperintensities (WMHs) and MRI-defined infarcts were investigated using multivariable regression models. RESULTS:The mean age of the participants was 62 years, 59.6% were women, and 48.6% were black. Lower 25(OH)D levels were not significantly associated with WMH score of severity, prevalent high-grade WMH score (?3), or prevalent infarcts in cross-sectional, multivariable-adjusted models (all P?>?.05). Similarly, no significant prospective associations were found for lower 25(OH)D levels with change in WMH volume, incident high WMH score (?3), or incident infarcts on the follow-up MRI, which occurred approximately 10 years later. CONCLUSIONS AND RELEVANCE:A single measure of 25(OH)D was not cross-sectionally associated with WMH grade or prevalent subclinical infarcts and was not prospectively associated with WMH progression or subclinical brain infarcts seen on serial cerebral MRIs obtained approximately 10 years apart. These findings do not support optimizing vitamin D levels for brain health.

Project description:ObjectiveTo examine the associations of prediabetes, diabetes, and diabetes severity (as assessed by HbA1c and diabetes duration) with brain volumes and vascular pathology on brain MRI and to assess whether the associations of diabetes with brain volumes are mediated by brain vascular pathology.Research design and methodsCross-sectional study of 1,713 participants in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) (mean age 75 years, 60% female, 27% black, 30% prediabetes, and 35% diabetes) who underwent 3T brain MRI scans in 2011-2013. Participants were categorized by diabetes-HbA1c status as without diabetes (<5.7% [reference]), with prediabetes (5.7 to <6.5%), and with diabetes ([defined as prior diagnosis or HbA1c ?6.5%] <7.0% vs. ?7.0%), with further stratification by diabetes duration (<10 vs. ?10 years).ResultsIn adjusted analyses, compared with participants without diabetes and HbA1c <5.7%, participants with prediabetes and those with diabetes and HbA1c <7.0% did not have significantly different brain volumes or vascular pathology (all P > 0.05), but those with diabetes and HbA1c ?7.0% had smaller total brain volume (? -0.20 SDs, 95% CI -0.31, -0.09), smaller regional brain volumes (including frontal, temporal, occipital, and parietal lobes; deep gray matter; Alzheimer disease signature region; and hippocampus [all P < 0.05]), and increased burden of white matter hyperintensities (WMH) (P = 0.016). Among participants with diabetes, those with HbA1c ?7.0% had smaller total and regional brain volumes and an increased burden of WMH (all P < 0.05) compared with those with HbA1c <7.0%. Similarly, participants with longer duration of diabetes (?10 years) had smaller brain volumes and higher burden of lacunes (all P < 0.05) than those with a diabetes duration <10 years. We found no evidence for mediation by WMH in associations of diabetes with smaller brain volumes by structural equation models (all P > 0.05).ConclusionsMore-severe diabetes (defined by higher HbA1c and longer disease duration) but not prediabetes or less-severe diabetes was associated with smaller brain volumes and an increased burden of brain vascular pathology. No evidence was found that associations of diabetes with smaller brain volumes are mediated by brain vascular pathology, suggesting that other mechanisms may be responsible for these associations.

Project description:BackgroundWhether high burden of subclinical vascular disease (SVD) is associated with increased premature mortality among middle-aged adults is not adequately understood. The association of midlife SVD burden with premature mortality among middle-aged adults free of clinical cardiovascular disease (CVD) could provide further insights into stratifying premature death beyond clinical CVD.ObjectiveTo determine whether high burden of subclinical vascular disease is associated with increased premature mortality among middle-aged adults.DesignWe leveraged data from the Atherosclerosis Risk in Communities Study.ParticipantsThirteen thousand eight hundred seventy-six community-dwelling blacks and whites aged 45-64 years from the Atherosclerosis Risk in Communities Study.Main measuresEach SVD measure-ankle-brachial index, carotid intima-media thickness, and electrocardiogram-was scored 0 (no abnormalities), 1 (minor abnormalities), or 2 (major abnormalities). An index was constructed as the sum of three measures, ranging from 0 (lowest burden) to 6 (highest burden). We used the Cox proportional-hazards model to determine the association of SVD burden with premature mortality (death before age 70) among persons free of clinical CVD. We then tested the difference in point estimates between SVD and clinical CVD.Key resultsAmong persons without CVD, the premature death was 1.7, 2.1, 2.5, and 3.8 per 1000 person-years among those with an SVD score of 0 (lowest burden), 1, 2, and 3-6 (highest burden), respectively. After multivariable-adjustment, highest SVD burden (score = 3-6; HR = 1.47) was significantly associated with premature death among persons initially without CVD. In the model where persons with and without CVD were included, high SVD burden (score: 3-6 vs. 0) and CVD did not have hugely different association with premature death (HR = 1.49 vs. 1.68; P = 0.32 for comparison).ConclusionsMidlife SVD burden was associated with premature mortality and it could stratify premature death beyond clinical CVD. It is important to take SVD into account when designing interventions for reducing premature mortality.

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Cardiovascular biomarkers and subclinical brain disease in the atherosclerosis risk in communities study.

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Cardiovascular biomarkers and subclinical brain disease in the atherosclerosis risk in communities study.

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