Background: Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP) predicts incidence of atrial fibrillation (AF), but the association of longitudinal changes in NT-proBNP concentrations with incident AF has not been explored.
Methods: We studied 9705 individuals without prevalent AF in 1996–1998 and with available NT-proBNP measurements obtained in samples collected during two visits in 1990–1992 (visit 2) and 1996–1998 (visit 4) in the Atherosclerosis Risk in Communities (ARIC) Study. Participants were followed through the end of 2013. AF was ascertained from electrocardiograms, hospital discharge codes, and death certificates. Multivariable Cox regression was used to evaluate the association of absolute change in log-transformed NT-proBNP [ln(NT-proBNP)] with incident AF. We also assessed the impact of adding ln(NT-proBNP) change as a predictor of AF by difference in the C-statistic and net reclassification improvement (NRI).
Results: Over a median follow up of 16 years, there were 1503 incident cases of AF. The means (SD) ln(NT-proBNP) at visit 2 and visit 4 were 3.83 (1.01) and 4.35 (0.94), respectively. There was a 0.52 (0.79) increase in ln(NT-proBNP) over the 6-year period. Greater increases in ln(NT-proBNP) were associated with higher risk of AF [hazard ratio, 2.82 (95% confidence interval 2.34, 3.39), comparing top to bottom quintiles, and 1.74 (1.61, 1.87) per 1-unit increase in ln(NT-proBNP)]. Adding ln(NT-proBNP) change to a model with multiple predictors including baseline NT-proBNP had relatively limited impact in the C-statistic (increase from 0.748, 95%CI 0.736–0.761, to 0.762, 95%CI 0.750, 0.774). Adding ln(NT-proBNP) change to initial predictive models resulted in a categorical NRI of 0.062 (95% CI 0.033, 0.092) and a continuous NRI of 0.092 (95%CI, 0.017, 0.182).
Conclusion: Positive NT-proBNP change is associated with an increased incidence rate of AF. Adding NT-proBNP change into the prediction model modestly improved incident AF prediction. Future studies should assess the value of monitoring NT-proBNP concentration among individuals at high risk of developing AF.
Background: Left ventricular hypertrophy (LVH) is an indicator of organ damage largely due to hypertension. We assessed whether LVH was associated with dementia and cognitive function in the Atherosclerosis Risk in Communities study.
Methods: Our analysis included 12,665 individuals (23% black race, 56% female, mean age 57) who attended visit 2 in 1990-1992. Cornell voltage (SV3 + RaVL) was derived from 12-lead electrocardiograms and dichotomized as LVH using sex-specific criteria (>28 mm men; >22 mm women). Incident dementia was defined by expert review using a predetermined algorithm, and cognitive function was measured longitudinally using 3 tests. A Cox model was used to evaluate the association between time-dependent LVH and dementia adjusted for time-varying covariates from 1990 to 2013. Linear regression models fit with generalized estimating equations were used to evaluate LVH with cognitive function.
Results: During a mean follow-up of 18 years, we identified 544 participants with LVH and 1,195 dementia cases. LVH was associated with a higher risk of dementia: multivariable hazard ratio = 1.90; 95% CI: 1.47-2.44. Those with LVH had lower cognitive scores at baseline; however, there was no difference in the rate of cognitive decline over 20 years in those with LVH versus those without LVH.
Conclusions: In this population-based study, LVH measured during midlife was associated with an increased risk of incident dementia; however, LVH was not associated with additional cognitive decline. These results underscore the need for hypertension control to prevent subclinical brain injury.
by
Oluwaseun E. Fashanu;
Di Zhao;
Andrea L. C. Schneider;
Andreaa M. Rawlings;
A. Richey Sharrett;
Pamela L. Lutsey;
Rebecca F. Gottesman;
Alden L. Gross;
Eliseo Guallar;
Alvaro Alonso;
Thomas H. Mosley;
Erin D. Michos
Background: Activated Vitamin D has anti-inflammatory properties and adequate 25-hydroxyvitamin D [25(OH)D] concentrations may be important for neurocognitive function and protection against neurologic injury. We examined whether mid-life 25(OH) D concentrations were associated with later-life performance on neuropsychological testing, functional ability, depressive symptoms, and incident dementia.
Methods: We studied 13,039 white and black ARIC participants who had serum 25(OH) D measured mid-life at visit 2 (1990-1992). Over the next ~ 20 years through visit 5 (2011-2013), participants underwent 3 additional in-person visits, annual telephone calls, and hospitalization surveillance. An extensive battery of neuropsychological outcomes were assessed at visit 5 using standardized protocols. Incident dementia was ascertained through a formal algorithm that included data from in-person cognitive testing, telephone interviews, hospital discharge codes, and death certificate codes. Diagnoses of dementia were adjudicated by expert clinician committee. For the primary cognitive analyses, we imputed for missing covariates and outcomes and used linear regression to evaluate non-concurrent cross-sectional associations of mid-life 25(OH) D (visit 2) with late-life neuropsychological outcomes (visit 5). We also used Cox regression models to examine associations of mid-life 25(OH) D and incident dementia.
Results: In mid-life, the mean (SD) age of participants was 57 (6) years, 57% were women, and 24% black. Mean (SD) 25(OH) D was 24.3 (8.6) ng/mL; 33% had deficient (< 20 ng/mL), 44% intermediate (20- < 30 ng/mL), and 23% sufficient (≥30 ng/mL) 25(OH) D concentrations. Association between mid-life 25(OH) D and late-life performance on neuropsychological testing were mostly null. There was no significant association with functional ability or depressive symptoms. Results were similar in a sensitivity analysis using complete-case data (no imputation). However, after a median follow-up of 20 years, low 25(OH) D concentrations were associated with increased risk for incident dementia (p = 0.01 for trend across categories), with HR of 1.26 (95% CI 1.06, 1.49) for participants with deficient 25(OH) D, compared to sufficient concentrations.
Conclusion: In this community cohort, mid-life serum 25(OH) D concentrations were associated with incident dementia but not with performance on neuropsychological testing, functional ability, or depressive symptoms, 20 years later. Whether serum 25(OH) D concentrations are causally related to dementia or confounded by poorer health status remains uncertain.
by
Jessica van Setten;
Niek Verweij;
Hamdi Mbarek;
Maartje N. Niemeijer;
Stella Trompet;
Dan E. Arking;
Jennifer A. Brody;
Ilaria Gandin;
Niels Grarup;
Leanne M. Hall;
Daiane Hemerich;
Leo-Pekka Lyytikainen;
Hao Mei;
Martina Mueller-Nurasyid;
Bram P. Prins;
Antonietta Robino;
Albert V. Smith;
Helen R. Warren;
Folkert W. Asselbergs;
Alvaro Alonso
Genome-wide association studies (GWAS) of quantitative electrocardiographic (ECG) traits in large consortia have identified more than 130 loci associated with QT interval, QRS duration, PR interval, and heart rate (RR interval). In the current study, we meta-analyzed genome-wide association results from 30,000 mostly Dutch samples on four ECG traits: PR interval, QRS duration, QT interval, and RR interval. SNP genotype data was imputed using the Genome of the Netherlands reference panel encompassing 19 million SNPs, including millions of rare SNPs (minor allele frequency < 5%). In addition to many known loci, we identified seven novel locus-trait associations: KCND3, NR3C1, and PLN for PR interval, KCNE1, SGIP1, and NFKB1 for QT interval, and ATP2A2 for QRS duration, of which six were successfully replicated. At these seven loci, we performed conditional analyses and annotated significant SNPs (in exons and regulatory regions), demonstrating involvement of cardiac-related pathways and regulation of nearby genes.
Background: Though it is a widely held belief that caffeinated beverages predispose individuals to arrhythmias, it is not clear whether regular coffee consumption is associated with development of atrial fibrillation (AF).
Objective: We examined the association between long-term coffee consumption and development of AF in both habitual (≥0.5 cups of daily coffee) and nonhabitual (<0.5 cups/day) drinkers.
Methods: A total of 5,972 men and women, aged 45-84 years and without a history of cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA) were followed from 2000 to 2014 for incident AF with baseline coffee consumption assessed in 2000-2002 via a Food Frequency Questionnaire and divided into quartiles of 0 cups/day, >0 to <0.5 cups/day, ≥0.5 to <1 cups/day, and ≥1.5 cups/day.
Results: Out of the 828 incident cases of AF, intermittent coffee consumption (>0 to 0.5 cups of daily coffee) was associated with a greater risk of incident AF (HR=1.22, 95% CI=1.01-1.48) relative to 0 cups/day in multivariable Cox proportional hazards models after adjustment for numerous AF risk factors. This relation was particularly pronounced in men (adjusted HR=1.36, 95% CI 1.04-1.77). Higher coffee consumption was not associated with AF risk (HR 1.03, 95%CI 0.93-1.14 for ≥0.5 to 1.5 cups/day and 1.05, 95%CI 0.97-1.13 for ≥1.5 cups/day).
Conclusions: While there appears to be no dose-response association between habitual coffee intake and AF risk, we found evidence that intermittent, but not habitual, coffee consumption is associated with a modestly increased risk of incident AF that deserves further study.
Objectives: To examine the association between hospitalization, critical illness, and infection occurring during middle- and late-life and structural brain abnormalities in older adults.
Design: Prospective cohort study. Setting: Atherosclerosis Risk in Communities (ARIC) Study. Participants: A community sample of adults who were 44 to 66 years of age at study baseline.
Measurements: Active surveillance of local hospitals and annual participant contact were used to gather hospitalization information (including International Classification of Diseases, Ninth Revision, codes) on all participants over a 24-year surveillance period. Subsequently, a subset of participants underwent 3-Tesla brain magnetic resonance imaging (MRI) to quantify total and regional brain volumes, white matter hyperintensity (WMH) volume, and white matter microstructural integrity (fractional anisotropy (FA) and mean diffusivity (MD) as measured using diffusion tensor imaging (DTI)).
Results: Of the 1,689 participants included (mean age at MRI 76±5), 72% were hospitalized, 14% had a major infection, and 4% had a critical illness during the surveillance period. Using covariate-adjusted regression, hospitalization was associated with 0.12–standard deviation (SD) greater WMH volume (95% confidence interval (CI)=0.00–0.24) and poorer white matter microstructural integrity (0.17-SD lower FA, 95% CI=–0.27 to –0.06; 0.16-SD greater MD, 95% CI=0.07–0.25) than no hospitalization. There was a dose-dependent relationship between number of hospitalizations, smaller brain volumes, and lower white matter integrity (p-trends ≤.048). In hospitalized participants, critical illness was associated with smaller Alzheimer's disease (AD) signature region (–1.64 cm3, 95% CI=–3.16 to –0.12); major infection was associated with smaller AD signature region (–1.28 cm3, 95% CI=–2.21 to –0.35) and larger ventricular volume (3.79 cm3, 95% CI= 0.81–6.77).
Conclusions: Whereas all-cause hospitalization was primarily associated with lower white matter integrity, critical illness and major infection were associated with smaller brain volume, particularly within regions implicated in AD.
Oral anticoagulants used for the primary treatment of venous thromboembolism (VTE) include warfarin and the more recently introduced direct oral anticoagulants (DOACs), including rivaroxaban, apixaban, dabigatran and edoxaban. Information on the comparative safety of these medications in routine clinical practice is lacking. We identified patients with diagnoses for VTE and prescriptions for oral anticoagulants using claims data from a large U.S. insurance database from 2012 to 2017. Marginal structural logistic models were used to examine associations between type of oral anticoagulant and risk of all-cause mortality. Of 62,431 enrolees in this analysis, 51% were female and the mean age was 61.9 years. Initial oral anticoagulant prescriptions were for warfarin (n = 35,704), rivaroxaban (n = 21,064) and apixaban (n = 5,663). A total of 1,791 deaths occurred within 6 months of the initial oral anticoagulant prescription. Risk of all-cause mortality was not associated with having a prescription for warfarin versus any DOAC or between any head-to-head DOAC comparisons. Also, associations generally did not vary when stratified by VTE type, sex, age, co-morbidities (including renal disease) or anti-platelet medication use. In this observational study, the associations with all-cause mortality comparing DOACs versus warfarin agree with results from previous clinical trials and observational studies, while the associations for head-to-head DOAC comparisons provide new information on the comparative safety of DOACs. Our findings suggest that other criteria such as patient preference, cost, recurrent VTE risk or bleeding risk should be used when determining the choice of anticoagulant for the primary treatment of VTE.
Background: Direct acting oral anticoagulants (DOACs) are associated with less bleeding than traditional venous thromboembolism (VTE) treatments in the general population but are little studied in cancer-associated VTE (CA-VTE).
Objective: To determine whether different anticoagulation strategies for CA-VTE have different hospitalized bleeding rates.
Patients/Methods: We conducted a retrospective study of patients with CA-VTE, diagnosed between 2011 and 2015, in a large administrative database. Using validated algorithms, we identified 26 894 CA-VTE patients treated with anticoagulants and followed them for hospitalized severe bleeding. Cox models were used to assess bleeding risk, adjusted for age, sex, high dimensional propensity score and frailty.
Results: Over 27 281 person-years of follow-up (median 0.6 years), 1204 bleeding events occurred, for a bleeding rate of 4.4% per patient-year. Bleeding rates varied by cancer type, with the highest rate for upper gastrointestinal cancers (8.6%) and the lowest for breast cancer (2.9%). In Cox models (hazard ratio [HR]; 95% confidence interval [CI]), compared with warfarin, DOACS and low-molecular-weight heparin (LMWH) had similar hazards of bleeding (HR, 0.88; 95% CI, 0.69–1.11 and 0.98; 0.85–1.13). Compared with LMWH, there was no difference in hazard of bleeding with DOACs (0.86; 0.66–1.12). There was heterogeneity in bleeding risk with DOACs by cancer type, with a higher risk of bleeding in upper gastrointestinal cancers and lower risk of bleeding in prostate cancer and hematologic cancers.
Conclusions: In this practice-based sample of CA-VTE patients, DOACs were associated with similar bleeding risks to warfarin and LMWH. These findings suggest a complex association of bleeding risk with anticoagulant choice in cancer patients.
Background: Hypertension is an established risk factor for the development of atrial fibrillation (AF). We evaluated the association and population impact of hypertension, defined using the new 2017 guidelines, on risk of AF.
Methods: In this analysis, we included 14,915 participants in the Atherosclerosis Risk in Communities study without history of AF. Participants underwent blood pressure measurements at baseline and their antihypertensive medication use was assessed. Incident AF was ascertained from study electrocardiograms, hospital records and death certificates. Cox proportional models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of AF among individuals with hypertension based on the JNC7 and 2017 ACC/AHA guidelines. Poisson models were used to obtain risk ratios and calculate population-attributable fractions (PAFs).
Results: We identified 2891 cases of incident AF during 21.4 years of mean follow-up. Prevalence of hypertension was 34 and 48% under the JNC7 and 2017 ACC/AHA definitions, respectively. HRs (95%CI) of AF in hypertensives versus non-hypertensives were 1.44 (1.32, 1.56) and 1.37 (1.26, 1.48) after multivariable adjustment under the old and new guidelines, respectively. The corresponding PAF (95%CI) using the old and new guidelines were 11% (8, 13%) and 13% (9, 16%), respectively.
Conclusions: Overall, our analysis shows that even though the prevalence of hypertension using the new criteria is 40% higher than with the old criteria, this does not translate into meaningful increases in AF attributable to hypertension. These results suggest that prevention or treatment of hypertension based on the new (versus old) guidelines may have limited impact on AF incidence.