Mary R. Rooney

Trends in use of high-dose Vitamin D supplements exceeding 1000 or 4000 international units daily, 1999-2014

Trends in Use of High-Dose Vitamin D Supplements Exceeding 1000 or 4000 International Units Daily, 1999-2014 Since 2000, there has been an increase in research on possible health benefits of vitamin D. However, a 2011 Institute of Medicine (IOM; now the National Academy of Medicine) report concluded that vitamin D was beneficial for bone health but evidence was insufficient for extraskeletal health.1 Several large-scale trials are ongoing to evaluate the effect of vitamin D supplementation on extraskeletal outcomes.2 The IOM report noted possible harm (eg, hypercalcemia, soft tissue or vascular calcification) for intakes above the tolerable upper limit, which is the highest level of intake likely to pose no risk of adverse effects for most adults.1 The recommended dietary allowance for vitamin D is 600 IU/d for adults 70 years or younger and 800 IU/d for those older than 70 years. The tolerable upper limit is 4000 IU/d; beyond this level risk of toxic effects increases.1 Multivitamins typically contain about 400 IU/d; consumption of 1000 IU or more daily likely indicates intentionally seeking supplemental vitamin D. We assessed trends in daily supplemental vitamin D intake of 1000 IU or more and 4000 IU or more from 1999 through 2014.

Abnormal P-Wave Axis and Ischemic Stroke: The ARIC Study (Atherosclerosis Risk In Communities)

Background and Purpose— Abnormal P-wave axis (aPWA) has been linked to incident atrial fibrillation and mortality; however, the relationship between aPWA and stroke has not been reported. We hypothesized that aPWA is associated with ischemic stroke independent of atrial fibrillation and other stroke risk factors and tested our hypothesis in the ARIC study (Atherosclerosis Risk In Communities), a community-based prospective cohort study. Methods— We included 15u2009102 participants (aged 54.2±5.7 years; 55.2% women; 26.5% blacks) who attended the baseline examination (1987–1989) and without prevalent stroke. We defined aPWA as any value outside 0 to 75° using 12-lead ECGs obtained during study visits. Each case of incident ischemic stroke was classified in accordance with criteria from the National Survey of Stroke by a computer algorithm and adjudicated by physician review. Multivariable Cox regression was used to estimate hazard ratios and 95% confidence intervals for the association of aPWA with stroke. Results— During a mean follow-up of 20.2 years, there were 657 incident ischemic stroke cases. aPWA was independently associated with a 1.50-fold (95% confidence interval, 1.22–1.85) increased risk of ischemic stroke in the multivariable model that included atrial fibrillation. When subtyped, aPWA was associated with a 2.04-fold (95% confidence interval, 1.42–2.95) increased risk of cardioembolic stroke and a 1.32-fold (95% confidence interval, 1.03–1.71) increased risk of thrombotic stroke. Conclusions— aPWA is independently associated with ischemic stroke. This association seems to be stronger for cardioembolic strokes. Collectively, our findings suggest that alterations in atrial electric activation may predispose to cardiac thromboembolism independent of atrial fibrillation.

Abnormal P-Wave Axis and Ischemic Stroke

Background and Purpose— Abnormal P-wave axis (aPWA) has been linked to incident atrial fibrillation and mortality; however, the relationship between aPWA and stroke has not been reported. We hypothesized that aPWA is associated with ischemic stroke independent of atrial fibrillation and other stroke risk factors and tested our hypothesis in the ARIC study (Atherosclerosis Risk In Communities), a community-based prospective cohort study. Methods— We included 15u2009102 participants (aged 54.2±5.7 years; 55.2% women; 26.5% blacks) who attended the baseline examination (1987–1989) and without prevalent stroke. We defined aPWA as any value outside 0 to 75° using 12-lead ECGs obtained during study visits. Each case of incident ischemic stroke was classified in accordance with criteria from the National Survey of Stroke by a computer algorithm and adjudicated by physician review. Multivariable Cox regression was used to estimate hazard ratios and 95% confidence intervals for the association of aPWA with stroke. Results— During a mean follow-up of 20.2 years, there were 657 incident ischemic stroke cases. aPWA was independently associated with a 1.50-fold (95% confidence interval, 1.22–1.85) increased risk of ischemic stroke in the multivariable model that included atrial fibrillation. When subtyped, aPWA was associated with a 2.04-fold (95% confidence interval, 1.42–2.95) increased risk of cardioembolic stroke and a 1.32-fold (95% confidence interval, 1.03–1.71) increased risk of thrombotic stroke. Conclusions— aPWA is independently associated with ischemic stroke. This association seems to be stronger for cardioembolic strokes. Collectively, our findings suggest that alterations in atrial electric activation may predispose to cardiac thromboembolism independent of atrial fibrillation.

Refining Prediction of Atrial Fibrillation Risk in the General Population With Analysis of P-Wave Axis (from the Atherosclerosis Risk in Communities Study)

Adverse atrial remodeling is associated with increased risk of atrial fibrillation (AF) and can be detected by a shift in P-wave axis. We aimed to determine whether an analysis of P-wave axis can be used to improve risk prediction of AF. We included 15,102 Atherosclerosis Risk in Communities Study participants who were free of AF at baseline. Abnormal P-wave axis (aPWA) was defined as any value outside 0 to 75 degrees on study visit 12-lead electrocardiograms. AF was determined using study visit electrocardiograms, death certificates, and hospital discharge records. Multivariable Cox regression was used to estimate hazard ratios and 95% confidence intervals (CIs) for the association of aPWA with AF. The Cohorts for Heart and Aging Research in Genomic Epidemiology-AF (CHARGE-AF) risk prediction model variables served as our benchmark. Improvement in 10-year AF prediction was assessed by C-statistic, category-based net reclassification improvement, and relative integrated discrimination improvement. During a mean follow-up of 20.2 years, there were 2,618 incident AF cases. aPWA was independently associated with a 2.34-fold (95% CI 2.12 to 2.58) increased risk of AF after adjusting for CHARGE-AF risk score variables. The use of aPWA improved the C-statistic from 0.719 (95% CI 0.702 to 0.736) to 0.722 (95% CI 0.705 to 0.739), which corresponded with a net reclassification improvement of 0.021 (95% CI 0.001, 0.040) and relative integrated discrimination improvement of 0.043 (95% CI 0.018, 0.069). In conclusion, aPWA is independently associated with AF in the general population. The use of this maker modestly improves AF prediction.

Markers of vitamin D metabolism and incidence of clinically diagnosed abdominal aortic aneurysm: The Atherosclerosis Risk in Communities Study:

Little is known about whether markers of vitamin D metabolism are associated with the development of abdominal aortic aneurysm (AAA), though these markers have been linked to other cardiovascular diseases. We tested the hypotheses that risk of AAA is higher among individuals with low serum concentrations of 25-hydroxy vitamin D [25(OH)D], and among those with elevated concentrations of calcium, fibroblast growth factor 23 (FGF23), phosphorus, and parathyroid hormone (PTH) using data from a cohort of black and white individuals with long-term follow-up. Markers of vitamin D metabolism were measured using serum collected in 1990–1992 from ARIC study participants (mean ± SD age 56.9 ± 5.7 years, 43.2% male, 23.9% black). A total of 12,770 participants were followed until 2011 for incident AAA. Multivariable-adjusted Cox regression models were used. A total of 449 incident AAA events occurred over a median follow-up of 19.7 years. For the association between serum calcium and risk of incident AAA there was evidence of interaction by sex (p-interaction 0.02). Among women, in the fully adjusted model, the hazard ratio (95% confidence interval) comparing the highest to lowest quartile was 2.43 (1.25–4.73), whereas in men it was 1.01 (0.72–1.43). Not associated with risk of incident AAA were 25(OH)D, FGF23, phosphorus, and PTH. In this large prospective cohort, there was little evidence that markers of vitamin D metabolism are associated with risk of incident AAA. The positive association of calcium with AAA among women may warrant further investigation and replication in other populations.

Anticoagulant Preferences and Concerns among Venous Thromboembolism Patients

Background u2003Warfarin and direct oral anticoagulants (DOACs) are used for the initial treatment and secondary prevention of venous thromboembolism (VTE), and have similar efficacy. Patient concerns and preferences are important considerations when selecting an anticoagulant, yet these are not well studied. Methods u2003VTE patients ( n u2009=u2009519) were surveyed from online sources (clotconnect.org, stoptheclot.org and National Blood Clot Alliance Facebook followers [ n u2009=u2009495]) and a haematology clinic in Vermont ( n u2009=u200924). Results u2003Patients were 83% females and on average (±standard deviation [SD]) 45.7u2009±u200913.1 years; 65% self-reported warfarin as their initial VTE treatment and 35% a DOAC. Proportions reporting being extremely concerned about the following outcomes were as follows: recurrent VTE 33%, major bleeding 21%, moderate bleeding 16% and all-cause death 29%. When asked about oral anticoagulant characteristics, patients strongly preferred anticoagulants that are reversible (53%), and for which blood drug levels can be monitored (30%). Lower proportions agreed with statements that regular blood testing is inconvenient (18%), that they are comfortable using the newest drug versus an established drug (15%) and that it is difficult to change their diet to accommodate their anticoagulant (17%). In multivariable-adjusted models, patients tended to have had as their initial treatment, and to currently be taking, the oral anticoagulant option they personally preferred. Discussion u2003Patients held the greatest concern for recurrent VTE and mortality, regardless of which treatment they were prescribed. Potential weaknesses of warfarin (e.g., dietary restrictions, regular monitoring) were generally not considered onerous, while warfarins advantages (e.g., ability to monitor) were viewed favourably.

Trends in calcium supplementation, National Health and Nutrition Examination Survey (NHANES) 1999–2014

BACKGROUNDnLong-term outcomes of supplemental calcium are inadequately understood. Recent research suggests that calcium from supplements may not be entirely free from unintended health consequences. Consequently, it is important to understand patterns and trends in use of calcium supplements.nnnOBJECTIVEnTo report trends in supplemental calcium intake between 1999 and 2014, using NHANES data, overall and stratified by sex, race/ethnicity and age.nnnMETHODSnA total of 42,038 adult NHANES participants were included in this analysis. For each survey period, we calculated the prevalence of calcium supplement use exceeding the Estimated Average Requirement (EAR) and Tolerable Upper Intake Levels (UL), and mean daily supplemental calcium dose among calcium-containing supplement users. Sample weights were applied. Linear regression was used to examine trends.nnnRESULTSnOverall, the prevalence of calcium supplement use at a dose ≥EAR increased between 1999 and 2000 and 2013-2014, from 2.5% (95% CI: 1.9-3.3%) to 4.6% (3.8-5.5%). Use ≥EAR peaked in 2003-2004 at 6.7% (5.3-8.5%) (p-quadratic trend<0.001). Mean supplemental calcium intake peaked in 2007-2008, thereafter decreasing (p-quadratic trend<0.001). The overall prevalence of intake ≥UL from supplemental calcium in 2013-2014 was 0.4% (0.2-0.8%). Use of supplemental calcium ≥UL peaked during 2007-2008 at 1.2% (0.7-2.0%). In all time periods, supplemental calcium intake tended to be greater among women, non-Hispanic whites and adults >60years.nnnCONCLUSIONSnWe described the prevalence of U.S. adults consuming supplemental calcium ≥UL and ≥ EAR. While few were consuming supplemental calcium ≥UL, consumption ≥EAR was not uncommon, especially among women, non-Hispanic whites and older adults.

Predictors of sudden cardiac death in atrial fibrillation: The Atherosclerosis Risk in Communities (ARIC) study

We previously reported that incident atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. We now aimed to identify predictors of SCD in persons with AF from the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort study. We included all participants who attended visit 1 (1987–89) and had no prior AF (n = 14,836). Incident AF was identified from study electrocardiograms and hospitalization discharge codes through 2012. SCD was physician-adjudicated. We used cause-specific Cox proportional hazards models, followed by stepwise selection (backwards elimination, removing all variables with p>0.10) to identify predictors of SCD in participants with AF. AF occurred in 2321 (15.6%) participants (age 45–64 years, 58% male, 18% black). Over a median of 3.3 years, SCD occurred in 110 of those with AF (4.7%). Predictors of SCD in AF included higher age, body mass index (BMI), coronary heart disease, hypertension, diabetes, current smoker, left ventricular hypertrophy, increased heart rate, and decreased albumin. Predictors associated only with SCD and not other cardiovascular (CV) death included increased BMI (HR per 5-unit increase, 1.15, 95% CI, 0.97–1.36, p = 0.10), increased heart rate (HR per SD increase, 1.18, 95% CI 0.99–1.41, p = 0.07), and low albumin (HR per SD decrease 1.23, 95% CI 1.02–1.48, p = 0.03). In the ARIC study, predictors of SCD in AF that are not associated with non-sudden CV death included increased BMI, increased heart rate, and low albumin. Further research to confirm these findings in larger community-based cohorts and to elucidate the underlying mechanisms to facilitate prevention is warranted.