Heidi T May

Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population.

Vitamin D recently has been proposed to play an important role in a broad range of organ functions, including cardiovascular (CV) health; however, the CV evidence-base is limited. We prospectively analyzed a large electronic medical records database to determine the prevalence of vitamin D deficiency and the relation of vitamin D levels to prevalent and incident CV risk factors and diseases, including mortality. The database contained 41,504 patient records with at least one measured vitamin D level. The prevalence of vitamin D deficiency (≤30 ng/ml) was 63.6%, with only minor differences by gender or age. Vitamin D deficiency was associated with highly significant (p <0.0001) increases in the prevalence of diabetes, hypertension, hyperlipidemia, and peripheral vascular disease. Also, those without risk factors but with severe deficiency had an increased likelihood of developing diabetes, hypertension, and hyperlipidemia. The vitamin D levels were also highly associated with coronary artery disease, myocardial infarction, heart failure, and stroke (all p <0.0001), as well as with incident death, heart failure, coronary artery disease/myocardial infarction (all p <0.0001), stroke (p = 0.003), and their composite (p <0.0001). In conclusion, we have confirmed a high prevalence of vitamin D deficiency in the general healthcare population and an association between vitamin D levels and prevalent and incident CV risk factors and outcomes. These observations lend strong support to the hypothesis that vitamin D might play a primary role in CV risk factors and disease. Given the ease of vitamin D measurement and replacement, prospective studies of vitamin D supplementation to prevent and treat CV disease are urgently needed.

Ischemic Heart Disease Events Triggered by Short-Term Exposure to Fine Particulate Air Pollution

Background— Recent evidence suggests that long-term exposure to particulate air pollution contributes to pulmonary and systemic oxidative stress, inflammation, progression of atherosclerosis, and risk of ischemic heart disease and death. Short-term exposure may contribute to complications of atherosclerosis, such as plaque vulnerability, thrombosis, and acute ischemic events. These findings are inconclusive and controversial and require further study. This study evaluates the role of short-term particulate exposure in triggering acute ischemic heart disease events. Methods and Results— A case-crossover study design was used to analyze ischemic events in 12 865 patients who lived on the Wasatch Front in Utah. Patients were drawn from the cardiac catheterization registry of the Intermountain Heart Collaborative Study, a large, ongoing registry of patients who underwent coronary arteriography and were followed up longitudinally. Ambient fine particulate pollution (particles with an aerodynamic diameter ≤2.5 &mgr;m; PM2.5) elevated by 10 &mgr;g/m3 was associated with increased risk of acute ischemic coronary events (unstable angina and myocardial infarction) equal to 4.5% (95% confidence interval, 1.1 to 8.0). Effects were larger for those with angiographically demonstrated coronary artery disease. Conclusions— Short-term particulate exposures contributed to acute coronary events, especially among patients with underlying coronary artery disease. Individuals with stable presentation and those with angiographically demonstrated clean coronaries are not as susceptible to short-term particulate exposure.

Circulating 25-Hydroxy-Vitamin D and Risk of Cardiovascular Disease A Meta-Analysis of Prospective Studies

Background—Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25-hydroxy-vitamin D (25[OH]-vitamin D) levels for potential cardiovascular health benefits remain unclear. Methods and Results—We searched MEDLINE and EMBASE from 1966 through February 2012 for prospective studies that assessed the association of 25(OH)-vitamin D concentrations with CVD risk. A total of 24 articles met our inclusion criteria, from which 19 independent studies with 6123 CVD cases in 65 994 participants were included for a meta-analysis. In a comparison of the lowest with the highest 25(OH)-vitamin D categories, the pooled relative risk was 1.52 (95% confidence interval, 1.30–1.77) for total CVD, 1.42 (95% confidence interval, 1.19–1.71) for CVD mortality, 1.38 (95% confidence interval, 1.21–1.57) for coronary heart disease, and 1.64 (95% confidence interval, 1.27–2.10) for stroke. These associations remained strong and significant when analyses were limited to studies that excluded participants with baseline CVD and were better controlled for season and confounding. We used a fractional polynomial spline regression analysis to assess the linearity of dose–response association between continuous 25(OH)-vitamin D and CVD risk. The CVD risk increased monotonically across decreasing 25(OH)-vitamin D below ≈60 nmol/L, with a relative risk of 1.03 (95% confidence interval, 1.00–1.06) per 25-nmol/L decrement in 25(OH)-vitamin D. Conclusions—This meta-analysis demonstrated a generally linear, inverse association between circulating 25(OH)-vitamin D ranging from 20 to 60 nmol/L and risk of CVD. Further research is needed to clarify the association of 25(OH)-vitamin D higher than 60 nmol/L with CVD risk and assess causality of the observed associations.

Atrial fibrillation is independently associated with senile, vascular, and Alzheimer's dementia

BACKGROUND The aging population has resulted in more patients living with cardiovascular disease, such as atrial fibrillation (AF). Recent focus has been placed on understanding the long-term consequences of chronic cardiovascular disease, such as a potential increased risk of dementia. OBJECTIVE This study sought to determine whether there is an association between AF and dementia and whether their coexistence is an independent marker of risk. METHODS A total of 37,025 consecutive patients from the large ongoing prospective Intermountain Heart Collaborative Study database were evaluated and followed up for a mean of 5 years for the development of AF and dementia. Dementia was sub-typed into vascular (VD), senile (SD), Alzheimers (AD), and nonspecified (ND). RESULTS Of the 37,025 patients with a mean age of 60.6 +/- 17.9 years, 10,161 (27%) developed AF and 1,535 (4.1%) developed dementia (179 VD, 321 SD, 347 AD, 688 ND) during the 5-year follow-up. Patients with dementia were older and had higher rates of hypertension, coronary artery disease, renal failure, heart failure, and prior strokes. In age-based analysis, AF independently was significantly associated with all dementia types. The highest risk was in the younger group (<70). After dementia diagnosis, the presence of AF was associated with a marked increased risk of mortality (VD: hazard ratio [HR] = 1.38, P = .01; SD: HR = 1.41, P = .001; AD: HR = 1.45; ND: HR = 1.38, P <.0001). CONCLUSION AF was independently associated with all forms of dementia. Although dementia is strongly associated with aging, the highest risk of AD was in the younger group, in support of the observed association. The presence of AF also identified dementia patients at high risk of death.

Relation of Heart Failure Hospitalization to Exposure to Fine Particulate Air Pollution

Cardiopulmonary disease has been associated with particulate matter (PM) air pollution. There is evidence that exposure to elevated PM concentrations increases risk of acute ischemic heart disease events, alters cardiac autonomic function, and increases risk of arrhythmias. It is plausible, therefore, that PM exposure may exacerbate heart failure (HF). A case-crossover study design was used to explore associations between fine PM (PM(2.5): particles with an aerodynamic diameter < or =2.5 microm) and 2,628 HF hospitalizations. Patients lived on Utahs Wasatch Front and were drawn from those hospitalized at Intermountain Healthcare facilities with a primary diagnosis of HF. A 14-day lagged cumulative moving average of 10 microg/m(3) PM(2.5) was associated with a 13.1% (95% confidence interval 1.3 to 26.2) increase in HF admissions. The strongest PM(2.5)-HF associations were for elderly patients who had previously been admitted for HF and who required only a short period of hospitalization. HF hospitalizations are associated with lagged cumulative exposure to PM(2.5) of approximately 2 weeks. In conclusion, particulate air pollution may play a role in precipitating acute cardiac decompensation in otherwise well-managed patients with HF, perhaps through effects of PM on myocardial ischemia, cardiac autonomic function, and/or arrhythmic effects.

Red cell distribution width, C-reactive protein, the complete blood count, and mortality in patients with coronary disease and a normal comparison population.

BACKGROUND Red cell distribution width (RDW) is associated with morbidity and mortality in coronary artery disease (CAD), but the connection of RDW with chronic inflammation is equivocal. METHODS In 1,489 patients with CAD and 8.4-15.2 years of follow-up all-cause mortality and RDW were studied using Cox regression. RDW and its associations with inflammation, liver function, renal function, and body mass were assessed. A population of 449 normal (No-CAD) patients also was evaluated. RESULTS RDW predicted all-cause mortality in a step-wise manner (HR=1.37 per quintile; 95% CI=1.29, 1.46; p-trend<0.001). A significant but meaningless correlation between RDW and high-sensitivity C-reactive protein (hsCRP) was identified (r=0.181; p<0.001). With full adjustment, RDW remained significant (p-trend<0.001) and the strongest predictor of mortality among all factors included in the model. RDW also strongly predicted all-cause mortality in the normal control population (HR=1.33 per quintile, CI=1.15, 1.55; p-trend<0.001), but hsCRP did not predict mortality among normal controls. CONCLUSIONS RDW was associated with mortality in patients with CAD and may provide clinically useful prognostication. Although RDW was correlated with hsCRP, they were independent predictors of mortality. RDW has been incorporated into risk prediction tool using data from basic chemistries available at: http://intermountainhealthcare.org/IMRS.

Association of vitamin D levels with incident depression among a general cardiovascular population.

BACKGROUND Depression is associated with cardiovascular (CV) disease, and it has been hypothesized that vitamin (vit)D deficiency may be associated with depression and a contributing factor to excess CV events. Therefore, we evaluated whether there is an association between vitD and incident depression among a CV population. METHODS Patients (N = 7,358) > or =50 years of age, with a CV diagnosis (coronary artery disease, myocardial infarction, congestive heart failure, cerebrovascular accident, transient ischemic accident, atrial fibrillation, or peripheral vascular disease), no prior depression diagnosis, and a measured vitD level were studied. Vitamin D (ng/mL) was stratified into 4 categories: >50 (optimal [O] n = 367), 31 to 50 (normal [N] n = 2,264), 16 to 30 (low [L] n = 3,402), and > or =15 (very low [VL] n = 1,325). Depression was defined by International Classification of Diseases, Ninth Edition, codes: 296.2 to 296.36, 311. VitD categories were evaluated by Cox hazard regression with adjustment by standard CV risk factors. RESULTS Age averaged 73.1 +/- 10.2 years, and 58.8% were female. When compared to O, VL, L, and N were associated with depression (adjusted: VL, hazard ratio [HR] 2.70 [1.35-5.40], P = .005; L, HR 2.15 [1.10-4.21], P = .03; N, HR 1.95 [0.99-3.87], P = .06). This association remained even after adjustment by parathyroid hormone levels. Parathyroid hormone was significantly associated with depression, however, became nonsignificant after adjustment by vitD. Winter (December-February) enhanced this association. Significant associations remained when stratifications were made by age (<65, > or =65), sex, and diabetes, although the associations among those age > or =65 and male sex were enhanced. CONCLUSION Among a CV population > or =50 years with no history of depression, vitD levels were shown to be associated with incident depression after vitD draw. This study strengthens the hypothesis of the association between vitD and depression.

Parathyroid hormone, vitamin D, renal dysfunction, and cardiovascular disease: Dependent or independent risk factors?

BACKGROUND Vitamin D (Vit D) deficiency has been associated with prevalent and incident cardiovascular (CV) disease, suggesting a role for bioregulators of bone and mineral metabolism in CV health. Vitamin D deficiency leads to secondary hyperparathyroidism, and both primary and secondary hyperparathyroidism are associated with CV pathology. Parathyroid hormone (PTH) is an important regulator of calcium homeostasis, and its impact on CV disease risk is of interest. We tested whether elevated PTH is associated with CV disease and whether risk associations depend on Vit D status and renal function. METHODS Patients in the Intermountain Healthcare system with concurrent PTH and Vit D as 25-hydroxy-vitamin D (25[OH]D) levels were studied (N = 9,369, age 63 ± 16 years, 36% male). Parathyroid hormone levels were defined as low (<15 pg/mL), normal (15-75 pg/mL), or elevated (>75 pg/mL). Prevalence and incidence of hypertension, diabetes, hyperlipidemia, coronary artery disease/myocardial infarction, heart failure, stroke, and peripheral vascular disease were determined by the International Classification of Diseases, Ninth Revision codes documented in electronic medical records at baseline and, for incident events, during an average of 2.0 ± 1.5 years (maximum 7.5 years) of follow-up. RESULTS Parathyroid hormone elevation at baseline was noted in 26.1% of the study population. Highly significant differential CV prevalence/incidence rates for most CV risk factors, disease diagnoses, and mortality were noted for PTH >75 pg/mL (by 1.25- to 3-fold). Parathyroid hormone correlated only weakly (r = -0.15) with 25(OH)D and moderately with glomerular filtration rate (r = -0.36). 25(OH)D, standard risk factors, and renal dysfunction variably attenuated PTH risk associations, but risk persisted after full multivariable adjustment. CONCLUSIONS Elevated PTH is associated with a greater prevalence and incidence of CV risk factors and predicts a greater likelihood of prevalent and incident disease, including mortality. Risk persists when adjusted for 25(OH)D, renal function, and standard risk factors. Parathyroid hormone represents an important new CV risk factor that adds complementary and independent predictive value for CV disease and mortality.

Atrial fibrillation ablation patients have long-term stroke rates similar to patients without atrial fibrillation regardless of CHADS2 score

BACKGROUND Atrial fibrillation (AF) is a leading cause of total and fatal ischemic stroke. Stroke risk after AF ablation appears to be favorably affected; however, it is largely unknown whether the benefit extends to all stroke CHADS2 risk profiles of AF patients. OBJECTIVE To determine if ablation of atrial fibrillation reduces stroke rates in all risk groups. METHODS A total of 4212 consecutive patients who underwent AF ablation were compared (1:4) with 16,848 age-/sex-matched controls with AF (no ablation) and to 16,848 age-/sex-matched controls without AF. Patients were enrolled from the large ongoing prospective Intermountain Atrial Fibrillation Study and were followed for at least 3 years. RESULTS Of the 37,908 patients, the mean age was 65.0 ± 13 years and 4.4% (no AF), 6.3% (AF, no ablation), and 4.5% (AF ablation) patients had a prior stroke (P < .0001). The profile of CHADS2 scores between comparative groups was similar: 0-1 (69.3%, no AF; 62.3%, AF, no ablation; 63.6%, AF ablation), 2-3 (26.5%, no AF; 29.7%, AF, no ablation; 28.7%, AF ablation), and ≥4 (4.3%, no AF; 8.0%, AF, no ablation; 7.7%, AF ablation). A total of 1296 (3.4%) patients had a stroke over the follow-up period. Across all CHADS2 profiles and ages, AF patients with ablation had a lower long-term risk of stroke compared to patients without ablation. Furthermore, AF ablation patients had similar long-term risks of stroke across all CHADS2 profiles and ages compared to patients with no history of AF. CONCLUSIONS In our study populations, AF ablation patients have a significantly lower risk of stroke compared to AF patients who do not undergo ablation independent of baseline stroke risk score.

HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention: the lipoprotein investigators collaborative

AIMS High-density lipoprotein (HDL) is highly heterogeneous and the link of its subclasses to prognosis remains controversial. We aimed to rigorously examine the associations of HDL subclasses with prognosis in secondary prevention. METHODS AND RESULTS We collaboratively analysed data from two, complementary prospective cohorts: the TRIUMPH study of 2465 acute myocardial infarction patients, and the IHCS study of 2414 patients who underwent coronary angiography. All patients had baseline HDL subclassification by vertical-spin density gradient ultracentrifugation. Given non-linearity, we stratified by tertiles of HDL-C and its two major subclasses (HDL2-C, HDL3-C), then compared multivariable-adjusted hazard ratios for mortality and mortality/myocardial infarction. Patients were middle-aged to elderly (TRIUMPH: 58.2 ± 12.2 years; IHCS: 62.6 ± 12.6 years), and the majority were men (TRIUMPH: 68.0%; IHCS: 65.5%). IHCS had lower mean HDL-C levels (34.6 ± 10.1 mg/dL) compared with TRIUMPH (40 ± 10.6 mg/dL). HDL3-C accounted for >3/4 of HDL-C (mean HDL3-C/HDL-C 0.78 ± 0.05 in both cohorts). During 2 years of follow-up in TRIUMPH, 226 (9.2%) deaths occurred, while death/myocardial infarction occurred in 401 (16.6%) IHCS patients over 5 years. No independent associations with outcomes were observed for HDL-C or HDL2-C. In contrast, the lowest tertile of HDL3-C was independently associated with >50% higher risk in each cohort (TRIUMPH: with middle tertile as reference, fully adjusted HR for mortality of HDL3-C, 1.57; 95% CI, 1.13-2.18; IHCS: fully adjusted HR for mortality/myocardial infarction, 1.55; 95% CI, 1.20-2.00). CONCLUSION In secondary prevention, increased risk for long-term hard clinical events is associated with low HDL3-C, but not HDL2-C or HDL-C, highlighting the potential value of subclassifying HDL-C.