Donald L. Lappé

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.

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.

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.

Warfarin Is Not Needed in Low‐Risk Patients Following Atrial Fibrillation Ablation Procedures

Background: The recently published HRS/EHRA/ECAS AF Ablation Consensus Statement recommended that warfarin should be used for at least 2 months following an AF ablation in all patients regardless of stroke risk factors. The objective of the study was to assess outcomes based upon anticoagulation practice after atrial fibrillation (AF) ablation to determine relative risk of a strategy of aspirin only in low‐risk patients.

Relation of Bisphosphonate Therapies and Risk of Developing Atrial Fibrillation

Bisphosphonates comprise the most common treatment for patients with osteoporosis and fracture risk. Large randomized trials have shown that these therapies may increase the risk of atrial fibrillation (AF). Controversy over the arrhythmia risk prompted the Federal Drug Administration to recently pursue an ongoing safety review to determine the cardiac risk across the entire drug class. Study patients came from 2 large prospective databases (ongoing registry of consecutive patients who underwent coronary angiography and the Intermountain Healthcare health plans database). Medical details regarding bisphosphonate use and cardiovascular risk factors were abstracted from the records. End points included AF, myocardial infarction, and death. In the angiographic database (n = 9,623), patients treated with bisphosphonates were older and more likely to have hypertension, a previous myocardial infarction, heart failure, and osteoporosis. Over 1,481 +/- 1,024 days we found no increased risk of AF in the drug-treated group (hazard ratio 0.90, 95% confidence interval 0.48 to 1.68, p = 0.74). In the Intermountain Healthcare health plans database (n = 37,485), patients treated with bisphosphonates were older and were more likely to have hyperlipidemia and osteoporosis. Over 1,667.5 +/- 557.0 days, there was no increased risk of AF (hazard ratio 0.82, 95% confidence interval 0.66 to 1.01, p = 0.63). In the 2 databases there was no statistical difference in long-term rates of myocardial infarction or mortality. In conclusion, in a long-term study of >47,000 patients, we were unable to find an association between bisphosphonate therapy and AF. However, patients who received bisphosphonates were older and had more cardiovascular disease that we suspect accounts for the increased arrhythmia risk reported in other trials.

Ranolazine Reduces Ventricular Tachycardia Burden and ICD Shocks in Patients with Drug‐Refractory ICD Shocks

Background:  There are limited options for patients who present with antiarrhythmic‐drug (AAD)‐refractory ventricular tachycardia (VT) with recurrent implantable cardioverter defibrillator (ICD) shocks. Ranolazine is a drug that exerts antianginal and antiischemic effects and also acts as an antiarrhythmic in isolation and in combination with other class III medications. Ranolazine may be an option for recurrent AAD‐refractory ICD shocks secondary to VT, but its efficacy, outcomes, and tolerance are unknown.

Exceptional Mortality Prediction by Risk Scores from Common Laboratory Tests

BACKGROUND Some components of the complete blood count and basic metabolic profile are commonly used risk predictors. Many of their components are not commonly used, but they might contain independent risk information. This study tested the ability of a risk score combining all components to predict all-cause mortality. METHODS Patients with baseline complete blood count and basic metabolic profile measurements were randomly assigned (60%/40%) to independent training (N = 71,921) and test (N = 47,458) populations. A third population (N = 16,372) from the Third National Health and Nutrition Examination Survey and a fourth population of patients who underwent coronary angiography (N = 2558) were used as additional validation groups. Risk scores were computed in the training population for 30-day, 1-year, and 5-year mortality using age- and sex-adjusted weights from multivariable modeling of all complete blood count and basic metabolic profile components. RESULTS Area under the curve c-statistics were exceptional in the training population for death at 30 days (c = 0.90 for women, 0.87 for men), 1 year (c = 0.87, 0.83), and 5-years (c = 0.90, 0.85) and in the test population for death at 30 days (c = 0.88 for women, 0.85 for men), 1 year (c = 0.86, 0.82), and 5 years (c = 0.89, 0.83). In the test, the Third National Health and Nutrition Examination Survey, and the angiography populations, risk scores were highly associated with death (P <.001), and thresholds of risk significantly stratified all 3 populations. CONCLUSION In large patient and general populations, risk scores combining complete blood count and basic metabolic profile components were highly predictive of death. Easily computed in a clinical laboratory at negligible incremental cost, these risk scores aggregate baseline risk information from both the popular and the underused components of ubiquitous laboratory tests.