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Background: Many landmark genetic breakthroughs, including the recent discovery of PCSK-9 inhibitor drugs, were accomplished with substantial contributions from evaluation of pedigrees. Finding and ascertaining high-value pedigrees is not trivial and requires considerable time and cost. Here, we describe the creation of the Intermountain Genealogy Registry for use in studying the genetics of cardiovascular and other diseases. Methods: Using publicly available pedigree records and probabilistic linkage techniques, we created a genealogy of ?~23 million records that we linked to 3.9 million patient records in the Intermountain Healthcare system. Analytical tools were developed to support this registry, including calculation of genealogical index of familiality (GIF), testing of familial coaggregation of diseases, and extraction of high-risk pedigrees. Results: A total of 658,822 (16.8%) patients were linked to a genealogy pedigree record. The average age of the linked patients was 53 years, the majority (89.0%) were Caucasian, and 50.5% were male. The GIFs for the leading cardiovascular conditions of atrial fibrillation, coronary artery disease, heart failure, and myocardial infarction (MI) were all 1.2 times greater than the GIFs of matched control sets (p < 0.001). For extreme values of lowdensity lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, the GIFs were each 1.5 times greater than those of matched control sets (p < 0.001). There was coaggregation with MI and the extreme lipid traits with the largest coaggregation being for MI and triglycerides. Conclusion: The Intermountain Genealogy Registry is a multifaceted resource created to provide insights into the genetic components of cardiovascular and other diseases. This registry provides the means for easy identification and ascertainment of high-risk pedigrees for discovery of genetic susceptibility variants. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a common disorder with a variable clinical course and it is associated with increased mortality. The Intermountain Risk Score (IMRS) is an electronic risk calculator that utilizes complete blood count (CBC) and basic metabolic panel (BMP) values to predict mortality in various healthcare populations. We hypothesized that IMRS would predict mortality in patients with CKD even with adjustment for serum phosphate and urinary albumin.Methods: Three thousand eight hundred seventy-two patients with CKD classes IIIA-V had IMRS calculated retrospectively and survival analysis was performed investigating 1- and 5-year mortality. Kaplan-Meier survival curves were generated for predefined IMRS groups of low, medium and high risk for CKD patients overall and by sex and CKD stage. Serum phosphate and urinary albumin/creatinine ratios were modeled in multivariate Cox-proportional hazard models. Receiver operator characteristic curves were used to determine c-statistics for mortality.Results: For all patients with CKD, mortality was significantly greater for those with medium- or high-risk compared to low-risk IMRS categories, among each CKD stage. Overall, IMRS was predictive of mortality at both 1 and 5 years, even when adjusted for CKD stage and predicted mortality more accurately than CKD stage alone. Albuminuria was not independently associated with mortality and serum phosphate weakly predicted mortality.Conclusion: IMRS is a strong predictor of mortality in patients with CKD and is robustly complementary to CKD stage in refining risk prediction. Given the universal availability and low cost of the CBC and BMP, IMRS may be of a substantial value in CKD risk assessment and management. [ABSTRACT FROM AUTHOR]

Background: Multiple factors influence warfarin metabolism and can significantly affect the risk of adverse events. The extent to which patients understand the modifiable factors that impact on warfarin safety and efficacy is unclear. Methods: A 52-item questionnaire related to knowledge of warfarin was administered to patients with atrial fibrillation in a face-to-face interview with a dietitian. Results were compiled based on five categories: general warfarin knowledge, compliance, drug interactions, herbal or vitamin interactions, and diet. Results: 100 patients were surveyed. Stroke risk factors included hypertension (57%), heart failure (36%), age >75 years (33%), diabetes (22%), and prior stroke/transient ischemic attack (29%). The majority were either high-school (49%) or college graduates (27%). Ten (10%) had a stroke while on warfarin, 11 (11%) had a blood transfusion, and 26 (26%) had at least one fall. The percentages correct for questionnaire items in the five categories were as follows: general knowledge (62%), compliance (71%), drug interactions (17%), herbal or vitamin interactions (7%), and diet (23%). Neither education level nor duration of therapy correlated with warfarin knowledge. Patients at highest risk of stroke had very low knowledge scores in general. Discussion: Patients on warfarin have a poor general understanding of the medication, particularly those at highest risk of stroke. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In patients with acute coronary syndrome (ACS), elevated levels of soluble CD40 ligand (sCD40L) are associated with increased risk of cardiovascular events. We evaluated sCD40L levels and future cardiovascular events in patients not experiencing ACS. Methods: Serum sCD40L levels were measured in 909 patients undergoing angiography. A three-way matching scheme (age, gender and catheterization time period) identified 303 patients with coronary artery disease (CAD) who experienced a cardiac event within 1 year (CAD/event), 303 patients with CAD free of events (CAD/no event) and 303 patients without CAD and free of events (no CAD). Results: Average age was 64 ± 11 years; 74% were males. Median (± SE) sCD40L levels were higher for no CAD patients (335 ± 60 pg/ml) compared to CAD (248 ± 65 pg/ml, p = 0.01) and to CAD/event (233 ± 63 pg/ml, p < 0.001). There was no significant difference in median sCD40L levels between CAD/no event and CAD/event patients. Higher sCD40L quartiles were associated with a significant decrease in the risk of CAD/event versus no CAD (quartile 4 versus quartile 1: odds ratio = 0.59, p = 0.03). There was a nonsignificant trend towards a decreased risk of CAD as compared to no CAD, and for CAD/event versus CAD. Conclusions: In non-ACS patients, higher sCD40L levels were associated with a decreased risk of CAD. This novel interaction of sCD40L raises interesting questions for CAD pathogenesis. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Increased homocysteine (HCY) is associated with increased risk of vascular disease. Whether HCY affects development of congestive heart failure (CHF) independent of coronary artery disease (CAD) is uncertain. We evaluated whether increased HCY predicts low ejection fraction or clinical CHF. Methods: Patients (n = 2,842) undergoing coronary angiography had HCY measured between 1994 and 1999 and were prospectively studied. Left ventricular dysfunction (LVD) was defined as ejection fraction ≤40%. Multivariable regressions assessed predictive strength of HCY for LVD or LVD/CHF. Results: The average age was 64 ± 12 years; 69% were men, and 74% had CAD. LVD was present in 12% and the combination of either LVD or clinical CHF was present in 21.9%. Quartiles of HCY were: ≤10.5 (Q1), 10.5–13.2 (Q2), 13.3–17.0 (Q3) and ≥17.1 μmol/l (Q4). LVD and LVD/CHF were more prevalent in Q3 (15, 25%) and Q4 (15, 27%) than in Q1 HCY (8.4, 18%; p < 0.001 vs. Q4). After adjustment, Q3 and Q4 HCY independently predicted LVD (OR = 1.7, 95% CI 1.2–2.5, p = 0.004; OR = 1.8, 95% CI 1.3–2.6, p = 0.002) or LVD/CHF (OR = 1.4, 95% CI 1.04–1.8, p = 0.03; OR = 1.7, 95% CI 1.3–2.2, p < 0.001). Findings did not differ by disease etiology: for Q4 among non-CAD patients, OR = 1.7 for LVD and OR = 1.7 for LVD/CHF. Further, there was no interaction of results with gender. Conclusion: High HCY levels (Q3/4 ≥13.3 μmol/l) are associated with LVD and combined endpoint of LVD/clinical CHF. This relationship is independent of CHF etiology and gender. Further research is indicated to distinguish between a causal or noncausal mechanism for this association. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) has been associated with atherosclerotic complications, and we hypothesized that CRP levels might also predict death in non-ischemic patients with left ventricular dysfunction. Two hundred and three patients with non-ischemic left ventricular dysfunction undergoing cardiac catheterization were included and were followed for 2.4 ± 1.4 years to determine the incidence of fatal events. Death occurred in 15% of patients with low CRP (1st and 2nd tertiles) and 30% of patients with high CRP (3rd tertile). After adjustment for 11 covariates, high CRP (p = 0.037, hazard ratio = 2.0) significantly and independently predicted mortality. Even in the absence of coronary artery disease, patients with left ventricular dysfunction are at increased risk of mortality based on their baseline CRP concentrations. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Uric acid is a nontraditional risk factor implicated in the development of coronary artery disease (CAD). This study prospectively evaluated the predictive value of serum uric acid (SUA) levels for mortality after angiographic diagnosis of CAD. Methods: Blood samples were collected from 1,595 consecutive, consenting patients with significant, angiographically defined CAD (stenosis 70%). Baseline and procedural variables were recorded and levels of SUA were measured. Patients were followed to death or to the time of contact (mean 2.6 years, range 1.8-5.0 years). Results: Patients averaged 65 +/- 11 years of age, 78% were male and 170 subjects died during the follow-up period. In univariate analysis of prospectively defined quintiles, SUA predicted all-cause mortality (fifth quintile vs. first four quintiles: hazard ratio 1.9, p < 0.001). In multivariable Cox regression controlling for 20 covariables, independent predictive value for mortality was retained by SUA (hazard ratio 1.5, confidence interval 1.02-2.1, p = 0.04). In subgroup analysis based on diuretic use status, SUA independently predicted mortality among patients not using diuretics, while SUA was not a significant predictor of mortality among those who used diuretics. Conclusions: In patients with significant, angiographically defined CAD, SUA predicted mortality independent of traditional risk factors. This suggests that elevated SUA may be a risk factor for mortality in patients with significant cardiovascular disease and may be a stronger secondary than primary risk factor in CAD. [ABSTRACT FROM AUTHOR]

Background: The prevalence of the metabolic syndrome (MS) is growing. The Adult Treatment Panel (ATP) III provided a uniform definition of MS but no information on its predictive ability. Methods: We tested the ability of MS and its components to predict angiographic coronary artery disease (CAD) and incident death/myocardial infarction (D/MI) over 2.8 ± 2.3 years in a large cohort of patients undergoing angiography. ATP-III criteria were used for fasting glucose (FG), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and blood pressure (BP); body mass index (BMI) >27 kg/m[sup 2] was used as a surrogate for waist circumference. Results: 3,128 subjects were studied; 65% had advanced CAD (≥70% stenosis), and 35%, no CAD. MS was present in 64% (high FG 40%; high TG 52%; low HDL 71%; high BP 76%; high BMI 58%). Presence of CAD was predicted by MS [adjusted odds ratio (OR) = 1.30, 95% CI 1.10–1.55, p = 0.003] and, individually, by high FG (OR = 1.90, CI 1.63–2.23) and low HDL (OR = 1.38, CI 1.18–1.62). In multivariable modeling, CAD was predicted by high FG (OR = 1.80, CI 1.51–2.16) and low HDL (OR = 1.57, CI 1.31–1.89) as well as by age, gender, family history, smoking, and LDL cholesterol (all p < 0.001). For secondary risk of incident D/MI, only high FG of MS features was predictive (adjusted hazard ratio 1.46, CI 1.17–1.82, p = 0.001), and this risk was carried by diabetes (adjusted hazard ratio 1.71, p < 0.001); other predictors were age, heart failure, revascularization strategy, renal insufficiency, prior MI, and number of diseased vessels. Conclusion: MS has primary predictive ability for CAD, carried primarily by high FG and low HDL. Secondary predictive ability of MS features for clinical outcomes, in the setting of established CAD, is carried by diabetes alone. Dysglycemia deserves specific attention as a target for prevention and treatment. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

It has been shown that endothelial cell adhesion molecules play an important role in the development of coronary atherosclerosis and inflammatory disease. We sought to test whether soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin are increased in patients with documented coronary artery disease (CAD). Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured in 40 patients with documented CAD, 20 subjects with angiographically documented normal coronary arteries, and 14 healthy volunteers. Patients with documented CAD exhibited significant elevation of VCAM-1 (535 ± 227.1 ng/ml, p = 0.0001), E-selectin (69.4 ± 29.4 ng/ml, p = 0.006), but not ICAM-1 (320.5 ± 65.1 ng/ml, p = 0.9) concentrations as compared to subjects with normal coronary arteries (252.3 ± 79.8, 49.7 ± 22.0 and 311.4 ± 40.2 ng/ml), and healthy controls (110.0 ± 17.7, 29.0 ± 2.0 and 237.5 ± 46.5 ng/ml), respectively. Soluble markers of endothelial injury are not uniformly increased in patients with documented CAD as compared to those with normal coronary arteries and healthy controls. However, VCAM-1 and E-selectin, but not ICAM-1 could identify endothelial injury in such patients.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]