Biomedical subjects

Benjamin D Horne

Publications and source records attributed to Benjamin D Horne.

At least 19 recordsLinked to original sources

PubMed2007

Asymmetric dimethylarginine, cortisol/cortisone ratio, and C-peptide: markers for diabetes and cardiovascular risk?

BACKGROUND: Diabetes and prediabetic conditions are growing cardiovascular risk factors. Better understanding and earlier recognition and treatment of dysglycemia-related risk are health priorities. We assessed the predictive value of 3 proposed new markers for diabetes and cardiovascular risk. We tested whether the plasma levels of (1) asymmetric dimethylarginine (ADMA), (2) cortisol/cortisone (Cl/Cn) ratio, and (3) C-peptide predicted glycemic status, coronary artery disease, and death or myocardial infarction (MI) in a nested case-control cohort (N = 850) with normal fasting glucose (< 110 mg/dL), impaired fasting glucose (110-125), or diabetic (> or = 126) status. METHODS: High-sensitivity C-reactive protein (hsCRP) served as a control risk marker. Follow-up averaged 2.6 +/- 1.4 years. High-pressure liquid chromatography with pre-column derivitization and fluorescence was used to assay ADMA, liquid chromatography/tandem mass spectrometry for Cl and Cn, and chemiluminescent immunoassay for C-peptide. RESULTS: Asymmetric dimethylarginine levels were positively associated with glycemic category (P < .001). Quartiles 2 to 4 ADMA also conferred increased risk of death/MI independent of hsCRP and other risk factors (adjusted hazard ratio, 2.1; P = .002). Cortisol/Cortisone ratios (P = .013) and C-peptide (P = .047) were associated with glycemic categories but less strongly than ADMA. Quartiles 2 to 4 Cl/Cn were protective against incident death/MI (adjusted hazard ratio, 0.48; P < .001), whereas C-peptide did not predict outcomes. CONCLUSIONS: Among a high coronary risk case-control cohort, ADMA (strongly), Cl/Cn (moderately), and C-peptide (weakly) predicted glycemic categories. Asymmetric dimethylarginine and Cl/Cn also predicted clinical outcome independent of and more strongly than hsCRP. Asymmetric dimethylarginine and Cl/Cn represent promising new candidate markers of dysglycemia and associated cardiovascular risk.

Arginine↗

PubMed2007

Multivariate predictors of heart transplantation outcomes in the era of chronic mechanical circulatory support.

BACKGROUND: Determining which pretransplantation (TX) characteristics predict the development of chronic renal dysfunction (CRD) or death after heart TX would enable more accurate risk assessment at the time of candidate evaluation. METHODS: A cohort of 278 patients underwent TX in three hospitals between 1993 and 2002. Predictive models for CRD (serum creatinine consistently above 2 mg/dL) and allograft loss (death or re-TX) were constructed using logistic and Cox regression, respectively. RESULTS: Using logistic regression, CRD was more likely to develop in TX patients if they had a larger body surface area (odds ratio [OR] = 5.8 per m2, 95% confidence interval [CI] = 1.04 to 31.9, p = 0.04) or were inotrope dependent (OR = 1.8, 95% CI = 0.90 to 3.7, p = 0.09). Notably, the implementation of mechanical circulatory support as bridge to transplantation decreased the risk of CRD (OR = 0.30, 95% CI = 0.12 to 0.72, p = 0.007). Cox analysis demonstrated independent predictive ability of improved survival for males (hazard ratio [HR] = 0.42, 95% CI = 0.21 to 0.83, p = 0.01). Worse survival was observed with prior sternotomy (HR = 3.5, 95% CI = 2.0 to 6.0, p < 0.001), diabetes mellitus (HR = 1.9, 95% CI = 0.98 to 3.9, p = 0.06), and elevated serum creatinine (HR = 2.8 per mg/dL, 95% CI = 1.3 to 5.8, p = 0.007). CONCLUSIONS: Certain pretransplant characteristics clearly predispose a patient to the development of CRD or increased mortality after heart transplantation. Interestingly, the risk of CRD after heart transplantation is greater for patients bridged to transplant with inotropes than with mechanical circulatory support. When hemodynamically indicated, timely implementation of pretransplant mechanical circulatory support should be considered.

Adult↗

PubMed2006

Comparison of effects of high (80 mg) versus low (20 mg) dose of simvastatin on C-reactive protein and lipoproteins in patients with angiographic evidence of coronary arterial narrowing.

Although previous studies have demonstrated that various "statins" decrease levels of high-sensitivity C-reactive protein (hs-CRP), the dose-response relation for lowering hs-CRP by the clinically important drug simvastatin compared with lipid lowering is unclear. A 16-week, randomized, double-blind study was performed in patients with stable coronary artery disease and high hs-CRP levels (>3 mg/L). Subjects were randomized to placebo, 20 mg of simvastatin, or 80 mg of simvastatin for 12 weeks. Those currently on a statin first underwent a 4-week washout. Of the 107 total patients randomized, 96 completed the trial, and 89 were able to be evaluated for efficacy. Changes in hs-CRP differed across simvastatin and placebo groups (change score +1.6 vs -0.6 mg/L, p = 0.004), but no dose response was observed when comparing 80 with 20 mg/day (-0.6 vs -0.5 mg/L, respectively). A strong dose response was observed for changes in total (p <0.01) and low-density lipoprotein (p <0.001) cholesterol. hs-CRP changes did not correlate with low-density lipoprotein changes. In conclusion, this randomized trial in patients with chronic stable coronary artery disease showed a strong dose response for simvastatin for total and low-density lipoprotein cholesterol lowering but not for hs-CRP.

Aged↗

PubMed2006

Usefulness of a complete blood count-derived risk score to predict incident mortality in patients with suspected cardiovascular disease.

The complete blood cell (CBC) count is an inexpensive, frequently obtained blood test whose information content is potentially underused. We examined the predictive ability of the CBC count for incident death in 29,526 consecutive consenting patients who underwent coronary angiography. Subjects were randomly assigned to training (60%) and test (40%) groups and were followed for an average of 4.9 years. Computed and integer risk score models for all-cause death were developed for 30 days and 1, 5, and 10 years using multivariable logistic regressions applied to CBC metrics, age, and gender. The study cohort was an average age of 61 years, 62% were men, and had a 3.3% annual risk of mortality. An integer (scalar) risk score (range 0 to 18) successfully separated patient cohorts into subgroups at markedly different mortality risks (<1% to >14% at 30 days). Predictive fractions (area under risk curve) at 30 days for the CBC-only model and the age- and gender-adjusted CBC model were 0.76 and 0.78, respectively, in the training set and 0.71 and 0.75, respectively, in the test set (all p values <<0.001). The CBC model was markedly more informative than models based only on hematocrit, white blood cell count, or age and gender and was superior to models with all 7 traditional risk factors. In conclusion, in a large, prospectively assembled database, a CBC risk model had high predictive ability for risk of incident mortality. A total CBC score is an important new addition to risk prediction, and it can be easily generated by computer for clinical use at negligible incremental cost.

Age Factors↗

PubMed2006

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 < or = 2.5 microm; PM2.5) elevated by 10 microg/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.

Adult↗

PubMed2006

Homocysteine levels are associated with increased risk of congestive heart failure in patients with and without coronary artery disease.

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 < or =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: < or =10.5 (Q1), 10.5-13.2 (Q2), 13.3-17.0 (Q3) and > or =17.1 micromol/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 > or =13.3 micromol/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.

Aged↗

PubMed2006

Relation of serum total cholesterol, C-reactive protein levels, and statin therapy to survival in heart failure.

Although increased cholesterol levels predict mortality in patients with coronary artery disease, it is unclear whether hypercholesterolemia is associated with adverse survival in patients with heart failure. A cohort of subjects derived from the Intermountain Heart Collaborative Study Registry (1993 to 2003) who had ejection fractions < or = 40% or clinical diagnoses of heart failure and long-term follow-up for death were studied (n = 1,646). Total cholesterol (TC) was divided into quartiles: quartile 1, < 141.3 mg/dl; quartile 2, 141.3 to 167.9 mg/dl; quartile 3, 168.0 to 201.0 mg/dl; and quartile 4, > 201.0 mg/dl. Multivariate Cox regression models were used to evaluate the associations of cholesterol, statin therapy, and C-reactive protein to mortality. The mean age was 65.5 years; 65% of the subjects were men and 65% had coronary artery disease. Although 53% were using statins, statin use was not different across TC quartiles. Average time to death was 2.4 years (maximum 10). Mortality for quartile 4 versus quartile 1 was not different (hazard ratio [HR] 1.12, p = 0.52); mortality was reduced for quartile 3 versus quartile 1 (HR 0.66, p = 0.027) and tended to be reduced for quartile 2 versus quartile 1 (HR 0.77, p = 0.14). Subanalysis of patients not using statins (n = 737, death = 20.2%) found no association between TC and survival (for quartile 3 vs quartile 1, HR 0.97, p = 0.89), but for patients using statins (n = 848, death = 16.3%), the effect was even greater for quartile 3 versus quartile 1 (HR 0.40, p = 0.002) than in the overall population. Nonsurvivors had higher levels of C-reactive protein than survivors. In conclusion, elevated TC appears to be associated with improved survival. The effect was stronger in patients receiving statin therapy, but the cause of this differential effect is uncertain.

Aged↗

PubMed2006

The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study.

OBJECTIVES: The primary objective was to determine the effect of statin-fibrate combination therapy on inflammatory biomarkers in patients with diabetes. BACKGROUND: Atherosclerosis is a long-term, chronic inflammatory disease that is exacerbated in patients with diabetes. METHODS: Patients (n = 300) with type II diabetes, mixed dyslipidemia (2 or more of low-density lipoprotein > or =100 mg/dl, triglycerides > or =200 mg/dl, or high-density lipoprotein <40 mg/dl), and no history of coronary heart disease were randomly assigned to receive simvastatin 20 mg, fenofibrate 160 mg, or a combination of simvastatin 20 mg and fenofibrate 160 mg daily. At 12 weeks after randomization, we measured levels of high-sensitivity C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA(2)). RESULTS: At 12 weeks, median hsCRP was significantly reduced (-14.6%, p = 0.004) from baseline, but the effect did not differ between treatments. The effect was greatest among patients with baseline hsCRP levels >2.0 mg/l (fenofibrate = -18.9%, p = 0.002 vs. baseline; simvastatin = -24.8%, p < 0.0001; combination = -27.3%, p = 0.002). Likewise, median Lp-PLA(2) levels in the overall study population were significantly reduced (-16.8%, p < 0.0001), and the effect did not differ among treatments. This effect also was greatest among patients with increased baseline levels of Lp-PLA(2) greater than the median of 320.9 ng/ml (fenofibrate = -41.3%, p < 0.0001; simvastatin = -47.5%, p < 0.0001; combination = -46.8%, p < 0.0001). CONCLUSIONS: Simvastatin, fenofibrate, and combination therapy each lowered hsCRP and Lp-PLA(2). These anti-inflammatory effects were most pronounced among patients with increased baseline levels. Combination therapy was no more effective than either form of monotherapy. (The DIACOR Study; http://www.clinicaltrials.gov/ct/show/NCT00309712?order=1).

Atherosclerosis↗

PubMed2006

Impact of transforming growth factor-beta1 on atrioventricular node conduction modification by injected autologous fibroblasts in the canine heart.

BACKGROUND: Atrioventricular (AV) nodal ablation for management of atrial fibrillation (AF) is irreversible and requires permanent pacemaker implantation. We hypothesized that as an alternative, implantation of autologous fibroblasts in the perinodal region would focally modify AV nodal conduction and that this modulation would be enhanced by pretreatment with transforming growth factor-beta1 (TGF-beta1), a stimulant of fibroblasts. METHODS AND RESULTS: Skin biopsies were taken from 12 mongrel dogs, and derived fibroblasts were dissociated and grown in culture for 2 weeks. Multiple injections (0.25 mL) were made through an 8F NOGA catheter along the fast/slow AV nodal pathways as guided by an electroanatomic mapping system. Seven dogs received fibroblasts alone (1x10(6) cells/mL), 7 dogs received TGF-beta1 (5 microg), 4 dogs received fibroblasts and TGF-beta1 (1x10(6) cells/mL+5 microg), and 4 dogs received saline only. AV node function was assessed at baseline and after 4 weeks. Saline (80 mL) with assigned therapy (0.25 mL per injection) was injected into the peri-AV nodal region in each dog. At baseline, the AH interval (66+/-3 ms) and the average RR interval (331+/-17 ms) in pacing-induced AF were similar in each cohort. The increase in AH interval in normal sinus rhythm was longer after fibroblast (23+/-4 versus 5+/-5 ms; P=0.05) and fibroblast plus TGF-beta1 (50+/-5 versus 5+/-5 ms; P<0.001) injections than with saline alone, with similar findings during high right atrium and distal coronary sinus pacing. The AH interval was not significantly increased after TGF-beta1 injections. The AH interval was significantly longer after fibroblast plus TGF-beta1 injections than with either therapy (TGF-beta1 or fibroblasts) alone. The RR interval during AF was increased in dogs that received fibroblasts alone (110+/-36 versus -41+/-34 ms) and to a greater extent with the addition of TGF-beta1 (294+/-108 versus -41+/-34 ms). No AV block was seen in any cohort at 4 weeks. Labeled fibroblasts that expressed vimentin were identified in all dogs that received cell injections at 4 weeks. CONCLUSIONS: AV nodal modification can be achieved with injected fibroblasts without the creation of AV block. The effect on AV node conduction is substantially enhanced by pretreatment of fibroblasts with TGF-beta1. These data have therapeutic potential for the management of rapid ventricular rate during AF without pacemaker implantation.

Animals↗

PubMed2006

Genotypes of the cytochrome p450 isoform, CYP2C9, and the vitamin K epoxide reductase complex subunit 1 conjointly determine stable warfarin dose: a prospective study.

BACKGROUND: Warfarin has a narrow therapeutic range and wide inter-individual dosing requirements that may be related to functional variants of genes affecting warfarin metabolism (i.e., CYP2C9) and activity (i.e., vitamin K epoxide reductase complex subunit 1-VKORC1). We hypothesized that variants in these two genes explain a substantial proportion of variability in stable warfarin dose and could be used as a basis for improved dosing algorithms. METHODS: Consecutive consenting outpatients (n = 213) with stable INR (2-3) for >1 month were enrolled. Buccal DNA was extracted using a Qiagen mini-column and CYP2C9*2 and VKORC1 genotyping performed by the Taqman 3' nuclease assay. Sequencing for CYP2C9*3, genotyping was done using Big Dye v3.1 terminator chemistry Dose by genotype was assessed by linear regression. RESULTS: Weekly warfarin dose averaged 30.8 +/- 13.9 mg/week; average INR was 2.42 +/- 0.72. CYP2C9*2/*3 genotype distribution was: CC/AA (wild-type [WT]) = 71.4%, CT/AA = 18.3%, CC/AC = 9.4%, and CT/AC = 1%; VKORC1 genotypes were CC (WT) = 36.6%, CT = 50.7%, and TT = 12.7%. Warfarin doses (mg/week) varied by genotype: for CYP2C9, 33.3 mg/week for WT (CC/AA), 27.2 mg/week for CT/AA (P = 0.04 vs. WT), 23.0 mg/week for CC/AC (P = 0.003), and 6.0 mg/week for CT/AC (P < 0.001), representing dose reductions of 18-31% for single and 82% for double variant carriers; for VKORC1: 38.4 mg/week for WT (CC), 28.6 mg/week for CT (P < 0.001 vs. WT), 20.95 mg/week for TT (P < 0.001). In multiple linear regression, genotype was the dominant predictor of warfarin dose (P = 2.4 x 10(-15)); weak predictors were age, weight, and sex. Genotype-based modeling explained 33% of dose-variance, compared with 12% for clinical variables alone. CONCLUSION: In this large prospective study of warfarin genetic dose-determinants, carriage of a single or double CYP2C9 variant, reduced warfarin dose 18-72%, and of a VKORC1 variant by 65%. Genotype-based modeling explained almost one-half of dose-variance. A quantitative dosing algorithm incorporating genotypes for 2C9 and VKORC1 could substantially improve initial warfarin dose-selection and reduce related complications.

Adult↗

PubMed2006

Identification of excess clustering of coronary heart diseases among extended pedigrees in a genealogical population database.

BACKGROUND: First-degree family history of early coronary artery disease (CAD) and myocardial infarction (MI) is prognostic among disease-free individuals but may be unreliable. This study evaluated deaths caused by CAD, MI, hypertensive heart disease (HtnHD), and congestive heart failure (CHF) among close and distant relatives. METHODS: The Utah Population Database contains >2.2 million individual records with genealogy data and 250,000 linked death certificates. Deaths caused by CAD (n = 28,469), MI (n = 26,468), HtnHD (n = 3933), and CHF (n = 11,784) were studied. Familial relative risks (FRRs) were assessed for first- and second-degree relatives. Familiality was also evaluated using the Genealogical Index of Familiality (GIF), which considers close and distant genetic relationships in the Utah Population Database. RESULTS: Familial relative risks in first-degree (FRR = 1.25, P < .0001) and second-degree (FRR = 1.06, P = .0002) relatives were significant for early age at MI death (<65 years old). Genealogical Index of Familiality analysis demonstrated excess relatedness for deaths caused by MI (case GIF 2.93, mean control GIF 2.73, P < .001) and CHF (2.92 vs 2.66, P < .001). For early age at death, GIFs were significant for MI (3.06 vs 2.54, P < .001), HtnHD (3.22 vs 2.44, P = .003), and CHF (2.64 vs 2.23, P = .003). CONCLUSIONS: Deaths caused by MI and CHF demonstrate a heritable component in close and distant relatives. For MI, CHF, and HtnHD, for which findings were more pronounced in early age at death, gene discovery may be most effective among early-onset clusters. Excess relatedness was not found for CAD death--perhaps because of heterogeneity within the phenotype--suggesting that this may be a suboptimal phenotype for genetic study.

Adult↗

PubMed2006

Lipoprotein-associated phospholipase A2 independently predicts the angiographic diagnosis of coronary artery disease and coronary death.

BACKGROUND: Whereas C-reactive protein (CRP) is a nonspecific marker of coronary artery disease (CAD) and cardiovascular (CV) events, Lp-PLA2 may be a nonvariable inflammatory biomarker. We evaluated the independent association of lipoprotein-associated phospholipase A2 (Lp-PLA2) to angiographic CAD and CV events adjusting for standard factors, lipids, and CRP. METHODS: Lipoprotein-associated phospholipase A2 (PLAC test, diaDexus, Inc, San Francisco, CA) and CRP were measured from samples donated by consecutive consenting patients (N = 1493) enrolled in the registry of the Intermountain Heart Collaborative Study. All patients underwent coronary angiography (1996-1998) for CAD determination and were followed for 6.7 +/- 0.5 years (range 5.7-7.9 years) for CV events (death [including all-cause, CAD, and non-CAD CV death], myocardial infarction, and cerebrovascular accident). RESULTS: Lipoprotein-associated phospholipase A2 weakly correlated with lipids (low-density lipoprotein: r = 0.22, P < .001; high-density lipoprotein: r = -0.13, P < .001), but not CRP (r = 0.03, P = .26). Increasing quartile (Q) of Lp-PLA2 predicted greater the presence of CAD (vs Q1) for Q2 (adjusted odds ratio [OR] 1.15, 95% CI 0.78-1.71, P = .48), for Q3 (OR 1.53, 95% CI 1.02-2.31, P = .042), and for Q4 (OR 2.44, 95% CI 1.58-3.79, P < .001), although CRP was also predictive (vs Q1, Q2: OR 1.47, P = .057; Q3: OR 1.93, P = .002; Q4: OR 3.43, P < .001). In Cox regression, Lp-PLA2 predicted CAD death (vs Q1; Q2: adjusted hazard ratio [HR] 1.27, 95% CI 0.58-2.78, P = .55; Q3: HR 2.18, 95% CI 1.04-4.57, P = .04; Q4: HR 1.73, 95% CI 0.84-3.61, P = .14). CONCLUSION: Lipoprotein-associated phospholipase A2 was confirmed to predict the presence of CAD, even among patients undergoing coronary angiography. Uniquely, Lp-PLA2 predicted the risk of CAD death, but not all-cause death, myocardial infarction, or cerebrovascular accident.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2006

High-resolution characterization of linkage disequilibrium structure and selection of tagging single nucleotide polymorphisms: application to the cholesteryl ester transfer protein gene.

Full characterization of intragenic variation may improve candidate gene associations. This study selected tagging (t) single nucleotide polymorphisms (SNPs) to comprehensively represent genetic variability in the cholesteryl ester transfer protein (CETP) gene. Nineteen SNPs were identified in 50 unrelated individuals in the SNP discovery phase, and 13 intronic SNPs were added from the literature. These 32 SNPs were genotyped in 339 apparently healthy individuals and 190 coronary artery disease (CAD) patients. Using phased haplotypes, linkage disequilibrium (LD) structure was characterized and tSNPs selected using a principal component analysis (PCA) method. In healthy individuals, seven LD groups were identified that accounted for 93.4% of the observed genetic variation. These LD groups highlighted a complex LD structure for CETP, including both recombination and mutation, and eleven tSNPs were selected. Among CAD patients the results were essentially the same. Results from PCA using diploid genotype data were reasonably comparable. Finally, the selected tSNPs successfully represented the association evidence discovered for all of the other SNPs studied. This study provides an optimal set of tSNPs for association analyses of CETP. The observed complexity of LD structure highlights the importance of using methods, such as PCA, that allow for multiple dynamics in intragenic LD structure.

Aged↗

PubMed2006

Risk factor analysis of plasma cytokines in patients with coronary artery disease by a multiplexed fluorescent immunoassay.

Coronary artery disease (CAD) is the leading cause of death in the United States. Increasing evidence suggests involvement of inflammation in the atherosclerotic process. We examined cytokines and other inflammatory markers in 865 patients with chest pain in whom coronary angiography revealed no evidence of CAD or CAD with or without concomitant myocardial infarction (MI). We developed a multiplexed immunoassay to simultaneously assess the plasma concentrations of 8 cytokines (interferon gamma, interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor alpha), IL-2r, and soluble CD40 ligand in the patient groups. Concentrations of C-reactive protein (CRP) and IL-18 also were determined. Significant differences (P < .05) between no CAD and combined CAD groups were found for IL-2, IL-4, IL-6, IL-12, and IL-18. When the no CAD group was compared with the group with CAD with subsequent MI, significant differences were found for proinflammatory markers IL-6 (P pound .001), IL-8 (P = .017), and CRP (P pound .001). Cytokine profiles may have a role in differentiating patients with CAD with MI from those with chest pain due to other disorders and in deciphering the role of inflammation in the pathogenesis of CAD.

Angina Pectoris↗

PubMed2005

Effect of mechanical circulatory support on outcomes after heart transplantation.

BACKGROUND: Mechanical circulatory support (MCS) before heart transplantation was previously associated with worse post-transplant outcomes than when MCS was not required. Given the changes in technology, expertise, patient selection, and timing of subsequent transplantation, we hypothesized that patients who require MCS before heart transplantation have similar outcomes after transplantation as those not requiring pre-transplant MCS. METHODS: We retrospectively reviewed 278 patients who underwent cardiac transplantation from 1993 to 2002. MCS was required in 72 patients (HeartMate LVAS in 66, CardioWest Total Artificial Heart in 6) and was not required in 206 patients. The influence of pre-transplant MCS on post-transplant outcomes was assessed in the 2 groups. RESULTS: Baseline clinical characteristics (age, gender, etiology of heart failure, history of diabetes mellitus, and donor age and gender) were similar in the 2 groups. One-month and 1-year survival after transplantation did not differ between the groups (MCS, 92% and 85%, respectively vs no MCS, 97% and 92%, respectively). Similar proportions of patients were free from rejection (International Society for Heart and Lung Transplantation score >or=3A) at 1 year of follow-up (MCS, 56% vs no MCS, 52%, p = 0.60). No difference was observed between MCS and no MCS patients in other post-transplant events such as hospital stay, intensive care unit stay, extubation time, acute allograft dysfunction, reoperation rates, acute renal dysfunction, acute hepatic dysfunction, infections, arrhythmias, thromboembolic complications, neurologic complications, gastrointestinal complications and the development of cardiac allograft vasculopathy. The incidence of chronic renal insufficiency was actually lower in the MCS Group (15.3% vs 37.9%, p = .001). CONCLUSION: Post-transplant outcomes after pre-transplant use of MCS are similar to those when MCS is not required.

Acute Disease↗

PubMed2005

C-reactive protein predicts death in patients with non-ischemic cardiomyopathy.

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.

Aged↗

PubMed2005

Left ventricular assist device malfunction: an approach to diagnosis by echocardiography.

OBJECTIVES: A protocol using transthoracic echocardiography was designed to diagnose the common malfunctions of patients on chronic support with a left ventricular assist device (LVAD). BACKGROUND: Mechanical circulatory support, primarily with a LVAD, is increasingly used for treatment of advanced heart failure as a bridge to transplant and for long-term treatment of heart failure. The LVAD dysfunction is a recognized complication. To date, no studies have defined the role of transthoracic echocardiography in evaluating long-term mechanical complications of chronic LVAD support. METHODS: Transthoracic echocardiography was used in a protocol designed to detect the common types of mechanical malfunction. Patients were followed up with serial echocardiograms, and clinical validations were made with findings from a catheter-based protocol and inspection at the time of cardiac transplant or corrective surgery. RESULTS: Thirty-two patients with 44 LVADs were followed up during a four-year period using this protocol that correctly identified 11 patients with inflow valve regurgitation, 2 with intermittent inflow conduit obstruction, 1 with severe kinking of the outflow graft, and 9 with new insufficiency of the native aortic valve. CONCLUSIONS: As LVAD use for end-stage heart failure becomes widespread, and durations of support are extended, dysfunction will be increasingly prevalent. Transthoracic echocardiography provides a practical method to accurately identify the causes of mechanical dysfunction with patients on chronic LVAD support.

Adult↗

PubMed2005

Do statins increase the risk of idiopathic polyneuropathy?

A recent European case-control study suggested that statins increase the risk for polyneuropathy, a rare but serious neurologic condition. This risk was assessed in 272 patients with idiopathic polyneuropathy and 1,360 matched controls in the Intermountain Health Care electronic database. It was found that statin use before diagnosis was not significantly greater in patients than controls (odds ratio 1.30, 95% confidence interval 0.3 to 2.1, p = 0.27), nor were doses different between patients and controls.

Case-Control Studies↗