Frederick F. Samaha

Social Support and Self-Care of Patients with Heart Failure

BackgroundSocial support can influence treatment adherence of patients with chronic illnesses, which may explain the positive effects of social support on heart failure (HF) outcomes.PurposeTo investigate the effects of social support among patients with HF, we examined whether aspects of social support were associated with self-care, including medication adherence, dietary adherence, and HF symptom monitoring functions.MethodsWe recruited 74 patients with HF from cardiology clinics of a Veterans Affairs Medical Center and a university-affiliated hospital, and tested the relationships between social support and the patients’ self-care.ResultsConsistent with previous research in older adults, family members, especially spouses, were often involved in the medical care of patients with chronic HF and provided a range of levels of support to patients. Self-care was generally poor, as measured across several self-care domains. Perceived social support was moderately associated with relatively better self-reported medication and dietary adherence, and other aspects of self-care such as daily weighing.ConclusionsThese findings suggest that a relatively higher level of self-care is an important correlate of social support and may explain how social support influences HF outcomes. This study also suggests that family members should play a greater part in clinical care focused on improving self-care.

Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia

Background Many patients with coronary heart disease do not achieve recommended LDL-cholesterol levels, due to either intolerance or inadequate response to available lipid-lowering therapy. Microsomal triglyceride transfer protein (MTP) inhibitors might provide an alternative way to lower LDL-cholesterol levels. We tested the safety and LDL-cholesterol-lowering efficacy of an MTP inhibitor, AEGR-733 (Aegerion Pharmaceuticals Inc., Bridgewater, NJ), alone and in combination with ezetimibe.Methods We performed a multicenter, double-blind, 12-week trial, which included 84 patients with hypercholesterolemia. Patients were randomly assigned ezetimibe 10 mg daily (n = 29); AEGR-733 5.0 mg daily for the first 4 weeks, 7.5 mg daily for the second 4 weeks and 10 mg daily for the last 4 weeks (n = 28); or ezetimibe 10 mg daily and AEGR-733 administered with the dose titration described above (n = 28).Results Ezetimibe monotherapy led to a 20–22% decrease in LDL-cholesterol concentrations. AEGR-733 monotherapy led to a dose-dependent decrease in LDL-cholesterol concentration: 19% at 5.0 mg, 26% at 7.5 mg and 30% at 10 mg. Combined therapy produced similar but larger dose-dependent decreases (35%, 38% and 46%, respectively). The number of patients who discontinued study drugs owing to adverse events was five with ezetimibe alone, nine with AEGR-733 alone, and four with combined ezetimibe and AEGR-733. Discontinuations from AEGR-733 were due primarily to mild transaminase elevations.Conclusions Inhibition of LDL production with low-dose AEGR-733, either alone or in combination with ezetimibe, could be an effective therapeutic option for patients unable to reach target LDL-cholesterol levels.

Effects of Pioglitazone on Lipoproteins, Inflammatory Markers, and Adipokines in Nondiabetic Patients with Metabolic Syndrome

Objective—The purpose of this research was to evaluate the short-term effects of pioglitazone (PIO) on high-density lipoprotein cholesterol (HDL-C) and other metabolic parameters in nondiabetic patients with metabolic syndrome (MetSyn). Methods and Results—Sixty nondiabetic adults with low HDL-C and MetSyn were randomized to PIO or matching placebo for 12 weeks. PIO increased HDL-C by 15% and 14% at 6 and 12 weeks, respectively, compared with placebo (P<0.001). Changes in HDL-C were correlated to changes in adiponectin (r=0.34; P=0.01) but not to changes in insulin resistance. PIO did not affect serum triglycerides or low-density lipoprotein (LDL) cholesterol concentrations but reduced the number of small LDL particles by 18% (P<0.001). PIO reduced median C-reactive protein levels by 31% (P<0.001) and mean resistin levels by 10% (P=0.02) while increasing mean serum levels of adiponectin by 111% (P<0.001) compared with placebo. PIO did not affect weight and modestly decreased insulin resistance. Conclusions—In nondiabetic patients with low HDL-C and MetSyn, PIO significantly raised HDL-C and favorably affected lipoprotein particle size, markers of inflammation, and adipokines without changes in triglycerides, LDL-C, or weight. These results suggest that PIO has direct effects on HDL, which may contribute to its antiatherogenic effects.

Effects of Rosiglitazone on Lipids, Adipokines, and Inflammatory Markers in Nondiabetic Patients With Low High-Density Lipoprotein Cholesterol and Metabolic Syndrome

Background—PPAR-γ agonists improve insulin sensitivity and glycemic control in type 2 diabetes and may reduce atherosclerosis progression. Thus, PPAR-γ agonists may be an effective therapy for metabolic syndrome. However, the full spectrum of potentially antiatherogenic mechanisms of PPAR-γ agonists have not been fully tested in nondiabetic patients with metabolic syndrome. Methods and Results—We performed a prospective, double-blinded, placebo-controlled study of 60 nondiabetic subjects with low high-density lipoprotein cholesterol (HDL-C) level and metabolic syndrome to rosiglitazone 8 mg daily or placebo for 12 weeks. We found no significant effect of rosiglitazone on HDL-C (+5.5% versus +5.8%, P=0.89), and an increase in total cholesterol (+8% versus −1%; P=0.03). Nevertheless, rosiglitazone significantly increased adiponectin (+168% versus +25%; P<0.001), and lowered resistin (−6% versus +4%; P=0.009), C-reactive protein (−32% versus +36%, P=0.002), interleukin (IL)-6 (−22% versus +4%, P<0.001), and soluble tumor-necrosis factor-α receptor-2 (−5% versus +7%, P<0.001). Conclusions—These findings suggest that rosiglitazone, presumably through its PPAR-γ agonist properties, has direct effects on inflammatory markers and adipokines in the absence of favorable lipid effects. These findings may help explain the mechanism underlying the possible antiatherosclerotic effects of rosiglitazone.

Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans.

The objective of this study was to determine whether warfarin dosing algorithms developed for Caucasians and African Americans on the basis of clinical, environmental, and genetic factors will perform better than an empirical starting dose of 5 mg/day. From April 2002 through December 2005, 259 subjects (Caucasians and African Americans) who started using warfarin were prospectively followed until they reached maintenance dose. The Caucasian algorithm included 11 variables (R2 = 0.43). This model (which predicted 51% of the doses to within 1 mg of the observed dose) performed better than 5 mg/day (which predicted 29% of the doses to within 5 ± 1 mg). The African‐American algorithm included 10 variables (R2 = 0.28). This model predicted 37% of the doses to within 1 mg of the observed dose, representing a small improvement compared with 5 mg/day (which predicted 34% of the doses to within 1 mg of 5 mg/day). These results were similar to the results we obtained from testing other published algorithms. The dosing algorithms explained <45% of the observed variability in Caucasians, and the algorithms performed only marginally better for African Americans when compared with giving 5 mg empirically.

Warfarin Response and Vitamin K Epoxide Reductase Complex 1 in African Americans and Caucasians

The objective of this study was to determine whether two vitamin K epoxide reductase complex 1 (VKORC1) polymorphisms contribute to the variability in warfarin response, particularly in African Americans. The effect of the VKORC1 1173C/T and −1639G/A polymorphisms was examined in a prospective cohort study of 338 warfarin users. Subjects carrying an 1173T allele had a lower warfarin maintenance dose compared with subjects with the CC genotype in African Americans (−12.10 mg/week±4.93; P=0.02) and Caucasians (−14.41 mg/week±3.28; P<0.001). Before reaching maintenance dose, only Caucasians with the T allele had significantly increased risk of international normalized ratio >3 (odds ratio=3.10; 95% confidence interval: 1.73–5.55) compared with Caucasians with the CC genotype. Polymorphisms in the VKORC1 gene are associated with warfarin maintenance dose requirements among both African Americans and Caucasians. However, these polymorphisms may not be as useful in predicting over‐anticoagulation among African Americans.

Warfarin and cytochrome P450 2C9 genotype: possible ethnic variation in warfarin sensitivity

INTRODUCTION Warfarin is a widely prescribed, efficacious oral anticoagulant. S-warfarin, the more active form, is metabolized by the cytochrome P450 (CYP)2C9 enzyme. The aim was to evaluate the influence of two CYP2C9 functional polymorphisms (*2 and *3) on warfarin dose in African-Americans, an unstudied population and Caucasians, and also to assess the effect of these polymorphisms on anticoagulation response after accounting for nongenetic factors and genetic factors that might also impact the dose-response relationship of warfarin. PATIENTS AND METHODS A prospective cohort of 362 patients with a target international normalized ratio of between 2.0 and 3.0 were genotyped. Warfarin sensitivity stratified by genotype was investigated using univariate and multivariate analyses. RESULTS The maintenance dose of warfarin was significantly related to genotype (p < 0.01) (variant carriers: 31.25 mg/week; wild-type: 37.5 mg/week), even after adjustment for possible confounding factors (p = 0.046). However, the effect of genotype was restricted to Caucasians, in whom variant carriers had a significantly lower maintenance dose compared with wild-type homozygotes (unadjusted: p < 0.01; adjusted: p = 0.02). There was a greater risk of over-anticoagulation among Caucasian variant carriers, although this was only observed prior to reaching maintenance dose. For African-American variant carriers, there was no difference in warfarin response based on CYP2C9 genotype. DISCUSSION CYP2C9 *2 and *3 variants provide predictive information in anticoagulation response. However, these variants may not be useful in African-Americans or as a marker of long-term over-anticoagulation once a stable dose is reached.

Usefulness of the TIMI risk score in predicting both short- and long-term outcomes in the Veterans Affairs Non–Q-Wave Myocardial Infarction Strategies In-Hospital (VANQWISH) Trial

We sought to test the validity and clinical utility of the Thrombolysis In Myocardial Infarction (TIMI) risk score for patients who have non-Q-wave myocardial infarction. A post hoc analysis of the Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) Trial was performed, wherein patients were assigned a TIMI risk score from which both 30-day and 12-month outcomes (death, nonfatal myocardial infarction, or urgent revascularization) were assessed. At 30 days, the TIMI risk score showed a close match between observed and predicted probabilities of events after adjustment for overall event rates. The event rate at 30 days was 6% for a score of 0 to 2, 10% for a score of 3, 13% for a score of 4, and 14% for a score of 5 to 7 (p = 0.003 and c statistic 0.59). Discriminative ability of the score was greater in the conservative group at 30 days (p = 0.0004, c statistic 0.67). The score remained modestly predictive of events at 1 year (c statistic 0.60). Conservative strategy patients had better 30-day outcomes than the invasive strategy patients if their score was 0 to 2 (odds ratio 0.24, 95% confidence interval 0.08 to 0.76). No significant difference in outcomes between strategies was detected for a score > or =3. The TIMI risk score provides moderate incremental prognostic information in high-risk patients, during both short- and long-term follow-up.

Stress test criteria used in the conservative arm of the FRISC-II trial underdetects surgical coronary artery disease when applied to patients in the VANQWISH trial.

OBJECTIVES We sought to determine whether the stringent stress test criteria for crossover to cardiac catheterization in the conservative arm of the Fast Revascularization During Instability in Coronary Artery Disease (FRISC-II) trial subjected this strategy to a disadvantage by failing to identify patients with surgical coronary artery disease (CAD). BACKGROUND In FRISC-II, an invasive strategy provided superior outcomes compared with a conservative strategy for patients with acute coronary syndromes. However, compared with the stress test criteria for crossover to catheterization in the Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) trial, the FRISC-II criteria were more restrictive and did not use nuclear imaging or pharmacologic stress testing. METHODS We analyzed the conservative arm of VANQWISH to identify the prevalence of surgical CAD in those patients who met the VANQWISH, but not FRISC-II, criteria for catheterization. RESULTS Of 385 VANQWISH patients, 90 (23%) met the FRISC-II criteria for catheterization. Another 98 patients (25%) met only VANQWISH stress test criteria (60 patients by exercise and 38 by pharmacologic nuclear stress testing). Among subjects who underwent predischarge angiography, those meeting only VANQWISH stress test criteria had a high prevalence of surgical CAD (51%), comparable to patients who met FRISC-II criteria (54%, p = 0.805). CONCLUSIONS The overly stringent risk stratification protocol for conservative-arm patients in FRISC-II could have failed to identify almost as many patients with surgical CAD as it identified. A lower threshold for catheterization in the FRISC-II conservative patients might have improved their outcomes and therefore diminished the putative benefit of an invasive strategy.

New International Measuring Stick for Defining Obesity in Non-Europeans

Body mass index (BMI) is a useful way of classifying the degree of excess weight in an individual. Defining BMI cut points at which adverse cardiovascular outcomes, diabetes mellitus, and other comorbidities are more likely to occur affords clinically relevant guidelines for patient care. Expert panels from both the National Institutes of Health and the World Health Organization1–3 have developed such cut points, which define overweight as a BMI (weight [in kilograms]/height [in meters squared]) of 25.0 to 29.9 kg/m2, mild or grade I obesity as a BMI of 30 to 34.9 kg/m2, grade II or more severe obesity as a BMI of 35 to 39.9 kg/m2, and extreme or grade III obesity as a BMI ≥40 kg/m2. Epidemiological studies focusing on persons of European descent have verified that these cut points are, indeed, associated with incremental risk for cardiovascular events and all-cause death.4–6 An awareness that appropriate BMI cut points for Asians may differ from those of Europeans has been largely based on observations that cardiovascular and metabolic risk in Asians occur at a lower BMI than in Europeans. For example, there is increasing evidence of a high prevalence of type 2 diabetes mellitus and elevated cardiovascular risk in certain Asian countries, despite an average BMI in these countries that is <25 kg/m2.7,8 Even for Asian-Americans, the prevalence of diabetes mellitus after adjustment for BMI is 60% higher than in their European counterparts.9 Article p 2111 The definition of clinically useful BMI cut points in Asian populations has been difficult, at least in part because of the limitations of previously used methodologies. Two general methodological approaches have been taken in the past to derive these BMI cut points in Asians: (1) recalculation of BMI cut …