Risk of nephropathy is not increased by the administration of larger volume of contrast during coronary angiography.

It is proposed that contrast-induced nephropathy (CN) correlates with the use of increasing contrast volumes during coronary angiography. This supposition has led to the current recommendation to limit the dose of contrast in patients at high risk for renal dysfunction. Limits in contrast dosing may negatively impact the evaluation of patients undergoing cardiac catheterization for myocardial infarction and acute coronary syndrome. The objective of this study was to empirically assess, in a large population, the presence and strength of this correlation. Baseline blood samples and clinical information were obtained from 5256 consenting patients hospitalized for coronary angiography. Levels of serum creatinine were measured pre- and postcatheterization, and the total change in serum creatinine was calculated. Nephropathy was defined as a change of > or =0.5 mg/dL. The total volume of contrast dye (iopamidol, nonionic) used during the angiography procedure was recorded. Logistic regression was used for the primary analysis.The average age was 64 +/- 14 years, and 67% of patients were male. Paradoxically, the incidence of CN was inversely related to the volume in the overall population: 16%, 14%, 8%, and 7% for quartile (Q) 1 (<115 mL), Q2 (115-160 mL), Q3 (161-225 mL), and Q4 (>225 mL) of contrast, respectively (P-trend <0.001). In multivariable regression, this trend toward lower CN remained (Q1 (referent) OR = 1.0, Q2: 1.02, Q3: 0.60, Q4: 0.53, P < 0.001). Other predictors included age, left ventricular ejection fraction, diabetes, and baseline creatinine level (all P < 0.001). For patients at high risk, with a baseline creatinine >2.0 mg/dL (n = 415), contrast volume (Q1: <75 mL, Q2: 75-120 mL, Q3: 121-170 mL, Q4: >170 mL) did not predict either increased or decreased risk of CN (48%, 42%, 49%, 43%, respectively, P-trend = 0.76). This lack of predictive value remained after multivariable adjustment.In this large population, no association was found between the amount of contrast used during angiography and the incidence of CN in patients at initial high risk. The apparent inverse relation of risk with volume in the overall population is likely explained by clinical practice bias. If confirmed, these results may have important clinical implications.

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.

Superior predictive ability for death of a basic metabolic profile risk score.

BACKGROUND: The basic metabolic profile (BMP) is a common blood test containing information about standard blood electrolytes and metabolites. Although individual variables are checked for cardiovascular health and risk, combining them into a total BMP-derived score, as to maximize BMP predictive ability, has not been previously attempted. METHODS: Patients (N = 279,337) that received a BMP and had long-term follow-up for death were studied. Risk models were created in a training group (60% of study population, n = 167,635), validated in a test group (40% of study population, n = 111,702), and confirmed in the NHANES III (Third National Health and Nutrition Examination Survey) participants (N = 17,752). The BMP models were developed for 30-day, 1-year, and 5-year death using logistic regression with adjustment for age and sex. The BMP parameters were categorized as low, normal, or high based on the standard range of normal. Glucose was categorized as normal, intermediate, and high. Creatinine >or=2 mg/dL was further categorized as very high. RESULTS: Average age was 53.2 +/- 20.1 years, and 44.3% were male. The areas under the curve for the training and test groups for 30-day, 1-year, and 5-year death were 0.887 and 0.882, 0.850 and 0.848, and 0.858 and 0.847, respectively. The predictive ability of these risk scores was further confirmed in the NHANES III population and independent of the Framingham Risk Score. CONCLUSION: In large, prospectively followed populations, a highly significant predictive ability for death was found for a BMP risk model. We propose a total BMP score as an optimization of this routine baseline test to provide an important new addition to risk prediction.

Usefulness of routine periodic fasting to lower risk of coronary artery disease in patients undergoing coronary angiography.

Coronary artery disease (CAD) is common and multifactorial. Members of the Church of Jesus Christ of Latter-day Saints (LDS, or Mormons) in Utah may have lower cardiac mortality than other Utahns and the US population. Although the LDS proscription of smoking likely contributes to lower cardiac risk, it is unknown whether other shared behaviors also contribute. This study evaluated potential CAD-associated effects of fasting. Patients (n(1) = 4,629) enrolled in the Intermountain Heart Collaborative Study registry (1994 to 2002) were evaluated for the association of religious preference with CAD diagnosis (> or = 70% coronary stenosis using angiography) or no CAD (normal coronaries, <10% stenosis). Consequently, another set of patients (n(2) = 448) were surveyed (2004 to 2006) for the association of behavioral factors with CAD, with routine fasting (i.e., abstinence from food and drink) as the primary variable. Secondary survey measures included proscription of alcohol, tea, and coffee; social support; and religious worship patterns. In population 1 (initial), 61% of LDS and 66% of all others had CAD (adjusted [including for smoking] odds ratio [OR] 0.81, p = 0.009). In population 2 (survey), fasting was associated with lower risk of CAD (64% vs 76% CAD; OR 0.55, 95% confidence interval 0.35 to 0.87, p = 0.010), and this remained after adjustment for traditional risk factors (OR 0.46, 95% confidence interval 0.27 to 0.81, p = 0.007). Fasting was also associated with lower diabetes prevalence (p = 0.048). In regression models entering other secondary behavioral measures, fasting remained significant with a similar effect size. In conclusion, not only proscription of tobacco, but also routine periodic fasting was associated with lower risk of CAD.

Real-world safety and efficacy of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention.

BACKGROUND: Large randomized clinical trials have demonstrated differences in the efficacy and safety of glycoprotein (GP) IIb/IIIa inhibitors, but little has been published regarding comparisons of these agents in a "real-world" setting. PURPOSE: This study evaluated the safety and efficacy of GP IIb/IIIa inhibitors in a large population of patients who underwent percutaneous coronary intervention (PCI) during a 5-year period. METHODS: Patients undergoing PCI from 2000 through 2004 were eligible for inclusion if they received any single GP IIb/IIIa inhibitor. Patients with significant comorbidities were included. Patients were excluded if they received more than one GP IIb/IIIa inhibitor or underwent catheterization without PCI. Target activated clotting time was 200-250 seconds. RESULTS: Of 5,055 patients undergoing PCI, 4,321 (85%) received a single GP IIb/IIIa inhibitor (abciximab, 1,178; eptifibatide, 1,698; tirofiban, 1,445). Major bleeding complications were rare, ranging from 1.9-3.1%, and transfusion rates were low, ranging from 0.8-2.1%, with no significant differences among the agents evaluated. No significant differences in 1-year mortality, myocardial infarction, urgent target vessel revascularization or composite endpoint rates were identified among the therapeutic agents. CONCLUSIONS: In this large study of PCI patients, GP IIb/IIIa inhibition was associated with a low incidence of major bleeding complications and requirement of transfusion. With appropriate management, GP IIb/IIIa inhibitor use can benefit patients undergoing PCI, with minimal risk of bleeding complications.

Comparison of effects of simvastatin alone versus fenofibrate alone versus simvastatin plus fenofibrate on lipoprotein subparticle profiles in diabetic patients with mixed dyslipidemia (from the Diabetes and Combined Lipid Therapy Regimen study).

Diabetes mellitus is a strong risk factor for atherosclerosis and is often characterized by dyslipidemia. Besides acting on traditional lipids, statins and fibrates may also exert beneficial effects on various pro- and antiatherogenic lipid subparticles. This analysis was undertaken to evaluate combination therapy on lipid subparticles in the Diabetes and Combined Lipid Therapy Regimen (DIACOR) study. Patients with type 2 diabetes mellitus and no histories of coronary heart disease were evaluated (n = 498). Eligible patients underwent a 6- to 8-week washout period of all lipid-lowering medications and were enrolled if they demonstrated mixed dyslipidemia (having >or=2 of the following 3 lipid parameters: low-density lipoprotein [LDL] cholesterol >or=100 mg/dl, triglycerides >or=200 mg/dl, and high-density lipoprotein cholesterol <40 mg/dl). Patients were randomized to simvastatin 20 mg, fenofibrate 160 mg, or combined simvastatin 20 mg and fenofibrate 160 mg. Lipid subparticles were assessed 12 weeks after randomization by the Vertical Auto Profile II method. A total of 300 patients (mean age 61.6 +/- 11.5 years, 55% men) were randomized. Combination therapy was superior in lowering LDL cholesterol pattern B (-33.9 mg/dl) and dense very low-density lipoprotein cholesterol (-10.0 mg/dl) and increasing high-density lipoprotein3 (+2.3 mg/dl) and exerted the greatest change in altering the LDL cholesterol size profile. A potential effect on lipoprotein(a) (-0.5 mg/dl) was also found. For those with triglycerides >170 mg/dl, combination therapy was superior in lowering dense very low density lipoprotein cholesterol (-10.7 mg/dl) and LDL cholesterol pattern B (-35.8 mg/dl), the lipids that tend to be formed in the presence of elevated triglycerides. In conclusion, in this trial of mixed dyslipidemic patients with diabetes, combination therapy was more effective in changing a variety of other cardiovascular risk markers.

Soluble CD40 ligand as a predictor of coronary artery disease and long-term clinical outcomes in stable patients undergoing coronary angiography.

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.

Surgical revascularization is associated with improved long-term outcomes compared with percutaneous stenting in most subgroups of patients with multivessel coronary artery disease: results from the Intermountain Heart Registry.

BACKGROUND: Coronary artery bypass surgery (CABG) and percutaneous coronary intervention with stenting (PCI-S) are both safe and effective approaches for revascularization in patients with multivessel coronary artery disease. However, conflicting information exists when comparing the efficacy of the two methods. In this study, we examined the outcomes of major adverse cardiovascular events and death for subgroups of typical "real-world" patients undergoing coronary revascularization in the modern era. METHODS AND RESULTS: Patients were included if they were revascularized by CABG or PCI-S, had > or = 5 years of follow-up, and had > or = 2-vessel disease. Patients were followed for an average of 7.0+/-3.2 years for incidence of death and major adverse cardiovascular events (death, myocardial infarction, or repeat revascularization). Multivariate regression models were used to correct for standard cardiac risk factors including age, sex, hyperlipidemia, diabetes mellitus, family history of coronary artery disease, smoking, hypertension, heart failure, and renal failure. Subgroup analyses were also performed, stratified by age, sex, diabetes, ejection fraction, and history of PCI-S, CABG, or myocardial infarction. A total of 6369 patients (CABG 4581; PCI-S 1788) were included. Age averaged 66+/-10.9 years, 76% were male, and 26% were diabetic. Multivariate risk favored CABG over PCI-S for both death (hazard ratio 0.85; P=0.001) and major adverse cardiovascular events (hazard ratio 0.51; P<0.0001). A similar advantage with CABG was also found in most substrata, including diabetes. CONCLUSIONS: In this large observational study of patients undergoing revascularization for multivessel coronary artery disease, a long-term benefit was found, in relationship to both death and major adverse cardiovascular events, for CABG over PCI-S regardless of diabetic status or other stratifications.

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.

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.

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).

Improved long-term survival associated with stent deployment during percutaneous coronary interventions: results from a registry of 3399 patients.

INTRODUCTION: The use of stents in percutaneous coronary intervention (PCI) improves procedural success and reduces restenosis. However, few studies have had a sufficient sample size or adequate follow-up to determine whether this advantage results in a positive effect on mortality. METHODS: A total of 3399 patients undergoing PCI (stented [with dual antiplatelet therapy]: n = 2456, nonstented [balloon PCI or rotational atherectomy]: n = 942) at a single institution from 1994 to 2001 were followed up prospectively (43 +/- 22 and 54 +/- 25 months, respectively) for acute and long-term clinical outcomes. RESULTS: Angiographic success (< 50% residual stenosis) (99.7% vs 97.7%, P < .001) and acute gain (3.02 +/- 0.55 vs 2.08 +/- 0.62 mm, P < .001) were both greater for stented lesions. Likewise, procedural complications of death (0.04% vs 0.4%, P = .02) and dissection (4.9% vs 8.0%, P = .001) were lower in the stent group, as were rates of 6-month clinical restenosis (10.3% vs 16.3%, P < .001). Eight-year mortality (12.0% vs 18.2%, hazard ratio = 0.78, P = .009) was lower among the stent group, as was long-term major adverse cardiac events (36.2% vs 50.6%, P < .001), but no difference in long-term myocardial infarction was found (6.5% vs 7.6%, P = .28). In multivariable Cox regression, stent use (hazard ratio = 0.76, 95% CI [0.58-0.99], P = .04) remained associated with significantly reduced mortality. CONCLUSION: This large prospective study demonstrates that, in addition to a general improvement in procedural success and a reduced need for repeat revascularization, the use of stents with dual antiplatelet therapy was associated with a significant reduction in long-term mortality. Consideration should be given for the use of stents whenever feasible during PCI.

Candidate gene susceptibility variants predict intermediate end points but not angiographic coronary artery disease.

BACKGROUND: Moderate-sized studies have suggested that variants of candidate genes can influence laboratory markers of coronary artery disease (CAD), but whether they predict parallel changes in clinical CAD risk is unknown. METHODS: We studied a single nucleotide polymorphism (SNP) from each of the 5 candidate genes for intermediate (laboratory) and clinical (angiographic CAD) end points in a large cohort of patients. The 5 gene SNPs were cholesteryl ester transfer protein (CETP) TaqIB (N = 3219), ATP-binding cassette (ABCA1) G596A (N = 3302), lipoprotein lipase (LPL) HindIII (N = 909), plasminogen activator inhibitor, type 1 (PAI1), 4G/5G (N = 1142), and hepatic lipase (HL) C-541T (N = 4704). Intermediate outcomes were high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs). Cases had 1- to 3-vessel CAD (> or = 70% stenosis); controls had angiographically normal coronaries. RESULTS: Cholesteryl ester transfer protein predicted HDL (mean, B1B1 35.0 mg/dL, B2B2 38.6 mg/dL; P < .001) but not CAD (B1B1 74%, B2B2 70%; adjusted P = .35, odds ratio [OR] = 0.89). ABCA1 predicted HDL (mean, GG = 36.4 mg/dL, AA = 39.2 mg/dL; P = .02) but not CAD (GG 74%, AA 75%; adjusted P = .96, OR = 0.99). HL predicted HDL (CC 37.1 mg/dL, TT 40.9 mg/dL; P = .002) but not CAD (CC 71%, TT 68%, adjusted P = .66, OR = 0.94). LPL predicted TG (median: [++] 134, [--] 98 mg/dL; P < .001) but not CAD ([++] 79%, [--] 79%; adjusted P = .99, OR = 1.00). PAI1 predicted TG (median, 4G4G 130 mg/dL, 5G5G 148 mg/dL; P = .16), but not CAD (4G4G 77%, 5G5G 76%; adjusted P = .62, OR = 1.11). CONCLUSIONS: Five SNPs predicted differences in risk-related lipids but not angiographic CAD. These discrepancies suggest that genetic determinants of CAD are complex and intermediate phenotypes are poor surrogates. These findings have important implications for future directions in genetic research.

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.

Serum uric acid independently predicts mortality in patients with significant, angiographically defined coronary disease.

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.

Early effects of statins in patients with coronary artery disease and high C-reactive protein.

Statins improve survival in patients with coronary artery disease, especially those with elevated C-reactive protein (CRP). Although some randomized studies have shown a delay in statin-related survival advantage of up to 2 years, recent studies demonstrated early (<2 months) survival benefit in certain patient groups. We hypothesized that this early benefit relates to baseline CRP concentration. Patients (n = 2,924) with significant, angiographically defined coronary artery disease (>/=70% stenosis in >/=1 coronary artery) were followed for an average of 2.4 years after discharged on a statin prescription. CRP was divided into tertiles (<1.2, 1.2 to 1.7, >1.7 mg/dl), and Kaplan-Meier methods were used to determine timing of statin benefit in both the overall population and a propensity score-matched subgroup. Cox regressions (multivariable and propensity score approaches) were used to predict mortality. Statins were prescribed for 28.4% of patients. In the first CRP tertile, no early statin benefit was observed (adjusted hazard ratio 0.69, 95% confidence interval [CI] 0.30 to 1.6, p = 0.39), and survival curves separated after >2 years. However, in the second and the third tertiles, statin survival curves separated much earlier ( approximately 3 months and 1 week, respectively) and statins predicted improved survival (second tertile: hazard ratio 0.63, 95% CI 0.32 to 1.2, p = 0.17; third tertile: hazard ratio 0.35, 95% CI 0.18 to 0.67, p = 0.002). Propensity score analysis confirmed both statin benefit and early timing. Thus, statin use in patients with high CRP provides not only a larger but also a significantly earlier absolute survival benefit than statin use in patients with lower CRP. This provides further evidence of an anti-inflammatory effect of statins.

Improvements in 1-year cardiovascular clinical outcomes associated with a hospital-based discharge medication program.

BACKGROUND: Despite recent advances in the treatment and prevention of cardiovascular disease, a treatment gap for secondary prevention medications still exists. OBJECTIVE: To develop and implement a program ensuring appropriate prescription of aspirin, statins, beta-blockers, angiotensin-converting enzyme inhibitors, and warfarin at hospital discharge. DESIGN: A nonrandomized before-after study comparing patients hospitalized before (1996-1998) and after (1999-2002) implementation of a discharge medication program (DMP). Patients were followed for up to 1 year. SETTING: The 10 largest hospitals in the Utah-based Intermountain Health Care system. PATIENTS: In the pre-DMP and DMP time periods, 26,000 and 31,465 patients, respectively, were admitted to cardiovascular services (n = 57,465). MEASUREMENTS: Prescription of indicated medications at hospital discharge; postdischarge death or readmission. RESULTS: By 1 year, the rate of prescription of each medication increased significantly to more than 90% (P < 0.001); this rate was sustained. At 1 year, unadjusted absolute event rates for readmission and death, respectively, were 210 per 1000 person-years and 96 per 1000 person-years before DMP implementation and 191 per 1000 person-years and 70 per 1000 person-years afterward. Relative risk for death and readmission at 30 days decreased after DMP implementation; hazard ratios (HRs) for death and readmission were 0.81 (95% CI, 0.73 to 0.89) and 0.92 (CI, 0.87 to 0.99) (P < 0.001 and P = 0.017, respectively). At 1 year, risk for death continued to decrease (hazard ratio, 0.79 [CI, 0.75 to 0.84]; P < 0.001) while risk for readmission stabilized (hazard ratio, 0.94 [CI, 0.90 to 0.98]; P = 0.002), probably because survivors had more opportunities to be readmitted. LIMITATIONS: The study design was observational and nonrandomized, and the authors could not control for potential confounders or determine the extent to which secular trends accounted for the observed improvements. CONCLUSIONS: A relatively simple quality improvement program aimed at enhancing the prescription of appropriate discharge medications among cardiovascular patients is feasible and can be sustained within an integrated multihospital system. Such a program may be associated with improvements in cardiovascular readmission rates and mortality.

Which features of the metabolic syndrome predict the prevalence and clinical outcomes of angiographic coronary artery disease?

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(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.

Effect of fasting glucose levels on mortality rate in patients with and without diabetes mellitus and coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Diabetes mellitus (DM) is predictive of increased mortality for patients with coronary artery disease (CAD). To what extent this risk extends below the diabetic threshold (fasting glucose level [FG] <126 mg/dL) is uncertain. METHODS: The study objective was to determine the risk associated with FG in a prospectively assembled cohort of 1612 patients with CAD who were undergoing percutaneous coronary intervention (PCI) and had a FG measured or a clinical diagnosis of DM (CDM). Patients were grouped as: CDM; no CDM, but FG > or =126 mg/dL (ADA-DM); impaired FG, 110-125 mg/dL (IFG); or normal FG, <110 mg/dL (NFG). Survival was assessed for 2.8 +/- 1.2 years. RESULTS: The average patient age was 62 +/- 12 years; 74% of the patients were men. Diagnostic frequencies were: CDM, 24%; ADA-DM, 18%; IFG, 19%; and NFG, 39%. Mortality rates were greater for patients in the CDM (44/394 [11.2%], P <.0001), ADA-DM (27/283 [9.5%], P <.001), and IFG (20/305 [6.6%], P =.04) groups than patients in the NFG group(12/630 [1.9%]). Independent receiver operating characteristic analysis chose FG > or =109 mg/dL as the best cutoff for increased risk (sensitivity, 81%; specificity, 51%). After adjustment with Cox regression analysis, CDM (hazard ratio [HR] = 5.0; 95% CI, 2.6-9.6; P <.001), ADA-DM (HR, 4.1; 95% CI, 2.1-8.2; P <.001), and IFG status (HR, 3.2; 95% CI, 1.5-6.5; P =.002) remained independent predictors of mortality. CONCLUSIONS: Prognostically significant abnormalities of FG are much more prevalent (61%) than expected in patients with CAD who are undergoing PCI. Despite revascularization, the associated mortality risk of even mild elevations in FG is substantial, emphasizing the importance of early detection and treatment of glycemia-related risk.