Timothy R. Wessel

Abnormal Coronary Vasomotion as a Prognostic Indicator of Cardiovascular Events in Women Results From the National Heart, Lung, and Blood Institute–Sponsored Women’s Ischemia Syndrome Evaluation (WISE)

Background—Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women. Methods and Results—As part of the Women’s Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less change in coronary cross-sectional area (&Dgr;CSA) in response to acetylcholine (P =0.0006) and nitroglycerin (P =0.04). In addition, women with abnormal coronary dilator response to acetylcholine had less time free from cardiovascular events (P =0.004). In multivariable analysis, after controlling for age, hypertension, diabetes, dyslipidemia, tobacco use, and CAD severity, %&Dgr;CSA with acetylcholine (P =0.001) independently predicted events. When the outcome was restricted to only death, myocardial infarction, congestive heart failure, and stroke, %&Dgr;CSA with acetylcholine remained a significant predictor (P =0.006). Conclusions—In women in this study, impaired coronary vasomotor response to acetylcholine was independently linked to adverse cardiovascular outcomes regardless of CAD severity.

Hemoglobin level is an independent predictor for adverse cardiovascular outcomes in women undergoing evaluation for chest pain

Objectives This study was designed to investigate the relationship between hemoglobin level (Hgb) and adverse cardiovascular outcomes in women with suspected ischemia. Background Low Hgb levels correlate with increased cardiovascular morbidity and mortality in patients presenting with acute myocardial infarction (MI) or congestive heart failure (CHF). However, the prognostic significance of Hgb in women with suspected ischemia is unclear. Methods As part of the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Womens Ischemia Syndrome Evaluation (WISE), we prospectively studied 936 women referred for coronary angiography to evaluate suspected ischemia. We compared Hgb levels with cardiovascular risk factors, core lab interpreted angiograms, inflammatory markers, and adverse cardiovascular outcomes. Results Of women enrolled, 864 (mean age 58.4 ±11.6 years) had complete Hgb, angiogram, and follow-up (mean 3.3 ± 1.7 years) data. The mean Hgb was 12.9 g/dl (range 7.7 to 16.4 g/dl) and 184 women (21%) were anemic (Hgb <12 g/dl). Anemic women had higher creatinine and were more likely to be nonwhite and have a history of diabetes, hypertension, and CHF (p < 0.05). However, we found no difference in EF or severity of coronary artery disease. Anemic women had a higher risk of death from any cause (10.3% vs. 5.4%; p = 0.02) and total adverse outcomes (26% vs. 16%, p < 0.01). In a multivariable model, decreasing Hgb was associated with significantly higher risk of adverse outcomes (hazard ratio = 1.20, p = 0.002). Also, anemic women had shorter survival time free of adverse outcome (p < 0.001). Conclusions Our findings extend previous reports, linking lower hemoglobin levels with higher risk for adverse cardiovascular outcomes, to women evaluated for suspected ischemia in the absence of acute MI or CHF.

Modulatory Effects of Atorvastatin on Endothelial Cell–Derived Chemokines, Cytokines, and Angiogenic Factors

Study Objective. To investigate the immunomodulatory effects of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (statins) by determining whether atorvastatin alters the production of specific endothelium‐derived immunoactive proteins and whether its treatment effects depend on its concentration and/or inhibition of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase.

Multimarker approach predicts adverse cardiovascular events in women evaluated for suspected ischemia: results from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation.

Inflammatory marker and hemoglobin levels (eg biomarkers) considered separately, predict adverse events in selected populations.

Complementary and alternative medicine use among individuals participating in research: implications for research and practice.

Study Objectives. To determine the frequency and type of complementary and alternative medicine (CAM) use among healthy volunteers participating in research, and to investigate the potential for interactions between commonly used CAM modalities and various drugs.

Atorvastatin Effect on Circulating and Leukocyte-Produced CD40 Ligand Concentrations in People with Normal Cholesterol Levels: A Pilot Study

Study Objectives. To investigate whether atorvastatin decreases serum or leukocyte‐produced CD40 ligand (CD40L) levels and whether these effects are dependent on reduction in low‐density lipoprotein cholesterol (LDL) levels in people without overt dyslipidemia.

OI-A-3

Leukocytes are important in initiation of cardiovascular disease (CVD), in part, through secretion of matrix metalloproteinases (MMPs). Statins may reduce MMP concentrations in hypercholesterolemia. No study has examined the effect of statins on MMP production from leukocytes in patients without overt dyslipidemia.

Commentary on "new and emerging theories of cardiovascular disease".

In Dr Alpert’s article “New and Emerging Theories of Cardiovascular Disease: Infection and Elevated Iron,” she reviews the possible contributions of chronic infection and chronic iron overload to the development and progression of coronary heart disease (CHD). These are 2 of a myriad of associated or postulated factors that may contribute to the number one cause of death in industrialized countries. In commentary, however, several observations can be made. First, although there is still much research to be done, the modifiable risk factors that seem to be most important in the development of CHD have been identified. Despite the assertion by some that conventional major cardiovascular risk factors account for less than 50% of the risk of developing CHD (Heller and others 1984; Hennekens 1998; Ridker and others 2002), recent work has emphasized that the traditional risk factors of diabetes mellitus, dyslipidemia, hypertension, and cigarette smoking have a much higher prevalence than previously noted. At least 1 of these risk factors was identified in 80% to 90% of patients with CHD (Greenland and others 2003; Khot and others 2003). Furthermore, other research has suggested that these conventional risk conditions are often undertreated (Klungel and others 1998; Mantel-Teeuwisse and others 2003; Saydah and others 2004). Thus, the identification and optimal management of the conventional risk factors for CHD should continue to be a number one priority. Second, although the role of infection in atherogenesis remains intriguing but investigational (Muhlstein and Anderson 2003), the central role of endothelial function in vascular health or disease states is increasingly recognized. The endothelium appears to be the key modulator of a host of homeostatic processes including maintenance of vascular tone, regulation of blood fluidity and thrombosis, and control of inflammatory processes through the production of mediators, expression of chemoattractants or adhesion molecules, regulation of permeability, and control of vascular growth. Under the influence of risk factors or conditions including chronic infection and inflammatory states, the endothelium becomes dysfunctional and homeostatic mechanisms are disrupted (Quyyumi 1998; Fahdi and others 2003; Keller and others 2003; Widlansky and others 2003). The endothelium appears to be the sensor on which individual factors act, and in this way it may be viewed as the transducer for global cardiovascular disease risk. The association of infections, immune mechanisms, and inflammation with atherosclerosis is likely mediated through the complex interactions resulting in endothelial injury and perhaps local inflammatory states. Recently, researchers have proposed that coronary artery disease is not likely to be the result of any one type of infection or infectious agent but that many different infections can injure the endothelium and lead to local and diffuse inflammation of the vasculature (Prasad and others 2002; Fahdi and others

OII-B-2Influence of SLCO1B1 (OATP1B1/OATP-C) gene polymorphisms on cholesterol responses to atorvastatin

The polymorphic SLCO1B1 gene encodes for the OATP‐C protein, which is important in hepatic uptake of many xenobiotics. The *5 allele has been recently shown to result in diminished hepatic uptake of atorvastatin, yet the clinical relevance is unclear. We hypothesized that *5 carriers would exhibit attenuated response to atorvastatin compared with wild‐type homozygotes (*1/*1).

PIII-13Effect of high-dose atorvastatin on serum leptin concentrations in non-diabetic, non-dyslipidemic individuals

Leptin is an adipocytokine associated with vascular inflammation. The effect of high dose atorvastatin (HDA) on circulating leptin concentrations has not been studied. We investigated whether HDA modulates leptin levels in non‐diabetic, normocholesterolemic individuals.