Michael E. Stillabower

Beneficial Effects of Cholesterol-Lowering Therapy on the Coronary Endothelium in Patients with Coronary Artery Disease

BACKGROUND Impaired endothelium-mediated relaxation contributes to vasospasm and myocardial ischemia in patients with coronary artery disease. We hypothesized that cholesterol-lowering therapy with the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor lovastatin could improve endothelium-mediated responses in patients with coronary atherosclerosis. METHODS In a randomized, double-blind, placebo-controlled trial, we studied coronary endothelial responses in 23 patients randomly assigned to either lovastatin (40 mg twice daily; 11 patients) or placebo (12 patients) plus a lipid-lowering diet (American Heart Association Step 1 diet). Patients were studied 12 days after randomization and again at 5 1/2 months. These patients had total cholesterol levels ranging from 160 to 300 mg per deciliter (4.1 to 7.8 mmol per liter) and were undergoing coronary angioplasty. At the initial and follow-up studies, patients received serial intracoronary infusions (in a coronary artery not undergoing angioplasty) of acetylcholine to assess endothelium-mediated vasodilatation. The responses of the coronary vessels were analyzed with quantitative angiography. RESULTS The patients in the placebo and lovastatin groups had similar responses to acetylcholine at a mean of 12 days of therapy (expressed as the percentage of change in diameter in response to acetylcholine doses of 10(-9) M, 10(-8) M, 10(-7) M, and 10(-6) M). In the placebo group, the respective mean (+/- SE) changes were 1 +/- 2, 0 +/- 2, -2 +/- 4, and -19 +/- 4 percent; in the lovastatin group, they were -2 +/- 2, -4 +/- 4, -12 +/- 5, and -16 +/- 7 percent (P = 0.32). (Coronary-artery constriction is reflected by negative numbers). The responses to acetylcholine in the placebo group after a mean of 5.5 months of therapy were -3 +/- 3, -1 +/- 2, -8 +/- 4, and -18 +/- 5 percent, respectively; there was significant improvement in the lovastatin group, which had responses of 3 +/- 3, 3 +/- 3, 0 +/- 2, and 0 +/- 3 percent (P = 0.004). CONCLUSIONS Cholesterol lowering with lovastatin significantly improved endothelium-mediated responses in the coronary arteries of patients with atherosclerosis. Such improvement in the local regulation of coronary arterial tone could potentially relieve ischemic symptoms and signal the stabilization of the atherosclerotic plaque.

Lack of Effect of Lovastatin on Restenosis after Coronary Angioplasty

BACKGROUND Experimental and clinical observations suggest that lowering serum lipid levels may reduce the risk of restenosis after coronary angioplasty. We report the results of a prospective, randomized, double-blind trial evaluating whether lowering lipid levels with lovastatin can prevent or delay restenosis after angioplasty. METHODS Seven to 10 days before angioplasty, we randomly assigned eligible patients to receive lovastatin (40 mg orally twice daily) or placebo. Patients who underwent successful, complication-free, first-time angioplasty of a native vessel (the index lesion) continued to receive therapy for six months, when a second coronary angiogram was obtained. The primary end point was the extent of restenosis of the index lesion, as assessed by quantitative coronary arteriography. Of 404 patients randomly assigned to study groups, 384 underwent angioplasty; 354 of the procedures were successful, and 321 patients underwent angiographic restudy at six months. RESULTS At base line, the patients in the lovastatin group (n = 203) and the placebo group (n = 201) were similar with respect to demographic clinical, angiographic, and laboratory characteristics. At base line the mean (+/- SD) degree of stenosis, expressed as a percentage of the diameter of the vessel, was 64 +/- 11 percent in the lovastatin group, as compared with 63 +/- 11 percent in the placebo group (P = 0.22). Despite a 42 percent reduction in the serum level of low-density lipoprotein cholesterol in the lovastatin group, after six months of treatment the amount of stenosis seen in the second angiogram was 46 +/- 20 percent in the placebo group, as compared with 44 +/- 21 percent in the lovastatin group (P = 0.50). Similarly, there were no significant differences in minimal luminal diameter or other measures of restenosis. A trend was noted toward more myocardial infarctions in the lovastatin group, as a result of acute vessel closure or restenosis at the site of angioplasty, but there were no other important differences between the two groups in the frequency of fatal or nonfatal events at six months. CONCLUSIONS Treatment with high-dose lovastatin initiated before coronary angioplasty does not prevent or delay the process of restenosis in the first six months after the procedure.

Effect of a High Saturated Fat and No-Starch Diet on Serum Lipid Subfractions in Patients With Documented Atherosclerotic Cardiovascular Disease

OBJECTIVE To determine whether a diet of high saturated fat and avoidance of starch (HSF-SA) results in weight loss without adverse effects on serum lipids in obese nondiabetic patients. PATIENTS AND METHODS Twenty-three patients with atherosclerotic cardiovascular disease participated in a prospective 6-week trial at the Christiana Care Medical Center in Newark, Del, between August 2000 and September 2001. All patients were obese (mean +/- SD body mass index [BMI], 39.0+/-7.3 kg/m2) and had been treated with statins before entry in the trial. Fifteen obese patients with polycystic ovary syndrome (BMI, 36.1+/-9.7 kg/m2) and 8 obese patients with reactive hypoglycemia (BMI, 46.8+/-10 kg/m2) were monitored during an HSF-SA diet for 24 and 52 weeks, respectively, between 1997 and 2000. RESULTS In patients with atherosclerotic cardiovascular disease, mean +/- SD total body weight (TBW) decreased 5.2%+/-2.5% (P<.001) as did body fat percentage (P=.02). Nuclear magnetic resonance spectroscopic analysis of lipids showed decreases in total triglycerides (P<.001), very low-density lipoprotein (VLDL) triglycerides (P<.001), VLDL size (P<.001), large VLDL concentration (P<.001), and medium VLDL concentration (P<.001). High-density lipoprotein (HDL) and LDL concentrations were unchanged, but HDL size (P=.01) and LDL size (P=.02) increased. Patients with polycystic ovary syndrome lost 14.3%+/-20.3% of TBW (P=.008) and patients with reactive hypoglycemia lost 19.9%+/-8.7% of TBW (P<.001) at 24 and 52 weeks, respectively, without adverse effects on serum lipids. CONCLUSION An HSF-SA diet results in weight loss after 6 weeks without adverse effects on serum lipid levels verified by nuclear magnetic resonance, and further weight loss with a lipid-neutral effect may persist for up to 52 weeks.

Limb venous tone and responsiveness in hypertensive humans.

Hypertensive (HTN) animal models demonstrate lower venous compliance as well as increased venous tone and responsiveness compared with normotensive (NTN) controls. However, the extent to which findings in experimental animals can be extended to humans is unknown. Forearm and calf venous compliance were quantified in 9 NTN (23 +/- 1 yr) and 9 HTN (24 +/- 1 yr) men at baseline, after administration of nitroglycerin (NTG), during a cold pressor test (CP), and post-handgrip exercise ischemia (PEI). Individual pressure-volume relationships from a cuff deflation protocol (1 mmHg/s) were modeled with a quadratic regression. Regression parameters beta(1) and beta(2) were used to calculate compliance. A one-way ANOVA was used to compare the beta parameters and a repeated-measures ANOVA was used to compare volumes across all pressures (between groups at baseline and within groups during perturbations). Limb venous compliance was similar between groups (forearm: NTN beta(1) = 0.11 +/- 0.01 and beta(2) = -0.00097 +/- 0.0001, HTN beta(1) = 0.10 +/- 0.01 and beta(2) = -0.00088 +/- 0.0001; calf: NTN beta(1) = 0.12 +/- 0.01 and beta(2) = -0.00102 +/- 0.0001, HTN beta(1) = 0.11 +/- 0.01 and beta(2) = -0.00090 +/- 0.0001). However, at baseline, volume across all pressures (i.e., capacitance) was lower in the forearm (P < or = 0.01) and tended to be lower in the calf (P = 0.08) in HTN subjects. Venous compliance was not altered by any perturbation in either group. Forearm volume was increased during NTG in HTN subjects only. While venous compliance was similar between NTN and HTN adults, HTN adults have lower forearm venous capacitance (volume) which is increased with NTG. These data suggest that young HTN adults may have augmented venous smooth muscle tone compared with NTN controls.

Celecoxib does not alter cardiovascular and renal function during dietary salt loading

1. Cyclo‐oxygenase‐2 (COX‐2)‐derived prostaglandins are important in controlling sodium excretion and renin release. In the present study, we tested the hypothesis that a clinical dose of celecoxib would impair urinary sodium excretion and elevate blood pressure (BP) during dietary salt loading.

Associations between scar characteristics by cardiac magnetic resonance and changes in left ventricular ejection fraction in primary prevention defibrillator recipients

BACKGROUND Left ventricular ejection fraction (LVEF) improves over time in 25%-40% of patients with cardiomyopathy with primary prevention implantable cardioverter-defibrillator (ICD). The determinants of LVEF improvement, however, are not well characterized. OBJECTIVES We sought to examine the associations of clinical risk factors and cardiac imaging markers with changes in LVEF after ICD implantation. METHODS We conducted a retrospective analysis of cardiac magnetic resonance images in 202 patients who underwent primary prevention ICD implantation to quantify the amount of heterogeneous myocardial tissue (gray zone), dense core, and total scar. LVEF was reassessed at least once after ICD implantation. RESULTS Over a mean follow-up of 3 years, LVEF decreased in 43 (21.3%), improved in 88 (43.6%), and was unchanged in 71 (35.1%) of the patients. Baseline LVEF and myocardial scar characteristics were the strongest determinants of LVEF trajectory with high scar burden and increasing lack of myocardial viability associated with a greater decline in LVEF. There was a trend toward an association between both changes in LVEF and scar extent with subsequent appropriate ICD shock. Changes in LVEF were also strongly associated with heart failure hospitalizations. CONCLUSION Scar burden and characteristics were strong determinants, independent of baseline LVEF and other traditional cardiovascular risk factors, of changes in LVEF. Both worsened LVEF and high scar extent were associated with a trend toward increased risk of appropriate shock. These findings suggest that baseline cardiac magnetic resonance imaging of the myocardial substrate may provide important prognostic information on subsequent left ventricular remodeling and adverse events.

UNDERSTANDING THE PATHOPHYSIOLOGY OF APICAL BALLOONING SYNDROME, A STEP CLOSER!

The pathophysiology of Takotsubos Cardiomyopathy (TC) remains unclear. Stress-induced epicardial coronary spasm or endothelial dysfunction induced myocardial stunning may be the mechanism for a distinctive left ventricular contraction pattern. We compared the patterns of coronary blood flow in

Higher 30-day readmission rate for suspicion of ACS : effect of kidney function

Current evidence suggests prolonged hospitalization for Acute Coronary Syndrome (ACS) in the setting of chronic kidney disease (CKD). What remains unclear is the impact of CKD on 30-day readmission rate for suspected ACS. All patients who came to the emergency department (ED) from 2004 to 2010 and