Gary D. Plotnick

Effect of a Single High-Fat Meal on Endothelial Function in Healthy Subjects

Although there is a well-established relation between serum cholesterol and coronary artery disease risk, individual and national variations in this association suggest that other factors are involved in atherogenesis. High-fat diet associated triglyceride-rich lipoproteins have also been suggested to be atherogenic. To assess the direct effect of postprandial triglyceride-rich lipoproteins on endothelial function, an early factor in atherogenesis--10 healthy, normocholesterolemic volunteers--were studied before and for 6 hours after single isocaloric high- and low-fat meals (900 calorie; 50 and 0 g fat, respectively). Endothelial function, in the form of flow-mediated vasoactivity, was assessed in the brachial artery using 7.5-MHz ultrasound as percent arterial diameter change 1 minute after 5 minutes of upper-arm arterial occlusion. Serum lipoproteins and glucose were determined before eating and 2 and 4 hours postprandially. Serum triglycerides increased from 94 +/- 55 mg/dl preprandially to 147 +/- 80 mg/dl 2 hours after the high-fat meal (p = 0.05). Flow-dependent vasoactivity decreased from 21 +/- 5% preprandially to 11 +/- 4%, 11 +/- 6%, and 10 +/- 3% at 2, 3, and 4 hours after the high-fat meal, respectively (all p <0.05 compared with low-fat meal data). No changes in lipoproteins or flow-mediated vasoactivity were observed after the low-fat meal. Fasting low-density lipoprotein cholesterol correlated inversely (r = -0.47, p = 0.04) with preprandial flow-mediated vasoactivity, but triglyceride level did not. Mean change in postprandial flow-mediated vasoactivity at 2, 3, and 4 hours correlated with change in 2-hour serum triglycerides (r = -0.51, p = 0.02). These results demonstrate that a single high-fat meal transiently impairs endothelial function. These findings identify a potential process by which a high-fat diet may be atherogenic independent of induced changes in cholesterol.

The postprandial effect of components of the Mediterranean diet on endothelial function.

OBJECTIVES This study investigated the postprandial effect of components of the Mediterranean diet on endothelial function, which may be an atherogenic factor. BACKGROUND The Mediterranean diet, containing olive oil, pasta, fruits, vegetables, fish, and wine, is associated with an unexpectedly low rate of cardiovascular events. The Lyon Diet Heart Study found that a Mediterranean diet, which substituted omega-3-fatty-acid-enriched canola oil for the traditionally consumed omega-9 fatty-acid-rich olive oil, reduced cardiovascular events. METHODS We fed 10 healthy, normolipidemic subjects five meals containing 900 kcal and 50 g fat. Three meals contained different fat sources: olive oil, canola oil, and salmon. Two olive oil meals also contained antioxidant vitamins (C and E) or foods (balsamic vinegar and salad). We measured serum lipoproteins and glucose and brachial artery flow-mediated vasodilation (FMD), an index of endothelial function, before and 3 h after each meal. RESULTS All five meals significantly raised serum triglycerides, but did not change other lipoproteins or glucose 3 h postprandially. The olive oil meal reduced FMD 31% (14.3 +/- 4.2% to 9.9 +/- 4.5%, p = 0.008). An inverse correlation was observed between postprandial changes in serum triglycerides and FMD (r = -0.47, p < 0.05). The remaining four meals did not significantly reduce FMD. CONCLUSIONS In terms of their postprandial effect on endothelial function, the beneficial components of the Mediterranean and Lyon Diet Heart Study diets appear to be antioxidant-rich foods, including vegetables, fruits, and their derivatives such as vinegar, and omega-3-rich fish and canola oils.

Changes in flow-mediated brachial artery vasoactivity with lowering of desirable cholesterol levels in healthy middle-aged men

Current National Cholesterol Education Program guidelines consider desirable total and low-density lipoprotein cholesterol levels to be < 200 and < 160 mg/dl, respectively, for healthy individuals without multiple coronary risk factors. To determine the extent to which these levels affect vascular function, we assessed flow-mediated (endothelium-dependent) brachial artery vasoactivity noninvasively before, during, and after cholesterol lowering (simvastatin 10 mg/day) in 7 healthy middle-aged men with cholesterol levels meeting current recommendations. Flow-mediated brachial artery vasoactivity was measured using 7.5 MHz ultrasound and expressed as percent diameter change from baseline to hyperemic conditions (1 minute following 5 minutes of blood pressure cuff arterial occlusion). Flow-mediated vasoactivity rose from 5.0 +/- 3.6% at baseline to 10.5 +/- 5.6%, 13.3 +/- 4.3%, and 15.7 +/- 4.9% (all p < 0.05) as cholesterol fell from 200 +/- 12 to 161 +/- 18, 169 +/- 16, and 153 +/- 11 mg/dl after 2, 4, and 12 weeks, respectively, of cholesterol-lowering therapy. Vasoactivity and cholesterol returned to baseline levels 12 weeks after simvastatin discontinuation. Overall, vasoactivity was found to correlate inversely with cholesterol levels (r = -0.47, p = 0.004). These data suggest that flow-mediated brachial artery vasoactivity responds rapidly to changes in cholesterol levels and that endothelial function improves by lowering cholesterol levels below recommendations of current guidelines.

Beneficial effects of metoprolol in heart failure associated with coronary artery disease: a randomized trial.

OBJECTIVES This clinical trial was performed to determine the safety and clinical impact of titrated metoprolol therapy in patients with heart failure, documented coronary artery disease and a low ejection fraction. BACKGROUND Despite known cardiodepressant effects, long-term use of beta-adrenergic antagonists appears to be beneficial in patients with idiopathic dilated cardiomyopathy. However, this therapy has not been critically evaluated in patients with heart failure and coronary artery disease. METHODS In 50 patients with heart failure, known coronary artery disease and an ejection fraction < or = 0.40, we examined the impact of metoprolol therapy in a 6-month double-blind, placebo-controlled randomized trial, assessing the frequency of heart failure exacerbations and changes in symptoms (New York Heart Association functional class), ejection fraction and exercise duration. Placebo-treated patients who completed 6-month follow-up studies then underwent a trial with metoprolol therapy (crossover group). RESULTS Metoprolol was titrated to a mean maximal dose of 87 mg/day (range 25 to 100) without serious adverse reactions. During double-blind therapy, use of a beta-blocker was associated with a significant reduction in the number of hospital admissions (4% vs. 32%, p < 0.05), overall improved functional class (p = 0.02), increased ejection fraction (4 +/- 7% [mean +/- SD] compared with 0 +/- 6%, p < 0.05) and a greater increase in exercise duration (193 +/- 276 vs. 38 +/- 213 s with placebo, p < 0.01). Crossover outcome paralleled the favorable impact seen during randomized metoprolol therapy. CONCLUSIONS Cautious use of titrated metoprolol appears to be safe and beneficial when added to standard heart failure therapy in patients with dilated cardiomyopathy associated with coronary artery disease.

Routine preoperative exercise testing in patients undergoing major noncardiac surgery

A prospective study of preoperative exercise testing was carried out in 200 patients older than 40 years scheduled for elective major noncardiac surgery under general anesthesia. The exercise test response was electrocardiographically positive in 32 patients (16%) (2 patients had a markedly positive test), equivocal in 11 patients (5.5%) and negative in 157 patients (78.5%). The patients were followed with serial pre- and postoperative electrocardiograms (ECGs) and determinations of serum creatine kinase (CK) and CK-MB. Six patients (3%) had primary endpoints: 3 (1.5%) died postoperatively and 3 (1.5%) had definite postoperative myocardial infarction. Secondary endpoints of suspected postoperative myocardial ischemia/injury diagnosed by ECG or elevation in CK-MB levels occurred in 27 patients (14%). Endpoint events were more common in patients aged 70 years or older. Endpoint events were also more common in patients with an abnormal (positive or equivocal) preoperative exercise test response than in those with a negative response (27% vs 14%); however, preoperative exercise results were not statistically significant independent predictors of cardiac risk. Using multivariate analysis, the only statistically significant independent predictor of risk was the preoperative ECG. Endpoint events were more common in patients with an abnormal than in those with a normal ECG (23% vs 7%, p less than 0.002). Because the results of exercise testing do not appear to add substantially to the risk separation provided by the ECG at rest, exercise testing is not recommended as a routine preoperative method for assessing perioperative risk in older patients who are being evaluated before major elective noncardiac surgery under general anesthesia.

Infarcts with a cardiac source of embolism in the NINCDS Stroke Data Bank Historical features

To gain insight into the historical features relevant to the diagnosis of cardiac embolie strokes, we studied the 1,290 patients with cerebral infarcts in the NINCDS Stroke Data Bank. Based solely on the presence of cardiac sources of embolism, we divided the patients into groups of high (n = 250), medium (n = 166), and low (n = 874) risk of a cardiogenic mechanism for their stroke. There was a highly significant graded relationship between increasing risk of a cardiac source and a history, or presence of, systemic embolism, abrupt onset, and diminished level of consciousness at onset. These clinical features may be useful for assessing the likelihood of a cardiac embolie mechanism in patients with cerebral infarcts.

Ulcerated atherosclerotic plaques in the thoracic aorta are associated with cryptogenic stroke: A multiplane transesophageal echocardiographic study

Atherosclerotic plaque ulcers > or = 2 mm in depth and width in the thoracic aorta have been implicated by autopsy study as a cause of unexplained or cryptogenic ischemic strokes. Transesophageal echocardiography (TEE) allows visualization of complex atherosclerotic lesions of the thoracic aorta. We compared the prevalence of thoracic aorta ulcerated plaques (ulcers > or = 2 mm in both depth and width) in three age-matched groups undergoing multiplane TEE: group 1, 23 patients with cryptogenic ischemic stroke; group 2, 26 patients with known-cause strokes; and group 3, 57 control patients without strokes. TEEs were interpreted in a blinded fashion. Ulcerated plaques were found in 9 (39%) group 1 patients but in only 2 (8%) group 2 patients and in only 4 (7%) group 3 patients (p < 0.001). There was an association between advancing age and the presence of ulcerated plaques (p < 0.02). We conclude that ulcerated atherosclerotic plaques in the thoracic aorta are associated with cryptogenic ischemic stroke and should be considered a potential source of cerebral emboli.

Effect of supplemental phytonutrients on impairment of the flow-mediated brachialartery vasoactivity after a single high-fat meal

OBJECTIVES Our objective was to determine if long-term daily administration of phytonutrient supplements can prevent the immediate adverse impact of a high-fat meal and increase the production of nitric oxide. BACKGROUND Ingestion of a high-fat meal impairs flow-mediated vasodilation of the brachial artery for at least 4 h; however, co-ingestion of vitamin antioxidants or a green salad has been shown to prevent this effect. METHODS Flow-mediated brachial artery reactivity test (BART) both before and 3 h after a 900 calorie 50 g fat meal was evaluated in 38 healthy volunteers (age 36.4 +/- 10.1 years). Subjects were randomized to four weeks of daily supplementation with a powdered fruit vegetable juice concentrate (Juice Plus [JP]) along with a complex supplement providing nutritional antioxidants and various herbal extracts (Vineyard [V]), JP alone, or a matching placebo. At three and four weeks, BART was repeated both before and after the high-fat meal. Serum nitrate/nitrite concentrations were measured at baseline and at four weeks. RESULTS Four weeks of the JP-V combination blunted the detrimental effect of the high-fat meal (-47.5 +/- 23.4% at baseline vs. -1.7 +/- 9.7% at four weeks [p < 0.05]). Four weeks of JP alone had a similar beneficial effect (-45.1 +/- 19.7% at baseline vs. -16.6 +/- 10.3% at four weeks [p < 0.05]), whereas there was no substantial effect of the placebo. In the subjects treated with supplements, concentrations of serum nitrate/nitrite increased from 78 +/- 39 to 114 +/- 62 microm/l (p < 0.02). CONCLUSIONS Daily ingestion of modest amounts of a fruit/vegetable juice concentrate with or without adjunctive phytonutrient supplementation can reduce the immediate adverse impact of high-fat meals on flow-mediated vasoactivity and increase nitrate/nitrite blood concentration.

Correlation of cold pressor and flow-mediated brachial artery diameter responses with the presence of coronary artery disease

Flow-mediated brachial and coronary artery vasoactivity are abnormal in patients with coronary artery disease (CAD) and cardiac risk factors. Cold pressor coronary artery vasoactivity is abnormal in patients with CAD, but brachial artery responses have not been studied. This study assesses whether cold pressor and flow-mediated brachial artery vasoactivity correlate independently with the presence of CAD. We studied 50 men (27 who were clinically normal, 23 with angiographically proven CAD) aged 23 to 59 years. With use of 7.5 MHz ultrasound, we measured brachial artery diameter and Doppler flow velocity at baseline, during contralateral ice water hand immersion (cold pressor), after 5 minutes of ipsilateral blood pressure cuff occlusion (flow-mediated), and after nitroglycerin administration. During cold pressor stimulation, mean brachial artery diameter increased 0.36 +/- 2.93% in normal subjects but decreased 2.38 +/- 3.32% in the CAD subjects (p = 0.006). Mean flow-mediated diameter increased 9.11 +/- 6.01% and 6.58 +/- 7.50% in normal and CAD subjects, respectively (p = NS). Responses to sublingual nitroglycerin were the same in the 2 groups. Multiple stepwise regression analysis revealed that cold pressor vasoactivity was found to correlate with smoking status (p = 0.0002) and the presence of CAD (p = 0.04). In the 32 nonsmokers undergoing assessment, only the presence of CAD correlated with cold pressor vasoactivity (p = 0.02). The associations of brachial artery vasoactivity with cardiac risk factors and CAD appear to be stimulus-dependent. Cold pressor vasoactivity correlates more closely with the presence of CAD than does flow-mediated vasoactivity.

Value and limitations of exercise radionuclide angiography for detecting myocardial ischemia in healed myocardial infarction

Exercise radionuclide angiography was performed in 65 normal subjects (group I), in 31 patients with exercise-induced transient thallium defects after acute myocardial infarction (AMI) (group II), and in 16 patients without exercise-induced transient thallium defects, angina or electrocardiographic changes after AMI (group III). Absolute left ventricular (LV) volumes were measured using a correction for attenuation in each patient. Similar peak heart rate-blood pressure products were achieved in groups II and III. Although the mean LV ejection fraction (EF) response to exercise in group III (increase of 0.11 +/- 0.10 units) closely resembled that of normal persons (increase of 0.14 +/- 0.09 units) and was significantly different from that of group II (decrease of 0.04 +/- 0.12), there was considerable individual variation. An abnormal EF response to exercise, defined as failure of EF to increase by at least 0.05 units, was found in 6 subjects (9%) in group I, 26 patients (84%) in group II, and 2 patients (13%) in group III. End-systolic volume failed to decrease in 10 subjects (15%) in group I, 25 patients (81%) in group II and 7 patients (44%) in group III. New regional wall motion abnormalities were found in no subject in group I, in 16 patients (52%) in group II and in only 1 patient (6%) in group III. Thus, although group responses of EF or end-systolic volume appeared to correlate with the presence or absence of ischemia, some patients with exercise-induced transient thallium defects after AMI responded normally to exercise radionuclide angiography stress testing and some patients without other evidence of exercise-induced ischemia after AMI responded to exercise radionuclide angiography testing abnormally.(ABSTRACT TRUNCATED AT 250 WORDS)