Influence of dietary fatty acid composition on the relationship between CETP activity and plasma lipoproteins in monkeys.

CETP activity, measured as transfer of cholesteryl ester from exogenous HDL to exogenous VLDL and LDL, reflecting CETP mass as determined by ELISA, was documented in three groups of St. Kitts vervet monkeys fed diets enriched in saturated (Sat), monounsaturated (Mono), or n-6 polyunsaturated (Poly) fatty acids. CETP activity was not different when comparing the three dietary fats. However, CETP activity was significantly higher when cholesterol was added to each of the diets. Significant positive associations between CETP activity and VLDL and LDL cholesterol concentrations were found whereas significant negative associations were seen between CETP activity and HDL cholesterol in each of the diet groups. The strength of these associations was highest in the Sat group. Cholesteryl ester (CE) fatty acid composition of lipoproteins varied widely among diet groups, with the more polyunsaturated CE of the Poly group being associated with a higher rate of CE transfer to endogenous acceptor apolipoprotein B-containing lipoproteins. Finally, only the Sat diet group showed significant positive correlations of CETP activity with LDL particle diameter (r = 0.76), cholesteryl ester percentage (r = 0.67), and a strong negative correlation (r = -0.86) with LDL receptor function, estimated as the difference between native and methylated LDL turnover rates. We speculate that strong associations between CETP and LDL metabolism may explain, at least in part, the increased atherogenicity of dietary saturated fat.

Platelet aggregation induced by ADP or epinephrine is enhanced in habitual smokers.

A novel system has been developed to evaluate biochemically induced platelet aggregation by means of a particle-counting technique that uses laser light scattering. Using this system, we compared the differences in platelet aggregability between 90 smoking healthy males after 10 hours of smoking abstinence and 141 age-matched nonsmoking healthy males. Smokers had more small spontaneous platelet aggregates and more medium and large aggregates induced by 1 or 5 microM of epinephrine than nonsmokers. No large aggregates with 5-microM epinephrine-induced platelet aggregation were seen in 10% of smokers and 24% of nonsmokers; these subjects showed no small aggregates in spontaneous aggregation at all. Smokers had significantly more small, medium, and large aggregates induced by 1 microM of adenosine diphosphate (ADP) than nonsmokers. Smokers showed a positive correlation between age and 1-microM epinephrine-induced large platelet aggregates, percent reduction of optical density, and 1-microM ADP-induced medium and large aggregates. Smokers also showed a positive correlation between fibrinogen concentration in plasma and small spontaneous aggregates. On the other hand, nonsmokers showed a significant positive correlation between age and small spontaneous aggregates, and a positive correlation between fibrinogen and 1- or 5-microM epinephrine-induced large aggregates, and between 1 microM ADP-induced large aggregates and percent reduction of optical density. These results confirmed that platelet aggregability is enhanced in smokers, and we speculate that long-term smoking might enhance the sensitivity of platelets to epinephrine or ADP.

Non-surgical reduction of septal myocardial mass in a patient with hypertrophic obstructive cardiomyopathy.

Non-surgical reduction of septal myocardial mass was performed with success in a 48-year-old male with hypertrophic obstructive cardiomyopathy. Angioplasty balloon inflated in the first septal branch of the left anterior descending artery dramatically reduced the pressure gradient across the outflow tract of the left ventricle. Following injections of absolute alcohol into the artery with the balloon kept inflated induced a small septal myocardial infarction. By hemodynamic evaluation, the peak pressure gradient of 108 mmHg before the procedure was decreased to 30 mmHg. Clinical improvement in New York Heart Association (NYHA) functional class was obtained. At 3-month follow-up, the patient was doing quite well; the gradient was only 10 mmHg at rest and 25 mmHg with Valsalva maneuver.

[Percutaneous transluminal septal ablation with ethanol in hypertrophic obstructive cardiomyopathy: a case report].

A 48-year-old man with hypertrophic obstructive cardiomyopathy was treated by nonsurgical septal ablation. He had previously received medical treatment using atenolol and verapamil, but severe symptoms of chest discomfort, dyspnea, and shortness of breath had persisted for 2 years. Under coronary angiography control, the first major septal branch of the anterior descending coronary artery was catheterized with a 2.0 mm coaxial percutaneous transluminal coronary angioplasty balloon catheter. After inflation of the balloon, 1.5 ml of absolute alcohol was slowly injected into the septal artery to induce a small septal infarction. The left ventricular outflow pressure gradient was decreased from 108 before to 30 mmHg after the procedure as measured by Doppler echocardiography. His chest symptom improved from New York Heart Association class III to II and left ventricular outflow gradient was maintained at 0 mmHg (at rest) at 3 months after treatment. This is a new, less invasive treatment using catheterization instead of surgical myectomy. The indication, complication, and long-term effect of the treatment must be carefully evaluated, but this is expected to become a useful method.

Platelet spontaneous aggregation in platelet-rich plasma is increased in habitual smokers.

Cigarette smoking is a well-known risk factor for atherosclerotic disorders. Several authors have suggested that platelet aggregability is important in smoking-induced vascular injury. When platelet-rich plasma is stirred at 37 degrees C in the absence of chemical stimulants, small aggregates of platelets may be formed, but it was difficult to detect small aggregates by conventional aggregometer using optical density. Recent technological advances have made it possible to detect small aggregates by using a newly developed assay system that employs laser light scattering. In the present study, we attempted to measure platelet aggregation by this method, using laser light scattering in 54 nonsmoking healthy males and 51 healthy male habitual smokers who were age matched. In smokers, blood was obtained after 10 hours of smoking abstinence. No significant difference in platelet aggregation was induced by 1 microM or 5 microM of ADP between smokers and nonsmokers. In smokers, plasma fibrinogen levels and the number of small aggregates formed in the absence of chemical stimulants was significantly higher than in nonsmokers. Small aggregates formed in the absence of stimulants correlated positively with the concentrations of von Willebrand factor (vWF) antigen (r=0.2654, p<0.01) and of fibrinogen (r=0.2834, p<0.01). The formation of these small aggregates was inhibited by monoclonal antibody against GPIIb/IIIa blocking fibrinogen binding to GPIIb/IIIa but not inhibited at all by monoclonal antibody against GPIb blocking vWF binding to GPIb. From these results, enhanced platelet aggregability in smokers was confirmed, and it was suggested that GPIIb/IIIa is concerned in platelet spontaneous aggregation, although vWF may not directly influence on the platelet spontaneous aggregation. Since the mechanism of spontaneous aggregation and the effect of increased spontaneous aggregability on the progression of atherosclerosis remains unclear, further study was considered necessary.

Alterations of sympathovagal balance in patients with hypertrophic and dilated cardiomyopathies assessed by spectral analysis of RR interval variability.

Spectral analysis of RR interval variability was performed in 35 ambulatory patients with early hypertrophic cardiomyopathy (HCMa, NYHA class I), 21 hospitalized patients with advanced hypertrophic cardiomyopathy (HCMh, NYHA class II or III), and 18 hospitalized patients with dilated cardiomyopathy (DCMh, NYHA class I, II or III). Twenty-nine ambulatory subjects (COTa) and 20 hospitalized volunteers (COTh) served as normal controls. The RR interval standard deviation (SD), the high-frequency power (HF: 0.15-0.40 Hz) corrected by the mean RR interval (CCVHF) and the normalized unit of the HF power (NUHF) served as markers of vagal modulation. Low-frequency power (LF: 0.04-0.15 Hz) corrected by the mean RR interval (CCVLF) and the normalized unit of LF power (NULF) were markers of sympathetic modulation. The LF/HF ratio was an index of sympathovagal balance. There was no significant difference in the SD, CCVHF, NUHF, CCVLF, NULF or the LF/HF ratio between the HCMa and COTa groups. At night, the SD was lower in the HCMh group relative to the COTh group (P < 0.01). The HCMh group demonstrated lower CCVHF and NUHF values (P < 0.01), higher NULF values (P < 0.01) and higher LF/HF ratios (P < 0.05) at night relative to the COTh group. Two patients who later died suddenly in the HCMh group had markedly reduced CCVHF values (0.2-0.8%) relative to the survivors in the group (mean +/- SD in the morning, afternoon and night, 1.07 +/- 0.43%).(ABSTRACT TRUNCATED AT 250 WORDS)

An adult case of cardiac fibroma.

The patient, a 48-year-old woman with cardiac fibroma, is the second oldest patient with this disease in Japan. Her electrocardiogram showed findings compatible with old high lateral, posterior and possibly lateral myocardial infarction, regions which corresponded to the tumor site. In patients whose electrocardiogram suggests a previous myocardial infarction (pseudo myocardial infarction), the possibility of intramyocardial tumor should be taken into consideration.

Effects of pravastatin on lipid transfer protein and lecithin cholesterol acyltransferase in heterozygous familial hypercholesterolemia.

The effects of HMG CoA reductase inhibitor PRAVASTATIN on plasma lipoprotein levels, lipid transfer protein (LTP) activity and lecithin cholesterol acyltransferase (LCAT) activity were investigated in 20 patients with heterozygous familial hypercholesterolemia. Plasma total cholesterol decreased from 299.2 +/- 45.2 to 245.9 +/- 45.1 (mean +/- SD in mg/dl) (p < 0.0001), low density lipoprotein (LDL) cholesterol from 221.1 +/- 47.6 to 164.9 +/- 48.1 (p < 0.0001) and LDL-triglycerides from 38.0 +/- 10.2 to 30.2 +/- 8.8 (p < 0.0001). High density lipoprotein (HDL) cholesterol increased from 60.1 +/- 13.9 to 63.1 +/- 17.0 (p = 0.0264). The HDL-cholesterol: HDL-triglycerides ratio increased from 3.91 +/- 1.14 to 4.91 +/- 1.65 (p = 0.0029). Lipid transfer protein (LTP) activity (as % of transferred cholesteryl ester (CE)) decreased from 4.68 +/- 2.47 to 3.70 +/- 2.31 (p = 0.0024) and LCAT activity decreased from 113.1 +/- 29.9 (U/L) to 97.0 +/- 22.7. There was a negative correlation between LTP/LCAT ratio and HDL-C levels. These results suggested that the changes in plasma HDL-cholesterol concentrations during treatment with pravastatin may be related to the decreases in LTP and LCAT activity due to this drug.

Effects of carvedilol on serum lipids in patients with essential hypertension.

The purpose of this study was to investigate the effect of carvedilol on serum lipids in patients with mild-to-moderate essential hypertension. Twenty-one patients with blood pressure greater than or equal to 160/95 mm Hg after a 4-week placebo run-in period were initially given 10 mg of carvedilol once daily. The dose was increased to 20 mg after 4 weeks if the target blood pressure was not achieved. The duration of treatment was 12 weeks. After 12 weeks of administration, blood pressure and the pulse rate (PR) declined significantly (blood pressure from 173/105 to 142/91 mm Hg, p less than 0.001; PR from 74 to 67 beats/min, p less than 0.001); however, serum lipids [total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein (HDL), HDL2, and HDL3], lipoprotein fraction (alpha, pre-beta, and beta), apoprotein fraction (A-I, A-II, CII, CIII, and E), and atherogenic index [(total cholesterol - HDL cholesterol) divided by HDL cholesterol] were not altered significantly. There were no side effects reported during the trial. From these results, it can be concluded that carvedilol has no adverse effect on the coronary risk profile as reflected by lipid measurements, and is an efficacious, safe, well-tolerated antihypertensive drug in patients with mild-to-moderate hypertension.