Quantity and function of high density lipoprotein as an indicator of coronary atherosclerosis

OBJECTIVES: To examine the association between the fractional esterification rate of cholesterol (C) in low density lipoprotein- and very low density lipoprotein-depleted plasma (FER(HDL)) and coronary artery disease (CAD) and the influence of serum HDL-C levels. BACKGROUND: The function of HDL in reverse cholesterol transport is involved in the antiatherogenic action of HDL, and FER(HDL) is a newly established quantitative measure of HDL function in vivo. METHODS: Cases (n = 185, F/M: 43/142) and controls (n = 74, F/M:27/47) were defined as subjects with/without angiographically proven CAD, respectively. RESULTS: The cases had significantly (p < 0.05) higher FER(HDL) values (13.2+/-0.3 %/h vs. 12.1+/-0.5 %/h) and lower HDL-C levels (39.0+/-1.0 mg/dL vs. 46.8+/-1.4 mg/dL) than the controls. The associations of FER(HDL) and HDL-C with CAD were linear and significant (p < 0.05). Multiple logistic regression analysis indicated that the association of FER(HDL) with CAD varied with the HDL-C level: significant for the low HDL-C tertile (chi-square = 6.20, p < 0.05) but not significant for the middle and high HDL-C tertiles (chi-square = 0.08 and 0.03, n.s.). The risk of CAD, relative to that in patients with low FER(HDL) and high HDL-C, was higher in patients with low FER(HDL) and low HDL-C (odds ratio [95% confidence interval]: 2.37 [1.12-4.97], p < 0.05) and was highest in patients with high FER(HDL) and low HDL-C (3.85 [1.84-8.06], p < 0.01). CONCLUSIONS: The functional assay of HDL (FER(HDL)) is an independent risk factor for CAD. The combination of FER(HDL) and HDL-C could be a potent indicator for CAD, and may reflect a potential mechanism of atherosclerosis.     

Cardiovascular risk factors associated with clinically isolated and diffuse atherosclerosis in Spanish patients with coronary artery disease

BACKGROUND: Patients with coronary artery disease (CAD) associated with peripheral (PAD) or cerebrovascular disease (CVD), a condition called diffuse atherosclerosis, have a higher risk of death than patients with isolated CAD. The prevalence of diffuse atherosclerosis and the atherogenic risk factors associated with this condition in our geographic area have not been described previously. METHODS: A cohort of 2597 patients (62 +/- 10.8 years, 665 women) consecutively admitted at Bellvitge Hospital because of acute coronary syndromes were studied. CAD patients were divided in two groups with diffuse and located atherosclerosis according to whether they had or they had not an associated PAD or CVD. Baseline history, physical data and lipid profile were recorded in each patient according to a standardized questionnaire. RESULTS: A total of 370 patients (14.2%) had diffuse atherosclerosis. Among them, there were more men and women older than 55 years than among those with isolated CAD. Patients with diffuse atherosclerosis were more frequently hypertensive, diabetic and former smokers than those with isolated CAD (60.5% vs. 49.4%, P < 0.01; 37.4% vs. 24.5%, P < 0.01; and 47% vs. 35.7%, P < 0.01, respectively). There were no significant differences in the mean values of total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C) and triglycerides between both groups of patients, but patients with diffuse atherosclerosis had a lower HDL-C/TC ratio, with borderline statistical significance (0.18 +/- 0.06 vs. 0.19 +/- 0.06, P = 0.06). Using multiple logistic regression analysis, the variables associated with diffuse atherosclerosis in men were age greater than 55 years (OR 1.97, CI 1.33-2.93), hypertension (OR 1.50, CI 1.14-2.20), diabetes (OR 1.78, CI 1.20-2.70), smoking (former smokers) (OR 2.09, CI 1.36-3.24) and HDL-C/TC < 0.20 (OR 1.60, CI 1.18-2.17); and in women hypertension (OR 3.43, CI 1.48-7.94) and diabetes (OR 2.58, CI 1.55-4.80). CONCLUSIONS: Clinically overt diffuse atherosclerosis is a relatively common disease. Older patients and those with hypertension, diabetes or low HDL-C/TC ratio are more likely to have diffuse atherosclerosis than those without these conditions.     

B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS)

OBJECTIVES: In this B-mode ultrasound study we assessed pravastatin treatment effects on carotid and femoral artery walls and investigated the correlations between the state and evolution of peripheral and coronary atherosclerosis. BACKGROUND: The Regression Growth Evaluation Statin Study (REGRESS) was an 11-center, 2-year, double-blind, placebo-controlled, prospective study of 885 men with coronary artery disease (CAD) (total cholesterol 4 to 8 mmol/liter). The study primarily investigated pravastatin treatment effects on the coronary lumen. This report focuses on the 255 patients who participated in the REGRESS ultrasound study. METHODS: Carotid and femoral artery walls were imaged at baseline and at 6, 12, 18 and 24 months. Pravastatin treatment effect was defined as the difference in progression of the combined intima-media thicknesses (IMT) between treatment groups. RESULTS: Pravastatin treatment effects were highly significant (combined IMT: p = 0.0085; combined far wall IMT: p < 0.0001; common femoral artery far wall IMT: p = 0.004). Correlations between the IMTs of the arterial wall segments ranged from -0.17 to 0.81. Baseline correlations between IMT and percent coronary lumen stenoses ranged from 0.23 to 0.36. Baseline IMT correlated with the mean coronary segment diameter (r = -0.32, p = 0.001) and minimal coronary obstruction diameter (r = -0.27, p = 0.005). There were no individual correlations between IMT and coronary lumen variables (p > 0.30). CONCLUSIONS: Pravastatin treatment effects on carotid and femoral artery walls were observed. B-mode ultrasound imaging studies of peripheral arterial walls could not describe the state and evolution of the coronary lumen in the individual patient, but proved to be a highly suitable tool for the assessment of antiatherosclerotic properties of agents.     

Effects of cigarette smoking on the angiographic evolution of coronary atherosclerosis. A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) Substudy. CCAIT Study Group

BACKGROUND: Although smoking increases both the risk of developing coronary disease and the risk of coronary events in patients with known coronary atherosclerosis, the effect of smoking on the evolution of coronary atherosclerosis as assessed by serial angiography is poorly defined. METHODS AND RESULTS: Ninety smokers with coronary atherosclerosis shown on a recent angiogram and with fasting cholesterol levels between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial of cholesterol-lowering therapy, along with 241 nonsmokers and exsmokers. Lovastatin at a mean dose of 36 mg/d lowered total and LDL cholesterol by 21 +/- 11% and 29 +/- 11%, respectively, but these levels changed by < 2% in placebo-treated patients. Coronary arteriography was repeated after 2 years in 72 smokers and their 557 lesions were measured blindly with an automated quantitative system, along with 1752 lesions in 227 nonsmokers. Coronary change score, the per-patient mean of the minimal lumen diameter changes for all qualifying lesions, worsened by 0.16 +/- 0.16 mm in smokers and by 0.07 +/- 0.15 mm in nonsmokers in the placebo group (P < .001). Lovastatin-treated smokers had less worsening (0.07 +/- 0.15 mm) than placebo-treated smokers (P = .024). One or more coronary lesions progressed in 16 of 34 lovastatin-treated smokers and in 28 of 38 placebo-treated smokers (47% versus 74%, P < .001). In the placebo group, new coronary lesions developed in 21 of 38 smokers and in 28 of 115 nonsmokers (55% versus 24%, P < .001); fewer lovastatin-treated smokers developed new lesions (15% versus 55%, P < .001). CONCLUSIONS: Smoking accelerates coronary progression and new lesion formation as assessed by serial quantitative coronary arteriography. Lovastatin slows the progression of coronary atherosclerosis and prevents the development of new coronary lesions in smokers.     

Decreased fecal bile acid output in patients with coronary atherosclerosis

In most patients with atherosclerosis, the underlying metabolic derangement remains undefined. Animal experiments have suggested that the ability to produce and excrete large amounts of bile acids may be an adaptation mechanism to cholesterol overload protecting against the atherogenic effects of cholesterol. However, there are very few data on bile acid excretion in human atherosclerosis. In the present study, we have investigated fecal bile acid secretion in subjects with and without coronary artery disease. The target group consisted of 30 patients with proven coronary artery disease and the control group consisted of 27 matched subjects without clinical or laboratory evidence of coronary atherosclerosis. Fecal bile acids were measured by gas-liquid chromatography from 24-hr stool collections under a controlled diet. The patients excreted significantly less bile acids than the controls (325+/-135 vs. 592+/-223 mg/day, respectively, p < 0.0001). The difference was primarily due to a reduced excretion of secondary bile acids. Less than 50% of deoxycholate was excreted by patients (180+/-81 mg/day) as compared to controls (367+/-168 mg/day, p < 0.0002), while lithocholic acid excretion was 111+/-62 mg/day in patients vs. 190 +/-70 mg/day in controls (p < 0.005). The fecal output of the two primary bile acids, cholic and chenodeoxycholic acid, did not differ significantly between patients and controls. The fecal output of total bile acids correlated with that of both secondary bile acids in patients as well as in controls. These findings suggest that patients with coronary heart disease are unable to excrete adequate amounts of bile acids to rid themselves of excess cholesterol, even if they are able to maintain a plasma cholesterol level comparable to that of healthy controls.     

The effect of pravastatin on prevention of restenosis after successful percutaneous transluminal coronary angioplasty

Numerous attempts have been made to prevent late restenosis after successful percutaneous transluminal coronary angioplasty (PTCA), but there is still no effective treatment. This report describes the effect of an oral lipid-lowering agent, pravastatin, on restenosis after successful PTCA. Sixty-six patients who underwent successful elective PTCA were assigned to a pravastatin-treated group (Group 1, n = 29) or an untreated group (Group 2, n = 37) in a prospective and randomized fashion. Pravastatin (5 mg or 10 mg twice a day) was given to Group 1 patients from day 3 after the procedure. Selective coronary angiography was repeated 3 to 5 months later, or sooner if the patient developed angina pectoris. The serum cholesterol level was decreased significantly in Group 1 (from 215.7 +/- 44.3 mg/dl to 181.2 +/- 30.3 mg/dl, p < 0.001), but not in Group 2 (from 191.9 +/- 30.8 mg/dl to 191.8 +/- 33.3 mg/dl, p = ns), at the time of repeat coronary angiography. However, there were no differences between the groups with regard to the recurrence of angina, the need for repeat PTCA, or restenosis, as assessed by quantitative analysis of coronary cineangiograms. These results suggest that oral pravastatin therapy does not effectively prevent late restenosis after successful PTCA by this mode of administration.     

Cloning of a mouse smoothened cDNA and expression patterns of hedgehog signalling molecules during chondrogenesis and cartilage differentiation in clonal mouse EC cells, ATDC5

The effects of simvastatin and pravastatin administered alone at initial doses of 5 and 10 mg/day, respectively, on normalization of abnormal lipid metabolism in patients with hypercholesterolemia were evaluated by a crossover method. Patients whose serum levels of total cholesterol (TC) were > or = 220 mg/dl were randomly divided into two groups, and one of the groups (group S-P: 17 patients) was treated with simvastatin first and then with pravastatin whereas the other group (group P-S: 19 patients) was treated with pravastatin first and then with simvastatin. Simvastatin or pravastatin was replaced with the other drug after 8-week administration in each group. These drugs were administered for 8 weeks each. Simvastatin and pravastatin significantly reduced the following serum lipids as compared with the levels in the observation period: TC by 23.2 +/- 8.1% and 18.1 +/- 10.9%, triglyceride (TG) by 13.0 +/- 24.7% and 5.8 +/- 47.1%, and low-density lipoprotein cholesterol (LDL-C) by 31.3 +/- 10.1% and 23.1 +/- 14.3%, respectively. TC and LDL-C levels were significantly (p < 0.001) lower and decreased to significantly (p < 0.001) greater degrees after simvastatin treatment than after pravastatin treatment. TC was normalized in 77.8% of the patients (28 of 36) after simvastatin treatment and in 68.9% of the patients (23 of 36) after pravastatin treatment. LDL-C was normalized in 63.9% of the patients (23 of 36) after simvastatin treatment and in 44.4% of the patients (16 of 36) after pravastatin treatment. The percentage of patients whose LDL-C was normalized by simvastatin was significantly (p < 0.05) higher as compared with pravastatin. Results of this trial, which was conducted by a crossover method, show that the initial dose of simvastatin reduces serum cholesterol and LDL-C more potently than the initial dose of pravastatin in patients with hypercholesterolemia.     

Reduced coronary flow reserve in familial hypercholesterolemia

Familial hypercholesterolemia (FH) presents the highest risk for coronary artery disease (CAD) among patients with hyperlipidemia. Therefore, early detection of coronary arterial atherosclerosis is important for the treatment of FH patients. The aim of this study was to detect early coronary arterial abnormalities that may relate to future atherosclerosis in asymptomatic FH patients by measuring coronary flow reserve (CFR) using PET and 13N-ammonia. METHODS: Twenty-five patients with FH (14 men, 11 women) without a history of myocardial ischemia and 14 control subjects (9 men, 5 women) were studied. Total serum cholesterol (mmole/liter) was 5.33 +/- 0.66 in control subjects and 7.90 +/- 0.77 in FH patients (p < 0.01 versus control subjects). RESULTS: Myocardial blood flow (MBF) at rest and during dipyridamole loading was measured using PET, and CFR was calculated. MBF (ml/min/100 g weight heart) at rest in the FH group (79.0 +/- 20.0) was comparable to that in control subjects (70.0 +/- 17.0). However, MBF during dipyridamole loading was significantly lower in FH patients (163.0 +/- 67.0) than in control subjects (286.0 +/- 120.0, p < 0.01). CFR in FH patients (2.09 +/- 0.62) was also significantly lower than that in control subjects (4.13 +/- 1.38, p < 0.01). CFR showed a gender-specific variance in FH patients (1.85 +/- 0.40 in men versus 2.55 +/- 0.74 in women p < 0.05) but not in control subjects. Significant inverse correlations between CFR and the total plasma cholesterol level as well as plasma LDL cholesterol were observed. CONCLUSION: The CFR was reduced in patients with FH. This abnormality was more prominent in men than in women patients. Noninvasive assessment of CFR by 13N-ammonia PET was useful to detect early abnormalities of the coronary arteries in asymptomatic patients with FH.     

beta-VLDL hypercholesterolemia relative to LDL hypercholesterolemia is associated with higher levels of oxidized lipoproteins and a more rapid progression of coronary atherosclerosis in rabbits

The accumulation of the oxidized apolipoprotein, apoB-100, containing lipoproteins in the arterial wall and the progression of coronary atherosclerotic lesions in rabbits with beta-VLDL and LDL hypercholesterolemia was compared. In New Zealand White (NZW) rabbits on a 0.125% cholesterol diet, LDL cholesterol levels increased from 14 +/- 1 mg/dL (mean +/- SEM; n = 9) to 170 +/- 34 mg/dL (n = 10, P = .0002). On 0.5% cholesterol, LDL cholesterol levels were similar, but beta-VLDL cholesterol levels increased from 60 +/- 4 mg/dL (n = 10) to 550 +/- 75 mg/dL (n = 8; P < .0001). In Watanabe heritable hyperlipidemic (WHHL) rabbits, LDL cholesterol levels were 2.3-fold higher (n = 13; P < .0001) than in NZW rabbits on 0.5% cholesterol, whereas their beta-VLDL cholesterol levels were 3.7-fold lower (P < .0001), resulting in similar total cholesterol levels. At 2 months, mean intimal areas of lesions in the coronary arteries of NZW rabbits on 0.125% cholesterol were 0.13 +/- 0.045 mm2 (n = 4; mean +/- SEM) and were 5.8-fold, (n = 4; P = .016) and 2.0-fold (n = 6; P = NS versus 0.125% cholesterol and P = .014 versus 0.5% cholesterol) higher in NZW rabbits on 0.5% cholesterol and in WHHL rabbits, respectively. At 5 months, mean intimal areas were 0.47 +/- 0.088 mm2 (n = 6) in NZW rabbits on 0.125% cholesterol and were 4.5-fold (n = 4; P = .0001) and 2.0-fold (n = 7; P = .012 and P = .0019) higher in rabbits on 0.5% cholesterol and in WHHL rabbits, respectively. Levels of oxidized apoB-100 containing lipoproteins (both beta-VLDL and LDL) in the lesions correlated with mean intimal area (r = .88; n = 31; P < .0001) of those lesions and with the plasma levels of total beta-VLDL/LDL (r = .72; P < .0001). Levels of oxidized apoB-100 containing lipoproteins in the arterial wall correlate with progression of hypercholesterolemia-induced coronary atherosclerotic lesions. Plasma levels of beta-VLDL relative to similar increases in LDL result in a more pronounced accumulation of oxidized apoB-100 containing lipoproteins in the arterial wall and in the plasma and a more rapid progression of coronary atherosclerosis.     

Plasminogen activator inhibitor-1 (PAI-1) promoter polymorphism and coronary artery disease in non-insulin-dependent diabetes

Elevated levels of PAI-1 are found in coronary artery disease (CAD) and non-insulin-dependent diabetes (NIDDM). PAI-1 may be involved in the pathogenesis of CAD through suppression of fibrinolysis, alternatively the high levels may result from vascular damage. There is evidence that PAI-1 levels are related to genotype at a PAI-1 promoter polymorphism. Genotype at this 4G/5G polymorphism was determined in 160 NIDDM (90 males and 70 females) patients with (n = 38) or without (n = 122) clinical evidence of CAD. Levels of cholesterol were higher (6.5 vs 5.9 mM, p < 0.01) and PAI-1 tended to be higher (PAI-1 activity 23.0 vs 20.4 U/ml) with CAD. The frequency of the 4G/4G genotype was increased and the 5G/5G genotype decreased, in the group CAD compared to those without (p < 0.05). These results suggest that possession of the 4G/4G PAI-1 promoter genotype is a risk factor for the development of CAD in subjects with NIDDM.     

Attempting to fathom the unfathomable: descriptive views of spirituality

PURPOSE: To evaluate short-term efficacy of awareness programs (AP) in reducing coronary heart disease risk factors (CHDRF). METHODS: High risk hypercholesterolemic patients were divided in 2 groups during 16 weeks. Group A (n = 417, 54.3 +/- 10.0 years, 55% males) received verbal and written orientation on CHDRF control, and group B (n = 180, 54.4 +/- 10.9 years, 45% males) received only verbal orientation. All participants received pravastatin 10 mg q.d. for 12 weeks. The evolution of body weight, arterial pressure, lipid profile, Castelli's I and II indexes (TC/HDL and LDL/HDL), and Framingham scores were evaluated. RESULTS: At baseline, A had a lower HDL-C (40.0 +/- 11.0 vs 43.0 +/- 11.0 mg/dl, p = 0.013) and a higher index I (8.2 +/- 3.0 vs 7.6 +/- 2.3, p = 0.008) than B. After 16 weeks, A had greater change than B in TC (-28.0 vs -25.0, p < 0.05), LDL-C (-29.0 vs -27.6, p < 0.05), HDL-C levels (+13.7 vs +10.8, p < 0.05) and in the Castelli's Index (-39.0 vs -33.0; p < 0.05). In both groups pravastatin use potentialized the effects of diet on the lipid profile. CONCLUSION: The AP seemed to be more effective than verbal orientation alone in CHDRF reduction at short-term.     

Risk factors for coronary atherosclerosis. Comparison between two Argentine regions

The prevalence of risk factors for coronary atherosclerosis were studied in two population samples, Northeast (Posadas, n = 498) and South (Viedma, C. Rivadavia and Cipolletti, n = 652) of 20 years and older, males and females. The diet in the Northeast (n = 102) contained more monounsaturated acids and polyunsaturated acids than the one in the South (n = 62), 9.5 +/- 4.1 vs. 8.1 +/- 3.5% TCV (Total Caloric Value) (P < 0.02) and 8.1 +/- 4.1 vs. 6.2 +/- 3.0% TCV (P < 0.001) respectively. The P/S relationship was greater in the Northeast, 1.02 +/- 0.44 vs. 0.85 +/- 0.50 (P < 0.001). Total cholesterol (TC) in the Northeast was less than in the South, in males 176 +/- 41 vs. 213 +/- 43 mg/dl (P < 0.001); CLDL (LDL cholesterol) 109 +/- 37 vs. 141 +/- 41 mg/dl (P < 0.001). The most frequent risk factors in the South vs. Northeast (males) were: TC > or = 240 mg/dl, 26.7% vs. 9.5% (P < 0.001); LDL-C > or = 160 mg/dl, 30.3% vs. 10.9% (P < 0.001); Cig > or = 10/d (equal or more than 10 cigarettes per day), 30.0% vs. 16.4% (P < 0.001). The hypertension prevalence (HTA, 160/95), in males, was higher in the Northeast than in the South, 23.7% vs. 11.5% (P < 0.001). BMI > 27 Kg/m2 was higher in the women of Northeast than in the South, 38.4% vs. 24.2% (P < 0.001). In the males of the Northeast, the combination Cig > or = 10/d and HTA, 4.1 vs 0.9% was more common; in the South Cig > or = 10/d and LDL-C > or = 160 mg/d, 8.2% vs. 1.8% (P < 0.001) was more common. The differences in the prevalence of the risk factors between the population samples indicate the need to plan the prevention of coronary atherosclerosis locally.     

Revascularization in patients with prior coronary bypass surgery

Increasingly over the past several years, patients have returned after coronary surgery for reintervention procedures. This reflects immediate postsurgical complications and the relentless progression of coronary artery disease in the native circulation and in the bypass grafts. Although there are randomized comparative data for coronary bypass surgery (CABG) versus percutaneous transluminal coronary angioplasty (PTCA) and medical therapy, these trials have always excluded patients with previous (GABG). OBJECTIVES: We attempted to compare the risks and benefits of percutaneous transluminal coronary angioplasty (PTCA) and repeat coronary artery bypass grafting (re-CABG) in patients with previous coronary bypass surgery (CABG). METHODS AND RESULTS: This study examines follow up data (15.4 +/- 11.0 months) from 130 patients with previous CABG, who required either PTCA (Group A, n = 73) or re-CABG (Group B; n = 57) at a single center from 1994 to 1997. Follow up data were obtained from subsequent office visits and telephone calls. The PTCA and re-CABG groups were similar with respect to gender (86% vs 94% males), mean age (62 +/- 9 vs 59 +/- 10 years), angina CCS classes 3 and 4 (73% vs 69%), diminished left ventricular function (23% vs 26%), risk factors such as diabetes (19% vs 17%), hypercolesterolemia (49% vs 45%) and smoking (48% vs 39%) and three-vessel native coronary artery disease (67% vs 72%). The symptomatic status prior to the revascularization procedure was similar in both groups. Complete and functional revascularization was achieved in 85% of the PTCA group and in 92% of those with re-CABG (p = NS). During the hospital stay the complication rates were lower in the PTCA group. Actuarial survival was different at follow up (p = 0.04). Both PTCA and re-CABG groups resulted in equivalent event-free survival (freedom from death, myocardial infarction, unstable angina and urgent revascularization). The need for repeat revascularization at follow up was significantly higher in the PTCA group (PTCA 28% vs re-CABG 10%, p < 0.01). CONCLUSIONS: In this non-randomized study of patients with previous CABG requiring revascularization procedures, PTCA resulted in lower procedural morbidity and mortality risks. At follow up, both PTCA or CABG were similar for event-free survival; PTCA offered lower overall mortality, although it is associated to a greater need for subsequent revascularization procedures.     

Effects of lowering average of below-average cholesterol levels on the progression of carotid atherosclerosis: results of the LIPID Atherosclerosis Substudy. LIPID Trial Research Group

BACKGROUND: Cholesterol lowering in patients with above-average cholesterol levels has been shown to reduce the progression of atherosclerosis and lower the risk of coronary heart disease events. However, there has been uncertainty about the effects of cholesterol lowering in patients with average or below-average cholesterol levels. METHODS AND RESULTS: In this study, 522 patients with a history of myocardial infarction or unstable angina and with baseline levels of total cholesterol between 4 and 7 mmol/L (mean, 5.7 mmol/L) were randomized to treatment with a low fat diet plus pravastatin (40 mg daily) or to a low fat diet plus placebo. Treatment with pravastatin reduced the levels of total cholesterol by 19%, LDL cholesterol by 27%, apolipoprotein B by 19%, and triglycerides by 13% (all 2P<.0001) and increased apolipoprotein A1 and HDL cholesterol levels by 4% (both 2P<.0005), in comparison with placebo. Carotid atherosclerosis was assessed from B-mode ultrasound measurements of the common carotid artery. After 4 years, mean carotid wall thickness had increased by 0.048 mm (SE=0.01) in the placebo group and declined by 0.014 mm in the pravastatin-treated group (SE=0.01) (2P for difference <.0001). The effect of treatment on wall thickness was similar in three groups classified by tertiles of total cholesterol at baseline, with mean levels of 4.8, 5.7, and 6.6 mmol/L, respectively (2P for interaction >.8). CONCLUSIONS: Treatment with pravastatin reduced the development of carotid atherosclerosis among patients with coronary heart disease and a wide range of pretreatment cholesterol levels. Treatment with this agent prevented any detectable increase in carotid wall thickening over 4 years of follow-up.     

Optimal coronary balloon angioplasty with provisional stenting versus primary stent (OCBAS): immediate and long-term follow-up results

OBJECTIVE: This study sought to compare two strategies of revascularization in patients obtaining a good immediate angiographic result after percutaneous transluminal coronary angioplasty (PTCA): elective stenting versus optimal PTCA. A good immediate angiographic result with provisional stenting was considered to occur only if early loss in minimal luminal diameter (MLD) was documented at 30 min post-PTCA angiography. BACKGROUND: Coronary stenting reduces restenosis in lesions exhibiting early deterioration (>0.3 mm) in MLD within the first 24 hours (early loss) after successful PTCA. Lesions with no early loss after PTCA have a low restenosis rate. METHODS: To compare angiographic restenosis and target vessel revascularization (TVR) of lesions treated with coronary stenting versus those treated with optimal PTCA, 116 patients were randomized to stent (n=57) or to optimal PTCA (n=59). After randomization in the PTCA group, 13.5% of the patients crossed over to stent due to early loss (provisional stenting). RESULTS: Baseline demographic and angiographic characteristics were similar in both groups of patients. At 7.6 months, 96.6% of the entire population had a follow-up angiographic study: 98.2% in the stent and 94.9% in the PTCA group. Immediate and follow-up angiographic data showed that acute gain was significantly higher in the stent than in the PTCA group (1.95 vs. 1.5 mm; p < 0.03). However, late loss was significantly higher in the stent than the PTCA group (0.63+/-0.59 vs. 0.26+/-0.44, respectively; p=0.01). Hence, net gain with both techniques was similar (1.32< or =0.3 vs. 1.24+/-0.29 mm for the stent and the PTCA groups, respectively; p=NS). Angiographic restenosis rate at follow-up (19.2% in stent vs. 16.4% in PTCA; p=NS) and TVR (17.5% in stent vs. 13.5% in PTCA; p=NS) were similar. Furthermore, event-free survival was 80.8% in the stent versus 83.1% in the PTCA group (p=NS). Overall costs (hospital and follow-up) were US $591,740 in the stent versus US $398,480 in the PTCA group (p < 0.02). CONCLUSIONS: The strategy of PTCA with delay angiogram and provisional stent if early loss occurs had similar restenosis rate and TVR, but lower cost than primary stenting after PTCA.     

Hyperinsulinism in patients with coronary artery disease

AIM: To assess the clinical impact of hyperinsulinism and major coronary risk factors in patients with angiographically documented or excluded coronary artery disease (CAD), a clinical study was carried out in 268 men admitted for left heart catheterization. METHODS: Fasting immunoreactive insulin (IRI) levels were correlated to all major cardiovascular risk factors and to the presence and degree of CAD. RESULTS: IRI levels were correlated significantly with the degree of CAD (one-vessel disease: mean IRI 9.45 microU/ml +/- 0.43 SEM; two-vessel disease: mean IRI 10.4 microU/ml +/- 0.71 SEM; three-vessel disease: mean IRI 11.88 microU/ml +/- 0.98 SEM) and inversely to the high-density lipoprotein level (P < 0.05). In patients with arterial hypertension, IRI levels were elevated, without a significant difference between those with and those without CAD, whereas the IRI levels of non-hypertensive men with CAD (n = 81; mean IRI 9.85 microU/ml +/- 0.51 SEM) differed significantly (P < 0.05) from those of non-hypertensive men without CAD (n = 59; mean IRI 7.76 microU/ml +/- 0.43 SEM). IRI levels were significantly higher (P < 0.05) in obese patients (n = 65; mean IRI 11.68 microU/ml +/- 0.70 SEM versus n = 203; mean IRI 9.32 microU/ml +/- 0.34 SEM), in patients with elevated triglycerides (n = 58 mean IRI 11.59 microU/ml +/- 0.81 SEM versus n = 210; mean IRI 9.42 microU/ml +/- 0.33 SEM), and in patients with lowered HDL cholesterol (n = 178; mean IRI 11.06 microU/ml +/- 0.63 SEM versus n = 90; mean IRI 9.29 microU/ml +/- 0.34 SEM). Diabetic patients on angiotensin converting enzyme inhibitor therapy (n = 11; mean IRI 7.91 microU/ml +/- 0.91 SEM) had significantly (P < 0.05) lower IRI levels than those not treated with ACE inhibitors (n = 25; mean IRI 12.96 microU/ml +/- 1.47 SEM). IRI levels exceeding 8 microU/ml were associated with a 1.98-fold risk for CAD compared with IRI levels below 8 microU/ml. Stepwise logistic regression showed that insulin was an independent determinant of CAD. CONCLUSION: Knowledge of the fasting insulin level is an important contribution to the identification of patients with, or at risk of, CAD.     

Role of nitric oxide in coronary arterial vasomotion and the influence of coronary atherosclerosis and its risks

Healthy coronary vascular endothelium releases nitric oxide to modulate resting and dynamic coronary arterial tone. We studied the impact of atherosclerosis and/or its risks on endothelial nitric oxide release in response to metabolic stimuli by evaluating coronary vasomotor responses to atrial pacing before and after the inhibition of nitric oxide production by intracoronary NG-monomethyl-L-arginine (L-NMMA) (20 micromol/min) infusion. The study includes 34 patients (15 with coronary disease, 11 with normal coronary arteries and > or =1 risk factor, and 8 with normal coronary arteries and no risks). Coronary blood flow was derived from Doppler flow velocity (0.018-inch Doppler wire) and coronary diameter. L-NMMA infusion reduced coronary blood flow by 18 +/- 16% and coronary diameter by 10 +/- 9%. Responses were identical in all subgroups. Coronary blood flow responses to pacing were similar in all subgroups and were unaffected by L-NMMA (11 +/- 11 vs 13 +/- 9 ml/min; p = 0.26). Epicardial coronary vasodilation to control pacing occurred in patients with normal coronary arteries with (4.0 +/- 5.2%, p = 0.01) or without (8.0 +/- 5.2%, p = 0.03) risks, but not in patients with coronary disease (2.8 +/- 5.9%). L-NMMA abolished pacing-induced epicardial vasodilation in patients without coronary artery disease, producing a 1.8 +/- 5.1% response, which was similar in all subgroups. We conclude that microvascular responses to rapid atrial pacing are not mediated by nitric oxide. Flow-mediated epicardial coronary arterial responses may be nitric oxide dependent.     

Preservation of regional myocardial function and myocardial oxygen tension during acute ischemia in pigs: comparison of selective synchronized suction and retroinfusion of coronary veins to synchronized coronary venous retroperfusion

OBJECTIVES: The efficacy of selective synchronized suction and retroinfusion of coronary veins was compared with synchronized coronary venous retroperfusion in preventing ischemic reduction of regional myocardial function and myocardial oxygen tension. BACKGROUND: Because incomplete protection by synchronized coronary venous retroperfusion during ischemia might result from nonselective retroinfusion and only passive drainage of the veins, a suction device was added to a retroinfusion system. METHODS: Regional myocardial function (ultrasonic crystals) and myocardial oxygen tension (polarographic electrodes) were studied in 30 pigs during 10-min occlusion of the left anterior descending coronary artery (ischemia), followed by reperfusion. During ischemia, group A (n = 10) was supported by selective synchronized suction and retroinfusion; group B (n = 10) was supported by synchronized coronary venous retroperfusion, and group C (n = 10) was not supported by retroinfusion. RESULTS: In group A, subendocardial segment shortening decreased from 21 +/- 4% (mean +/- SD) before ischemia to 11 +/- 5% during ischemia. In contrast, systolic dyskinesia was observed in group B (-2 +/- 4%, p < 0.001) and group C (-2 +/- 5%, p < 0.001). During ischemia, the decrease in intramyocardial oxygen tension was less pronounced in group A (41 +/- 15 vs. 27 +/- 12 mm Hg) than in group B (40 +/- 10 vs. 19 +/- 10 mm Hg, p = 0.1) or group C (33 +/- 11 vs. 12 +/- 8 mm Hg, p = 0.002). During ischemia, myocardial surface oxygen tension was preserved > 0 mm Hg only in group A. CONCLUSIONS: Preservation of regional myocardial function and myocardial oxygen tension was substantially higher by selective synchronized suction and retroinfusion of coronary veins than by synchronized coronary venous retroperfusion in pigs.     

Blood levels of homocysteine in patients under 55 years of age with acute coronary insufficiency

OBJECTIVES: High blood levels of homocysteine have been recently described as a risk factor for thromboembolic events and early development of atherosclerosis. The aim of this work was to study homocysteine blood levels in patients under 55 years of age with acute coronary artery disease. PATIENTS AND METHODS: The study included 110 patients (98 men, 12 women) with poorly controlled angina pectoris (n = 35) or in the acute phase of myocardial infarction (n = 65). Homocysteine was assayed by liquid chromatography in all patients on the day of the acute episode and 24 hours later. Homocysteine levels were also determined in 40 controls under 55 years of age with no history of coronary artery disease. RESULTS: Blood level of homocysteine was 10.6 +/- 6.2 mumol/l in the patients and 7.7 +/- 2.5 mumol/l in the controls (p < 0.01). The difference was greater in the 30-40 year age rang with 14.4 +/- 2 mumol/l in patients versus 6.4 +/- 1.5 mumol/l in controls (p < 0.001). The assays were reproducible at 24 hours (difference less than 10%). The levels were significantly higher in patients with several diseased arteries than those with single-artery disease. The difference between patients and controls was especially remarkable for non-smokers and those with high cholesterol levels. CONCLUSION: Hyperhomocysteinemia would be a factor favoring early development of coronary atherosclerosis.     

Comparison of coronary endothelial dynamics with electrocardiographic and left ventricular contractile responses to stress in the absence of coronary artery disease

Coronary artery endothelial dysfunction has been proposed as a cause of myocardial ischemia and symptoms in patients with angina-like chest pain despite normal coronary angiograms, especially those with ischemic-appearing ST-segment depression during exercise (syndrome X). We measured coronary vasomotor responses to acetylcholine (3 to 300 microg/min) in 42 patients (27 women and 15 men) with effort chest pain and normal coronary angiograms who also had normal electrocardiograms and echocardiograms at rest. All patients underwent treadmill exercise testing and measurement of systolic wall thickening responses to dobutamine (40 microg/kg/min) during transesophageal echocardiography. There were no differences in the acetylcholine-stimulated epicardial coronary diameter (+5+/-13% vs +1+/-13%, p=0.386) and flow (+179+/-90% vs +169+/-96%, p=0.756), or in the systolic wall thickening responses (+134+/-65% vs +118+/-57%, p=0.445) from baseline values in the 12 syndrome X patients compared with the 30 patients with negative exercise test results. In patients in the lowest quartile of coronary flow responses to acetylcholine, dobutamine increased systolic wall thickening by 121+/-73%; 3 had ischemic-appearing ST-segment depression during this stress. This contractile response to dobutamine was no different than the increase in systolic wall thickening (129+/-48%, p=0.777) in patients in the highest quartile of coronary flow responses, 3 of whom also had ischemic-appearing ST-segment depression during this stress. Thus, coronary endothelial dysfunction in the absence of coronary artery disease does not account for ischemic-appearing ST-segment depression in patients with chest pain despite normal coronary angiograms. Further, coronary endothelial dysfunction is not associated with myocardial contractile responses to stress consistent with myocardial ischemia.