Usefulness of follow-up low-density lipoprotein cholesterol level as an independent predictor of changes of coronary atherosclerotic plaque size as determined by intravascular ultrasound analysis after statin (atorvastatin or simvastatin) therapy

Using serial intravascular ultrasound (IVUS), we identified independent predictors of changes in coronary plaque size in relation to serum lipid levels. One hundred three patients with nonstenotic coronary plaques underwent baseline and 12-month follow-up IVUS studies; 54 patients (52%) were treated with statins. Standard IVUS analyses were performed. Baseline IVUS study showed no statistical differences in mean external elastic membrane, lumen, and plaque/media (P&M) area between statin-treated and nonstatin-treated patients. Although there was an increase in mean P&M cross-sectional area in nonstatin-treated patients, mean P&M cross-sectional area decreased in statin-treated patients (0.11 +/- 0.24 vs -0.20 +/- 0.30 mm(2), p <0.001). There was a positive relation between changes in mean P&M area and follow-up low-density lipoprotein (LDL) cholesterol level (r = 0.430, p <0.001), follow-up total cholesterol level (r = 0.365, p <0.001), changes in LDL cholesterol level (r = 0.312, p = 0.002), and changes in total cholesterol level (r = 0.252, p = 0.012). In multivariate linear regression analysis, the only independent predictor of changes in mean P&M area was follow-up LDL cholesterol level (r = 0.469, p <0.001, 95% confidence interval 0.003 to 0.006). The cut-off value of follow-up LDL cholesterol for no change or a decrease in mean P&M area was <100 mg/dl at regression analysis. In conclusion, the present 12-month follow-up IVUS study showed that follow-up LDL cholesterol level was the only independent predictor of changes in coronary plaque size. When patients achieved a follow-up LDL cholesterol level <100 mg/dl, regression or no progression of coronary plaque was expected. Aggressive lipid-lowering treatments with statins to decrease the follow-up LDL cholesterol level to <100 mg/dl are recommended.     

Meta-analysis of the studies assessing temporal changes in coronary plaque volume using intravascular ultrasound

To assess the temporal effect of statin therapy on coronary atherosclerotic plaque volume measured by intravascular ultrasound (IVUS), we searched PubMed for eligible studies published between 1990 and January 2006. Inclusion criteria for retrieved studies were (1) IVUS volume analysis at baseline and follow-up and (2) statin therapy in > or =1 group of patients. All data of interest were abstracted in prespecified structured collection forms. Statistical analysis was performed with Review Manager 4.2. Random-effect weighted mean difference (WMD) was used as summary statistics for comparison of continuous variables. Nine studies of 985 patients (with 11 statin treatment arms) were selected. After a mean follow-up of 9.8 +/- 4.9 months, we found a significant decrease in coronary plaque volume (WMD -5.77 mm(3), 95% confidence interval -10.36 to -1.17, p = 0.01), with no significant heterogeneity across studies (p = 0.47). Prespecified subgroup analyses showed similar trends. Studies in which the achieved low-density lipoprotein (LDL) cholesterol level was <100 mg/dl showed a trend for plaque regression (WMD -7.88 mm(3), 95% confidence interval -16.31 to 0.55, p = 0.07), whereas studies in which the achieved level of LDL cholesterol was > or =100 mg/dl, the trend was less evident (WMD -4.22 mm(3), 95% confidence interval -10.27 to 1.82, p = 0.17). Plaque volume remained essentially unchanged in patients not treated with statins (WMD 0.13 mm(3), 95% confidence interval -4.42 to 4.68, p = 0.96). In conclusion, statin therapy, particularly when achieving the target LDL level, appears to promote a significant regression of coronary plaque volume as measured by IVUS.     

Relation between plaque progression and low-density lipoprotein cholesterol during aging as assessed with serial long-term (> or =12 months) follow-up intravascular ultrasound of the left main coronary artery

Because of the clinical benefit of lipid lowering in older patients, we hypothesized that the relation between low-density lipoprotein (LDL) cholesterol serum levels and coronary plaque progression may persist throughout aging. We analyzed serial intravascular ultrasound (IVUS) data of 60 left main stems (18 +/- 9 months apart) and evaluated the relation between LDL cholesterol levels and coronary plaque progression at different ages. The population (n = 60) was divided into 3 groups according to age: tertile 1 (n = 20) was a mean age of 48 +/- 6 years (median 51, range 33 to 55), tertile 2 (n = 20) was a mean age of 58 +/- 2 years (median 59, range 55 to 61), and tertile 3 (n = 20) was a mean age of 66 +/- 6 years (median 65, range 61 to 83). Between groups, there was no significant difference in non-age-related demographics, clinical data, lipid profiles, or medications (e.g., statins). There was a positive linear relation between LDL cholesterol and annual changes in plaque plus media area in all age tertiles, which was statistically significant in tertiles 2 and 3 (r = 0.56, p <0.01; r = 0.50, p <0.02) and showed a strong trend in tertile 1 (r = 0.41, p = 0.07). The estimated LDL cholesterol thresholds, which, as determined by regression analysis, would correspond to no plaque progression, were 74, 60, and 78 mg/dl, respectively, in tertiles 1, 2, and 3. In conclusion, serial IVUS data in left main coronary arteries suggest that the relation between LDL cholesterol serum levels and plaque progression persists during aging.     

One-year follow-up after intravascular ultrasound assessment of moderate left main coronary artery disease in patients with ambiguous angiograms.

OBJECTIVES: The purpose of this study was to correlate angiographic and intravascular ultrasound (IVUS) findings in left main coronary artery (LMCA) disease and identify the predictors of coronary events at one year in patients with LMCA stenoses. BACKGROUND: Significant (> or =50% diameter stenosis [DS]) LMCA disease has a poor long-term prognosis. METHODS: One hundred twenty-two patients who underwent angiographic and IVUS assessment of the severity of LMCA disease and who did not have subsequent catheter or surgical intervention were followed for one year. Standard clinical, angiographic and IVUS parameters were collected. RESULTS: The quantitative coronary angiography (QCA) reference diameter (3.91 +/- 0.76 mm, mean +/- 1 SD) correlated moderately with IVUS (4.25 +/- 0.78 mm, r = 0.492, p = 0.0001). The lesion site minimum lumen diameter (MLD) (2.26 +/- 0.82 mm) by QCA correlated less well with IVUS (2.8 +/- 0.82 mm, r = 0.364, p = 0.0005). The QCA DS measured 42 +/- 16%. During the follow-up period, 4 patients died, none had a myocardial infarction, 3 underwent catheter-based LMCA intervention and 11 underwent bypass surgery. Univariate predictors of events (p < 0.05) were diabetes, presence of another lesion whether treated with catheter-based intervention or untreated with DS > 50% and IVUS reference plaque burden and lesion lumen area, maximum lumen diameter, MLD, plaque area and area stenosis. Using logistic regression analysis diabetes mellitus, an untreated vessel (with a DS > 50%) and IVUS MLD were independent predictors of cardiac events. CONCLUSIONS: In selected patients assessed by IVUS, moderate LMCA disease had a one-year event rate of only 14%. Intravascular ultrasound MLD was the most important quantitative predictor of cardiac events. For any given MLD, the event rate was exaggerated in the presence of diabetes or another untreated lesion (>50% DS).     

Progression and regression of minor coronary arterial narrowings by quantitative angiography after fenofibrate therapy

To study the effects of fenofibrate, a lipid-lowering medication, on patients with coronary artery disease, 191 minor coronary narrowings in 42 patients with coronary artery disease were analyzed by quantitative coronary angiography using computer-assisted contour detection. Computed parameters were percent diameter reduction and percent plaque area. A prospectively formed intervention group of 21 patients treated with special diet and fenofibrate (200 to 400 mg/day) was checked every 6 weeks with regard to risk factors. After a mean interval of 21 months, coronary angiography was repeated, using the same x-ray system and nearly identical projections. The intervention group was angiographically compared at follow-up with an untreated comparison group, also comprising 21 patients. Both groups had high initial serum cholesterol (mean 311 mg/dl) and low-density lipoprotein (LDL) cholesterol levels (mean 235 mg/dl). Only among the treated patients did lipid levels change significantly: cholesterol, -19%; LDL cholesterol, -20%; high-density lipoprotein cholesterol, +19%; and triglycerides, -30%. At angiographic follow-up, the changes in percent diameter reduction and percent plaque area correlated positively with the mean serum and LDL cholesterol levels of the intervention group. Significant differences were found in the change in percent plaque area between both groups. The intervention subgroup with angiographic regressions (11 patients) had significantly lower serum and LDL cholesterol levels than the intervention subgroup with angiographic progressions (10 patients). These results indicate the beneficial effect of fenofibrate on minor coronary narrowings. Because of its high reproducibility in measuring minor narrowings, quantitative coronary angiography proved to be a suitable method for angiographic follow-up.     

Incidence of new atherothrombotic brain infarction in older persons with prior myocardial infarction and serum low-density lipoprotein cholesterol >or=125 mg/dl treated with statins versus no lipid-lowering drug

BACKGROUND: We report the incidence of new atherothrombotic brain infarction (ABI) in older men and women with prior myocardial infarction and a serum low-density lipoprotein (LDL) cholesterol of >or=125 mg/dl treated with statins and with no lipid-lowering drug. METHODS: The incidence of new ABI was investigated in an observational prospective study of 1410 men and women, mean age 81 +/- 9 years, with prior myocardial infarction and a serum LDL cholesterol of >or=125 mg/dl treated with statins (679 persons or 48%) and with no lipid-lowering drug (731 persons or 52%). Follow-up was 36 +/- 21 months. RESULTS: At follow-up, the stepwise Cox regression model showed that significant independent predictors of new ABI were age (risk ratio = 1.04 for a 1-year increase in age), cigarette smoking (risk ratio = 3.5), hypertension (risk ratio = 3.1), diabetes mellitus (risk ratio = 2.3), initial serum LDL cholesterol (risk ratio = 1.01 for each 1 mg/dl increase), initial serum high-density lipoprotein cholesterol (risk ratio = 0.97 for each 1 mg/dl increase), prior stroke (risk ratio = 2.5), and use of statins (risk ratio = 0.40). The Cochran-Armitage test showed a trend in the reduction of new ABI in persons treated with statins as the level of serum LDL cholesterol decreased ( p <.0001). CONCLUSIONS: Use of statins caused a 60%, significant, independent reduction in new ABI in older men and women with prior myocardial infarction and a serum LDL cholesterol of >or=125 mg/dl.     

Association of cholesterol levels and occurrence of angiographically detectable endothelial disruption during coronary angioplasty

BACKGROUND: Disruption of the atherosclerotic plaque is a common feature of both acute coronary syndromes and balloon dilatation of coronary artery stenoses. HYPOTHESIS: The study was undertaken to evaluate whether the known association of cholesterol levels and acute coronary syndromes also exists for the occurrence of angiographically detectable endothelial disruption (ED) following coronary angioplasty. METHODS: For this purpose, we examined 79 consecutive patients (men/women 58/21; mean age: 62 +/- 11 years), with a noncalcified, de novo, significant stenosis in a single native coronary artery, undergoing elective coronary intervention because of stable effort angina. Coronary angioplasty was performed using regular balloon catheters, aiming for a balloon/ artery ratio of 1, with stent implantation allowed only provisionally. Following balloon dilatation, patients were divided into two groups according to the presence or absence of angiographically detectable ED. RESULTS: Endothelial disruption occurred in 28 patients (35%). The two groups with and without ED were comparable with respect to clinical, angiographic, and procedural parameters. A history of hypercholesterolemia was significantly more frequent in patients with ED (93 vs. 2%; p < 0.001). Total and low-density lipoprotein (LDL) cholesterol levels were significantly higher in the group with ED (230.1 +/- 46.5 vs. 204.4 +/- 30.2 mg/dl, p < 0.05; and 150.6 +/- 39.2 vs. 125.8 +/- 26 mg/dl, p < 0.03, respectively). A cut-off value of LDL cholesterol > or = 135 mg/dl identified patients at higher risk of developing ED. CONCLUSION: High cholesterol levels appear to favor the occurrence of ED during coronary angioplasty. Aggressive lipid-lowering therapy and a more careful procedural approach may be warranted in patients with hypercholesterolemia undergoing coronary interventions in order to decrease the occurrence of ED and the associated clinical (acute ischemia) and procedural (stent implantation) consequences.     

Relation between lipoprotein(a) and fibrinogen and serial intravascular ultrasound plaque progression in left main coronary arteries.

OBJECTIVES: Patients with elevated lipoprotein(a) [Lp(a)] and fibrinogen levels have an increased risk of coronary heart disease and adverse cardiovascular events. There is evidence that coronary plaque progression is linked to a higher risk for future cardiovascular events. BACKGROUND: There are no data demonstrating a relation between Lp(a), fibrinogen, and directly measured coronary plaque progression over time. METHODS: We performed a retrospective analysis of serial intravascular ultrasound (IVUS) studies of 60 left main stems (18 +/- 9 months apart) to evaluate plaque progression in relation to Lp(a) and fibrinogen levels and association with adverse cardiovascular events. RESULTS: There was a positive correlation between Lp(a) (r = 0.58; p < 0.0001), fibrinogen (r = 0.48; p < 0.0001), and changes in plaque-plus-media area. Patients with plaque progression (n = 41) had higher Lp(a) (30 +/- 26 mg/dl vs. 14 +/- 9 mg/dl; p < 0.0012) and fibrinogen (295 +/- 88 mg/dl vs. 240 +/- 72 mg/dl; p = 0.019) levels than patients with plaque regression (n = 19). Multivariate linear regression analysis showed Log Lp(a) (regression coefficient = 9.45; p = 0.0008) but not fibrinogen to be independently associated with plaque progression. A total of 19 patients suffered from adverse cardiovascular events; they had higher Lp(a) (44 +/- 30 mg/dl vs. 16 +/- 12 mg/dl; p < 0.0001) and fibrinogen (342 +/- 73 mg/dl vs. 248 +/- 76 mg/dl; p < 0.0001) levels. Multivariate logistic regression analysis showed Log Lp(a) (odds ratio 10.20, 95% confidence interval 2.36 to 44.13; p = 0.0019) and fibrinogen (odds ratio 1.01, 95% confidence interval 1.00 to 1.03; p = 0.018) were independently associated with adverse cardiovascular events. CONCLUSIONS: Serial IVUS showed a positive correlation between Lp(a) and fibrinogen levels and plaque progression. Lp(a), but not fibrinogen, remains independently associated with plaque progression. In addition, the present data suggest a considerable incremental value of Lp(a) in predicting cardiovascular risk.     

Insufficient treatment of hypercholesterolemia among patients hospitalized with chest pain

BACKGROUND: Although morbidity and mortality from coronary artery disease can be improved with a variety of pharmacologic interventions, many patients remain undertreated. HYPOTHESIS: This study sought to assess whether hospitalization for possible coronary artery disease would prompt initiation of appropriate lipid-lowering therapy. METHODS: This prospective, observational study was conducted on consecutive patients with active chest pain admitted to the Emergency Department of the hospital for suspected myocardial ischemia. Elevated cholesterol, defined as low-density lipoprotein (LDL), was >100 mg/dl with a prior history or a new diagnosis of coronary artery disease, or an LDL >130 mg/dl without known coronary artery disease. Data were recorded at the time of admission, discharge, and at 4-month follow-up. RESULTS: Of the patients with hyperlipidemia, 65% men and 55% women were on medication at the time of admission (p = 0.30), while at discharge, 79% men and 60% women were on treatment (p = 0.002), with similar rates of treatment at 4-month follow-up (p = 0.030). At discharge, two variables were independently associated with patients receiving lipid-lowering therapy: age > or =65 years (odds ratio = 2.3; 95% confidence interval 1.2-4.5) and male gender (2.7; 15-5.0). CONCLUSIONS: In patients hospitalized with chest pain, particularly in women, the initiation of treatment of hyperlipidemia frequently does not happen. This oversight represents a lost opportunity for making an impact on the health of this population.     

Reduction of new coronary events and new atherothrombotic brain infarction in older persons with diabetes mellitus,prior myocardial infarction,and serum low-density lipoprotein cholesterol >/=125 mg/dl treated with statins

BACKGROUND: We report the incidence of new coronary events and new atherothrombotic brain infarction (ABI) in older men and women with diabetes mellitus, prior myocardial infarction, and a serum low-density lipoprotein (LDL) cholesterol of >/=125 mg/dl treated with statins and with no lipid-lowering drug. METHODS: The incidence of new coronary events and of new ABI was investigated in an observational prospective study of 529 diabetics, mean age 79 +/- 9 years, with prior myocardial infarction and a serum LDL cholesterol of >/=125 mg/dl treated with statins (279 persons or 53%) and no lipid-lowering drug (250 persons or 47%). Follow-up was 29 +/- 18 months. RESULTS: At follow-up, the stepwise Cox regression model showed that after controlling for other risk factors, the use of statins was associated with a 37% significant independent reduction in the incidence of new coronary events and with a 47% significant independent reduction in the incidence of new ABI. CONCLUSIONS: Use of statins was associated with a 37% significant, independent reduction in new coronary events and a 47% significant, independent reduction in new ABI in older men and women with diabetes mellitus, prior myocardial infarction, and a serum LDL cholesterol of >/=125 mg/dl. Elderly diabetics with prior myocardial infarction and increased serum LDL cholesterol should especially be treated with statins.     

Cardiovascular features of homozygous familial hypercholesterolemia: analysis of 16 patients

Familial hypercholesterolemia (FH) is characterized by an autosomal codominant inheritance, an abnormality in low-density lipoprotein (LDL) receptor function, elevated plasma cholesterol levels and premature atherosclerosis. Sixteen patients with homozygous FH were studied to correlate the extent of their atherosclerotic disease with their lipid levels and receptor function. The age range at initial presentation was 3 to 38 years (mean 12), and at the last examination, 6 to 43 years (mean 20). The mean pretreatment total plasma cholesterol concentration for all patients was 729 +/- 58 mg/dl (+/- standard error of the mean), and the mean LDL cholesterol level was 672 +/- 58 mg/dl (normal 60 to 176). High-density lipoprotein cholesterol was 28 +/- 3 mg/dl (normal 30 to 74). In the 7 patients with FH who had symptoms of myocardial ischemia (Group I), the mean pretreatment LDL cholesterol value (817 +/- 62 mg/dl) was higher than that of the 9 asymptomatic patients (Group II) (560 +/- 74 mg/dl). In Group I, 5 of 7 patients had left or right coronary ostial narrowing and 3 had significant left ventricular outflow obstruction. Most coronary arterial narrowing occurred in the right coronary and left anterior descending arteries and the least amount in the left circumflex coronary artery. A femoral bruit was the physical finding that correlated best with the Group I population; brother:sister pairs revealed a milder clinical course for the female. Seven of the 16 patients have survived into their third decade without symptoms. Comparison of these persons with those in whom angina developed reveals a marked heterogeneity in their clinical course, which appears to be associated with receptor negative/defective status.     

Impact of lipid-lowering therapy with pitavastatin, a new HMG-CoA reductase inhibitor, on regression of coronary atherosclerotic plaque.

BACKGROUND: Recent lipid-lowering trials have reported that statin therapy may retard progression or stimulate regression of human coronary plaque. In the present study volumetric intravascular ultrasound (IVUS) analyses were performed to investigate the effect of pitavastatin, a newly developed statin, on regression of human coronary plaque. METHODS AND RESULTS: Eighty-two patients matched for age and gender from 870 consecutive patients undergoing IVUS guided percutaneous coronary intervention were retrospectively assigned to either lipid-lowering therapy (n=41; pitavastatin 2 mg/day) or control group (n=41; diet only). Serial volumetric IVUS analyses of a matched left main coronary arterial site were performed. A significant reduction in low-density lipoprotein-cholesterol (LDL-C) level of 33.2% (p<0.001) was observed in the pitavastatin group. Plaque volume index (PVI) was significantly reduced in the pitavastatin group (10.6+/-9.4% decrease) compared with the control group (8.1+/-14.0% increase, p<0.001). There were positive correlations between the percent change in the PVI and follow-up LDL-C level (r=0.500, p<0.001) and the percent change in LDL-C level (r=0.479, p<0.001). CONCLUSION: Lipid-lowering therapy with pitavastatin induced significant coronary plaque regression, associated with a significant reduction in the LDL-C level. The percent change in the PVI showed a significant positive correlation with the percent change in LDL-C level.     

Ergonovine-Induced Changes of Coronary Artery Diameter in Patients with Nonsignificant Coronary Artery Stenosis

BACKGROUND AND PURPOSE: Serum cholesterol is positively associated with the risk of developing coronary heart disease. The aim of this study was to determine the relation between response of coronary arteries to ergonovine provocation and lipid profile in patients with nonsignificant coronary artery disease. PATIENTS AND METHODS: 105 patients (46 male, 59 female, mean age 52 +/- 8 years) with chest pain syndrome and nonsignificant coronary artery stenosis (< 50% diameter stenosis) were analyzed. Ergonovine test was performed at the end of diagnostic catheterization. Coronary spasm was defined as total or near total obstruction of the coronary artery. By quantitative coronary arteriography, changes of minimal luminal diameter (MLD) during ergonovine provocation were evaluated. Total cholesterol, LDL and HDL cholesterol, and triglycerides were measured. RESULTS: There was a significant negative correlation between resting MLD and LDL cholesterol (r = -0.215; p = 0.034), and a significant positive correlation between MLD decrease provoked by ergonovine and total cholesterol (r = 0.275; p = 0.006), as well as LDL cholesterol (r = 0.284; p = 0.004), but not for HDL cholesterol and triglycerides (p = NS [not significant]). CONCLUSION: In patients with nonsignificant coronary artery stenosis evaluated by ergonovine provocation, there was not only a significant negative correlation between MLD and LDL cholesterol, but also a positive correlation between coronary vasoconstriction induced by ergonovine provocation and both total and LDL cholesterol.     

Effect of atorvastatin on postcardiac transplant increase in low-density lipoprotein cholesterol reduces development of intimal hyperplasia and progression of endothelial dysfunction

Following cardiac transplantation, accelerated coronary disease limits long-term survival. Because statins may reduce the progression of the disease in part by their anti-inflammatory effects, this study was designed to assess if atorvastatin prevented neointimal hyperplasia and endothelial dysfunction independently of baseline cholesterol levels. Patients were randomized to usual therapy (n = 13) or to 10 to 20 mg of atorvastatin (n = 12). Control subjects received niacin when their low-density lipoprotein (LDL) cholesterol levels were >130 mg/dl (n = 4). Neointimal hyperplasia by intracoronary ultrasonography, endothelial dependent vascular reactivity, and coronary flow reserve were measured at baseline and 1 year. Control group total cholesterol (203 +/- 11 to 200 +/- 13 mg/dl) and LDL (116 +/- 10 to 119 +/- 11 mg/dl) remained stable, whereas there was a nonsignificant reduction at 12 months in the atorvastatin group (total cholesterol 216 +/- 28 to 178 +/- 21 mg/dl; LDL 126 +/- 17 to 100 +/- 18 mg/dl). At 2 to 3 months there was a significant increase in total cholesterol and LDL cholesterol that was reduced with atorvastatin. At 1 year, patients taking atorvastatin showed a decrease in new or progressing lesions (2.5 +/- 1.7 vs 4.2 +/- 1.8 lesions/patient, p = 0.02), progression of maximal intimal thickness (0.12 +/- 0.07 vs 0.52 +/- 0.17 mm, p = 0.04), and percent area stenosis (5.9 +/- 2.2% vs 19.0 +/- 5.5%, p = 0.04). Atorvastatin ameliorated progressive endothelial dysfunction, whereas coronary flow reserve was unchanged in both groups. Atorvastatin administered to patients with normal or mild hypercholesterolemia in the initial year after transplant reduced the initial increase in LDL cholesterol, and, by doing so, prevented the development and progression of coronary artery lesions and endothelial dysfunction with only mild long-term decreases in cholesterol levels.     

Benefits of lipid-lowering therapy in men with elevated apolipoprotein B are not confined to those with very high low density lipoprotein cholesterol

Objectives. Do the benefits of intensive lipid-lowering therapy extend to patients with only borderline or moderately elevated levels of low density lipoprotein (LDL) cholesterol?Background. The merits of the present LDL cholesterol treatment goal of ≤100 mg/dl need to be clarified for patients without high levels of LDL cholesterol, particularly for those patients previously classified as having only borderline high (130 to 159 mg/dl) or desirable (101 to 130 mg/dl) levels.Methods. Disease change and clinical events were examined in LDL cholesterol subgroups in the Familial Atherosclerosis Treatment Study (FATS) trial, a randomized, blinded, quantitative arteriographie comparison of one conventional and two intensive lipid-lowering strategies in men with coronary artery disease, a positive family history and apolipoprotein B ≥125 mg/dl. The primary end point, disease change per patient, was measured as the mean change in severity of stenosis (Δ%S_Prox) among nine standard proximal segments.Results. Of the 120 patients completing the 30-month protocol, 60 had a baseline LDL cholesterol <90th percentile (mean LDL cholesterol 152 mg/dl) and 60 >90th percentile (mean LDL cholesterol 221 mg/dl). Thirty-one patients had levels <160 mg/dl (mean LDL cholesterol 134 mg/dl) and 89 >160 mg/dl (mean LDL cholesterol 205 mg/dl). Patients with LDL cholesterol <90th percentile benefited angiographically from therapy (Δ%S_Prox= −1.5% diameter stenosis [regression] during intensive therapy vs. 4-2.3% diameter stenosis [progression] during conventional therapy, p < 0.01), as did patients with LDL cholesterol <160 mg/dl (Δ%S_Prox= −4.2% vs. +3.3% diameter stenosis, p = 0.0001). By comparison, angiographie benefit was less pronounced among those entdring with very high LDL cholesterol (Δ%S^Prox= −0.2% vs. +1.9% diameter stenosis, p = 0.07) or with LDL cholesterol ≥160 mg/dl (Δ%S_Prox= +0.2% vs. +1.6% diameter stenosis, p = 0.13). Intensive therapy resulted in a statistically significant reduction in clinical events only in the subgroup with baseline LDL cholesterol < 90th percentile (2 of 42 vs. 8 of 29 patients initially enrolled, p = 0.01) and a trend toward fewer events in patients with LDL cholesterol < 160 mg/dl (2 of 20 vs. 6 of 15 patients, p = 0.05). No such difference was seen in the higher LDL cholesterol subgroups.Conclusions. Treatment benefit in the FATS trial was not confined to patients with very high levels of LDL cholesterol and was in fact particularly evident in those patients with levels < 160 mg/dl. Such patients should be considered more likely, not less, to benefit from intensive lipid-lowering therapy.     

Long-term effect of perindopril on coronary atherosclerosis progression (from the perindopril's prospective effect on coronary atherosclerosis by angiography and intravascular ultrasound evaluation [PERSPECTIVE] study)

The multicenter EUROPA trial of 12,218 patients showed that perindopril decreased adverse clinical events in patients with established coronary heart disease. The PERSPECTIVE study, a substudy of the EUROPA trial, evaluated the effect of perindopril on coronary plaque progression as assessed by quantitative coronary angiography and intravascular ultrasound (IVUS). In total 244 patients (mean age 57 years, 81% men) were included. Evaluable paired quantitative coronary angiograms were obtained from 96 patients randomized to perindopril and from 98 patients to placebo. Concomitant treatment at baseline consisted of aspirin (90%), lipid-lowering agents (70%), and beta blockers (60%). The primary and secondary end point was the difference of minimum and mean lumen diameters (quantitative coronary angiography) or mean plaque cross-sectional area (IVUS) measured at baseline and 3-year follow-up between the perindopril and placebo groups. After a median follow-up of 3.0 years (range 1.9 to 4.1), no differences in change in quantitative coronary angiographic or IVUS measurements were detected between the perindopril and placebo groups (minimum and mean luminal diameters -0.07 +/- 0.4 vs -0.02 +/- 0.4 mm, p = 0.34; mean luminal diameter -0.05 +/- 0.2 vs -0.05 +/- 0.3 mm, p = 0.89; mean plaque cross-sectional area -0.18 +/- 1.2 vs -0.02 +/- 1.2 mm(2), p = 0.48). In conclusion, we found no progression in coronary artery disease by quantitative coronary angiography and IVUS with long-term administration of perindopril or placebo, possibly because most patients were on concomitant treatment with a statin.     

Impact of intravascular ultrasound guidance on directional coronary atherectomy

In contrast to the luminogram of coronary angiography, intravascular ultrasound (IVUS) has proven to accurately assess both coronary lumen and vessel morphology due to its 360 degrees imaging capacity. Directional coronary atherectomy (DCA) improves the coronary lumen by removing plaque mass rather than stretching the vessel and compressing the plaque as with conventional percutaneous transluminal coronary angioplasty. In an attempt to optimize the procedural result of DCA we prospectively investigated the impact of IVUS guidance in a head to head comparison to on-line quantitative coronary angiography (QCA) on the result of DCA. In 16 consecutive patients IVUS demonstrated significant residual plaque mass after DCA irrespective of a satisfactory angiographic result. After a mean of 9 +/- 2 cuts luminal improvement was obtained with an area stenosis by angiography of 39 +/- 17% and by IVUS of 50 +/- 10% (p < 0.05), a diameter stenosis by angiography of 23 +/- 10% and IVUS of 35 +/- 14% (p < 0.05) and finally a minimal lumen diameter (MLD) by angiography of 2.9 +/- 0.5 mm and by IVUS of 2.3 +/- 0.5 mm (p < 0.005). After both on-line QCA and IVUS measurements a second series of 7 +/- 2 cuts were initiated to debulk more atheroma and improve stenosis dimensions. After additional cuts IVUS revealed further luminal improvement with an area stenosis by angiography of 25 +/- 16% and IVUS of 21 +/- 18% (n.s.), a diameter stenosis by angiography of 16 +/- 11% and by IVUS of 13 +/- 19% (n.s.) and finally a MLD by angiography of 3.1 +/- 0.5 mm and by IVUS of 2.8 +/- 0.3 mm (p < 0.05). Intraprocedural use of IVUS is superior to on-line QCA to assess the immediate result of DCA. IVUS-guided DCA results in more effective atheroma debulking than luminographic evaluation. Results of larger follow-up studies are needed to substantiate the intraprocedural advantage of IVUS with DCA.     

Effects of lipid-lowering therapy on coronary artery remodeling

BACKGROUND: Although lipid-lowering therapy affects the luminal size of atherosclerotic coronary arteries the role of vascular remodeling has not been systematically studied. DESIGN/METHODS: Serial three-dimensional volumetric intravascular ultrasound (IVUS) was used to study remodeling, which was defined as changes in arterial size independent of or dependent on changes in plaque size. Using an automated contour detection algorithm, a 1 mm segment of a moderate atherosclerotic lesion at the site of the maximal plaque volume at baseline was analysed. After 12 months the relationship between the absolute change in vessel volume and plaque volume was calculated in 99 patients. There was a significant relationship between changes in plaque and vessel volume, independent of plaque progression or plaque regression (decrease in plaque size, r = 0.60, P < 0.0001 and increase in plaque size, r = 0.49, P < 0.0008, respectively; the slopes of the regression equation were 1.03 and 0.80). By means of an analysis of covariance we tested whether the regression slopes were equal between groups of patients as defined by the low-density lipoprotein-cholesterol (LDL-c) level achieved with lipid-lowering therapy. RESULTS: Only patients with plaque progression and a LDL-c level < 100 mg/dl had a significantly smaller slope than patients with a LDL-c level > 100 mg/dl (-0.14 compared with 1.14, P = 0.003 ), indicating diminished coronary remodeling. CONCLUSIONS: Serial volumetric IVUS confirms the existence of both positive and negative remodeling in relation to an increase and decrease in plaque volume. It has been shown that the outward remodeling process is diminished in patients with plaque progression and intensive lipid-lowering therapy.     

Identification of mildly oxidized low-density lipoprotein (electronegative LDL) and its auto-antibodies IgG in children and adolescents hypercholesterolemic offsprings

BACKGROUND: Oxidative modification of low-density lipoproteins (LDL) is an essential step in atherogenesis, generating minimally oxidized LDL, also called electronegative LDL [LDL(-)], which has chemotactic, cytotoxic and immunogenic properties. METHODS AND RESULTS: Serum LDL(-) and anti-LDL(-) auto-antibodies (IgG) were evaluated in 28 children and adolescents with familial hypercholesterolemia (FH) antecedents, with or without early coronary artery disease in first-degree relatives (eCAD), hypercholesterolemic (hc) or normocholesterolemic (nc) versus a control group of normocholesterolemic children without pathologic antecedents (C). ELISA method was used for detection of LDL(-) and anti-LDL(-) IgG. LDL(-) serum levels did not differ among the four groups (FH-eCAD-hc 41.4 +/- 24.9 microg/dl; FH-hc 38.3 +/- 11.2 microg/dl; FH-nc 47.3 +/- 17.0 microg/dl and C 44.2 +/- 28.8 microg/dl, p = 0.659). However, IgG anti-LDL(-) auto-antibodies were significantly higher in the control group in comparison to the FH groups with or without eCAD, independent of hypercholesterolemia or normocholesterolemia (FH-eCAD-hc 0.825 +/- 0.289 microg/dl; FH-hc 0.667 +/- 0.307 microg/dl; FH-nc 0.763 +/- 0.204 microg/dl and C 1.105 +/- 0.233 microg/dl, p = 0.006). When the auto-antibodies of groups with FH, with or without eCAD and with or without hypercholesterolemia were compared, no differences were found (p = 0.509). CONCLUSION: These results showed that FH and/or eCAD children and adolescents have lower titers of auto-antibodies anti-LDL(-) than children from normal families, independent of serum LDL-cholesterol or serum LDL(-).     

Regression of a large lipid-rich pool in the coronary artery during treatment with statin detected by intravascular ultrasound: a case report

A 54-year-old man with unstable angina presented with severe stenosis of the middle segment of the left anterior descending coronary artery. Percutaneous coronary stent implantation and serial intravascular ultrasound (IVUS) were performed. IVUS detected a non-culprit coronary plaque with a large lipid-rich pool in the proximal segment of the left anterior descending coronary artery. Atorvastatin 10 mg/day was given to reduce his cholesterol level for 2 years after the stent implantation. This patient had no cardiac events, and the low-density lipoprotein-cholesterol level reduced from 171 to 88 mg/dl at follow-up. Two-year follow-up IVUS examination revealed the reduction of plaque burden associated with regression of the lipid-rich pool size. This case may indicate that statin could contribute to the regression of lipid-rich plaque and to the stability of coronary plaque.