A. Torri

Accuracy of calculated serum low-density lipoprotein cholesterol for the assessment of coronary heart disease risk in NIDDM patients

OBJECTIVE To evaluate the accuracy of LDL cholesterol calculated with Friedewalds equation in the assessment of cardiovascular risk in NIDDM patients. RESEARCH DESIGN AND METHODS The calculation of LDL cholesterol according to Friedewalds formula was compared with the measurement of LDL cholesterol separated by ultracentrifugation in 151 NIDDM patients with fairly good metabolic control (HbA1c ≤10%) and in 405 nondiabetic subjects. RESULTS Measured and calculated LDL cholesterol was found to be well correlated in both diabetic (r = 0.95) and nondiabetic (r = 0.97) subjects. Compared with measured LDL cholesterol, the calculated LDL cholesterol differed by ≥10% in 34% of samples from diabetic patients and in 26% of samples from nondiabetic subjects (χ2 = 3.885, P < 0.05). The percentage of error increased when the serum triglyceride (TG) level was ≥200 mg/dl (2.26 mmol/l) and when the ratio of VLDL cholesterol to TG was <0.20 or >0.29 in both groups of subjects. Although the percentage of error from calculated LDL cholesterol was greater in diabetic than in nondiabetic subjects because of the greater prevalence of hypertriglyceridemia in the former group, the misclassification of coronary heart disease risk, according to the cutoff points of the National Cholesterol Education Program (NCEP), was similar in the two groups (25% in diabetic and 22% in nondiabetic subjects). In both groups of patients, the misclassification of coronary heart disease risk was higher when calculation of LDL cholesterol produced values near the cutoff points. CONCLUSIONS Although accuracy in the estimation of LDL cholesterol is less than ideal, Friedewalds equation seems to be of value in the correct assignment of coronary heart disease risk classes in the great majority of diabetic as well as nondiabetic subjects. Caution must be exercised for subjects in whom calculated LDL cholesterol is close to the cutoff points of the NCEP guidelines.

Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia

BACKGROUND Simvastatin 40 to 80 mg/d has been found to increase high-density lipoprotein cholesterol (HDL-C) levels significantly more than atorvastatin at equipotent doses (ie, 20-80 mg/d). Data on the effects of lower doses of the 2 drugs on HDL-C levels are conflicting. OBJECTIVE The purpose of this study was to investigate the effects of simvastatin 20 mg/d and atorvastatin 10 mg/d on HDL-C levels in patients with hypercholesterolemia. METHODS Patients with primary hypercholesterolemia (total cholesterol [TC] >250 mg/dL) who were not taking any lipid-lowering agents and who were following a low-fat diet were randomized to receive 1 of 2 treatments: simvastatin 20 mg/d or atorvastatin 10 mg/d. Serum TC, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and HDL-C levels were measured using standard methods after 2 months of therapy. In a secondary analysis, lipids and lipoprotein cholesterol were measured after 1 year in patients who continued treatment. RESULTS Of the 240 patients enrolled (108 men and 132 women; age range, 23-77 years, mean [SEM] 56.7 [0.69]), 235 completed the study. After 2 months of therapy, TC, LDL-C, and serum TG levels decreased significantly versus baseline in both groups (P < 0.001), with no significant differences between treatment groups. HDL-C levels increased by 9.0% (P < 0.001 vs baseline) in the simvastatin group and by 4.3% (P < 0.02) in the atorvastatin group. The difference between the 2 groups in the percentage increase in HDL-C was statistically significant (P < 0.05). In 113 patients who continued treatment, HDL-C levels at 1 year were still significantly higher than baseline levels in the simvastatin group (6.3%, P = 0.034), but not in the atorvastatin group (2.8%, P = 0.587). CONCLUSIONS The findings from this study suggest that the HDL-C-increasing effect of simvastatin 20 mg is significantly greater than that of atorvastatin 10 mg. Since increasing HDL-C levels is thought to lower the risk for atherosclerosis and coronary heart disease, these results warrant further investigation.

Changes in serum triglycerides and high-density lipoprotein concentration and composition after a low-fat mixed meal. Effects of gender and insulin resistance

ObjectivePostprandial lipaemia is generally studied after a test meal that provides most of the calories as fat and that does not reflect the common food intake. We investigated postprandial changes in serum triglycerides (TG) and in high-density lipoprotein (HDL) concentration and composition after a regular meal poor in fat (30% of calories).MethodsFifty-four women and 54 men had breakfast at 8:00 a.m. (12% of daily calories) and lunch at 12:30 p.m. (53% of daily calories).ResultsWith respect to fasting values, TG increased more in men (24% at 2:30 p.m. and 30% at 5:00 p.m.) than in women (19% and 23%, respectively). HDL cholesterol decreased by 4% both in men and women at 2:30 p.m., and in both genders levels returned towards baseline levels at 5:00 p.m. Apolipoprotein A-I (apo A-I) significantly decreased in men (−3% at 2:30 p.m.), but did not change in women. The apo A-I/HDL cholesterol ratio significantly increased by 3% in men at 2:30 p.m. and by 5% both in men and women at 5:00 p.m. Postprandial serum TG were higher and HDL cholesterol and apo A-I were lower in subjects of both genders with insulin resistance (high HOMAIR) than in those with low HOMAIR. The greatest increase in serum TG (39%) was observed in men with high HOMAIR. HDL cholesterol and apo A-I significantly decreased and the apo A-I/HDL-C ratio significantly increased only in this subgroup of subjects.ConclusionsIngestion of low doses of fat in a mixed meal is followed by variable increases of serum TG, and the greatest response is found in insulin-resistant men. In this subset of subjects, postprandial hypertriglyceridaemia is associated with alterations in HDL that might be consistent with an increased risk of cardiovascular disease.

Changes in Serum Lipids and Blood Glucose in Non Diabetic Patients with Metabolic Syndrome after Mixed Meals of Different Composition

Aims. To investigate the postprandial changes in serum lipoproteins and blood glucose and to verify whether different nutrient composition of the meal elicits different response in patients with (MetS+) and without (MetS−) metabolic syndrome. Research Design and Methods. 50 MetS+ patients and 50 age- and sex-matched MetS− consumed a regular lunch chosen among those more similar to their usual diet. Blood was drawn in the morning after 12-hour fasting and 2 and 4:30 hours after the meal. Results. Serum triglycerides increased more in MetS+ (35%, 4:30 hours after the meal) than in MetS− (29%), HDL-cholesterol decreased 2 hours after the meal in both groups (−4% and −5%, resp.). Blood sugar similarly increased in both groups (19%, 2 hours after the meal in MetS+ and 17% in MetS−) and plasma insulin increased more and remained high longer in MetS+ (73.5 and 52.3 μU/mL, 2 and 4:30 hours after the meal) than in MetS− (46.7 and 21.6 μU/mL). Difference in nutrient composition of the meal (carbohydrate 57%, fat 28% versus carbohydrate 45%, fat 35%) was not associated with differences in postprandial levels of triglycerides, HDL-cholesterol, glucose, and insulin within each group. Conclusions. As compared with MetS−, MetS+ patients show a greater hypertriglyceridemic and hyperinsulinemic response to a regular lunch whatever the carbohydrate or fat content of the meal.

Effects of atorvastatin 10 mg and simvastatin 20 mg on serum triglyceride levels in patients with hypercholesterolemia

Abstract Background: Some reports suggest that atorvastatin is more effective than other statins in decreasing serum triglyceride (TG) levels in patients with hypercholesterolemia. Objective: The aim of this study is to compare the hypotriglyceridemic activity of atorvastatin and simvastatin at doses that elicit similar hypocholesterolemic effects. Methods: Outpatients with primary hypercholesterolemia that was not adequately controlled with a stable low-fat, low-cholesterol diet were randomized to 1 of 2 treatments: atorvastatin 10 mg daily (n = 100) or simvastatin 20 mg daily (n = 100) for up to 6 months. Serum TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured at baseline and after 2 and 6 months of therapy. Results: After 2 months of therapy, serum TG, TC, and LDL-C levels significantly decreased ( P P Conclusions: In patients with hypercholesterolemia, atorvastatin 10 mg/d and simvastatin 20 mg/d had similar effects on serum TG, TC, and LDL-C levels. Both drugs increased HDL-C levels, but the effect of simvastatin was significantly greater than that of atorvastatin.

Effects of Simvastatin on Blood Pressure in Hypercholesterolemic Patients: An Open-Label Study in Patients with Hypertension or Normotension

BACKGROUND Simvastatin has been reported to improve endotheliumdependent vascular relaxation in patients with hypercholesterolemia. The consequent decrease in arterial stiffness might be associated with a decrease in blood pressure (BP). OBJECTIVE The aim of this study was to determine whether simvastatin 20 and 40 mg/d have an effect on systolic and diastolic blood pressure (SBP and DBP, respectively) in patients with hypercholesterolemia, and, if so, whether the effect is dose dependent and/or is related to the changes in the serum lipid profile. METHODS This 6-month, open-label study was conducted at the Lipid Clinics of the Department of Internal Medicine, University of Milan, Maggiore Hospital IRCCS, and of the Department of Internal Medicine 1, G. Salvini Hospital, Garbagnate Milanese (Milan, Italy). Patients aged 18 to 80 years with primary hypercholesterolemia who were following a low-fat, low-cholesterol diet for >2 months before the study were enrolled. Patients at high risk for cardiovascular disease (CVD), according to the National Cholesterol Education Program Adult Treatment Panel II guidelines, were given simvastatin 20 mg (tablet) QD for 3 months, and those at low risk for CVD continued with diet only for 3 months (controls). Efficacy variables included body weight, SBP, DBP, and serum lipid levels (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high density lipoprotein cholesterol [HDL-C], and triglycerides [TG]). At 3 months, patients in the simvastatin + diet group who reached their therapeutic goal continued to receive simvastatin 20 mg/d for 3 additional months. In simvastatintreated patients who were normotensive at baseline or who became normotensive at 3 months but who did not reach the therapeutic goal, the simvastatin dosage was increased to 40 mg/d. Patients in both groups who remained hypertensive at 3 months were switched to hypotensive therapy. In the diet-only group, patients who were formerly normotensive or who became normotensive at 3 months but who did not reach their therapeutic goal continued with diet only or started lipid-lowering therapy. All other patients in the diet-only group continued to be treated with diet only, for 3 additional months. Efficacy variables were measured again at 6 months. Tolerability of simvastatin was assessed at each visit using patient interview and measurement of serum aminotransferase and creatine phosphokinase levels. RESULTS The study population comprised 222 patients (132 women, 90 men; mean [SEM] age, 53.9 [0.95] years [range, 23-76 years]); 115 high-risk patients (57 with untreated stage 1 hypertension) were assigned to the simvastatin + diet group, and 107 low-risk patients (29 with untreated stage 1 hypertension) were assigned to the diet-only group. In the simvastatin group, after 3 months of therapy, mean SBP was decreased by 3.9 (1.49) mm Hg (change, -2.9%), mean DBP decreased by 3.0 (0.87) mm Hg (change, -3.7%), mean TC decreased by 90.6 (3.98) mg/dL (change, -27.0%), mean LDL-C decreased by 88.9 (3.88) mg/dL (change, -35.6%), and mean TG decreased by 26.3 (7.34) mg/dL (change, -15.8%) (all, P < 0.001). Mean HDL-C increased by 3.6 (1.16) mg/dL (change, 6.9%; P < 0.001). The BP-lowering effect was found only in patients with hypertension at baseline (n = 57); in these patients, mean SBP decreased by 7.2 (2.44) mm Hg (change, -4.8%; P < 0.005 vs baseline) and DBP decreased by 4.8 (1.29) mm Hg (change, -5.6%; P < 0.001 vs baseline). Also in the simvastatin group, 26 patients (22.6%) achieved their target SBP/DBP. In patients with normotension at baseline (n = 58), neither SBP nor DBP was changed significantly (changes, -0.8 [1.65] and -1.4 [1.15] mm Hg, respectively [-0.6% and -1.8%, respectively]). The changes in serum lipid levels were similar between hypertensive and normotensive patients in the simvastatin group. Forty-one patients (18 hypertensive and 23 normotensive at baseline) were treated with simvastatin 40 mg/d plus diet between months 3 and 6. At 6 months, no further significant decrease was observed in mean BP. In contrast, the expected dose-dependent response was observed for TC and LDL-C levels. In the diet-only group, no significant changes occurred in BP or serum lipid levels. Changes in BP, TC, LDL-C, TG, and HDL-C were significantly greater in the simvastatin + diet group than in the diet-only group (all, P < 0.001). Body weight did not change significantly in either group. CONCLUSIONS In this group of patients with hypercholesterolemia, the starting dosage of simvastatin (20 mg/d) was associated with reductions in SBP and DBP within 3 months of treatment in patients with hypertension, and this effect was independent of the lipid-lowering properties of the drug. Although the decrease in BP was modest, it is likely clinically relevant. Further studies on this topic are advisable.

Estimation of cardiovascular risk: total cholesterol versus lipoprotein profile

SummaryThe complete lipoprotein profile is thought to give more information about the individual risk of coronary heart disease than total cholesterol alone. Although total cholesterol has a low sensitivity in the correct assessment of the risk of coronary heart disease, it may be of value in screening programs because of its low cost. In this study of 5,335 subjects, total cholesterol gave a different assessment of coronary heart disease risk (United States National Cholesterol Education Program guidelines) in 25% of subjects than the complete lipoprotein profile. Differences in risk assignment were mainly accounted for by high- and low-density lipoprotein-cholesterol (Friedewald equation). The calculated low-density lipoprotein-cholesterol was highly correlated with the value measured with a mixed ultracentrifugation and precipitation procedure. However, calculated values gave estimates of coronary heart disease risk which were 20% different from those from measure values. In 200 subjects in whom the lipoprotein profile was assessed three times in 1 year, the total cholesterol low-density lipoprotein-cholesterol varied by more than 30 mg/dl (0.78 mmol/l) in 52% and 50%, respectively, triglycerides by more than 30 mg/dl (0.34 mmol/l) in 75%, and high-density lipoprotein-cholesterol by more than 15 mg/dl (0.39 mmol/l) in 34%. Compared with the mean of the measurements, the single measurement of total cholesterol misclassified 48% of subjects, low-density lipoprotein-cholesterol 60%, high-density lipoprotein-cholesterol 12%, and 28%. We conclude that total cholesterol alone may be misleading in the assignment of coronary heart disease risk. Calculation of low-density lipoprotein-cholesterol, although less accurate than desirable, is the only way of evaluating this in clinical practice. Finally, repeated lipid measurements are required to assess coronary heart disease risk accurately.