A. Branchi

Lowering effects of four different statins on serum triglyceride level

AbstractObjectives: The main effect of statins is the decrease of serum level of low-density lipoprotein (LDL) cholesterol, due to the inhibition of intracellular cholesterol biosynthesis which brings about an upregulation of LDL receptors. A minor effect is the decrease of serum triglycerides. The present study was undertaken to verify whether all statins are effective in reducing serum triglycerides and whether their effect on triglycerides is related to the LDL cholesterol lowering activity. Methods: Of 197 hypercholesterolaemic patients on stable low-fat low-cholesterol diet, 49 were put on atorvastatin 10 mg per day, 48 on fluvastatin 40 mg per day, 50 on pravastatin 20 mg per day and 50 on simvastatin 10 mg per day. Results: After 2 months, mean percentage change in serum triglycerides and LDL cholesterol resulted to be significantly different among the four treatment groups, whereas the ratio between the percentage decrease in serum triglycerides and that of LDL cholesterol (Δtriglyceride/ΔLDL cholesterol ratio) was not significantly different. Only baseline serum triglycerides resulted to be significantly associated with Δtriglycerides/ΔLDL cholesterol ratio. All statins are then effective in decreasing triglyceride levels. Conclusion: The lack of a significant difference in Δtriglycerides/ΔLDL cholesterol ratio among the treatment groups suggests that the more effective the statin is in decreasing LDL cholesterol, the more it will also be in decreasing serum triglycerides.

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.

Is thyroid-stimulating hormone within the normal reference range a risk factor for atherosclerosis in women?

The relationship between overt hypothyroidism and cardiovascular risk has been well documented and some data also suggest an association between cardiovascular risk and subclinical hypothyroidism. The aim of our study was to investigate, in a large cohort of euthyroid women, the association of thyroid stimulating hormone (TSH) within the normal reference range with cardiovascular risk factors. The study was carried out on 744 women with normal thyroid function (TSH 0.3–4.9 μU/mL). Women with TSH above the median (≥2.1 μU/mL) were more obese, had greater waist girth, were more hypertensive and had higher levels of total cholesterol (TC), serum triglycerides (TG), blood sugar (BG) and lower levels of HDL-cholesterol (HDL-C) than women with TSH below the median. TSH was significantly correlated with body mass index (BMI), waist circumference, BG, TG, TC, HDL-C and hypertension. Multiple backward stepwise regression analysis with age, waist circumference and TSH as independent variables confirmed the strong association of TSH with BG, TG, HDL-C and hypertension. A total of 205 patients (28%) fulfilled the definition criteria of the metabolic syndrome and the prevalence of metabolic syndrome was significantly greater in patients with TSH above than in patients with TSH below the median. Results of logistic analysis, including age and TSH as predictor variables, confirmed the association of TSH with metabolic syndrome.The results of this study suggest that TSH in the upper limits of the reference range (above 2.1 μU/ml) is associated with a less favourable cardiometabolic profile and consequently with a higher risk of developing cardiovascular diseases.

Serum cholesterol levels in patients with cancer. Relationship with nutritional status.

Epidemiological surveys indicate an inverse relationship between cancer occurrence and serum cholesterol. Low serum cholesterol might be either a risk factor for cancer or the effect of factors associated with cancer itself, such as biological properties of malignant cells, tumor mass, and poor nutritional status. We have measured serum cholesterol in 975 selected patients admitted to our hospital; 496 (272 males, 224 females) had solid tumors and 479 (253 males, 226 females) had non-neoplastic diseases. Serum cholesterol was positively correlated with body mass index, serum albumin, hemoglobin, and cholinesterase in both cancer and non-cancer subjects. Cholesterol was significantly lower in cancer patients than in age- and sex-matched non-cancer subjects. After adjustment for nutritional variables (analysis of covariance), the difference in cholesterol level between cancer and non-cancer subjects lost statistical significance in all but patients with tumors of the upper gastrointestinal tract. No difference was found in adjusted mean serum cholesterol between cancer patients subdivided according to the extension of the tumor was defined by the TNM system. In patients with solid tumors, serum cholesterol seems to be more related to the nutritional status than the presence and extension of cancer.

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.

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.

Differential effects of simvastatin and bezafibrate on apolipoprotein-defined high-density lipoprotein subfractions in patients with hypercholesterolemia

Abstract Our study goal was to determine whether two hypolipidemic drugs, each with a different mechanism of action, have different effects on serum levels of high-density lipoprotein (HDL) subpopulations, as defined by the presence of apolipoprotein (apo) A-I (Lp A-I) and of both apo A-I and A-II (Lp A-I:A-II). Nineteen patients with primary hypercholesterolemia were treated for 3 months with simvastatin 20 mg once daily and 19 patients were treated with sustained-release bezafibrate 400 mg/d. Seventeen patients following a stable low-cholesterol, low-fat diet served as a reference group. In both the diet-only and simvastatin groups, no significant change in HDL-cholesterol (HDL-C), apo A-I, apo A-II, Lp A-I, and Lp A-I:A-II occurred; in the bezafibrate group, HDL-C increased by 10%, apo A-I by 15%, and apo A-II by 43%. Lp A-I decreased by 15% and Lp A-I:A-II increased by 33% in the bezafibrate group. The relevance to the risk of coronary heart disease of the decrease of Lp A-I after bezafibrate therapy is uncertain, although Lp A-I—but not Lp A-I:A-II—has been suggested to account for the protective role of HDL.

Interrelationships between body mass and lipid and lipoprotein triglycerides and cholesterol in obese women

SummaryIn 72 obese women body mass index positively correlated with age and both showed multiple correlations with serum lipids and lipoprotein lipids. After adjustment for age (partial correlation procedure), body mass index resulted to be positively correlated with serum triglycerides, VLDL lipids, HDL-triglycerides and negatively correlated with HDL-cholesterol. The decrease in HDL-cholesterol concentration along with the increase in body weight was due to the reduction of cholesterol in DHL2 subfraction, while HDL3-cholesterol did not show any significant correlation with body mass index. The negative correlation between HDL2-cholesterol and body mass index was independent of other lipoprotein variables and in particular of VLDL lipid levels that were, as expected, inversely related to HDL2-cholesterol. HDL2-cholesterol is believed to be a strong protective factor against atherosclerosis, while doubts exist on the meaning of VLDL lipids as risk factors. Thus, the decrease in HDL2-cholesterol concentration, rather than the increase in VLDL lipids, might give a rational basis to the high incidence rate of vascular disease in obese subjects.