D. Sommariva

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.

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.

Effects of slow release bezafibrate on the lipid pattern and on blood glucose of type 2 diabetic patients with hyperlipidaemia

Ninety-eight type 2 diabetic patients with hyperlipidaemia in stable metabolic control with diet alone (41) or diet plus hypoglycaemic agents (57) were divided into two groups: group 1 was put on treatment with slow release bezafibrate 400 mg a day, while group 2 was considered as control. In group 1, after 1 month of bezafibrate, serum triglycerides fell by 47% and cholesterol by 13%. HDL cholesterol showed a non-significant trend toward an increase. Fasting blood glucose significantly decreased by 6%, fructosamine and glycated haemoglobin by 5%. During OGTT, the area under the curve of both serum C-peptide and blood glucose showed a trend toward a decrease after bezafibrate. However, the difference did not reach statistical significance. Thirty-six patients continued the treatment with the drug for 4 months and 23 for 8 months, without further changes of the lipid pattern and glycaemic control. In the control group no significant variation of the lipid levels occurred and diabetic control slightly worsened during the study. Bezafibrate has been proved to be effective in the treatment of hyperlipidaemia in type 2 diabetic patients. The drug seems moreover to improve glycaemic control. The mechanism by which bezafibrate produces this latter effect remains to be elucidated, though an increase of peripheral insulin sensitivity might be suggested.

Bezafibrate inhibits HMG-CoA reductase activity in incubated blood mononuclear cells from normal subjects and patients with heterozygous familial hypercholesterolaemia.

In incubated blood mononuclear cells from normal subjects bezafibrate inhibited the incorporation of 14C-acetate into squalene, methylsterols and cholesterol. Similarly, the drug produced a sharp decrease of the incorporation of labelled 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) into non-saponifiable lipids, while the incorporation of 14C-mevalonate was unaffected by the presence of bezafibrate in the incubation mixture. This strongly suggests that bezafibrate inhibits HMG-CoA reductase activity. In cultured cells from patients with heterozygous familial hypercholesterolaemia the presence of bezafibrate in the incubation medium resulted in an inhibition of the incorporation of labelled acetate into non-saponifiable lipids. Bezafibrate then inhibits cholesterol biosynthesis in cells from normal and hypercholesterolaemic patients and this effect is likely, to contribute to the hypocholesterolaemic activity of the drug.

Fenofibrate therapy of hypertriglyceridaemias. Differential effects on LDL cholesterol level in Type IV and in Type IIb primary hyperlipoproteinaemia

SummaryTwenty five hypertriglyceridaemic patients (16 Type IV and 9 Type IIb) were treated with fenofibrate 300 mg/d. In Type IV patients serum triglycerides and VLDL cholesterol decreased, while LDL and HDL cholesterol rose significantly. In Type IIb patients, triglycerides and total, VLDL, IDL and LDL cholesterol were significantly reduced by the treatment. The correction of hypertriglyceridaemia by fenofibrate seems, therefore, to induce different changes in lipoproteins in Type IIb and in Type IV hyperlipoproteinaemic patients. The practical implications of these results are discussed.

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.

Low-fat diet versus low-carbohydrate diet in the treatment of type IV hyperlipoproteinaemia.

The response to dietary management was studied in 24 hypertriglyceridaemic out-patients. Fourteen patients were kept on a diet low in fat and cholesterol and high in polyunsaturated fatty acids; 10 of these patients subsequently followed a period of low-carbohydrate diet. At the end of the first period a significant decrease of serum triglyceride, cholesterol and beta-lipoproteins was observed; after the second feeding period no substantial change of serum lipoprotein pattern occurred. Ten patients were given a low-carbohydrate diet that produced a significant fall of the levels of triglycerides and pre-beta-lipoproteins. Six of these subjects continued the experiment with the low-fat diet; during this period a further trend toward reduction of serum triglyceride, cholesterol and beta-lipoproteins was observed which, however, was not statistically significant. We conclude that serum triglyceride levels can be lowered both by a low-carbohydrate diet and by a low-fat diet, but the latter has the advantage of also producing a significant fall of serum cholesterol and beta-lipoproteins.