Impact of hand and face disabilities on global disability and quality of life in systemic sclerosis patients.

OBJECTIVES: In systemic sclerosis (SSc), the frequent involvement of hand and face leads to their disability. We aimed to assess influence of hand and face disability on global disability and Health related Quality of life (HRQoL). METHODS: 119 SSc patients were assessed for global disability by HAQ, HRQoL, by SF36; hand disability by HAMIS, CHFDS, fist closure and hand opening measures; face disability by MHISS and mouth opening measure. RESULTS: Diffuse SSc (dSSc) patients present higher HAQ, lower Summary Physical Index (SPI) of SF36, major hand disability at hand (higher HAMIS, CHFDS, fist closure, lower hand opening) and face (lower mouth opening, higher MHISS) than lSSc patients (p<0.05). SPI of SF36 is negatively correlated with MHISS, CHFDS, HAMIS and positively correlated to mouth and hand opening (p<0.05). Summary Mental Index (SMI) of SF36 is negatively correlated with MHISS (p<0.05). HAQ is negatively correlated with mouth opening and positively correlated to MHISS, HAMIS, CHFDS (p<0.05). By hierarchical multiple linear regression, SPI of SF36 is significantly associated with total MHISS (B=-0.34; t=-3.78; p<0.001) and CHFDS (B=-0.27; t=-3.01; p=0.003), together, explaining 22% of SPI variance. SMI of SF36 is significantly associated only with MHISS total score (B=-0.22; t=-2.41; p=0.017), explaining 4% of its variance. HAQ is significantly associated with CHFDS score (B=0.61; t=7.90; p<0.001), explaining 36% of HAQ variance. CONCLUSIONS: dSSc patients present higher global and local disability, and lower HRQoL in SPI than lSSc patients. Local disabilities, assessed by CHDFS and MHISS, are independently related to global disability and HRQoL.

Early peripheral nerve abnormalities in impaired glucose tolerance.

Increased prevalence of impaired glucose tolerance (IGT) has been recently detected in patients with painful sensory neuropathy. To determine whether nerve abnormalities are present in IGT we investigated IGT subjects without clinical neuropathy. Nerve conduction studies (NCS) were performed in 12 subjects with IGT without symptoms and signs of neuropathy. The results were compared with those obtained from 12 patients with type 2 diabetes (DM) without clinical neuropathy and 12 healthy controls. Sensory NCS of the sural nerve were performed on different segments, the distal-leg (10 cm proximal to the lateral malleolus) and the proximal-leg segment (10 cm more proximal). The distal conduction velocity of the sural nerve was increased in IGT subjects, compared both to healthy controls and DM patients. No difference was found among the groups with respect to the sensory conduction velocity of the sural nerve fibers in the proximal-leg segment. A reduction of both distal and proximal amplitudes of the sural nerve action potentials was detected in DM patients compared with IGT subjects and controls. The abnormal conduction velocity in the distal segment of the sural nerve, observed in IGT subjects without clinical neuropathy, suggests that the myelin dysfunction of the distal sensory fibers represents the earliest detectable nerve response to the hyperglycemia. The reduced amplitude of the sural nerve action potential in asymptomatic patients with DM arises from the axonal degeneration and represents a more advanced stage of nerve disease.

Massive spontaneous perirenal hematoma and accelerated hypertension in a patient with polyarteritis nodosa.

A 43-year-old Albanian man is presented who underwent nephrectomy for a huge right spontaneous perirenal hematoma. The diagnosis of polyarteritis nodosa as the etiology of the hematoma has been made only by histological examination, because of the quick and unforeseeable onset of this complication and the nonspecificity of symptoms. We hypothesize a relationship between reactivation of polyarteritis nodosa and treatment with rifampicin and isoniazid.

Atorvastatin increases HDL cholesterol in hypercholesterolemic patients. Evidence of a relationship with baseline HDL cholesterol.

BACKGROUND AND AIM: It has been reported that atorvastatin increases high-density lipoprotein cholesterol (HDL-C) more in patients with low than in those with high baseline HDL-C levels. This may have a biological explanation, but also suggests a statistical artifact known as the regression to the mean. METHODS AND RESULTS: Atorvastatin 10 mg/day led to a 4% increase in HDL-C after two months in 67/121 patients with hypercholesterolemia (55%), who had lower baseline HDL-C levels than the patients in whom HDL-C did not increase. In the patients with baseline HDL-C below the median, HDL-C significantly increased whereas no change was observed in patients with baseline HDL-C above the median. The correlation coefficient between pre- and post-treatment HDL-C was 0.84, thus suggesting a regression to the mean. However, the regression artifact did not entirely explain the increase in HDL-C in patients with low baseline HDL-C or the lack of an increase in those with high baseline HDL-C. The adjusted mean increase was 5.4% in patients with low pretreatment HDL-C, and 2.4% in the patients with high pretreatment HDL-C. Multiple regression analysis with the changes in HDL-C as the dependent variable showed that baseline HDL-C and the changes in serum triglycerides independently contributed to the change in HDL-C levels. CONCLUSIONS: Atorvastatin 10 mg/day increases HDL-C more in patients with low pretreatment HDL-C levels, an effect that seems to be related to the hypotriglyceridemic activity of the drug.

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.

Serum lipoprotein profile in patients with cancer. A comparison with non-cancer subjects.

The association of cancer with low serum total cholesterol is well established. Less clear is the relationship of cancer with the cholesterol distribution among the different lipoprotein classes. Conflicting results have been reported on low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and serum triglyceride levels in different types of tumor. Total serum cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and serum triglycerides were analyzed in 530 patients with newly diagnosed cancer (97 with hematological malignancies, 92 with tumor of the lung, 108 of the upper digestive system, 103 of colon, 32 of breast, and 98 of the genitourinary system) and in 415 non-cancer subjects. Anthropometric (body mass index) and biochemical (serum albumin) indices of nutritional status were also determined in all subjects. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum albumin, and body mass index were significantly lower in cancer than in non cancer-subjects. The lowest values of total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were recorded in patients with hematological malignancies and the highest in patients with breast tumor. All the cancer groups, with the exception of women with breast cancer, showed significantly lower total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol than age- and sex-matched non-cancer subjects. Multiple regression analysis with low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides as dependent variables and sex, age, body mass index, albumin, and cancer (dummy variable) as independent variables, showed that cancer was independently associated with low levels of low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol and with high values of serum triglycerides. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum triglycerides, body mass index and serum albumin were significantly lower in patients with metastatic than in patients with non-metastatic solid tumor. The significant difference in low-density lipoprotein-cholesterol and serum triglycerides between patients with metastatic and non-metastatic cancer was lost when lipoprotein cholesterol and serum triglyceride levels were adjusted for nutritional variables. The lipid profile in cancer patients is characterized by low low-density lipoprotein-cholesterol, low high-density lipoprotein-cholesterol and relatively high serum triglycerides. The abnormality is a common feature of both hematological and solid tumors and is not entirely explained by poor nutrition.

Lowering effects of four different statins on serum triglyceride level.

OBJECTIVES: 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 (Deltatriglyceride/DeltaLDL cholesterol ratio) was not significantly different. Only baseline serum triglycerides resulted to be significantly associated with Deltatriglycerides/DeltaLDL cholesterol ratio. All statins are then effective in decreasing triglyceride levels. CONCLUSION: The lack of a significant difference in Deltatriglycerides/DeltaLDL 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.

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 Friedewald's equation in the assessment of cardiovascular risk in NIDDM patients. RESEARCH DESIGN AND METHODS: The calculation of LDL cholesterol according to Friedewald's formula was compared with the measurement of LDL cholesterol separated by ultracentrifugation in 151 NIDDM patients with fairly good metabolic control (HbA1c < or =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 > or =10% in 34% of samples from diabetic patients and in 26% of samples from nondiabetic subjects (chi(2) = 3.885, P < 0.05). The percentage of error increased when the serum triglyceride (TG) level was > or =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, Friedewald's 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.

Association of alcohol consumption with HDL subpopulations defined by apolipoprotein A-I and apolipoprotein A-II content.

OBJECTIVE: To investigate the relationship between alcohol intake and serum level of high-density lipoprotein (HDL) subfractions defined on the basis of their apolipoprotein A-I and A-II content (LpA-I and LpA-I: A-II). DESIGN: Observational study. SETTING: Institute of Internal Medicine and Medical Physiopathology, IRCCS Maggiore Hospital, University of Milan. SUBJECTS: One hundred healthy males with a mean age of 42 +/- 11.1 y, selected among blood donors. RESULTS: Both LpA-I and LpA-I:A-II were significantly higher in men drinking more than 30 g a day of alcohol than in non-drinkers (LpA-I: difference between means 6.5 mg/dL, 95% C.I. 1.14-11.9; LpA-I:A-II difference between means 11.5 mg/dL, 95% C.I. 0.52-22.5). The association of alcohol consumption with LpA-I and LpA-I:A-II levels was independent from age, body mass index, physical activity, serum triglycerides and diet composition. CONCLUSIONS: Alcohol consumption is associated with an increase of serum levels of both LpA-I and LpA-I:A-II particles and this may, at least in part, explain the reduced cardiovascular morbidity observed in subjects drinking moderate amounts of alcoholic beverages. SPONSORSHIP: Supported by grants from Ricerca Corrente Ospedale Maggiore di Milano IRCCS, Milan Italy.

The effect of simvastatin on HDL cholesterol in hyperlipidemic patients. Evidence of a relationship with the changes in serum triglyceride level.

The main effect of simvastatin is the decrease of serum cholesterol due to the reduction of LDL. A decrease of serum triglycerides and an increase of HDL-C are commonly observed during the treatment. The reduction of triglycerides is accounted for by the increased catabolism of apo B-containing lipoproteins whereas the mechanisms bringing about the increase of HDL-C are still unknown. We treated 318 patients with primary hyperlipidemia (227 with phenotype IIa and 91 with phenotype IIb) with simvastatin 10 mg a day and after 6 weeks we found a mean 3% increase in HDL-C. HDL-C increased only in about half of the patients and the patients in whom HDL-C increased had baseline higher serum triglycerides and had a greater hypotriglyceridemic response than patients in whom HDL-C did not increase. Accordingly, HDL-C increased in type IIb patients who experienced a greater change in triglycerides than type IIa patients, in whom HDL-C did not increase significantly. Apo A-I levels did not change and apo A-I/HDL-C ratio significantly decreased. At a daily dose of 40 mg, administered to 51 treatment-resistant patients, simvastatin produced a marginally greater decrease in serum cholesterol and LDL-C, but not in serum triglycerides and HDL-C, than at the daily dose of 10 mg. An increase in HDL-C was associated with a reduction in serum triglycerides. The decrease in apo A-I/HDL-C ratio suggests that the increase in HDL-C after simvastatin must be regarded as an enrichment of the cholesterol core of HDL particles. The effect is likely to be due to the decrease of the serum concentration of VLDL bringing about a reduction of cholesterol transfer from apo A-I to apo B-containing lipoproteins.

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 bezafibrate and of 2 HMG-CoA reductase inhibitors on lipoprotein (a) level in hypercholesterolemic patients.

Lp(a) level is relatively stable in each individual and is mainly under genetic control. Attempts made to lower Lp(a) with pharmacological means gave conflicting results. In order to further evaluate the effect of hypocholesterolemic drugs on Lp(a) level, 66 patients with primary hypercholesterolemia were selected. The vast majority of the patients had Lp(a) concentration at the low end of the range of distribution, 7 had undetectable Lp(a) levels and only 2 had Lp(a) higher than 30 mg/dl. No relationship was found between Lp(a) level and serum and lipoprotein lipids. In 12 patients serum cholesterol was well controlled by diet alone and the patients continued the diet for up to 8 months. The other patients were randomly subdivided into 3 groups of therapy. The first group received slow release bezafibrate 400 mg once a day, the second one pravastatin 20 mg once a day and the third one simvastatin 10-40 mg once a day. Drug therapy lasted for 8 months. At the end of the period, 22 of 29 patients treated with the 2 HMG-CoA reductase inhibitors had Lp(a) higher than baseline. The difference was statistically significant in both groups of patients. No significant change in Lp(a) was observed in diet and in bezafibrate group. Serum and LDL cholesterol significantly decreased in all the 3 drug groups. The increase in Lp(a) after the 2 HMG-CoA reductase was small enough to have negligible effects on cardiovascular risk, but raises the problem of the role of LDL receptor in the catabolism of Lp(a).

Effect of bezafibrate on HDL with APO A-I and APO A-II and on HDL with APO A-I without APO A-II in hyperlipidaemic patients.

On the basis of apoprotein composition, high-density lipoprotein (HDL) particles may be subdivided into two main subpopulations defined by the presence in the lipoprotein molecule of apo A-I (Lp A-I) and of both apo A-I and apo A-II (Lp A-I:A-II). The effect of slow-release bezafibrate 400 mg a day on Lp A-I and Lp A-I: A-II was evaluated in 34 hyperlipidaemic patients (19 with hypercholesterolaemia and 15 with hypertriglyceridaemia). Seventeen patients on low-fat low-cholesterol diet only were taken as the reference group. In the reference group, no change in HDL-C, apo A-I, apo A-II, Lp A-I and Lp A-I:A-II occurred during the 3 months of observation. In patients on bezafibrate, HDL-C, apo A-I and apo A-II significantly increased. Lp A-I:A-II increased by 33% in hypercholesterolaemic and by 29% in hypertriglyceridaemic patients. Lp A-I decreased by 15% in hypercholesterolaemic patients and did not change significantly in hypertriglyceridaemic patients. This differential effect of bezafibrate on apo-A-defined HDL subpopulations in hypertriglyceridaemia and in hypercholesterolaemia is in accord with previous studies on the effect of the drug on HDL subfractions defined by their density.

Estimation of cardiovascular risk: total cholesterol versus lipoprotein profile.

The 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of three fibrate derivatives and of two HMG-CoA reductase inhibitors on plasma fibrinogen level in patients with primary hypercholesterolemia.

In order to evaluate the effects of hypocholesterolemic drugs on plasma fibrinogen concentration, six groups of subjects with primary hypercholesterolemia have been put on treatment with diet alone or diet plus fenofibrate (100 mg t.i.d.), slow release bezafibrate (400 mg once a day), gemfibrozil (600 mg b.i.d.), simvastatin (20 mg once a day) or pravastatin (20 mg once a day) respectively. After 1 month of therapy, plasma fibrinogen significantly decreased by 9% and 15% in fenofibrate and bezafibrate groups respectively and increased by 19% in gemfibrozil treated patients. After 4 months of therapy the changes were -16% with fenofibrate, -10% with bezafibrate and +20% with gemfibrozil. No significant changes were observed in patients treated with diet alone, simvastatin or pravastatin. The fibrinogen lowering effect of fenofibrate and bezafibrate does not seem to be related to the hypolipidemic activity of the drugs.

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.

Effects of serum storage on the determination of cholesterol.

Cholesterol determined by 4 different enzymatic commercial kits and by the dry chemistry Reflotron system was higher in serum stored at 4 degrees C and at -20 degrees C than in fresh serum. The effects of storage seem to be temperature-dependent. In fact, cholesterol values significantly increased only after 2h of freezing. The prolongation of freezing up to 2 weeks was not followed by further significant changes. In serum stored at 4 degrees C the increase in cholesterol was slower than in frozen serum. Both free and esterified cholesterol underwent an increase after storage. When cholesterol was determined by a chemical method (sulfuric acid-ferric chloride) after extraction with ethyl acetate and ethanol, no difference was observed in fresh and stored serum. Cholesterol, triglycerides and apoproteins A-I and B underwent parallel changes after storage both in whole serum and fractionated lipoproteins. Our findings strongly suggest that in serum stored at positive or negative temperature there is an alteration of the lipoprotein molecules which allows an easier availability of cholesterol for the enzyme-substrate reaction than in fresh serum. Current enzymatic methods underestimate (about 10%) cholesterol when the analysis is performed on fresh serum.

Cholesterol distribution between HDL subfractions. A study of 498 subjects.

In 498 subjects (205 normolipidemics and 293 hyperlipidemics) of both sexes, the cholesterol content of high density lipoprotein (HDL) subfractions has been determined. The serum concentration of total HDL-cholesterol appears to be more strictly related to the cholesterol content of HDL2 than to that of HDL3. This latter one, however, gives a contribution to the variability of HDL-cholesterol so that the value of HDL-cholesterol cannot be assumed as a reliable estimate of the serum level of the more anti-atherogenic HDL2 subfraction. The cholesterol content of HDL and its subfractions is higher in women than in men and decreases with increasing serum VLDL-cholesterol level and body weight. Both HDL2- and HDL3-cholesterol appear to largely depend from the metabolism of triglyceride-rich lipoproteins in accordance with the data of experimental studies.

Relationship of serum triglyceride concentration to lipoprotein composition and concentration in normolipidemic and hyperlipidemic subjects.

In a series of 438 subjects (184 normolipidemics and 254 hyperlipidemics) the relationship among serum concentration of triglycerides, lipoprotein lipids and apoproteins A-I and B has been evaluated. The results show that as serum triglyceride level increases, VLDL rise and become enriched in triglycerides. The increase of VLDL is associated with a reduction of serum levels of LDL and HDL which appear to be rich in triglycerides and poor in cholesterol. The decrease in serum HDL level is mainly due to a reduction in serum concentration of the HDL2 subfraction. The triglyceride content of HDL2 and HDL3 rises with increasing serum triglycerides. The increase in serum triglyceride concentration seems then to be associated with a complex metabolic derangement which involves all the lipoprotein fractions.

Changes in serum and lipoprotein lipids, and apolipoprotein B and A-I, in patients with different types of primary hyperlipoproteinaemia treated with gemfibrozil.

Gemfibrozil was given at the dose of 600 mg twice daily to 16 type IIa, 13 type IIb and 11 type IV hyperlipoproteinaemic patients for four months. At the end of the fourth month of therapy low-density lipoprotein (LDL) cholesterol decreased on the average by 18% in type IIa, by 11% in type IIb and increased by 37% in type IV patients. Very-low-density lipoprotein (VLDL) cholesterol and triglycerides fell by 57% in type IIb and by 58% and 76% respectively in type IV subjects. High-density lipoprotein (HDL) cholesterol rose in all groups of patients owing to the increase of the HDL2 subfraction. However, in type IIa the change did not reach the level of statistical significance. Apoprotein B decreased in type IIa and in type IIb patients and apoprotein A-I significantly increased in type IIb and IV patients. The individual changes in total VLDL and LDL lipids and in apoprotein B could be related to their pretreatment level. The cholesterol triglyceride ratio significantly increased in LDL and HDL fractions and the effect was greater in the subgroup of patients with the greatest abnormality in lipoprotein lipid composition. On the whole the differential effects of gemfibrozil on serum lipoprotein concentration and composition in the various types of hyperlipoproteinaemia can be regarded as a trend toward a normalization and may be explained by the multiple effects of the drug on lipid metabolism.