Lipid and lipoprotein profile in HIV-infected patients treated with lopinavir/ritonavir as a component of the first combination antiretroviral therapy.

We characterized lipid and lipoprotein changes associated with a lopinavir/ritonavir-containing regimen. We enrolled previously antiretroviral-naive patients participating in the Swiss HIV Cohort Study. Fasting blood samples (baseline) were retrieved retrospectively from stored frozen plasma and posttreatment (follow-up) samples were collected prospectively at two separate visits. Lipids and lipoproteins were analyzed at a single reference laboratory. Sixty-five patients had two posttreatment lipid profile measurements and nine had only one. Most of the measured lipids and lipoprotein plasma concentrations increased on lopinavir/ritonavir-based treatment. The percentage of patients with hypertriglyceridemia (TG >150 mg/dl) increased from 28/74 (38%) at baseline to 37/65 (57%) at the second follow-up. We did not find any correlation between lopinavir plasma levels and the concentration of triglycerides. There was weak evidence of an increase in small dense LDL-apoB during the first year of treatment but not beyond 1 year (odds ratio 4.5, 90% CI 0.7 to 29 and 0.9, 90% CI 0.5 to 1.5, respectively). However, 69% of our patients still had undetectable small dense LDL-apoB levels while on treatment. LDL-cholesterol increased by a mean of 17 mg/dl (90% CI -3 to 37) during the first year of treatment, but mean values remained below the cut-off for therapeutic intervention. Despite an increase in the majority of measured lipids and lipoproteins particularly in the first year after initiation, we could not detect an obvious increase of cardiovascular risk resulting from the observed lipid changes.

Lipoprotein(a) in patients initiating antiretroviral therapy.

OBJECTIVES: The interaction between lipoprotein(a), an emerging cardiovascular risk factor, and antiretrovirals (ARVs) has been less well studied than the interaction between either cholesterol or triglycerides and these drugs. In this study we assessed the effect of initiating antiretroviral therapy (ART) on lipoprotein(a) levels. METHODS: Fasting samples from 95 patients initiating ART with nucleoside/nucleotide reverse transcriptase inhibitors plus nonnucleoside reverse transcriptase inhibitors or protease inhibitors were obtained. Lipids and lipoproteins were determined until week 48. RESULTS: As in the general population, the study population showed a highly skewed lipoprotein(a) distribution (median 9.9 mg/dL, range 0.1-110 mg/dL). The study population was divided into individuals with lipoprotein(a) >or=30 mg/dL at baseline (n=28) and those with <30 mg/dL (n=67). Almost exclusively, patients with high lipoprotein(a) at baseline (median 51.6 mg/dL) showed a profound increase of median 26.7 mg/dL (week 24). This effect was not associated with specific ARVs and was independent of changes in other lipids. The low-lipoprotein(a) group (baseline median 7 mg/dL) showed a small increase of median 2.6 mg/dL (week 24). CONCLUSIONS: Marked increases in lipoprotein(a) after initiation of ART were mainly restricted to patients with high baseline levels. This may have clinical implications as patients with high lipoprotein(a) are at higher risk for myocardial infarction and stroke.

[Food allergies are often an unrecognized cause of clinical complaints]. / Allergie, Unverträglichkeit oder Pseudoallergie? Dicke Lippe nach der Gemüsepizza

While 6% of children under three years of age suffer from a food allergy, the figure for adults varies between 1.5 and 3%. Leading allergens in foodstuffs are glycoproteins having a molecular weight of between 10,000 and 60,000. The symptoms of an immediate type nutrient allergy mediated by IgE usually manifest within a matter of a few minutes to two hours after ingestion of the offending nutrient and take the form, for example, of tingling and itching, tissue swelling in the mouth, hoarseness, asthma, gastrointestinal complaints or acute urticaria; in severe cases anaphylactic shock may even occur. In contrast, no IgE antibodies are to be found in nutrient-induced enterocolitis, which is associated with diarrhea and vomiting occurring after a delay of one to six hours. Differential diagnostic considerations must include intolerance for certain foodstuffs, such as lactose intolerance, or pseudoallergic reactions.

[Diet in disordered lipid metabolism. A culinary balance act]. / Ernährung bei entgleisten Lipiden. Ein kulinarischer Balanceakt.

When LDL cholesterol is elevated, HDL cholesterol is low or triglycerides are raised, dietary changes form the basis of treatment. Such changes are most important in the case of hypertriglyceridemia. Some 3 to 4 hours after a meal, triglycerides increase to an extent determined by the composition of the meal. Hypertriglyceridemia cannot be successfully treated unless alcohol is banished and rapidly assimilatable carbohydrates are restricted. In patients with elevated LDL cholesterol, a change in eating habits can have an appreciable effect (on average 10-15%). Since this measure can save the use or reduce the dose of medications, its value is obvious, and it must not be neglected. The measures aimed at elevating HDL cholesterol have only a moderate effect, so that more importance should be attached to lowering the LDL fraction.

Long-chain omega-3 fatty acids from fish reduce sudden cardiac death in patients with coronary heart disease.

An increase in the uptake of long-chain Omega-3 fatty acids from fish with the diet or as ethyl esters resulted in a decreased risk for cardiac death. As mechanism for this rapidly occurring benefit (within 90 days of treatment significantly different to placebo) antiarrhythmic effects at cardiac myocytes and plaques stabilization can be discussed. The results of the GISSI Prevenzione Trial show that 175 patients have to be treated for one year to avoid one death. Regarding other available data for secondary prevention this efficacy is superior to pravastatin and at the same level as simvastatin or aspirin. Only beta-blocking agents are superior, but it is of interest that long-chain Omega-3 fatty acids from fish display their beneficial effects even in patients already treated with beta-blockers. As the intake of 0.85 g of long-chain Omega-3 fatty acids from fish per day can be regarded as save and the positive effect on total mortality occurs already after 90 days their regular use is a promising additional measure for secondary prevention.

Fatty acids and breast cancer--is there a relationship?

In 1997 the current database for the relation of polyunsaturated fatty acids in the diet to breast cancer was extensively reviewed by expert committees of the American Institute for Cancer Research and the World Cancer Research Fund. They concluded: "Diets high in polyunsaturated or vegetable fats possibly have no relationship with the risk of breast cancer, independent of any contribution to total fat intake". On the other hand they stated that "Diets high in saturated fat possibly increase the risk of breast cancer" and "Diets high in monounsaturated fat per se possibly have no relationship with the risk of breast cancer, independent of that of total fat." The data in literature clearly confirm these interpretations. No new data exist which have changed the knowledge on the association between intake of fatty acids and breast cancer.

RheoSorb: a specific adsorber for fibrinogen elimination in clinical situations with impaired rheology.

A functional microcirculation is crucial for the normal function of an organism. In many physiopathological situations, impaired microcirculation may contribute to the development or progress of diseases. Microcirculation is closely interrelated with blood and especially plasma rheology. Thus, improvement of plasma viscosity has beneficial effects on rheology, microcirculation, and the related tissue microenvironment. However, at best tools that only have a minor influence on plasma viscosity exist so far. Fibrinogen is known to be the major contributor to plasma viscosity, making it an interesting target for therapeutic intervention. An adsorber specific for fibrinogen was developed on the basis of the TheraSorb technology. The TheraSorb technology (PlasmaSelect AG, Teterow, Germany) allows the selective removal of components from human blood plasma by means of an affinity chromatography column. A ligand specific for a defined plasma component is coupled to a solid matrix (sepharose) thus binding and eliminating the target molecule from plasma. Using a fibrinogen specific pentapeptide as ligand, selective removal of fibrinogen, fibrin, and degradation products, containing the target sequence of these molecules, can be obtained. The LIFE-18, a state-of-the-art integrated plasma therapy instrument, is used to perform the treatment. The procedure improves plasma and whole blood viscosity in a dose dependent manner as shown in Phase 1 and 2 clinical trials. This article describes the first clinical experience in patients with diabetic foot syndrome and provides an outlook for further clinical and scientific investigations related to this promising new procedure.

Hemorrheologic abnormalities in defined primary dyslipoproteinemias with both high and low atherosclerotic risks.

Dyslipoproteinemias are associated with hemorrheologic abnormalities (elevated fibrinogen concentration, higher viscosity of plasma and blood). Epidemiologic data suggest that not only elevated lipoprotein concentrations (eg, low-density lipoprotein [LDL] cholesterol), but also hemorrheologic abnormalities could causally be involved in the atherosclerotic process. To elucidate potential effects of hemorrheological disturbances, we investigated patients suffering from primary hyperlipoproteinemias with both low (familial hypertriglyceridemia, n = 25) and high (type III hyperlipoproteinemia, n = 21; familial hypercholesterolemia, n = 19; mixed hyperlipoproteinemia, n = 19) atherosclerotic risk, as well as healthy controls (n = 49) in a cross-sectional design. Dyslipoproteinemias were classified by lipoprotein measurements (using ultracentrifugation), family history, and apolipoprotein E phenotype. Hemorrheology was characterized by the measurement of fibrinogen concentration, viscosity of plasma and blood at different shear rates, and red cell aggregation (RCA) at stasis and low shear. Fibrinogen concentration was lower in controls (2.38 +/- 0.09 g/L) compared with familial hypercholesterolemia (3.19 +/- 0.19 g/L), to type III hyperlipoproteinemia (3.02 +/- 0.12 g/L), to familial hypertriglyceridemia (2.95 +/- 0.21 g/L) and to mixed hyperlipoproteinemia (3.01 +/- 0.12 g/L) (P < .05, respectively) without differences between dyslipoproteinemia groups. Plasma viscosity was higher in patients with type III hyperlipoproteinemia (1.42 +/- 0.03 mPas), with familial hypertriglyceridemia (1.47 +/- 0.04 mPas), and with mixed hyperlipoproteinemia (1.43 +/- 0.02 mPas) compared with controls (1.29 +/- 0.01 mPas) (P < .05, respectively). After including 6 lipoprotein parameters in a general linear model, plasma viscosity, blood viscosity, and RCA were higher in familial hypertriglyceridemia compared with healthy controls and familial hypercholesterolemia (P < .05, respectively). As most of the hemorrheologic abnormalities were still significant after adjusting for lipoprotein concentrations, they seem to be at least partly independent from direct lipoprotein effects. Hemorrheologic abnormalities in familial hypertriglyceridemia (low atherosclerotic risk) were at least as marked as in dyslipoproteinemias with high atherosclerotic risk, suggesting that it might be most important to determine lipoprotein concentrations and to define exactly the type of dyslipoproteinemia for estimating the individual cardiovascular risk in these patients.

Fibrinogen adsorption in the diabetic foot syndrome and peripheral arterial occlusive disease: first clinical experience.

The elimination of fibrinogen from plasma improves plasma viscosity and whole-blood viscosity. For extracorporeal adsorption of fibrinogen, the pentapeptide gly-pro-arg-pro-lys was coupled to sepharose CL-4B3. Adsorbers containing 135 ml of coupled sepharose CL-4B were used to eliminate fibrinogen from the plasma of 7 men and 3 women (48-75 years old). Nine patients suffered from diabetes mellitus, 1 patient from peripheral arterial occlusive disease, and 5 patients were on regular hemodialysis. Treatments were scheduled on Days 1, 2, 4, 6, 8, 10, 13, 16, 19, 22, 25, and 28. One hundred forty-four treatments with fibrinogen adsorption were performed. No clinical side effects due to the fibrinogen adsorption procedure were observed. In these 10 patients, fibrinogen concentration before the first treatment was 473.7 +/- 183.7 mg/dl. In the first treatment session, fibrinogen concentration was lowered to 241.4 +/- 125.8 mg/dl by treating 4,270 +/- 1,180 ml of plasma. In the following 134 treatments, the pretreatment concentration of fibrinogen was 262.6 +/- 83.4 mg/dl, and the posttreatment concentration was 120.6 +/- 37.2 mg/dl. The mean amount of plasma treated was 3,737 +/- 1,643 ml, and the mean duration of a treatment session (except first treatment) was 143.7 +/- 63.1 min. In 7 patients, a mean posttreatment fibrinogen concentration of < or = 123 mg/dl was obtained; in the other patients, concentrations of 133, 177, and 184 mg/dl were obtained. Yet, the decrease of fibrinogen concentration was also pronounced in these 3 patients: -82%, -67%, and -73%, respectively. During the treatment period of 28 days, wound healing was observed in 9 of the 10 patients. In conclusion, affinity chromatography using the pentapeptide gly-pro-arg-pro-lys is an effective, selective, and safe procedure to lower fibrinogen concentration in plasma. It could be a therapeutic option in severe blood vessel disease in which drug therapy is not sufficient and invasive procedures such as bypass or angioplasty cannot be applied. Yet, more information is needed, for example, about the fibrinogen concentration that has to be reached to get the maximal improvement of micro- and/or macrocirculation.

Contribution of fibrinogen and lipoproteins to plasma viscosity in hypercholesterolemia and hypertriglyceridemia: evaluation by selective depletion of low-density lipoproteins or fibrinogen.

Epidemiological studies suggest that the plasma fibrinogen concentration is the main determinant of plasma viscosity (PV), but the concentration of other macromolecules (eg, immunoglobulins) and low-density lipoprotein (LDL) cholesterol and triglycerides are also correlated with PV. However, only a few data exist concerning the in vitro effects of these plasma constituents on PV. Therefore, we investigated PV before and after the specific elimination of fibrinogen and LDL in hypercholesterolemic and hypertriglyceridemic plasma. First, hypercholesterolemic samples (n = 7) were pumped simultaneously through 2 columns: a fibrinogen-depleting column containing the pentapeptide Gly-Pro-Arg-Pro-Lys (GPRPK) and a LDL-depleting column containing specific antibodies against apolipoprotein B-100. In the plasma and in each fraction from the column, the cholesterol level was measured enzymatically, fibrinogen was determined by immunonephelometry, and PV was analyzed using a low-shear rotation viscosimeter. After the fibrinogen-depleting column, the fibrinogen concentration decreased from 3.21 +/- 0.20 to 0.94 +/- 0.16 g/L (P < .005), inducing a decrease in PV from 1.27 +/- 0.02 to 1.17 +/- 0.01 mPas (milliPascal seconds) (P < .005). Despite a marked reduction of the LDL cholesterol after the LDL-depleting column (from 6.40 +/- 0.23 to 4.08 +/- 0.32 mmol/L, P < .005), PV remained unchanged. Second, hypertriglyceridemic samples (n = 7) were pumped through the fibrinogen-depleting column, which reduced the fibrinogen concentration from 4.29 +/- 0.79 to 1.62 +/- 0.69 g/L (P < .001) and PV from 1.42 +/- 0.06 to 1.03 +/- 0.05 mPas (P < .01) while the triglyceride concentration remained unchanged. Our results confirm the epidemiological correlation between the fibrinogen concentration and PV in patients with hypercholesterolemia and hypertriglyceridemia. The influence of fibrinogen on PV seems much more pronounced than the direct effect of lipoprotein concentrations. Therefore, the elevated PV in patients with hypercholesterolemia and especially with hypertriglyceridemia seems mainly due to elevated fibrinogen levels.

The prevention education program (PEP). A prospective study of the efficacy of family-oriented life style modification in the reduction of cardiovascular risk and disease: design and baseline data.

We describe design and baseline data of the Prevention Education Program (PEP), a home-based and family-oriented intervention program, aimed to assess and improve cardiovascular risk factors in school children and their families during an intervention period of 10 years. Started in 1994 in the German town of Nuremberg, currently 37 elementary schools (22 control and 15 intervention schools) are enrolled including 1740 families (1740 first graders, 3046 parents, and 1521 siblings). Major cardiovascular risk factors as well as dietary behavior are evaluated yearly using structured interview, physical examination, laboratory analysis, and seven-day-dietary protocols. The intervention package is applied to all families from intervention schools using regular home visits, health curricula and group sessions. Primary outcome is any reduction in cardiovascular risk factors by dietary intervention and health education compared to the control group getting only written information on the individual risk profile. The presented baseline data showing a high prevalence of cardiovascular risk factors in adults and in their children underline the need for such an intervention program in Germany.

Low-density lipoprotein (LDL) oxidizability before and after LDL apheresis.

Oxidation of low-density lipoprotein (LDL) plays a major role in the development of atherosclerosis. Hypercholesterolemia has been associated with enhanced in vitro oxidation of LDL, and lipid-lowering therapy reduces LDL oxidizability. In the present study, we investigated whether LDL apheresis performed with different techniques affects in vitro diene formation (lag phase) and modification of apolipoprotein B-100 (apoB). Baseline and posttreatment diene formation was correlated with the baseline pattern of plasma total fatty acids. We then performed a computer-simulation study to test the hypothesis that LDL apheresis-induced changes in LDL oxidizability are related to changes in the mass ratio between freshly produced and older LDL. In 19 patients aged 49+/-7 years with heterozygous familial hypercholesterolemia (FH) regularly treated with either immunoadsorption, heparin-induced LDL precipitation (HELP), or dextran sulfate (DS) adsorption, we determined lipoprotein levels, the lag phase, apoB modification, and the fatty acid pattern in plasma samples drawn at the onset and termination of one LDL apheresis. LDL apheresis significantly decreased total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and triglycerides by 50.4%, 14.9%, 62.6%, and 33.6%, respectively. The lag phase increased by a significant mean of 9.8%; the charge of apoB was not altered. The lag phase before treatment positively correlated with the baseline concentration of plasma total palmitic, myristic, and oleic acid. The increase in the lag phase during treatment correlated with a high pretreatment concentration of lauric, linoleic, and docosahexanoic acid. The simulation study indicates that a temporary imbalance between two LDL compartments, one representing freshly secreted LDL and the other representing older LDL, could explain the observed increase in the lag phase after LDL apheresis. In conclusion, in patients with heterozygous FH, LDL apheresis performed with different techniques decreases the susceptibility of LDL to oxidation. This decrease may be related to a temporary mass imbalance between freshly produced and older LDL particles. Furthermore, the baseline fatty acid pattern influences pretreatment and posttreatment susceptibility to oxidation.

Three low density lipoprotein apheresis techniques in treatment of patients with familial hypercholesterolemia: a long-term evaluation.

Low density lipoprotein (LDL) apheresis is a treatment option for patients with severe hypercholesterolemia not adequately responding to drug treatment who have developed coronary heart disease. We regularly treated 18 patients with immunoadsorption, 8 with heparin induced extracorporeal LDL precipitation (HELP) and 8 with dextran sulfate adsorption for a mean of 4.6 +/- 2.6 years. The effects on LDL cholesterol, high density lipoprotein (HDL) cholesterol, and lipoprotein (a) were comparable among all 3 techniques. Twelve patients were treated for longer than 5 years and 18 patients for longer than 3 years. The evaluation of coronary angiograms (23 patients) revealed a definite regression of coronary lesions in 3 patients; in all other patients, there was a halt in progression. Three patients suffered a sudden cardiac death and 1 patient a nonfatal myocardial infarction due to the occlusion of a coronary bypass. In 9 of 11 patients, no atherosclerotic lesions developed in the coronary bypasses. No severe side effect of either procedure was observed. In conclusion, aggressive lipid lowering by LDL apheresis can stabilize coronary atherosclerosis in most patients.

[How safe are the new obesity drugs? Indications and contraindications of orlistat and sibutramine]. / Wie sicher sind die neuen Adipositasmedikamente? Indikationen und Kontraindikationen von Orlistat und Sibutramin.

Sibutramine and Orlistat are suitable "supporting drugs" for use in patients trying to lose weight. Orlistat reduces the absorption of fat from the intestine by about one-third. Over the long term too, the weight loss achieved under Orlistat (9%) has been greater than that seen under placebo (6.5%). Increased fat losses via the stools are associated with side effects and abandonment of treatment. Sibutramine inhibits the uptake of serotonin and noradrenaline in the synaptic gap, thus enhancing the CNS effects of these two transmitters, and prolonging the sensation of satiety. The most common side effects of sibutramine are dry mouth, headache and fatigue. The effects of sibutramine on weight reduction are similar to those of orlistat. For both drugs, the indications have been defined, and in the case of sibutramine, interactions with other medications have to be taken into account.

Effects of acipimox on haemorheology and plasma lipoproteins in patients with mixed hyperlipoproteinaemia.

AIMS: Epidemiological data have shown that haemorheological disorders are associated with an increased risk of atherosclerosis. We evaluated the effect of the nicotinic acid derivative acipimox on haemorheological and lipid parameters in 18 patients with mixed hyperlipoproteinaemia using a randomized, double-blind, placebo-controlled, cross-over study protocol. METHODS: Patients (7 women, 11 men, aged 49.3+/-3.0 years) were investigated with acipimox (dose adjusted to weight, 500 or 750 mg daily) compared with placebo treatment each for 12 weeks. Lipid parameters, whole blood viscosity, plasma viscosity, fibrinogen, and red cell aggregation at native and standardized (0.45) haematocrit as well as red cell filterability were measured at baseline, at week 12 (change of therapy), and at week 24. RESULTS: Total cholesterol concentration (8.30+/-0.32 vs 8.72+/-0.36 mmol/l(-1)) and apolipoprotein B (198.5+/-9.9 vs 217+/-9.9 mg dl(-1)) were significantly lower (P<0.05) during acipimox therapy compared with placebo, no significant changes were observed for triglycerides and low-density lipoprotein [LDL] cholesterol. However, total high-density lipoprotein [HDL] cholesterol (1.24+/-0.05 vs 1.10+/-0.05 mmol l(-1), P<0.001) as well as HDL2 and HDL3 cholesterol (P<0.05) were significantly higher during acipimox therapy. The LDL cholesterol to HDL cholesterol ratio significantly improved during acipimox therapy (4.63+/-0.25 vs 5.49+/-0.26, P<0.001). Red cell aggregation at native and standardized haematocrit were the only haemorheological parameters which improved during acipimox therapy in comparison with placebo (shear rate 3 s(-1):10.69+/-0.40 vs 11.50+/-0.44 U, P<0.05, for native red cell aggregation; 10.40+/-0.36 vs 11.28+/-0.39 U, P<0.05, for standardized red cell aggregation). CONCLUSIONS: We conclude, that the cardiovascular risk profile improves during acipimox therapy due to an elevation in HDL cholesterol and its subfractions as well as a decrease in red cell aggregation.

Long-term effect of low-density lipoprotein apheresis on plasma lipoproteins and coronary heart disease in native vessels and coronary bypass in severe heterozygous familial hypercholesterolemia.

Low-density lipoprotein (LDL) apheresis is a potent treatment for patients with coronary heart disease and severe hereditary forms of LDL hypercholesterolemia not adequately responsive to drug treatment. Until now, the beneficial effect of aggressive reduction of LDL cholesterol by LDL apheresis on the course of coronary heart disease has been demonstrated in one 3-year study and several studies lasting 2 years. We now report on the clinical course, lipoprotein concentrations, coronary angiograms, and side effects in patients undergoing LDL apheresis for as long as 8.6 years. Thirty-four patients (21 men and 13 women) with coronary heart disease and heterozygous familial hypercholesterolemia (FH) not adequately responsive to lipid-lowering drugs received weekly (four patients biweekly) LDL apheresis for 4.6 +/- 2.6 years under diet and lipid-lowering drug therapy; after 0.5 to 3 years, simvastatin in the maximal tolerable dose was added. The baseline LDL cholesterol concentration was 6.9 +/- 1.6 mmol/L. Combined treatment in the steady state yielded a pretreatment and posttreatment LDL cholesterol concentration of 4.8 +/- 0.9 and 1.8 +/- 0.4 mmol/L, respectively. The calculated interval mean LDL cholesterol was 3.3 +/- 0.6 mmol/L. Evaluation of the coronary angiographies revealed a definite regression of coronary lesions in four patients (11.8%); in 19 patients, there was a cessation of progression. Two patients developed atheromatous lesions in bypass grafts (L.H., 60% stenosis; S.M., occlusion). Of 23 patients eligible for the scoring of anginal symptoms, five (21.7%) reported a reduction of the frequency and severity of angina pectoris. The mean coronary symptom score in 23 patients changed from 1.65 +/- 0.83 at baseline to 1.39 +/- 0.66 at the end of the study. During the whole observation period, we observed three sudden deaths, one nonfatal myocardial infarction, and five patients requiring hospital admission because of unstable angina pectoris, one of which was followed by a transluminal coronary angioplasty. Aggressive reduction of LDL cholesterol with combined LDL apheresis and drugs induced regression of coronary lesions in four of 34 patients and prevented progression in 29 patients for as long as 8.6 years. The effect on LDL and high-density lipoprotein (HDL) cholesterol and lipoprotein(a) [Lp(a)] was comparable with all three apheresis techniques. Therefore, no obvious difference between the three techniques was found regarding changes in coronary lesions.

Plasma total homocysteine levels in patients with early-onset coronary heart disease and a low cardiovascular risk profile.

Mild hyperhomocysteinemia has been associated with an increased risk to develop premature coronary heart disease. Recently, the homocysteine concentration has been positively correlated with several main cardiovascular risk factors. We addressed the issue as to whether patients with coronary heart disease and a low cardiovascular risk profile also have a higher prevalence of hyperhomocysteinemia than matched controls. Ninety-five patients (aged 50.5 +/- 6.6 years) and 34 controls (50.0 +/- 6.7 years) less than 60 years of age were selected from a sample of patients after coronary angiography. Subjects with hypertension, diabetes, and moderate or severe hyperlipidemia were excluded. We determined plasma aminothiols (total homocysteine, cysteine, and glutathione), lipoprotein fractions, fibrinogen, and uric acid, the body mass index (weight in kilograms divided by height in meters squared), and the waist to hip ratio. Furthermore, 37 healthy subjects aged 30.8 +/- 7.5 years underwent aminothiol determinations. Patients and controls were similar with regard to age and primary cardiovascular risk factors. Total homocysteine concentrations in the patient group (9.2 +/- 2.4 micromol/L) were significantly higher than in the healthy subjects (8.0 +/- 2.0 micromol/L). However, they did not differ from the levels in the age-matched controls (9.3 +/- 3.0 micromol/L). Neither total cysteine nor glutathione concentrations were significantly different between patients and controls. Male patients (n = 85) had higher mean very-low-density lipoprotein (VLDL) triglycerides (1.36 +/- 0.90 mmol/L) and lower high-density lipoprotein 3 (HDL3) cholesterol (0.75 +/- 0.21 mmol/L) than male controls (n = 28; 1.01 +/- 0.62 and 0.88 +/- 0.26 mmol/L, respectively). Female patients did not have any significant differences in lipoprotein concentrations versus the controls. Among further cardiovascular risk factors, we found a higher prevalence of central obesity in male patients. In conclusion, there was not a higher incidence of hyperhomocysteinemia among patients with premature coronary heart disease and a low cardiovascular risk profile. The higher prevalence of hyperhomocysteinemia found in other studies may be related to the primary risk factors seen in these populations, and may therefore be an indicator of the global cardiovascular risk.

Postprandial hemorrheology and apolipoprotein B metabolism in patients with familial hypertriglyceridemia.

Impaired postprandial lipoprotein metabolism has been found to be related to the extent of coronary artery disease. Moreover, since dyslipoproteinemias are associated with impaired hemorrheology, we investigated the effect of postprandial hypertriglyceridemia on hemorrheological parameters before and after triglyceride-lowering therapy. Triglyceride-rich lipoproteins (TRLs) separated by ultracentrifugation (d < 1.006 g/dL) and chylomicrons and chylomicron remnants (quantified by apolipoprotein [apo] B-48 determination) were determined after a fat load in 10 patients with familial hypertriglyceridemia before and after therapy with gemfibrozil (900 mg daily). Lipid and hemorrheological parameters (plasma and whole-blood viscosity [PV and BV], red cell aggregation [RCA], hematocrit, and fibrinogen) were determined at baseline and every hour up to 6 hours postprandially. Fasting total triglycerides and TRL triglycerides significantly decreased with gemfibrozil therapy (P < .01). Total triglycerides postprandially increased from 9.53 +/- 1.72 to 14.47 +/- 2.07 mmol/L (TRL triglycerides by 61%) before therapy (P < .05) and from 4.61 +/- 1.28 to 7.17 +/- 0.99 mmol/L (TRL triglycerides by 57%) after therapy (P < .05). The postprandial TRL apo B increase was reduced with gemfibrozil (from 11.6 +/- 2.8 to 20.7 +/- 5.0 mg/dL with therapy v 19.0 +/- 7.6 to 33.0 +/- 12.5 mg/dL before therapy, P < .05, respectively) with a proportionally greater increase in apo B-48 (119% and 169%, respectively) compared with apo B-100 (64% and 64%, respectively). Fasting RCA was improved with lipid-lowering therapy (P < .05), but PV, BV, RCA, and fibrinogen did not show any statistically significant postprandial changes either before or after lipid-lowering therapy. In summary, we did not find any statistically significant changes in hemorrheological parameters, despite a strong postprandial increase of triglycerides. In particular, these findings were independent of fasting triglyceride levels. We conclude that triglyceride-lowering therapy by gemfibrozil had no substantial beneficial effects with respect to hemorrheology in patients with familial hypertriglyceridemia.