[Determinants of the intention of post-secondary students to eat at least five servings of vegetables and fruit daily]. / Déterminants de l'intention de consommer au moins cinq portions de légumes et de fruits chaque jour chez des jeunes adultes aux études postsecondaires.

BACKGROUND: Vegetable and fruit consumption helps reduce the occurrence of overweight, obesity, and other chronic diseases. However, only 50% of young adults eat at least five servings of these foods daily. Based on the construct of the Theory of planned behaviour of Ajzen (1991) to which other constructs were added (descriptive norm, perceived regularity of the behaviour and past behaviour), this study aims at identifying the determinants in the intention of young adults in postsecondary education institutions to eat at least five servings of vegetables and fruit daily during the next three months. METHODS: A sample of 385 students in two CEGEP (junior college institutions) in the Quebec City area participated in this correlation study on a volunteer basis. While attending class, they completed a self-administered questionnaire. RESULTS: Hierarchical regression analyses showed that perceived behavioural controls and the perceived weight of facilitating factors and barriers to the behaviour, explained 75% of the intention variance. Another 4% was explained when the perceived regularity of the behaviour, the descriptive norm, and past-behaviour, were added to the analysis. Logistic regression analyses show that individuals presenting weak/strong intention can be differentiated among themselves as to the perception of benefits derived from a daily consumption of vegetables and fruit (such as maintaining good health, eating foods that taste good), and as to facilitating factors/barriers that assist or inhibit such consumption (possessing more information on the nutritional value and taste of vegetables and fruit, or disposing of sufficient time to prepare them). CONCLUSION: To our knowledge, this is the first study done in Quebec using a recognized theoretical model to identify the determinants of the intention to eat at least five servings of vegetables and fruit daily in a sample of young adults in postsecondary education institutions. The results may be helpful in designing the contents of interventions aimed at maintaining and increasing daily consumption of vegetables and fruit by young adults.

[Psychosocial determinants of drug users to use a new syringe]. / Déterminants psychosociaux d'utilisateurs de drogues d'utiliser une seringue neuve.

BACKGROUND: A limited number of injection drug users are hard to reach through needle-exchange programs. They obtain their injection material from drug-using peers. This dependence on others can make them more at risk of contracting HIV through sharing non-sterile syringes. The aim of this study is to identify determinants of the intention to systematically resort to use of a new syringe by injection drug users rarely or never involved in needle-exchange programs in Quebec. METHODS: A cross-sectional survey was conducted in Québec city by means of a questionnaire measuring variables from the theory of planned behavior and past behavior. Participants (n=97) were recruited by acquaintances who kept regular contacts with the local needle-exchange programs. Multiple linear regression was used to identify the psychosocial determinants of the intention, and beliefs underlying those determinants were identified using multiple logistic regression. RESULTS: Half of participants reported using a new syringe for each injection in the last month. In multivariate analyses, this past behavior together with theory of planned behavior constructs explained 70% of the variation in participants intent to use a new syringe for each injection (control beliefs: beta=0.39; past behavior: beta=0.27; attitude: beta=0.21; perceived behavioral control: beta=0.20; subjective norm: beta=0.12). In logistic regression, six important beliefs were identified. CONCLUSION: This study resulted in the development of a predictive model of intention to use always a new syringe for each injection among a population of injection drug users in Quebec. Study results could serve as the foundation for the development of interventions to promote this behavior.

Vascular calcifications in homozygote familial hypercholesterolemia.

BACKGROUND: Patients with homozygous familial hypercholesterolemia (hmzFH) attributable to LDL receptor gene mutations have shown a remarkable increase in survival over the last 20 years. Early onset coronary heart disease (CHD) and calcific aortic valve stenosis are the major complications of this disorder. We now report extensive premature calcification of the aorta in patients with hmzFH. METHODS AND RESULTS: We examined 25 hmzFH patients from Canada; mean age was 32 years (range 5 to 54), and mean baseline cholesterol before treatment was 19+/-5 mmol/L (737+/-206 mg/dL). Aortic calcification was quantified using computed tomography (CT). An elevated mean calcium score was found in patients by age 20 and correlated with age (r(2)=0.53, P=0.001). One quarter (24%) of patients underwent aortic valve surgery. CONCLUSIONS: We document premature severe aortic calcifications in all adult hmzFH patients studied. These presented considerable surgical management challenges. Strategies to identify and monitor aortic calcification in hmzFH by noninvasive techniques are required, as are clinical trials to determine whether additional or more intensive therapies will prevent the progression of such calcifications. Whether vascular calcifications in hmzFH subjects are related to sustained increases in LDL-C levels or to other mechanisms, such as abnormal osteoblast activity, remains to be determined.

Alterations in erythrocyte membrane lipid composition and fluidity in primary lipoprotein lipase deficiency.

Lipid composition of plasma lipoproteins and erythrocyte ghost membranes has been studied in 16 healthy normolipidaemic subjects and in 16 patients affected by primary lipoprotein lipase deficiency, resulting in severe chylomicronaemia and in cholesterol-depleted low-density lipoproteins and high-density lipoproteins. A significant decrease in membrane cholesterol/phospholipid ratio was observed in lipoprotein lipase deficient patients compared to controls (3.27 +/- 0.33 vs. 3.95 +/- 0.50, mean +/- S.D.; P less than 0.0001). There was also an increase in the erythrocyte membrane phosphatidylcholine/sphingomyelin ratio in lipoprotein lipase deficient patients compared to controls (1.53 +/- 0.10 vs. 1.05 +/- 0.13; P less than 0.0001) due to a concurrent increase in phosphatidylcholine and decrease in sphingomyelin relative concentrations in these patients. Erythrocyte ghost membrane fluidity was determined by fluorescence anisotropy and found to be higher in membranes from lipoprotein lipase deficient patients. This increase in membrane fluidity can be attributed in part to changes in membrane cholesterol and phospholipid concentrations in response to abnormal plasma lipoprotein composition.

Hyperinsulinemia and abdominal obesity affect the expression of hypertriglyceridemia in heterozygous familial lipoprotein lipase deficiency.

We have reported three missense mutations (G188E, P207L, and D250N) in the lipoprotein lipase (LPL) gene among French-Canadians, resulting in the absence of measurable postheparin plasma LPL activity in homozygotes. Presence of triglyceride- and cholesterol-rich VLDL, as well as cholesterol-poor HDL particles, has been shown in heterozygotes affected by partial reduction in postheparin LPL activity. However, significant heterogeneity in their plasma triglyceride levels has been found, even among individuals carrying the same LPL gene mutation, indicating that factors other than LPL deficiency could affect the phenotypic expression of hypertriglyceridemia in the heterozygous state. The aim of the present study was to examine the combined effects of abdominal fat accumulation and hyperinsulinemia on plasma triglyceride levels among heterozygous patients for familial LPL deficiency. Based on sex and BMI, 43 heterozygotes (25 women and 18 men) were matched with noncarrier control subjects. Our data indicate that heterozygotes with higher abdominal fat deposition, as defined as waist girth values above the 50th percentile, had higher plasma triglyceride levels than nonobese heterozygotes. However, an important proportion of male heterozygote subjects were hypertriglyceridemic, even in absence of abdominal obesity, suggesting that another factor(s) was involved in the modulation of hypertriglyceridemia in these subjects. Indeed, multivariate analyses revealed that fasting hyperinsulinemia was a significant correlate of hypertriglyceridemia among these heterozygotes. Results of the present study indicate that abdominal obesity and hyperinsulinemia both have deleterious effects on plasma triglyceride levels in familial LPL deficiency. It is suggested that heterozygotes with moderate obesity and/or insulin resistance may be at higher risk of coronary artery disease because of the expression of an atherogenic lipoprotein phenotype among these patients.

Molecular pathobiology of the human lipoprotein lipase gene.

Lipoprotein lipase (LPL; E.C. 3.1.1.34) is a key enzyme in the metabolism of lipids. Many diseases, including obesity, coronary heart disease, chylomicronemia (pancreatitis), and atherosclerosis, appear to be directly or indirectly related to abnormalities in LPL function. Human LPL is a member of a superfamily of lipases that includes hepatic lipase and pancreatic lipase. These lipases are characterized by extensive homology, both at the level of the gene and the mature protein, suggesting that they have a common evolutionary origin. A large number of natural mutations have been discovered in the human LPL gene, which are located at different sites in the gene and affect different functions of the mature protein. There is a high prevalence of two of these mutations (207 and 188) in the Province of Québec, and one of them (207) is almost exclusive to the French-Canadian population. A study of these and other naturally occurring mutant LPL molecules, as well as those created in vitro by site-directed mutagenesis, indicate that the sequence of LPL is organized into multiple structural and functional units that act in concert in the normal enzyme. In this review, we discuss the interrelationships of LPL structure and its function, the molecular etiology of abnormal LPL in humans, and the clinical and therapeutic aspects of LPL deficiency.

Effects of dextrothyroxine on the pituitary-thyroid axis in hypercholesterolemic children and goitrous adults.

To evaluate the effects of dextrothyroxine (D-T4) on the pituitary-thyroid axis, we have measured the secretion of TSH in response to TRH in six goitrous adults and six euthyroid children with familial hypercholesterolemia. Since the effects of thyroid hormones appear to be mediated by specific nuclear receptors, the binding affinity of D-T4 was also studied. In both groups of subjects, D-T4 completely abolished the expected TRH stimulation of TSH and T3 secretion. The in vitro binding of D-T4 to rat pituitary nuclear receptors is only 3% that of L-T3, but the binding of D-T3 was similar to that of L-T4 (13% and 11%, respectively). The high circulating levels of D-T4 and possibly of D-T3 after chronic administration of D-T4 may be responsible for the saturation of pituitary nuclear T3 receptors, resulting in the suppression of the TRH-induced TSH response. During the treatment period, total cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol were significantly decreased by 18%, 18%, and 19%, respectively. Plasma triglyceride levels and the ratio of total to high density lipoprotein cholesterol were not affected. Although D-T4 lowers cholesterol levels, in view of its suppressive effect on the pituitary-thyroid axis, caution must be exercised with regard to its long term use in children.

A hepatic lipase gene mutation associated with heritable lipolytic deficiency.

Absent hepatic lipase (HL) activity results in dyslipidemia and premature atherosclerosis. DNA sequencing of the HL gene from subjects with heritable HL deficiency identified a new C to T substitution within exon 8 that in the mature enzyme caused a threonine to methionine change at position 383 (T383M). With a rapid DNA detection method we observed that all 6 individuals with complete HL deficiency from 2 families had the T383M mutation. None of 50 random unrelated unaffected subjects had this mutation. We propose that T383M is specific to families with heritable HL deficiency. Furthermore, structural variation at the HL gene, possibly in combination with other factors, appears to be etiologic in HL deficiency.

Changes in plasma lipoproteins during various androgen suppression therapies in men with prostatic carcinoma: effects of orchiectomy, estrogen, and combination treatment with luteinizing hormone-releasing hormone agonist and flutamide.

Cardiovascular complications are a well recognized side-effect of antihormonal therapy in men with prostatic carcinoma. We studied changes in plasma lipoproteins in patients with prostate cancer during treatment with several androgen suppression therapies. Estrogen, orchiectomy, and a combination of LHRH agonist and antiandrogen (flutamide) reduced plasma testosterone concentrations (89-92%) and plasma estradiol decreased by 85%, 44%, and 54%, respectively. Estrogen induced hypertriglyceridemia and elevation of plasma HDL cholesterol, phospholipid, and apolipoprotein A-I and A-II concentrations. Low density lipoprotein (LDL) cholesterol decreased but LDL apolipoprotein B did not. These results suggest that the cardiovascular complications that occur during estrogen administration are not mediated through changes in lipoprotein profile, other than the hypertriglyceridemic effect. Orchiectomy caused hypercholesterolemia and an increase in both total and LDL apolipoprotein B, all of which are strong determinants of cardiovascular disease. The high density lipoprotein (HDL) concentration was not affected despite a reduction in plasma testosterone, perhaps due to a simultaneous decrease in estradiol. Combination therapy had no effect on plasma lipid and apolipoprotein B concentrations, but very low density lipoprotein (VLDL) apolipoprotein B decreased, and LDL apolipoprotein B increased. The HDL cholesterol and apolipoprotein A-I concentrations increased but A-II and phospholipids did not. These results suggest enhanced lipoprotein lipase activity, consistent with the reciprocal changes in VLDL and LDL apolipoprotein B levels, apolipoprotein B enrichment of LDL particles, and increase in HDL cholesterol. The higher apolipoprotein A-I to A-II ratio indicates an increase in HDL2 subfraction due to inhibition of endothelial hepatic lipase, increased secretion of apolipoprotein A-I, or both. These effects are attributed to estradiol, which decreased less than after orchiectomy, and to additional adrenal androgen inhibition by flutamide. We conclude that estradiol plays an important role in determining plasma lipoprotein concentrations in men, and androgens exert an antagonist effect. The lipoprotein profile resulting from the combination treatment is more beneficial than that resulting from orchiectomy or estrogen administration.

Dose-response to tibric acid: a new hypolipidemic drug in type IV hyperlipoproteinemia.

This double-blind study compares the effects of tibric acid at four different doses to that of placebo in type IV hyperlipidemic patients. Fifty patients, divided at random in five groups of 10 patients each, received one of the following treatments: placebo, tibric acid 500 mg, 750 mg, 1,000 mg, or 1,250 mg per 24 hr. The data suggest that the 1,000 mg and the 1,250 mg doses are effective in lowering the serum triglyceride levels after 6 wk of treatment; the effect on total cholesterol is less pronouced. No effect is observed on the concentration of serum esterified cholesterol, phospholipids, and free fatty acids. It is also shown that in the dose range studied, the best fitting curve defining the four mean values of triglycerides and total cholesterol obtained with the four active treatments did not deviate significantly from linearity. Due to lack of toxicity, tibric acid may be useful in the treatment of type IV hyperlipoproteinemia.

Effects of a soy-protein beverage on plasma lipoproteins in children with familial hypercholesterolemia.

The effects of soy protein (35% of protein energy) given as a beverage and those of cow-milk proteins were investigated on plasma lipoprotein concentrations in children with familial hypercholesterolemia (FH). Subjects were randomly assigned to either the soy-protein or cow-milk-protein experimental period, with subsequent crossover after a washout period, each period lasting 4 wk. Diets were planned to provide 20% energy as protein, 28% as fat (polyunsaturated:monounsaturated:saturated fatty acids, 1:3:3) and less than 200 mg cholesterol/d. No changes were observed in either plasma cholesterol, low-density-lipoprotein cholesterol, or apolipoprotein concentrations. However, the soy beverage significantly reduced the concentrations of triglyceride and very-low-density-lipoprotein cholesterol (P less than 0.05) and significantly increased the concentrations of high-density-lipoprotein cholesterol (HDL-C) and HDL3-C (P less than 0.04 and P less than 0.03, respectively). These results indicate that the administration of soy protein may induce clinically beneficial effects in children with FH.

Heterozygous familial hypercholesterolemia in children: low-density lipoprotein receptor mutational analysis and variation in the expression of plasma lipoprotein-lipid concentrations.

The phenotypic expression of heterozygous familial hypercholesterolemia (FH) is variable form biochemical and clinical standpoints and several genetic and environmental factors could contribute to explain this variability. We have compared, in a cohort of 266 heterozygous FH children and adolescents (1-19 years), the variation in plasma lipoprotein-lipid levels among patients defined by three mutations in the low density lipoprotein receptor (LDLR) gene. Comparison of the plasma total and LDL-cholesterol (LDL-C) levels among the three mutation groups revealed significant differences. Plasma total and LDL-C levels were significantly higher (P < 0.05) in the group bearing the French-Canadian delta > 15 kb null allele mutation (8.17 +/- 1.45 and 6.58 +/- 1.42 mmol/l) and in the group with the defective allele C646Y missense mutation (8.18 +/- 1.53 and 6.65 +/- 1.50 mmo/l) compared to the group with the defective allele W66G missense mutation (7.19 +/- 1.23 and 5.62 +/- 1.16 mmol/l). Comparisons of other lipoprotein-lipid parameters between FH heterozygotes and normolipemic (n = 120) children indicated that all mutation groups had significantly (P = 0.0001) lower plasma HDL-cholesterol (HDL-C) levels and a higher total cholesterol (TC) to HDL-C ratio (P < 0.05). Among FH heterozygote groups, the W66G group had the lowest TC to HDL-C ratio. Multivariate analyses revealed that in FH heterozygotes as well as in controls, HDL-C levels contributed to a greater proportion of the variation in TC to HDL-C ratio than TC. In order to examine the age effect, control and FH heterozygote delta > 15 kb groups were then subdivided into four groups (1-4; 5-8; 9-13, and 14-19 years). The variation in HDL-C and triglycerides with age in heterozygous FH children showed a pattern which was similar to the one noted in the control group. In conclusion, the present study demonstrated that the overall contribution of age to variation in the lipoprotein profile of heterozygous FH children is similar to the effect observed among healthy children. The effect of LDLR gene in FH is dominant and there was no difference in plasma TC and LDL-C due to gender. Finally, this study indicates that the LDLR gene type mutations are a modulator of the magnitude of the increase in plasma TC and LDL-C levels noted among FH heterozygote children.

Fine mapping of low-density lipoprotein receptor gene by genetic linkage on chromosome 19p13.1-p13.3 and study of the founder effect of four French Canadian low-density lipoprotein receptor gene mutations.

Familial hypercholesterolemia (FH) is one of the most common autosomal codominant diseases. FH is caused by mutations in the low-density lipoprotein receptor (LDLR) gene and is characterized by raised plasma LDL-cholesterol, tendon xanthomas, and premature coronary heart disease. The frequency of FH among French Canadians in northeastern Quebec is higher than in most other populations, 1:154 vs. 1:500 due to high prevalence of few recurrent mutations in the LDLR gene. In the French Canadian population, 11 mutations in the LDLR gene have been found to occur in geographically diverse areas and account for > 90% of cases. We have first constructed a high-resolution genetic map to locate several highly polymorphic markers close to LDLR locus, thus providing the necessary tools to study the origin of the four most common mutations which account for approximately 80% of our FH patients. We have then genotyped five markers (D19S413, D19S865, D19S221, D19S914, D19S586) in 102 heterozygotes (38 del > 15kb; 36 W66G; 16 C646Y; 12 E207K), two compound heterozygotes (del > 15kb/W66G; del > 15kb/C646Y) and seven homozygotes (three del > 15 kb; three W66G: one E207K) with FH unrelated to the first and second degree. We have found that patients bearing the same LDLR gene mutation carry a common haplotype at the LDLR locus although there is evidence for the early occurrence of a recombinational event between the LDLR and the D19S221 locus in the French Canadian patients bearing the W66G mutation. The fine mapping of LDLR gene close to several highly informative microsatellite markers provide fine mapping details of the LDLR region and additional tools for studies of association between plasma lipoprotein levels and LDLR gene.

Contribution of receptor negative versus receptor defective mutations in the LDL-receptor gene to angiographically assessed coronary artery disease among young (25-49 years) versus middle-aged (50-64 years) men.

Elevated plasma LDL-cholesterol (LDL-C) levels are associated with an increased risk of coronary artery disease (CAD). Familial hypercholesterolemia (FH), a monogenic trait due to mutations in the LDL-receptor (R) gene is characterized by raised plasma LDL-C levels and premature CAD. The aim of the present investigation, derived from the study of a population of 1465 unrelated men aged 25 to 64 years, was to compare the expression of CAD assessed by coronary angiography in young (aged 25-49 years) versus middle-aged (50-64 years) heterozygous FH patients of French Canadian descent. Furthermore, the relationship of binding-defective versus receptor negative mutations in the LDL-R to premature CAD ( < 50 years) was examined and compared with men displaying a normal plasma lipoprotein-lipid profile. From the original study sample, a total of 100 men met the clinical criteria of heterozygous FH. Among them, 30 were carriers of a receptor negative mutation (deletion > 15 kb or point mutations Y468X or R329X) whereas 64 were carriers of a receptor defective mutation (W66G, E207K or C646Y). As expected, in both age groups (25-49 years vs. 50-64 years), carriers of a receptor negative mutation had higher plasma cholesterol and LDL-C levels than carriers of a defective allele or men with a normal plasma lipoprotein-lipid profile. In addition, the mean number of diseased vessels (with > 50% stenosis) was higher in men aged 50-64 years compared to those aged 25 49 years. In the two age groups, FH patients were characterized by a higher number of stenosed coronary vessels than the normal phenotype group. Within each group (either receptor negative, receptor defective or normal phenotype) plasma cholesterol, LDL-C, HDL-C, triglyceride and apolipoprotein B levels were similar irrespective of age (25 49 years vs. 50-64 years). Finally, multiple logistic regression analyses revealed that compared to non-FH men, the relative odds of being affected by CAD before the age of 50 years was 7.3-fold higher for carriers of a receptor negative mutation and 2.7-fold higher for men with a receptor defective mutation at the LDL-R locus. These results suggest that CAD could be an earlier event among heterozygous FH subjects bearing a receptor negative mutation compared to LDL-R defective patients. It also suggest that the selective screening for mutations in the LDL-R gene may allow a better assessment of the individual risk and facilitate the development of family-based preventive strategies or intervention programs in FH.

Treatment of familial hypercholesterolemia in children and adolescents: effect of lovastatin. Canadian Lovastatin in Children Study Group.

OBJECTIVE: Familial hypercholesterolemia (FH), an inherited autosomal dominant disorder of lipoprotein metabolism, is associated with premature atherosclerosis. The recommended pediatric therapy consists of dietary intervention and, when necessary, treatment with bile acid-binding resins. However, compliance has been poor in many children. Therefore, our objectives were to determine the efficacy, safety, and tolerance of the short-term use of lovastatin, a 3-hydroxy 3-methylglutaryl coenzyme A reductase inhibitor, in the control of severe FH in a male pediatric population and to evaluate the dose-response relationship. METHODS: Sixty-nine male patients with FH 12.9 +/- 2.4 years of age (mean +/- SD) participated in this multicenter, randomized, double-blind trial. After a 4-week placebo period, the patients were allocated to four treatment groups (lovastatin 10, 20, 30, 40 mg/d) for 8 weeks. Plasma lipid and apolipoprotein (Apo) concentrations were measured every 2 weeks. Clinical and laboratory evidence of adverse events was monitored periodically throughout the study. RESULTS: All lovastatin doses reduced total cholesterol (-17% to -29%), low density lipoprotein cholesterol (-21% to -36%), and ApoB (-19% to -28%) concentrations. A dose-response relationship was seen, and between-group comparisons showed that results were significantly improved up to a dose of 30 mg/d. We observed a 7% increase in high-density lipoprotein cholesterol and a 4% increase in ApoA1 concentrations. The medication was well tolerated by all patients. No serious clinical adverse experience was reported. Lovastatin increased aspartate aminotransferase concentrations, but there was no evidence of a dose-response relationship, and no value exceeded two times the upper limit of normal. No significant change in alanine aminotransferase was observed. Three patients had marked (more than three times the upper limit of normal) asymptomatic elevations in their creatine kinase values, which returned spontaneously to normal, and no action was required regarding the drug.

Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia.

In a comparative study, 158 patients with type IIa or IIb primary hypercholesterolemia received either placebo, nicotinic acid extended-release capsules (0.5 to 1.0 g twice daily), pravastatin (40 mg at bedtime), or the combination for a short-term, 8-week period. A long-term, 88-week phase followed in which the addition of other lipid-lowering agents was permitted. During the short-term phase, low-density lipoprotein cholesterol levels were lower, in relation to baseline, with nicotinic acid treatment (-21%) than with placebo (P < or = 0.05), with pravastatin (-33%) than with either placebo (p < or = 0.001) or nicotinic acid (p < or = 0.05) and with combination therapy (-49%) than with the other 3 treatments (p < or = 0.05) at all weeks measured. At week 8, high-density lipoprotein cholesterol levels were increased, in relation to placebo, by nicotinic acid treatment (12%; p < or = 0.05), pravastatin therapy (13%; p < or = 0.01) and combination therapy (16%; p < or = 0.01). Adverse events were less frequent in the pravastatin and placebo groups (p < or = 0.05). In comparison with placebo, treatment with nicotinic acid resulted in significant increases in aspartate and alanine aminotransferase. The placebo and pravastatin groups did not differ significantly regarding adverse events or laboratory parameters. Similar results were observed in the long-term phase. Therefore, pravastatin is very effective and well tolerated in the treatment of type IIa or IIb primary hypercholesterolemia, and is superior to nicotinic acid in both efficacy and adverse event profile.(ABSTRACT TRUNCATED AT 250 WORDS)

Relative contribution of low-density lipoprotein receptor and lipoprotein lipase gene mutations to angiographically assessed coronary artery disease among French Canadians.

Men with low-density lipoprotein receptor gene mutations causing familial hypercholesterolemia (FH) are at high risk of premature coronary artery disease (CAD). The dyslipidemic state found among patients who are heterozygous for mutations in the lipoprotein lipase (LPL) gene may also increase the risk of CAD. In the present study, the association of the heterozygous forms of low-density lipoprotein receptor gene mutations causing FH as well as of LPL gene mutations causing (P207L and G188E) or not causing (D9N and N291S) complete loss of LPL activity with angiographically assessed CAD was estimated in a cohort of 412 French Canadian men aged <60 years who consecutively underwent coronary angiography for the investigation of retrosternal pain. The frequency of FH as well as of LPL gene mutations tended to increase with the number of narrowed coronary arteries. However, CAD occurred earlier in FH patients than in partly LPL-deficient patients. Indeed, the proportion of men affected by FH was of 16.4% in those <45 years of age, and solely 4.3% among those between 56 and 60 years of age (p <0.0001). In contrast, the LPL gene defect was found in only 4.0% of men aged <45 years, whereas this prevalence reached 8.3% among those aged 56 to 60 years. In multivariate analyses, the association of LPL with CAD was not independent of age, high-density lipoprotein cholesterol concentrations, and other covariates included at baseline, and was not affected by the type of mutation in the LPL gene. In contrast, FH was associated with CAD with minimal contribution of other cardiovascular risk factors. However, the relation between FH and CAD was at least partly dependent on plasma apolipoprotein B concentrations. In the different regression models, fasting insulin and plasma high-density lipoprotein cholesterol concentrations were important covariates of CAD, whether or not patients were affected by FH or LPL deficiency. In conclusion, the association of LPL gene mutations with CAD was delayed compared with FH, appeared to be markedly exacerbated by the presence of additional risk factors, and was not affected by the type of mutation in the LPL gene.

Influence of zofenopril and low doses of hydrochlorothiazide on plasma lipoproteins in patients with mild to moderate essential hypertension.

The effects of zofenopril (ZOF) calcium, an anticonverting enzyme inhibitor, and of hydrochlorothiazide (HCT) on plasma lipids, lipoproteins and apoproteins were compared in 37 patients with sitting diastolic blood pressure (SDBP) of 95 to 110 mm Hg at the end of a placebo period of 4 weeks. In the randomized double-blind experiment, 16 males and 21 females were treated with either ZOF, 30 mg (n = 18) or HCT, 25 mg (n = 19), once daily. When a SDBP of less than 90 mm Hg was not reached after 4 weeks, the dose of the initial treatment was doubled. Lipoprotein determinations were repeated after 12 weeks of active treatment. Statistically significant decrease in blood pressure (P less than .001) was demonstrated in both treated groups. Total, low density (LDL) and high density (HDL) lipoprotein, cholesterol and triglyceride concentrations were not modified either by ZOF or HCT. Furthermore, LDL/HDL and HDL-2/HDL-3 ratios, apoproteins B, A and A-1 levels did not show any significant differences. Thus, ZOF and small doses of HCT do not cause deleterious effects in lipoprotein composition as reported in previous studies with higher dosage.

Beneficial effects of the calcium antagonist isradipine on apolipoproteins in hypertensive patients.

The objective of the study was to assess the effects of the calcium antagonist isradipine on plasma lipids, lipoproteins, and apolipoproteins in patients with essential hypertension. After a four-week placebo wash-out period, 73 patients (41 men, 32 women) were studied in a double-blind, randomized, crossover study comparing sustained-release isradipine (isradipine SR) with the standard isradipine formulation. Nineteen patients received 5 mg/day and 54 patients 10 mg/day. Lipids were evaluated at the end of the placebo period and after 12 weeks of treatment with isradipine. In both treatment groups, lipid and lipoproteins were not modified. However, apolipoprotein A-I levels increased significantly (P less than .001) and the ratio of apolipoprotein B to apolipoprotein A-I concentration decreased significantly (P less than .01) irrespective of gender. These data show that the levels of plasma apolipoprotein A-I, a strong predictor of coronary heart disease, are favorably affected by isradipine of either formulation. The mechanisms of this effect remain to be elucidated.

Effect of hyperchylomicronemia on the measurement of hemoglobin.

The effects of plasma triglyceride levels on the measurement of hemoglobin and other erythrocyte indices have been studied in blood samples from ten healthy controls, 11 patients with type IV hyperlipoproteinemia, and five patients with hyperchylomicronemia (type I or V). Measurements were made using erythrocytes in their own plasmas and repeated after resuspension of the cells in physiologic saline solution. Hemoglobin, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were decreased by removal of plasma in erythrocytes from three patients with hyperchylomicronemia. It is concluded that the triglyceride contained in very-low-density lipoprotein does not affect hemoglobin measurement, while triglyceride contained in chylomicrons increased hemoglobin readings linearly.