Biomedical subjects

Benoît Lamarche

Publications and source records attributed to Benoît Lamarche.

At least 37 records · Page 2Linked to original sources

PubMed2005

Insulin resistance syndrome, body mass index and the risk of ischemic heart disease.

BACKGROUND: Many people who are not obese according to standard height and weight criteria may still display features of insulin resistance syndrome and thus be at high risk of ischemic heart disease. We sought to investigate the effect of cumulative features of insulin resistance syndrome on the risk of ischemic heart disease associated with variations in body mass index (BMI) among men who participated in the Quebec Cardiovascular Study. METHODS: A cohort of 1824 nondiabetic men free of ischemic heart disease was evaluated at the 1985 baseline evaluation and followed for a period of 13 years, during which 284 first ischemic heart disease events were recorded. Relative hazards (RHs) of ischemic heart disease in 3 BMI groups (normal weight, overweight and obese) were estimated using Cox proportional hazards regression. RESULTS: Although obese men (BMI > or = 30 kg/m2) were the most likely to accumulate features of insulin resistance syndrome, the univariate risk of ischemic heart disease in this group was not significantly increased compared with normal-weight men (BMI < 25 kg/m2) (RH 1.26, 95% confidence interval [CI] 0.88-1.80). However, obese men who accumulated more than 4 features of insulin resistance syndrome were at increased risk of ischemic heart disease (RH 1.81, 95% CI 1.02-3.19) compared with normal-weight men who had fewer than 3 features of the syndrome. Conversely, having more than 4 features of insulin resistance syndrome was associated with a 3-fold increase in the risk of ischemic heart disease among normal-weight men (RH 3.01, 95% CI 1.70-5.32). INTERPRETATION: Although obesity is an important risk factor for ischemic heart disease, variations in BMI alone poorly reflect the risk of ischemic heart disease associated with features of insulin resistance syndrome.

Adult↗

PubMed2005

Comparison of the impact of atorvastatin and simvastatin on apoA-I kinetics in men.

BACKGROUND: The impact of simvastatin and atorvastatin, two HMG-CoA inhibitors, on plasma HDL-C concentrations has been shown to be inconsistent, simvastatin being reported to induce greater increases in HDL-C than atorvastatin. The physiological mechanisms underlying this diverging effect are still unknown. OBJECTIVES: To compare the impact of simvastatin and atorvastatin on apoA-I kinetics in vivo. METHODS: In this double-blind, cross-over study, seven men with relatively low baseline HDL-C were assigned in random order to one of two experimental 8-week treatments (atorvastatin 40 mg or simvastatin 80 mg), each separated by a 6-week washout period. After each phase, apoA-I kinetics were measured using a primed-constant infusion of l-(5,5,5-D3) leucine for 12 h with patients being kept in constant fed, steady state. Isotopic enrichment of apoA-I over time was assessed by gas chromatography-mass spectrometry and kinetic parameters were calculated by multicompartmental modeling. RESULTS: Both treatments reduced plasma LDL-C levels to a similar extent while HDL-C levels remained statistically unchanged after both experimental phases. However, compared to atorvastatin, plasma apoA-I concentrations were significantly higher after treatment with simvastatin (1.33 +/- 0.07 g/L versus 1.23 +/- 0.07 g/L, P = 0.05). Treatment with simvastatin also induced a significant increase in apoA-I production rate compared to atorvastatin (15.2 +/- 3.0 mg/kg/d versus 13.2 +/- 2.6 mg/kg/d, P = 0.05). There was no statistical difference in apoA-1 fractional catabolic rate between simvastatin and atorvastatin (0.26 +/- 0.05 pool/d versus 0.24 +/- 0.04 pool/d). CONCLUSIONS: These results suggest that the diverging impact of simvastatin and atorvastatin on plasma HDL-C levels in humans may be attributable, at least partly, to a greater production rate of apoA-I with simvastatin.

Apolipoprotein A-I↗

PubMed2005

Plasma metabolism of apoB-containing lipoproteins in patients with hepatic lipase deficiency.

The metabolism of apoB-containing lipoproteins was investigated in the fasted state in three complete and three partial hepatic lipase (HL)-deficient subjects as well as in seven normotriglyceridemic (NTG) and two hypertriglyceridemic (HTG) controls using a 12 h primed-constant infusion of L-[5,5,5-D(3)]-leucine. Two males with complete HL deficiency had increased plasma pool sizes of VLDL and IDL apoB-100 due to substantial reductions in fractional catabolic rate (FCR) of VLDL and IDL apoB-100 compared with both NTG and HTG controls. Reductions in LDL apoB-100 production rate (PR) were also observed in these two patients compared with NTG and HTG controls. Complete HL deficiency in the female proband was associated with normal VLDL apoB-100 kinetics, while plasma IDL apoB-100 pool size was increased by 124% due to an 82% decrease in the FCR of IDL apoB-100. The FCR and PR of LDL apoB-100 were reduced by 64 and 51%, respectively, in the proband compared with sex-matched controls. Partial HL-deficient patients were characterized by apoB-containing lipoprotein metabolism similar to that of controls. These results indicate that complete HL deficiency is associated with a potentially atherogenic apoB-containing lipoprotein metabolism that can be modulated considerably by secondary factors such as gender and abdominal obesity.

Apolipoproteins B↗

PubMed2005

Detection of a major gene effect for LDL peak particle diameter and association with apolipoprotein H gene haplotype.

Low-density lipoprotein (LDL) size, a coronary heart disease risk factor, is influenced by both genetic and environmental factors. Results from the Quebec Family Study (QFS) revealed that the LDL peak particle diameter (LDL-PPD) aggregates in families with a heritability coefficient above 50% and is affected by a major quantitative trait locus on chromosome 17q (LOD=6.8). Complex segregation analyses have consistently demonstrated a major gene effect influencing LDL size. In the present study, we report a similar analysis in the QFS cohort, which suggests that a major gene explains 23% of the variance in age-body mass index and triglyceride-adjusted LDL-PPD. The most intuitive positional candidate gene on chromosome 17q is the apolipoprotein H gene. Direct sequencing of the promoter, coding regions, and exon-intron splicing boundaries of this gene revealed the presence of three missense mutations and two polymorphisms in the untranslated regions. Using family-based association tests, none of these variants was individually associated with LDL-PPD. However, analysis of the haplotypes constructed from the three missense mutations, suggested that one particular haplotype (frequency=20.9%) was associated with a significant increase in LDL-PPD trait values (p=0.046). Taken together, these results suggest the presence of a major gene effect influencing LDL-PPD and a positive association with a positional candidate gene located on chromosome 17q. Replication of the association between apolipoprotein H gene haplotype and LDL-PPD is required before reaching firm conclusion.

Adult↗

PubMed2005

Inflammatory markers and long-term risk of ischemic heart disease in men A 13-year follow-up of the Quebec Cardiovascular Study.

We tested the hypothesis that elevated plasma interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen concentrations are independent risk factors and interact in increasing the long-term risk of ischemic heart disease (IHD) in men. A total of 1982 IHD-free men from the Quebec Cardiovascular Study were followed over a period of 13 years during which 210 first fatal IHD events and non-fatal myocardial infarctions were recorded. Increased CRP levels (4th versus 1st quartile) were not associated with an increased risk of IHD after adjustment for non-lipid risk factors (age, body mass index, systolic blood pressure, diabetes, smoking and medication use at baseline), lipid risk factors (LDL and HDL cholesterol and triglyceride levels) and for IL-6 and fibrinogen (RR=0.70, 95% CI=0.43-1.13). High plasma IL-6 levels (4th versus 1st quartile) were associated with a 70% greater risk of IHD independent of confounding risk factors and of the other 2 inflammatory markers (RR=1.71, 95% CI=1.07-2.75). The relationship between high fibrinogen levels (4th versus 1st quartile) and IHD risk was borderline significant in multivariate analyses (RR=1.53, 95% CI=0.97-2.43). An inflammation score based on plasma IL-6 and fibrinogen levels improved the IHD risk predictive value of a multivariate model of traditional risk factors (p=0.03). Including plasma CRP levels into the inflammatory score provided no additional predictive value. In conclusion, elevated plasma IL-6 concentrations are more strongly related to IHD risk than CRP and fibrinogen. An inflammation score based on high plasma IL-6 and fibrinogen levels used in combination with traditional risk factors may improve our ability to adequately identify high risk individuals.

Adult↗

PubMed2005

Changes in plasma antioxidant capacity and oxidized low-density lipoprotein levels in men after short-term cranberry juice consumption.

Low-density lipoprotein (LDL) oxidation is closely implicated in the development of atherosclerotic cardiovascular disease (CVD), and thus, reducing LDL susceptibility to oxidation with antoxidants could be of importance in CVD prevention. Flavonoids, polyphenolic compounds found in a large selection of fruits and vegetables, have been characterized as having a strong antioxidant potential, and intake of flavonoid-rich foods has been related to decreased morbidity and mortality from heart disease. The present study was therefore undertaken to investigate the effect of flavonoid-rich cranberry juice supplementation on plasma lipoprotein levels and LDL oxidation. For that purpose, 21 men (age +/- SD, 38 +/- 8 years) were enrolled in a 14-day intervention and instructed to drink cranberry juice 7 mL/kg body weight per day. Physical and metabolic measures including plasma lipid and oxidized LDL (OxLDL) concentrations as well as antioxidant capacity were performed before and after the intervention. At baseline, we found that plasma OxLDL levels were significantly associated with waist circumference ( r = 0.47, P = .0296) as well as plasma triglyceride ( r = 0.68, P = .0007) and apolipoprotein B ( r = 0.91, P < .0001) concentrations. The intervention led to a reduction in plasma OxLDL levels (-9.9% +/- 17.8%, P = .0131) and increase in antioxidant capacity (+6.5% +/- 10.3%, P = .0140). However, no relationship was found between both of these changes ( r = -.01, not significant). The intervention did not result in any improvement of plasma lipoprotein-lipid or inflammatory marker concentrations. Our results show that short-term cranberry juice supplementation is associated with significant increase in plasma antioxidant capacity and reduction in circulating OxLDL concentrations. Although the physiological relevance of our observations needs to be further examined, our study supports the potential role of antioxidant-rich foods in maintaining health and preventing CVD.

Adult↗

PubMed2005

Variations in plasma apolipoprotein C-III levels are strong correlates of the triglyceride response to a high-monounsaturated fatty acid diet and a high-carbohydrate diet.

The objective of this study was to examine how a diet rich in carbohydrates (high-CHO) vs a diet rich in monounsaturated fatty acids (high MUFA) consumed ad libitum modulated plasma apolipoprotein C-III (apo C-III) levels and to examine the extent to which diet-induced changes in plasma apo C-III were associated with concurrent variations in plasma triglyceride (TG) levels. Forty-seven men (mean age, 35.7 +/- 11.4 years; body mass index, 29.0 +/- 5.1 kg/m2) were randomly assigned to either a high-CHO diet (CHO, 58%; fat, 26%; n = 23) or a high-MUFA diet (CHO, 45%; fat, 40%; MUFA, 22.5%; n = 24), which they consumed for 6 to 7 weeks. Fasting and postprandial lipemia after an oral fat load and fasting plasma apo C-III were measured at the beginning and at the end of the dietary intervention. Ad libitum consumption of the high-CHO diet induced a significant reduction in body weight (-2.6%, P < .0001), but had no impact on plasma apo C-III concentrations and on fasting and postprandial plasma TG levels. In contrast, ad libitum consumption of the high-MUFA diet also resulted in a significant reduction in body weight (-2.3%, P < .01) as well as in significant reductions in plasma apo C-III (-11%, P = .05) and fasting plasma TG (-17%, P < .01). Diet-induced variations in plasma apo C-III concentrations were correlated with changes in fasting and postprandial TG levels both in the high-CHO (r > 0.70, P < .001) and the high-MUFA groups (r > 0.42, P < .05). These results indicate that variations in plasma apo C-III levels are strong correlates of the fasting and postprandial plasma TG responses to high-MUFA and high-CHO diets.

Adult↗

PubMed2005

Features of the metabolic syndrome and the risk of cardiovascular disease.

The metabolic syndrome is being increasingly recognized as an important risk factor for cardiovascular disease (CVD). While several clinical definitions have been proposed to identify patients with this syndrome, additional metabolic markers may be considered to improve one's ability to assess and predict the risk of CVD in this population. The objective of this short review is to provide an overview of the risk of CVD associated with specific features of the metabolic syndrome. The extent to which these markers may be used one day in clinical practice in primary prevention is also briefly discussed.

Animals↗

PubMed2005

The peroxisome proliferator-activated receptor alpha Leu162Val polymorphism influences the metabolic response to a dietary intervention altering fatty acid proportions in healthy men.

BACKGROUND: Serum lipid responses to dietary modification are partly determined by genetic factors. OBJECTIVE: We tested whether plasma lipoprotein and lipid responsiveness to a modification in the dietary ratio of polyunsaturated to saturated fatty acids (P:S) is influenced by the peroxisome proliferator-activated receptor alpha (PPARalpha) Leu162Val polymorphism in healthy men. DESIGN: Ten carriers of the V162 allele and 10 L162 homozygotes were matched according to age and body mass index (BMI). During the protocol, all subjects followed the National Cholesterol Education Program Step I diet, but intake of saturated and polyunsaturated fatty acids was adjusted to obtain a P:S of 0.3 for the first 4-wk period (low-P:S diet) and a P:S of 1.0 for the next 4-wk period (high-P:S diet). RESULTS: At screening, the PPARalpha Leu162Val polymorphism was not associated with anthropometric indexes or plasma lipoprotein and lipid concentrations. After the high-P:S diet, a significant gene-by-diet interaction was observed for changes in plasma total cholesterol, apolipoprotein (apo) A-I, and cholesterol concentrations in small LDL particles (P <or= 0.05). Mean differences after the high-P:S diet were observed between genotype groups for plasma apo A-I concentrations (P<0.05). Changes in BMI, waist circumference, and concentrations of triacylglycerol, phospholipid, and apo B did not differ significantly between groups. CONCLUSION: The PPARalpha Leu162Val polymorphism may contribute to interindividual variability in plasma lipoprotein and lipid response after modification of the dietary P:S ratio.

Adult↗

PubMed2005

Lack of effect of dietary conjugated linoleic acids naturally incorporated into butter on the lipid profile and body composition of overweight and obese men.

BACKGROUND: Dietary conjugated linoleic acid (CLA) is known to reduce atherosclerosis, plasma total and LDL-cholesterol concentrations, and body fat accumulation in several animal species. Of the few studies that investigated the effects of CLA supplementation in humans, all used commercially formulated oral supplements made from a mixture of CLA isomers. OBJECTIVE: We compared the effects on plasma lipoproteins and body composition of the consumption of a modified butter naturally enriched with CLA (CLA-B: 4.22 g CLA/100 g butter fat) by the addition of sunflower oil to the diet of dairy cows with the consumption of a control butter (CON-B) that was low in CLA (0.38 g CLA/100 g butter fat). DESIGN: In a crossover design study including an 8-wk washout period, 16 men [x +/- SD age: 36.6 +/- 12.4 y; body mass index (in kg/m2): 31.2 +/- 4.4] were fed each of the 2 experimental isoenergetic diets, providing 15% of energy as protein, 45% as carbohydrates, and 40% as lipids, of which >60% was derived from experimental fats, for 4 wk. RESULTS: Consumption of the CLA-B diet induced a significantly (P < 0.05) smaller reduction in plasma total cholesterol and in the ratio of total to HDL cholesterol (-0.02 mmol/L and -0.00, respectively) than did consumption of the CON-B diet (-0.26 mmol/L and-0.34, respectively). Abdominal adipose tissue area measured by computed tomography showed no difference in accumulation of either visceral or subcutaneous adipose tissue after the 2 experimental diets. CONCLUSION: These results suggest that a 10-fold CLA enrichment of butter fat does not induce beneficial metabolic effects in overweight or obese men.

Adipose Tissue↗

PubMed2005

A nutritional intervention promoting the Mediterranean food pattern is associated with a decrease in circulating oxidized LDL particles in healthy women from the Québec City metropolitan area.

The aim of the present study was to evaluate the effect of a nutritional intervention promoting the Mediterranean food pattern under free-living conditions on circulating oxidized LDL (ox-LDL) in a group of 71 healthy women from the Quebec City metropolitan area. The 12-wk nutritional intervention consisted of 2 courses on nutrition and 7 individual sessions with a dietitian. A score based on the 11 components of the Mediterranean pyramid was established to determine the women's adherence to the Mediterranean food pattern. Plasma ox-LDL concentrations were measured by a monoclonal antibody mAb-4E6-based competition ELISA. Among all women, plasma ox-LDL decreased by 11.3% after 12 wk of nutritional intervention (P < 0.0001) despite a lack of change in plasma LDL cholesterol (LDL-C). Also, an increase in the Mediterranean dietary score was significantly correlated with a decrease in ox-LDL concentrations (r = -0.30; P = 0.01). More specifically, increases in servings of fruits (r = -0.25; P < 0.05) and vegetables (r = -0.24; P < 0.05) were associated with decreases in ox-LDL concentrations. Changes in the food pattern in response to a nutritional intervention promoting the Mediterranean food pattern were accompanied by beneficial effects in circulating ox-LDL concentrations in healthy women.

Body Mass Index↗

PubMed2004

Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Québec Cardiovascular Study.

OBJECTIVE: The objective of the present study was to investigate the association between large and small low-density lipoprotein (LDL) and long-term ischemic heart disease (IHD) risk in men of the Quebec Cardiovascular Study. METHODS AND RESULTS: Cholesterol levels in the large and small LDL subfractions (termed LDL-C> or =260A and LDL-C<255A, respectively) were estimated from polyacrylamide gradient gel electrophoresis of whole plasma in the cohort of 2072 men of the population-based Quebec Cardiovascular Study. All men were free of IHD at the baseline examination and followed-up for a period of 13 years, during which 262 first IHD events (coronary death, nonfatal myocardial infarction, and unstable angina pectoris) were recorded. Our study confirmed the strong and independent association between LDL-C<255A levels as a proxy of the small dense LDL phenotype and the risk of IHD in men, particularly over the first 7 years of follow-up. However, elevated LDL-C> or =260A levels (third versus first tertile) were not associated with an increased risk of IHD over the 13-year follow-up (RR=0.76; P=0.07). CONCLUSIONS: These results indicated that estimated cholesterol levels in the large LDL subfraction were not associated with an increased risk of IHD in men and that the cardiovascular risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles.

Adult↗

PubMed2004

Validity and reproducibility of an interviewer-administered food frequency questionnaire for healthy French-Canadian men and women.

OBJECTIVE: To evaluate the validity (study 1) and the reproducibility (study 2) of an interviewer-administered food frequency questionnaire (FFQ). METHOD: The FFQ was designed at Laval University and contains 91 items and 33 subquestions. STUDY 1: The FFQ was compared against a 3-day food record (2 week-days and 1 weekend-day), at week 0, 6 and 12 of a nutritional intervention. STUDY 2: In order to evaluate the reproducibility of the FFQ, 2 registered dietitians administered the FFQ 4-weeks apart among subjects who were not part of the nutritional intervention. RESULTS: STUDY 1: Mean values for intake of most nutrients assessed by the FFQ and by the 3-day food record were not statistically different. Energy-adjusted correlation coefficients for major macronutrients ranged from 0.36 for proteins to 0.60 for carbohydrates (p < or = 0.01). Agreement analysis revealed that on average, 35% of the subjects were classified in the same quartile when nutrients were assessed by either the 3-day food record or the FFQ. STUDY 2: Significant associations were observed between dietary measurements derived from the two FFQs administered 4 weeks apart. Correlation coefficients for the reproducibility of macronutrients ranged from 0.66 for carbohydrates to 0.83 for lipids after energy adjustment. On average, 46% of the subjects were classified in the same quartile when nutrient intakes were assessed by either FFQ. CONCLUSION: These data indicated that the FFQ developed has a good validity and is reproducible.

Journal Article↗

PubMed2004

Apolipoprotein A-I, A-II, and VLDL-B-100 metabolism in men: comparison of a low-fat diet and a high-monounsaturated fatty acid diet.

The impact of a low-fat diet and a high-MUFA diet on apolipoprotein A-I (apoA-I), apoA-II, and VLDL-apoB-100 metabolism in conditions of unrestricted (ad libitum) energy intake was compared in 65 men randomly assigned to one of two predefined experimental diets. A subsample of 18 men participated in the kinetic study. Before and after the 6-7 week dietary intervention, kinetic subjects received a primed-constant infusion of [5,5,5-2H3]L-leucine for 12 h under feeding conditions. ApoA-I production rate (PR; -31.5%; P <0.001) and fractional catabolic rate (FCR; -24.3%; P <0.05) were significantly decreased after the low-fat diet. These changes in apoA-I PR and FCR with the low-fat diet were also significantly different from those observed with the high-MUFA diet (P <0.01 and P <0.05, respectively). ApoA-II FCR was significantly increased in the high-MUFA group only. No significant within- or between-diet difference was found in VLDL-apoB-100 PR or FCR. These results emphasize the differential impact of the low-fat diet and high-MUFA diet on HDL metabolism.

Adult↗

PubMed2004

Relationship between cholesteryl ester transfer protein and LDL heterogeneity in familial hypercholesterolemia.

Small, dense LDL particles have been associated with an increased risk of coronary artery disease, and cholesteryl ester transfer protein (CETP) has been suggested to play a role in LDL particle remodeling. We examined the relationship between LDL heterogeneity and plasma CETP mass in familial hypercholesterolemia (FH). LDL particles were characterized by polyacrylamide gradient gel electrophoresis in a total of 259 FH heterozygotes and 208 nonFH controls. CETP mass was measured by enzyme-linked immunosorbent assay in a subgroup of 240 participants, which included 120 FH patients matched with 120 controls. As compared with controls, FH subjects had an 11% higher CETP mass. Moreover, LDL-peak particle diameter (LDL-PPD) was significantly smaller in FH heterozygotes than in controls (258.1 +/- 4.8 vs. 259.2 +/- 4.1 A; P = 0.01) after adjustment for covariates. There was also an inverse relationship between LDL-PPD and CETP mass (R = -0.15; P = 0.02), and this relationship was abolished by adjustment for the FH/control status, indicating that LDL-PPD changes in FH are mediated, at least in part, by an increase in plasma CETP mass concentrations. These results suggest that increased plasma CETP mass concentrations could lead to significant LDL particle remodeling in FH heterozygotes and could contribute to the pathogenesis of atherosclerosis.

Adolescent↗

PubMed2004

Increased production of VLDL apoB-100 in subjects with familial hypercholesterolemia carrying the same null LDL receptor gene mutation.

Early radiokinetic studies revealed that the classical metabolic defect in patients with familial hypercholesterolemia (FH) is hypocatabolism of LDL due to decreased LDL receptor activity. However, recent studies have suggested that hepatic oversecretion of apolipoprotein B-100 (apoB-100)-containing lipoproteins could also contribute to the markedly elevated plasma concentrations of LDL-cholesterol found in FH. The aim of this study was to examine the kinetics of apoB-100 labeled with a stable isotope (l-[5,5,5-D(3)] leucine) in five normolipidemic controls and in seven well-characterized FH subjects that included six FH heterozygotes and one FH homozygote carrying the same null LDL receptor gene mutation. As compared with controls, the VLDL apoB-100 production rate was increased by 50% in the FH heterozygotes and by 109% in the FH homozygote. Furthermore, FH subjects had significantly higher LDL apoB-100 pool size and lower LDL apoB-100 fractional catabolic rate than controls. These results indicate that the elevation of plasma LDL-cholesterol found in FH is attributable to both decreased clearance of LDL and increased hepatic production of apoB-100-containing lipoproteins.

Adult↗

PubMed2004

Diet and low-density lipoprotein particle size.

Small, dense low-density lipoprotein (LDL) particles are being increasingly recognized as an important risk factor for cardiovascular disease. This paper provides an overview of how different diets and macronutrients modulate the LDL size phenotype. Data reviewed indicated that several components of the LDL size phenotype should be measured concurrently in order to fully appreciate the impact of diet on this complex trait. Data also suggested that numerous dietary elements have a significant impact on several characteristics of the LDL size phenotype, thus providing further evidence to the concept that specific dietary modifications can beneficially alter cardiovascular disease risk beyond their known and demonstrated effects on plasma LDL cholesterol concentrations.

Cardiovascular Diseases↗

PubMed2004

Lack of evidence for reduced plasma apo B48 catabolism in patients with heterozygous familial hypercholesterolemia carrying the same null LDL receptor gene mutation.

Increasing evidence suggests that remnants of chylomicrons and very low density lipoprotein (VLDL) also known as triglyceride-rich lipoproteins (TRL) are directly related to the pathogenesis of atherosclerosis. While studies in animals suggest that low density lipoprotein (LDL) receptor deficiency delays clearance of chylomicron remnants, human data supporting this hypothesis are conflicting. The objective of this study was to compare the fractional catabolic rate (FCR) and production rate (PR) of TRL apolipoprotein B48, the principal structural protein of intestinally derived chylomicron remnants, between familial hypercholesterolemic (FH) heterozygotes and non-FH controls. This was achieved by examining the kinetics of TRL apo B48 labelled with a stable isotope (L-(5,5,5-D3)leucine) in five normolipidemic males (age: 24.7 +/- 1.3 years; body mass index (BMI): 23.9 +/- 1.4 kg/m2) and six genetically defined FH heterozygous males (age: 29.7 +/- 9.9 years; (BMI): 22.0 +/- 4.3 kg/m2) carrying the same null LDL receptor gene mutation. All participants were apo E3 homozygotes. During the kinetic study, the subjects consumed 1/30 of their daily food intake every 30 min over a 15 h period. No significant difference was observed between FH heterozygotes and controls for FCR of TRL apo B48 (7.9 +/- 2.1 versus 7.9 +/- 2.6 pools per day, P = 0.99) while the TRL apo B48 pool size (10.5 +/- 5.4 versus 5.7 +/- 2.4 mg, P = 0.03) and PR (1.1 +/- 0.3 versus 0.6 +/- 0.3 mg kg(-1) per day, P = 0.02) were significantly higher among FH than in controls. In conclusion, this study shows no evidence for reduced plasma apo B48 catabolism in patients with heterozygous FH carrying the same null LDL receptor gene mutation and suggests that the plasma levels of intestinally derived TRL are elevated in FH due to an increased production rate.

Adult↗