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S Moorjani

Publications and source records attributed to S Moorjani.

At least 19 recordsLinked to original sources
PubMed1999

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.

Adult↗
PubMed1999

Apolipoprotein E polymorphism and the relationships of physical fitness to plasma lipoprotein-lipid levels in men and women.

PURPOSE: A high level of cardiovascular fitness is generally associated with a plasma lipoprotein-lipid profile predictive of a low cardiovascular disease risk. We have investigated whether apolipoprotein (apo) E polymorphism could alter the relationships of physical fitness to plasma lipoprotein-lipid levels in a sample of healthy untrained subjects (64 premenopausal women and 65 men). METHODS: Subjects were grouped according to gender and apo E phenotype determined by isoelectric focusing electrophoresis. RESULTS: In both genders, VO2max expressed in mL x kg(-1) x min(-1) was negatively correlated with plasma triglyceride levels in apo E2 carriers and apo E3 homozygotes (-0.55< or =r< or =0.31; P<0.05), whereas these associations were not found in apo E4 groups. Plasma low-density lipoprotein (LDL)-C levels were negatively associated with VO2max (r = -0.39; P<0.05) only in women homozygotes for apo E3 whereas VO2max was positively correlated with plasma high-density lipoprotein (HDL)2-C levels only in men (r = 0.51; P<0.001) and women (r = 0.65; P<0.001) who were apo E3 homozygotes. A control for concomitant association with body fat mass and glucose intolerance performed by partial correlation analyses revealed that, with the exception of the plasma HDL2-C levels in the apo E3 homozygotes, most of the significant associations between VO2max (mL x kg(-1) x min(-1)) and plasma lipoprotein-lipid levels were mediated by concomitant variation in body fatness and glucose tolerance. CONCLUSIONS: These results suggest that the magnitude of the relationships between VO2max and plasma lipoprotein-lipid levels is influenced by the apo E polymorphism. Thus, apo E2 carriers may be particularly responsive to improved fitness, thereby preventing the development of hypertriglyceridemia and type III dyslipoproteinemia.

Adult↗
PubMed1998

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.

Alleles↗
PubMed1998

Relationships of abdominal obesity and hyperinsulinemia to angiographically assessed coronary artery disease in men with known mutations in the LDL receptor gene.

BACKGROUND: Patients with a mutation in the LDL receptor gene (familial hypercholesterolemia, or FH) are characterized by substantial elevations in plasma LDL cholesterol and are at higher risk of developing coronary artery disease (CAD). Correlates of abdominal obesity may also contribute to the risk of ischemic cardiac events. Whether the hyperinsulinemic-insulin-resistant state of abdominal obesity affects coronary atherosclerosis among FH patients has not been determined. METHODS AND RESULTS: The relation of abdominal adiposity and hyperinsulinemia to angiographically assessed CAD was evaluated in a sample of 120 French Canadian men aged <60 years who were heterozygotes for FH and in a group of 280 men without FH. In the present study, the risk of CAD associated with abdominal obesity, as estimated by the waist circumference, was largely dependent on the concomitant variation in plasma lipoprotein and insulin concentrations. In contrast, the association between fasting insulin and CAD was independent of variations in waist girth, triglyceride, HDL, and apolipoprotein B concentrations (odds ratio, 1.86; P=.0005). However, the most substantial increase in the risk of CAD was observed among abdominally obese (waist circumference >95 cm) and hyperinsulinemic FH patients (odds ratio, 12.9; P=.0009). This increase in risk remained significant even after adjustment for LDL cholesterol or apolipoprotein B concentrations. CONCLUSIONS: Results of the present study provide support for the notion that the hyperinsulinemic-insulin-resistant state of abdominal obesity is a powerful predictor of CAD in men, even in a group of patients with raised LDL cholesterol concentrations due to FH.

Body Constitution↗
PubMed1998

Is lipoprotein(a) an independent risk factor for ischemic heart disease in men? The Quebec Cardiovascular Study.

OBJECTIVES: This study was undertaken to determine whether lipoprotein(a) [Lp(a)] is an independent risk factor for ischemic heart disease (IHD) and to establish the relation of Lp(a) to the other lipid fractions. BACKGROUND: Several, but not all, studies have shown that elevated Lp(a) concentrations may be associated with IHD; very few have been prospective. METHODS: A 5-year prospective follow-up study was conducted in 2,156 French Canadian men 47 to 76 years old, without clinical evidence of IHD. Lipid measurements obtained at baseline included total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, apoprotein B and Lp(a). During the follow-up period, there were 116 first IHD events (myocardial infarction, angina, death). Adjusted proportional hazards models were used to estimate the relative risk for the different variables. The cohort was also classified according to Lp(a) levels and other lipid risk factor tertiles to evaluate the relation of elevated Lp(a) levels to these risk factors. A cutoff value of 30 mg/dl was used for Lp(a). Risk ratios were calculated using the group with low Lp(a) levels and the first tertile of lipid measures as a reference. RESULTS: Lp(a) was not an independent risk factor for IHD but seemed to increase the deleterious effects of mildly elevated LDL cholesterol and elevated total cholesterol and apoprotein B levels and seemed to counteract the beneficial effects associated with elevated HDL cholesterol levels. CONCLUSIONS: In this cohort, Lp(a) was not an independent risk factor for IHD but appeared to increase the risk associated with other lipid risk factors.

Adult↗
PubMed1998

Leptinemia is not a risk factor for ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study.

OBJECTIVE: To investigate the possibility that leptin levels may be predictive of the risk of ischemic heart disease (IHD) through the relationship of leptin to body fat. RESEARCH DESIGN AND METHODS: The Quebec Cardiovascular Study cohort consisted of 2,103 French-Canadian men without IHD in 1985 who were followed until 1990, by which time 114 had experienced an IHD event. These 114 men were then individually matched for age, BMI, cigarette smoking, and alcohol intake with 114 subjects who were free of IHD at follow-up. After exclusion of diabetic patients and those in whom leptin levels could not be measured, we were able to compare the initial metabolic profiles of 86 men in the IHD group and of 95 control subjects. RESULTS: Plasma leptin concentrations were positively correlated with BMI (r = 0.67, P < 0.0001) and with fasting insulin concentrations (r = 0.46, P < 0.0001) in the overall sample. These significant associations were also observed when men with IHD and the control subjects were examined separately (control subjects: r = 0.68 for BMI and r = 0.45 for insulin; IHD subjects: r = 0.65 for BMI and r = 0.50 for insulin). With the exception of plasma triglyceride (r = 0.25, P < 0.001), no significant association was found between leptin and plasma lipoprotein and lipid concentrations. Furthermore, plasma insulin remained significantly associated with leptin levels even after adjustment for BMI (r = 0.22, P < 0.005). There was no difference in baseline leptin levels among men who developed IHD versus men who remained IHD-free during the 5-year follow-up (5.56 +/- 3.12 vs. 5.36 +/- 2.90 ng/ml, respectively). Thus, although significantly correlated with the BMI and fasting insulin levels, plasma leptin concentration was not a significant predictor of the 5-year incidence of IHD. This lack of a relationship to IHD was noted when leptin levels were analyzed as tertiles and when leptin concentration was analyzed as a continuous variable. CONCLUSIONS: These prospective results suggest that leptinemia, despite being a strong correlate of obesity, does not appear to be an independent risk factor for the development of IHD in men.

Aged↗
PubMed1997

The MspI polymorphism of the apolipoprotein A-II gene as a modulator of the dyslipidemic state found in visceral obesity.

The aim of the present study was to examine the effect of variation at the apolipoprotein (apo) A-II gene locus on lipoprotein levels in visceral obesity. A total of 145 sedentary men, free from metabolic disorders requiring pharmacotherapy, were classified into two groups on the basis of their apo A-II-MspI genotype determined by the polymerase chain reaction: 1) 43 M1 carriers or M1M2, including two M1M1 homozygotes and 41 M1M2 heterozygotes, and 2) 102 M2M2 homozygotes for the presence of a MspI restriction site. The two genotypic groups did not differ for body mass index (BMI, expressed in kg/m2), body fat mass, visceral adipose tissue (AT) accumulation, as well as for insulin, glucose and free fatty acids levels measured in the fasting state and in response to an oral glucose tolerance test. In addition, 65 and 63% of M1 carriers had plasma HDL2 cholesterol levels and a HDL2/HDL3 cholesterol ratio below the 50th percentile of their distributions compared with 45%(P < 0.05) and 46%(P = 0.06), respectively, in M2M2 homozygotes. When subjects were further divided on the basis of visceral AT accumulation (below and above a value of 130 cm2), M1 carriers with low levels of visceral AT were characterized by high plasma HDL cholesterol and HDL2 cholesterol concentrations as well as by a higher HDL2/HDL3 ratio, compared with M1 carriers with high levels of visceral AT (> 130 cm2), or with M2M2 homozygotes with either a high or a low accumulation of visceral AT. Furthermore, M1 carriers with high levels of visceral AT showed a trend for lower plasma HDL2 cholesterol levels and were characterized by a significantly lower HDL2/HDL3 cholesterol ratio compared with the other three groups. No difference in HDL and HDL2 cholesterol levels and in the HDL2/HDL3 cholesterol ratio was noted when M2 homozygotes with lower versus higher levels of visceral AT were compared. The contribution of hyperinsulinemia was also examined by dividing subjects on the basis of the 50th percentile of the integrated insulin response to an oral glucose challenge. Significantly lower plasma HDL2 cholesterol levels and a reduced HDL2/HDL3 cholesterol ratio were noted among M1 carriers with high plasma insulin responses compared with M1 carriers with low insulin responses. Among M2M2 homozygotes, no difference was noted in plasma HDL cholesterol and in HDL2 cholesterol concentrations between men with low versus high insulin responses to the oral glucose load. These results suggest that the apo A-II-MspI polymorphism could modulate plasma HDL cholesterol levels among visceral obese, insulin-resistant men.

Adipose Tissue↗
PubMed1997

Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study.

BACKGROUND: Case-control studies have reported that patients with ischemic heart disease (IHD) have a higher proportion of small, dense LDL particles than do healthy control subjects. The extent to which the risk attributed to small LDL particles may be independent of concomitant variations in plasma lipoprotein-lipid concentrations remains to be clearly determined, however, particularly through prospective studies. METHODS AND RESULTS: Baseline characteristics were obtained in 2103 men initially free of IHD, among whom 114 developed IHD during a 5-year follow-up period. These 114 case patients were matched with healthy control subjects for age, body mass index, smoking habits, and alcohol intake. LDL peak particle diameter (PPD) was measured a posteriori in 103 case-control pairs by nondenaturing gradient gel electrophoresis of whole plasma. Conditional logistic regression analysis of the case-control status revealed that men in the first tertile of the control LDL-PPD distribution (LDL-PPD < or = 25.64 nm) had a 3.6-fold increase in the risk of IHD (95% CI, 1.5 to 8.8) compared with those in the third tertile (LDL-PPD > 26.05 nm). Statistical adjustment for concomitant variations in LDL cholesterol, triglycerides, HDL cholesterol, and apolipoprotein B concentrations had virtually no impact on the relationship between small LDL particles and the risk of IHD. CONCLUSIONS: These results represent the first prospective evidence suggesting that the presence of small, dense LDL particles may be associated with an increased risk of subsequently developing IHD in men. Results also suggest that the risk attributed to small LDL particles may be partly independent of the concomitant variation in plasma lipoprotein-lipid concentrations.

Adult↗
PubMed1997

Comparison of the effect of two low-density lipoprotein receptor class mutations on coronary heart disease among French-Canadian patients heterozygous for familial hypercholesterolaemia.

The aim of this study was to compare the age at first elective coronary angiogram and the age at first revascularization (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) in 102 patients without familial hypercholesterolaemia (FH), who were matched for age and sex with 76 heterozygous FH patients carrying a defective allele at the low-density lipoprotein (LDL) receptor gene (LDL-R) and 26 heterozygous FH patients bearing a null mutation at the LDL-R. The prevalence of diabetes was significantly higher in the non-FH group than in the two FH groups (P < 0.05). Furthermore, mean body mass index (BMI) and waist circumference values were also higher in the non-FH group than in the two FH heterozygous groups (P < 0.005). However, FH patients who were null allele carriers had the highest plasma total and LDL-cholesterol levels and the highest cholesterol/HDL-cholesterol ratio, whereas the defective allele carriers group had intermediate levels between null allele carriers and non-FH patients. Comparison of the age at first coronary angiography revealed that the null allele carriers group were younger at first angiogram than the non-FH patients (P < 0.005). In addition, a trend was observed for a younger age at first angiogram in FH heterozygotes bearing a null allele than in carriers of a defective allele (P = 0.06). Moreover, null allele carriers were younger at first revascularization than defective allele carriers (P < 0.005) or non-FH patients (P < 0.005). Finally, the mean number of diseased vessels with > 50% stenosis was higher in null allele carriers than in non-FH patients and tended to be higher than among defective allele carriers (P < 0.01). Although no difference in plasma Lp(a) levels were noted between null allele carrier and non-FH patients, plasma Lp(a) concentrations were higher in the defective allele group than in the other two groups. In summary, the development of coronary artery disease as estimated by the age at first elective coronary angiography or at first revascularization is premature in FH patients carrying a null mutation compared with defective allele carriers or with non-FH patients. Moreover, the higher number of stenosed vessels among null allele carriers suggests that coronary artery disease was more severe in FH subjects with a null allele at the LDL-R locus.

Adult↗
PubMed1997

Simvastatin further enhances the hypocholesterolemic effect of soy protein in rabbits.

OBJECTIVE: The effects of three dietary proteins (casein, cod, soy) and low dose simvastatin, an inhibitor of hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, on serum lipids were investigated. METHODS: New Zealand rabbits were fed purified diet (20% protein, 11% fat and 0.06% cholesterol) for 28 days. Animals received either 1.4 mg simvastatin or placebo orally during the last 14 days. A randomized 3 x 2 factorial design was used for the administration of diet and drug treatments. RESULTS: Mean food intake and body weight of the animals in all groups were similar. In placebo groups, soy protein decreased (p = 0.06) total cholesterolemia with significantly (p = 0.009) lower high-density lipoprotein (HDL) cholesterol, and significantly (p = 0.004) higher very low-density lipoprotein (VLDL) triglycerides (TG), compared to animal proteins. Addition of low dose simvastatin to soy protein induced a further decrease of serum total cholesterol, decreased VLDL and low-density lipoprotein (LDL) cholesterol, and LDL (apolipoprotein B), as well as improved VLDL-TG and HDL cholesterol levels. No similar reduction was seen when simvastatin was combined with casein or cod protein. CONCLUSION: These results show that low dose simvastatin may enhance the hypocholesterolemic effect of soy protein compared to animal proteins in the rabbit.

Animals↗
PubMed1997

Geographic distribution of French-Canadian low-density lipoprotein receptor gene mutations in the Province of Quebec.

A total of 35 homozygous and 1320 heterozygous patients with familial hypercholesterolemia (FH) was screened for the presence of six low-density lipoprotein receptor (LDLR) gene mutations previously reported among French-Canadians. The geographic distribution of patients' birthplaces and the relative prevalence of these six mutations in the LDLR gene in the province of Quebec were compared. For this purpose, the 16 administrative regions of the province of Quebec were grouped into seven geographic regions. The relative frequency of the six mutations differed in the seven regions: the > 15 kb deletion (delta > 15 kb) had the highest relative frequency in the Bas St-Laurent/Gaspésie region, and the point mutation in exon 3 had the highest relative frequency in the Saguenay-Lac-St-Jean/Côte-Nord region. In the Montreal area, the delta > 15 kb and the mutation in exon 3 had prevalence rates of 71.2% and 13.0%, respectively, whereas the relative frequencies of the delta > 15 kb and the point mutation in exon 3 in the Quebec city region were 57.5 and 21.8%, respectively. Finally, in Saguenay-Lac-St-Jean/Côte-Nord, the relative frequency of the delta > 15 kb only reached 31.5% and the point mutation in exon 3, 59.2%. Thus, on the north shore of the St. Lawrence River, the prevalence of the delta > 15 kb decreases from west to north-east, whereas the relative frequency of the mutation in exon 3 appears to increase. These observations provide a better characterization of FH among French-Canadians of Quebec, a Canadian province with a high prevalence of this inherited disease.

Exons↗
PubMed1997

Associations of HDL2 and HDL3 subfractions with ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study.

Individuals with elevated plasma concentrations of HDL cholesterol are at lower risk for ischemic heart disease (IHD). Whether the cardioprotective effects of HDL can be attributed to one or both HDL subfractions (HDL2 and HDL3) remains, however, controversial. The relationship of HDL subfractions to the incidence of IHD was investigated in a sample of 1169 French-Canadian men younger than 60 years and living in the Quebec City suburbs. Between 1980 to 1981 and 1990, 83 of the 944 men with complete follow-up in 1990 (80.8%) had a first IHD. Men who developed IHD had lower HDL, HDL2, and HDL3 cholesterol concentrations at baseline than men who remained free from IHD. Adjusted relative risk (RR) of IHD was calculated among quartiles of HDL cholesterol and HDL subfractions with the use of Cox survival models. Men in the fourth quartile of HDL2 (RR = 0.21; 95% confidence interval [CI], 0.08 to 0.56) and HDL3 cholesterol distributions (RR = 0.37; 95% CI, 0.15 to 0.94) were at lower risk for IHD than men in the first quartile. Despite the fact that the respective contributions of HDL2 and HDL3 to IHD risk were of the same magnitude in a multivariate model that included both subfractions, the contribution of the HDL2 subfraction was statistically significant (standardized RR = 0.84; 95% CI, 0.74 to 0.95), whereas it did not reach significance for HDL3 (standardized RR = 0.87; 95% CI, 0.69 to 1.11). Neither the linear combination of HDL2 and HDL3 nor their ratio provided further information on the risk of IHD compared with HDL cholesterol alone or with the ratio of total to HDL cholesterol. From a statistical standpoint, the present data suggest that the HDL2 subfraction may be more closely related to the development of IHD than the HDL3 subfraction. However, the qualitative difference in the relative predictive value of each subfraction was trivial, since it only corresponded to a modest quantitative difference. Thus, the possibility that a significant proportion of the cardioprotective effect of elevated HDL cholesterol levels may be mediated by the HDL3 subfraction still cannot be excluded. Finally, from a clinical point of view and within the limits of resolution provided by these data, the measurement of HDL subfractions does not appear to provide any additional information on the risk of IHD than HDL cholesterol alone or the ratio of total to HDL cholesterol.

Adult↗
PubMed1996

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.

Adolescent↗
PubMed1996

Apolipoprotein A-I and B levels and the risk of ischemic heart disease during a five-year follow-up of men in the Québec cardiovascular study.

BACKGROUND: Results obtained largely from case-control studies have suggested that an elevated plasma concentration of apolipoprotein (apo) B may be considered an important risk factor for ischemic heart disease (IHD). Prospective data on the relevance of measuring apo A-I and apo B levels in the assessment of IHD risk, however, remain sparse as well as controversial. METHODS AND RESULTS: Plasma lipid, apo B, and apo A-I levels as well as other risk factors were evaluated at baseline in 1985 in a sample of 2155 men (45 to 76 years old) who were followed for a period of 5 years for clinical signs of IHD. Proportional-hazards analyses indicated that plasma apo B concentrations measured at entry were strongly associated with onset of IHD (relative rate, 1.4; 95% confidence interval [CI], 1.2 to 1.7), independent of covariables such as age, smoking, diabetes mellitus, and systolic blood pressure. Controlling for triglycerides, HDL cholesterol, and total/HDL cholesterol ratio did not eliminate the relationship between plasma apo B levels and IHD. The association between apo A-I and IHD was of lower magnitude (relative rate, 0.85; 95% CI, 0.7 to 1.0), and adjustment for selected plasma lipid and lipoprotein levels eliminated this association. Stepwise logistic regression analysis revealed that, among metabolic variables, apo B was the strongest correlate of IHD. CONCLUSIONS: These prospective results emphasize the importance of apo B as a risk factor for IHD. Apo B may be regarded as a relevant tool in the assessment of IHD risk in men, because it may provide information that would not be obtained from the conventional lipid-lipoprotein profile.

Aged↗
PubMed1996

Hyperinsulinemia as an independent risk factor for ischemic heart disease.

BACKGROUND: Prospective studies suggest that hyperinsulinemia may be an important risk factor for ischemic heart disease. However, it has not been determined whether plasma insulin levels are independently related to ischemic heart disease after adjustment for other risk factors, including plasma lipoprotein levels. METHODS: In 1985 we collected blood samples from 2103 men from suburbs of Quebec City, Canada, who were 45 to 76 years of age and who did not have ischemic heart disease. A first ischemic event (angina pectoris, acute myocardial infarction or death from coronary heart disease) occurred in 114 men (case patients) between 1985 and 1990. Each case patient was matched for age, body-mass index, smoking habits, and alcohol consumption with a control selected from among the 1989 men who remained free of ischemic heart disease during follow-up. After excluding men with diabetes, we compared fasting plasma insulin and lipoprotein concentrations at base line in 91 case patients and 105 controls. RESULTS: Fasting insulin concentrations at base line were 18 percent higher in the case patients than in the controls (P<0.001). Logistic-regression analysis showed that the insulin concentration remained associated with ischemic heart disease (odds ratio for ischemic heart disease with each increase of 1 SD in the insulin concentration, 1.7; 95 percent confidence interval, 1.3 to 2.4) after adjustment for systolic blood pressure, use of medications, and family history of ischemic heart disease. Further adjustment by multivariate analysis for plasma triglyceride, apolipoprotein B, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol concentrations did not significantly diminish the association between the insulin concentration and the risk of ischemic heart disease (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.3). CONCLUSIONS: High fasting insulin concentrations appear to be an independent predictor of ischemic heart disease in men.

Aged↗
PubMed1996

Triglycerides and HDL-cholesterol as risk factors for ischemic heart disease. Results from the Québec cardiovascular study.

The relative importance of reduced plasma high density lipoprotein-cholesterol (HDL-C) levels and elevated plasma triglyceride (TG) concentrations as risk factors for ischemic heart disease (IHD) was examined in a sample of 2177 men from the Québec City suburbs. The sample included 202 men with known IHD. The relationship between HDL-C and TG levels, although significant (r = -0.49, P < 0.0001), was not linear, as most of the variation in HDL-C levels was observed within TG levels below 2.5 mmol/l. Reduced HDL-C (< 0.9 mmol/l) was a prevalent condition in men with IHD (50%) compared to those without IHD (30%). On the other hand 26% and 20% of men with and without IHD, respectively, had elevated TG levels (TG > 2.3 mmol/l). A 2-fold increase in prevalence odds ratio (OR) was observed in men with TG levels > 2.3 mmol/l (95% confidence intervals (CI) [1.2;3.3]). No residual association between elevated TG levels and IHD was found, however, after adjustment for HDL-C concentrations (OR 1.2, 95% CI 0.7;2.1). On the other hand, HDL-C remained a significant predictor of IHD after adjustment for other risk factors (OR 0.3, 95%, CI 0.2;0.6). Men with reduced HDL-C levels were also characterized by a cluster of risk factors such as obesity, diabetes mellitus and hypertension, which may contribute to increase the risk of IHD. Finally, the independent interpretation of cholesterol, TG or LDL-C levels may lead to an inadequate prediction of risk, as a large number of IHD patients showed a cluster of risk factors which included low HDL-C concentrations.

Adult↗