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Biomedical subjects

Michael C Costanza

Publications and source records attributed to Michael C Costanza.

At least 19 recordsLinked to original sources
PubMed2006

Concordant association of lipid gene variation with a combined HDL/LDL-cholesterol phenotype in two European populations.

OBJECTIVE: SNP/phenotype associations are difficult to validate. This comparative study demonstrates significant contribution of candidate genes to the variation of a complex cholesterol phenotype, measured in two general populations by a gene-based approach. METHODS: Independent samples of normolipidemic subjects from two Caucasian populations (371 Swiss and 157 Germans) were selected for a case-control-study (high LDL/low HDL versus low LDL/high HDL) with SNP genotypes as independent factors. We examined locus-specific common SNPs that densely cover the genomic regions of 10 lipid genes. RESULTS: Genotype effects were concordant in both ethnic samples, showing that APOE, ABCA1, CETP, and to a lesser degree LDLR, LIPC, and PLTP explained a substantial part of the genetic variation, whereas LPL was associated in only one sample. APOA1, LCAT, and SRB1 exerted no measurable influence. CONCLUSION: This comparison showed that sets of common SNPs representing candidate regions reproducibly validate significant linkage disequilibrium association with a complex metabolic trait.

ATP Binding Cassette Transporter 1↗
PubMed2006

Gender differentials in the evolution of cigarette smoking habits in a general European adult population from 1993-2003.

BACKGROUND: Describe the recent evolution of cigarette smoking habits by gender in Geneva, where incidence rates of lung cancer have been declining in men but increasing in women. METHODS: Continuous cross-sectional surveillance of the general adult (35-74 yrs) population of Geneva, Switzerland for 11 years (1993-2003) using a locally-validated smoking questionnaire, yielding a representative random sample of 12,271 individuals (6,164 men, 6,107 women). RESULTS: In both genders, prevalence of current cigarette smoking was stable over the 11-year period, at about one third of men and one quarter of women, even though smoking began at an earlier age in more recent years. Older men were more likely to be former smokers than older women. Younger men, but not women, tended to quit smoking at an earlier age. CONCLUSION: This continuous (1993-2003) risk factor surveillance system, unique in Europe, shows stable prevalence of smoking in both genders. However, sharp contrasts in age-specific prevalence of never and former smoking and of ages at smoking initiation indicate that smoking continues a long-term decline in men but has still not reached its peak in women.

Adult↗
PubMed2006

Converging prevalences of obesity across educational groups in Switzerland.

OBJECTIVE: To assess whether the rapid increase in obesity prevalence among persons with higher education levels observed in one U.S. study is also observed in a European adult population. RESEARCH METHODS AND PROCEDURES: This study involved continuous surveillance of the adult population of Geneva, Switzerland (1993 to 2004), with annual random, independent, cross-sectional, representative samples (6635 men and 6558 women, ages 35 to 74 years) and analysis of 12-year trends in obesity prevalence across educational level subgroups. RESULTS: Obesity prevalence in men had an upward trend in the medium education subgroup (p < 0.02), a borderline upward trend in the high education subgroup (p < 0.08), but no trend in the low education subgroup. There was a borderline trend interaction between the male low and medium education subgroups (p < 0.09). Obesity prevalence in women had a borderline increase in the low education subgroup (p < 0.08), an almost borderline increase in the high education subgroup (p = 0.11), but no significant trend in the medium education subgroup. There was no evidence of trend interaction between the female education groups. DISCUSSION: In Geneva, as in the United States, the inverse association between education level and obesity rates has weakened over time among men, but, inconsistent with the U.S. findings, has persisted for women. Explanations may include more physically demanding occupations for men with low education levels and different attitudes toward body image between the sexes.

Adult↗
PubMed2005

Relative contributions of genes, environment, and interactions to blood lipid concentrations in a general adult population.

The authors evaluated the contributions of nine genetic (G) variants (selected from 275 single nucleotide polymorphisms in 11 reverse cholesterol transport pathway genes), five environmental (E) factors (selected from 10), and G x G, E x E, and G x E interactions in explaining population variance of blood lipid concentrations. Total cholesterol, triglycerides, and high density lipoprotein (HDL) cholesterol were measured, and low density lipoprotein (LDL) cholesterol and HDL cholesterol/LDL cholesterol ratio were calculated in a population-based random sample of 1,543 men and women in Geneva, Switzerland, aged 35-74 years in 1999-2001. Explained variances (R2) for HDL cholesterol/LDL cholesterol ratio, HDL cholesterol, and LDL cholesterol, respectively, were 34%, 33%, and 19%, decomposed into main effects of G (6%, 4%, and 5%) and E (25%, 28%, and 11%), with just 3%, 2%, and 3% due to G x G, E x E, and G x E interactions, respectively. Risk factor clustering was only moderate: 70% of study subjects had < or =3 variants, 75% had < or =2 environmental exposures, and 69% had < or =5 of both types of factors. Multiple genes with weak associations, together with more dominating environmental factors, are involved in determining blood lipid concentrations. Interactions added little explained variance. Increasing trends in hypercholesterolemia are attributable to environmental changes affecting populations as a whole. Reducing obesity and smoking and moderating alcohol intake in entire populations should remain the primary strategies for lipid control.

Adult↗
PubMed2005

In a quasi-simultaneous assessment, imprecise cholesterol monitoring and screening tests were improved.

OBJECTIVE: To calibrate Reflotron-measured capillary total cholesterol (cTC) relative to a laboratory-measured venous total cholesterol (vTC) criterion standard for monitoring and screening hypercholesterolemia. STUDY DESIGN AND SETTING: Quasi-simultaneous assessment in 1999-2002 of Reflotron cTC and laboratory vTC in a random sample of 4,269 adult residents of Geneva, Switzerland (calibration development subsample n=3,067; validation subsample n=1,172), by means of bias, precision, correlation, sensitivity, and false positive percentage (calculated as 100-specificity) analyses of Reflotron cTC vs. laboratory vTC measures for predicting hypercholesterolemia. RESULTS: Total bias was small (-0.26 mmol/L), but there was substantial negative drift in Reflotron cTC (annual biases +0.08, -0.17, -0.27, and -0.60 mmol/L in 1999-2002). Overall, 57% of Reflotron cTC measurements for 894 hypercholesterolemic patients underestimated laboratory vTC (2%, 57%, 71%, and 98% in 1999-2002). Prior to calibration, sensitivity was 73% for the development and 35% for the validation subsample, with false positive at 4% (development) and 0.1% (validation). After calibration, sensitivity was 78% for the development and 37% for the validation subsample, with false positive at 5% (development) and 0.2% (validation). Using 95% upper prediction limits (UPL) for individual vTC values increased sensitivity to 99% and 83% and false positive percentage to 30% and 7% for the development and validation subsamples, respectively. CONCLUSION: Crude results of Reflotron-measured cTC have poor sensitivity. Instead, 95% UPL can be used for monitoring and screening. Simply adding 0.8 mmol/L to a patient's observed Reflotron cTC value provides a very good approximation to the 95% UPL.

Adult↗
PubMed2005

The obesity epidemic as harbinger of a metabolic disorder epidemic: trends in overweight, hypercholesterolemia, and diabetes treatment in Geneva, Switzerland, 1993-2003.

Increases in obesity, hypercholesterolemia, and diabetes may be under way in Europe. We have reported the only data available from the 1990s for continuous monitoring of chronic disease risk factors in random samples of a general European population. In random surveys (1993-2003) of 6164 men and 6107 women in Geneva, overweight and obesity combined increased in both men and women; hypercholesterolemia prevalence also rose; diabetes treatment increased in men. Only population-based interventions can prevent the impending epidemic of obesity-related disorders.

Adult↗
PubMed2004

Binary classification of dyslipidemia from the waist-to-hip ratio and body mass index: a comparison of linear, logistic, and CART models.

BACKGROUND: We sought to improve upon previously published statistical modeling strategies for binary classification of dyslipidemia for general population screening purposes based on the waist-to-hip circumference ratio and body mass index anthropometric measurements. METHODS: Study subjects were participants in WHO-MONICA population-based surveys conducted in two Swiss regions. Outcome variables were based on the total serum cholesterol to high density lipoprotein cholesterol ratio. The other potential predictor variables were gender, age, current cigarette smoking, and hypertension. The models investigated were: (i) linear regression; (ii) logistic classification; (iii) regression trees; (iv) classification trees (iii and iv are collectively known as "CART"). Binary classification performance of the region-specific models was externally validated by classifying the subjects from the other region. RESULTS: Waist-to-hip circumference ratio and body mass index remained modest predictors of dyslipidemia. Correct classification rates for all models were 60-80%, with marked gender differences. Gender-specific models provided only small gains in classification. The external validations provided assurance about the stability of the models. CONCLUSIONS: There were no striking differences between either the algebraic (i, ii) vs. non-algebraic (iii, iv), or the regression (i, iii) vs. classification (ii, iv) modeling approaches. Anticipated advantages of the CART vs. simple additive linear and logistic models were less than expected in this particular application with a relatively small set of predictor variables. CART models may be more useful when considering main effects and interactions between larger sets of predictor variables.

Adult↗
PubMed2004

Population-based study of SR-BI genetic variation and lipid profile.

The variability of the Class B Type I Scavenger Receptor (SR-BI) gene in human populations and the relation of its variants to blood lipids was investigated in a random sample of 1756 untreated adult residents of Geneva, Switzerland, during 1999-2000. A three-step study approach yielded the following results: (1) resequencing the gene's exons and flanking regions in 95 subjects identified four common single nucleotide polymorphisms (SNPs with rare allele frequency >3%); (2) association study of the four common SNPs in subjects with extreme HDL-cholesterol (HDL-C) and LDL-C phenotypes (186 "atherogenic cases" and 185 "non-atherogenic controls") showed that the synonymous exon 8 C-T (allelic frequency 48%) polymorphism, A350A, was associated with atheroprotection in men (odds ratios (OR) = 0.36, 95% confidence intervals (CI) = 0.15-0.90, P < 0.03), but not in women (2.09, 0.79-5.49, P = 0.14); and (3) population clinical effects of A350A genotypes assessed in all 1756 subjects, showed that the case-control study findings reflected a protective HDL-C effect in men (CC: 1.17 mmol/L, CT: 1.22 mmol/L, and TT: 1.24 mmol/L, trend P = 0.0062) and a deleterious LDL-C effect in women (CC: 3.58 mmol/L, CT: 3.72 mmol/L, and TT: 3.79 mmol/L, trend P = 0.014). The allelic frequencies of the common SR-BI variants appear to be very similar in European and North American populations. The HDL-C effect increased with age. SR-BI A350A appears to have gender-specific and age-related effects on cholesterol transport lipoproteins.

Adult↗
PubMed2004

Association of physical activity intensity levels with overweight and obesity in a population-based sample of adults.

BACKGROUND: Clarify the association between physical activity intensity and overweight/obesity. METHODS: Population-based 1997-2001 survey in Geneva, Switzerland (n=5,757, ages 35 to 74). Intensity of physical activity energy expenditure (EE) defined as percentage of total EE in moderate activities [3-3.9 x basal metabolism rate (BMR), e.g., normal walking, household chores] and high-intensity activities (> or =4 x BMR, e.g., brisk walking, sports). Overweight or obesity based on measured body mass index (BMI). RESULTS: Comparing participants in the lowest vs. the highest tertile of the percentage of high-intensity EE, the odds ratios (ORs) were, for obesity vs. normal weight, 2.8 (95% confidence interval: 2.0-3.8, P<0.0001) in men and 2.4 (1.7-3.4, P<0.0001) in women. For obese vs. overweight, the men/women ORs were 1.9 (1.4-2.6, P<0.0001)/1.5 (1.0-2.2, P<0.05). For overweight vs. normal weight, the men/women ORs were 1.4 (1.1-1.7, P<0.002)/1.7 (1.3-2.1, P<0.0001). Less or no relationship was found for the percentage of moderate-intensity EE. CONCLUSIONS: This cross-sectional study cannot determine whether exercise is an effective strategy for weight control or whether overweight or obese people exercise less. However, clear dose-response associations in both genders between obesity or overweight and energy expenditure in high (but not in moderate)-intensity activities are findings with potentially major public health implications meriting validation in an experimental intervention study.

Adult↗
PubMed2004

Does walking 15 minutes per day keep the obesity epidemic away? Simulation of the efficacy of a populationwide campaign.

Small physical activity increases may prevent weight gain in most populations. Geneva residents completed validated quantitative physical activity frequency questionnaires from 1997 to 2001. Fifteen minutes per day of moderate or brisk walking, or 30 minutes per day of slow walking, could increase physical activity at the population level; however, if the specific goal is to approach expending 420 kJ/d (100 kcal/d) through walking, the duration should be closer to 60 minutes for slow walking and 30 minutes for moderate or brisk walking.

Adult↗
PubMed2003

Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors.

This study explored the genetic basis of the combination of extreme blood levels of HDL-C and LDL-C, a well-studied endophenotype for CVD, which has several attractive features as a target for genetic analysis: (1) the trait is moderately heritable; (2) non-genetic risk factors account for a significant but still limited portion of the phenotypic variance; (3) it is known to be moderated by a number of gene products. We exhaustively surveyed 11 candidate genes for allelic variation in a random population-based sample characterized for known CVD risk factors and blood lipid profiles. With the goal of generating specific etiological hypotheses, we compared two groups of subjects with extreme lipid phenotypes, from the same source population, using a case-control design. Cases (n=186) were subjects, within the total sample of 1708 people, who scored in the upper tertile of LDL-C and the lowest tertile of HDL-C, while controls (n=185) scored in the lowest tertile of LDL-C and the upper tertile of HDL-C. We used logistic regression and a four-tiered, systematic model building strategy with internal cross-validation and bootstrapping to investigate the relationships between the trait and 275 genetic variants in the presence of 10 non-genetic risk factors. Our results implicate a subset of nine genetic variants, spanning seven candidate genes, together with five environmental risk factors, in the etiology of extreme lipoprotein phenotypes. We propose a model involving these 14 genetic and non-genetic risk factors for evaluation in future independent studies.

Adult↗
PubMed2003

More insight into the fate of biomedical meeting abstracts: a systematic review.

BACKGROUND: It has been estimated that about 45% of abstracts that are accepted for presentation at biomedical meetings will subsequently be published in full. The acceptance of abstracts at meetings and their fate after initial rejection are less well understood. We set out to estimate the proportion of abstracts submitted to meetings that are eventually published as full reports, and to explore factors that are associated with meeting acceptance and successful publication. METHODS: Studies analysing acceptance of abstracts at biomedical meetings or their subsequent full publication were searched in MEDLINE, OLDMEDLINE, EMBASE, Cochrane Library, CINAHL, BIOSIS, Science Citation Index Expanded, and by hand searching of bibliographies and proceedings. We estimated rates of abstract acceptance and of subsequent full publication, and identified abstract and meeting characteristics associated with acceptance and publication, using logistic regression analysis, survival-type analysis, and meta-analysis. RESULTS: Analysed meetings were held between 1957 and 1999. Of 14945 abstracts that were submitted to 43 meetings, 46% were accepted. The rate of full publication was studied with 19123 abstracts that were presented at 234 meetings. Using survival-type analysis, we estimated that 27% were published after two, 41% after four, and 44% after six years. Of 2412 abstracts that were rejected at 24 meetings, 27% were published despite rejection. Factors associated with both abstract acceptance and subsequent publication were basic science and positive study outcome. Large meetings and those held outside the US were more likely to accept abstracts. Abstracts were more likely to be published subsequently if presented either orally, at small meetings, or at a US meeting. Abstract acceptance itself was strongly associated with full publication. CONCLUSIONS: About one third of abstracts submitted to biomedical meetings were published as full reports. Acceptance at meetings and publication were associated with specific characteristics of abstracts and meetings.

Biomedical Research↗
PubMed2003

Association between lipoprotein lipase (LPL) gene and blood lipids: a common variant for a common trait?

S447X, a serine substitution by a stop codon on base 99 of exon 9 of the lipoprotein lipase (LPL) gene, has beneficial effects on blood lipids. Other LPL alleles are associated with lipid levels, but whether one of these variants predominates remains elusive. We performed a systematic survey to identify single-nucleotide polymorphisms (SNPs) in all 10 LPL exons and flanking regions by resequencing the gene in 95 subjects. Of 24 variants, 14 were common (> or = 3%). We assayed the common SNPs in 186 cases with atherogenic lipid profiles (low HDL, high LDL) and 185 nonatherogenic controls (high HDL, low LDL). Only S447X and exons 6 (base +73) and 10 (base -11) were individually associated with case-control status (P<0.05, adjusted for major nongenetic covariates with known lipid effects). There were no significant SNP x gender interactions. In adjusted multi-SNP and haplotypic analyses, S447X was interpretable as the sole predictor, with a 2-3-fold reduction in the odds of being atherogenic vs. nonatherogenic (adjusted OR, 0.39; 95% CI, 0.21-0.73). S447X and base -11 of exon 10 were statistically interchangeable because they are strongly associated (r=0.92, P<0.0001), but we posit that the LPL association with lipid profile is more likely attributable to the functional S447X rather than the nonfunctional exon 10 SNP. It appears that the S447X variant of LPL may be another rare example (like APOE4, factor V-Leiden, and PPAR gamma Pro12Ala) of a common variant predisposing to a common disorder.

Case-Control Studies↗