Biomedical subjects

Francois Cambien

Publications and source records attributed to Francois Cambien.

5 recordsLinked to original sources

PubMed2006

Comparative impact of multiple biomarkers and N-Terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study.

BACKGROUND: Individual markers of inflammation may add incremental predictive value in the context of conventionally available risk factors. We evaluated the ability of 9 inflammatory biomarkers, microalbuminuria, and N-terminal pro-brain natriuretic peptide (Nt-proBNP) to improve cardiovascular risk prediction beyond that obtained from traditional risk factors in a secondary-prevention population. METHODS AND RESULTS: We measured biomarkers representing the acute-phase reaction (C-reactive protein, fibrinogen, and interleukin-6), proinflammatory pathways (soluble tumor necrosis factor receptor-1 and -2, soluble interleukin-1 receptor antagonist, and interleukin-18), endothelial activation (soluble vascular adhesion molecule-1 and soluble intercellular adhesion molecule-1), Nt-proBNP, and microalbuminuria in 3199 study individuals of the Heart Outcomes Prevention Evaluation (HOPE) Study and assessed their association with risk of myocardial infarction, stroke, or cardiovascular death (primary outcome, n=501) over 4.5 years of follow-up. In a backward Cox regression procedure that included risk factors and biomarkers, Nt-proBNP (hazard ratio [HR] 1.72 per increment SD, 95% CI 1.39 to 2.12; P<0.0001), soluble intercellular adhesion molecule-1 (HR 1.46, 95% CI 1.19 to 1.80; P=0.0003), microalbuminuria (HR 1.55, 95% CI 1.22 to 1.98; P=0.0004), soluble interleukin-1 receptor antagonist (HR 1.30, 95% CI 1.05 to 1.61; P=0.02), and fibrinogen (HR 1.31, 95% CI 1.05 to 1.62; P=0.02) remained significantly related to the primary outcome. Only inclusion of Nt-proBNP provided incremental information above that obtained by models of traditional risk factors. CONCLUSIONS: Although levels of various inflammatory biomarkers are significantly related to future cardiovascular risk, their incremental predictive value is modest. A model consisting of simple traditional risk factors and Nt-proBNP provided the best clinical prediction in the secondary-prevention population.

Aged↗

PubMed2005

Atherosclerosis: from genetic polymorphisms to system genetics.

It is generally considered that the genetics of atherosclerosis and its complications involves a large number of genes with common alleles having weak effects on disease risk but possibly interacting with each other and with non-genetic factors. In such a complex system, absence of marginal effects (effects of polymorphisms considered one at a time) is insufficient to exclude the implication of a polymorphism on disease risk. Investigating polymorphisms and even genes one by one is no longer appropriate. It is necessary to focus on biological systems and integrate the contribution of genetic as well as non-genetic factors and their interactions. Hopefully, system genetics will ultimately improve our understanding of the genetic architecture of complex traits.

Animals↗

PubMed2004

In-depth haplotype analysis of ABCA1 gene polymorphisms in relation to plasma ApoA1 levels and myocardial infarction.

OBJECTIVE: By regulating the cellular cholesterol efflux from peripheral cells to high-density lipoprotein, the ABCA1 protein is suspected to play a key role in lipid homeostasis and atherosclerosis. Twenty-six polymorphisms of the ABCA1 gene were genotyped and tested for association with plasma levels of ApoA1 and myocardial infarction (MI) in the ECTIM study. METHODS AND RESULTS: In addition to single-locus analysis, a systematic exploration of all possible haplotype effects was performed, with this exploration being performed on a minimal set of "tag" polymorphisms that define the haplotype structure of the gene. Two polymorphisms were associated with plasma levels of ApoA1, 1 in the promoter (C-564T) and 1 in the coding (R1587K) regions, whereas only 1 polymorphism (R219K) was associated with the risk of MI. However, no haplotype effect was detected on ApoA1 variability or on the risk of MI. CONCLUSIONS: ABCA1 gene polymorphisms but not haplotypes are involved in the variability of plasma ApoA1 and the susceptibility to coronary artery disease.

ATP Binding Cassette Transporter 1↗

PubMed2003

Long-term renoprotective effects of losartan in diabetic nephropathy: interaction with ACE insertion/deletion genotype?

OBJECTIVE: Several observational follow-up studies have found that the D allele of the insertion (I)/deletion (D) polymorphism of the ACE gene (ACE/ID) is associated with an increased risk of renal function loss, even during ACE inhibition. Therefore, we investigated the long-term effect of the angiotensin II subtype-1 (AT1) receptor antagonist losartan (100 mg o.d.) on kidney function in II and DD type 1 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: A total of 54 hypertensive type 1 diabetic patients with diabetic nephropathy homozygous for the insertion (n = 26) or the deletion (n = 28) allele were included in the study. After a 4-week washout, the patients received losartan (tablet, 100 mg o.d.) and were followed prospectively with a mean follow-up period of 36 months. Patients and investigators were blinded to ACE genotypes. At baseline, after 2 and 4 months and every 6 months thereafter, glomerular filtration rate (GFR), albuminuria, and 24-h blood pressure were determined. RESULTS: At baseline, GFR, albuminuria, and blood pressure were similar in the two genotype groups, II versus DD: mean (SD), 86 (22) vs. 88 (24) ml. min(-1). 1.73 m(-2); median (interquartile range), 1,134 (598-2,023) vs. 1,451 (893-1,766) mg/24 h; and mean (SD), 156/82 (17/9) vs. 153/80 (17/11) mmHg, respectively. GFR decreased similarly in both genotype groups, versus DD, respectively (P = 0.4): geometric mean (95% CI), 2.9 (2.0-4.2) vs. 3.4 (2.3-5.1) ml. min(-1). year(-1). Albuminuria and arterial blood pressure were significantly reduced during the study; no differences were noted between groups. During follow-up, albuminuria was decreased by 75% (95% CI 59-85) and 73% (56-83) in the II and DD groups, respectively (P < 0.01 vs. baseline). Mean systolic and diastolic blood pressures were 139/74 mmHg (14/8) in both genotype groups during the study (P < 0.01 vs. baseline). CONCLUSIONS: In contrast to previous observational studies with ACE inhibitors, long-term treatment with losartan has similar beneficial renoprotective effects on progression of diabetic nephropathy in hypertensive type 1 diabetic patients with ACE II and DD genotypes.

Adult↗

PubMed2002

Renoprotective effects of losartan in diabetic nephropathy: interaction with ACE insertion/deletion genotype?

BACKGROUND: The beneficial short- and long-term renoprotective effects of angiotensin I-converting enzyme (ACE) inhibition are lower in albuminuric diabetic patients homozygous for the deletion compared to the insertion polymorphism of the ACE gene. In an attempt to overcome this interaction, we evaluated the short-term renoprotective effect in diabetic nephropathy of the angiotensin II receptor antagonist losartan in patients homozygous for the insertion or the deletion allele. METHODS: Fifty-four hypertensive type 1 diabetic patients with diabetic nephropathy homozygous for the insertion (I; N = 26) or the deletion (D; N = 28) allele of the ACE/ID polymorphism were included. After four weeks of washout, the patients received losartan 50 mg daily followed by 100 mg in two treatment periods each lasting two months. Patients and investigators were blinded to ACE genotypes. At baseline and in the end of the treatment periods, 24-hour blood pressure, albuminuria and glomerular filtration rate values were determined. RESULTS: At baseline, blood pressure, albuminuria and glomerular filtration rate (GFR) values were similar in the two genotype groups [II vs. DD, 1134 (238 to 5302) vs. 1451 (227 to 8129) mg/24 h, median (range); 156/82 (17/9) vs. 153/80 (17/11) mm Hg, mean (SD); and 86 (22) vs. 88 (24) mL/min/1.73 m2, respectively]. Both doses of losartan significantly lowered blood pressure, albuminuria, and GFR (P < 0.05 vs. baseline). Losartan 100 mg was more effective than 50 mg in reducing albuminuria, 51% (95% CI; 40 to 61) versus 33% (23 to 42), respectively (P < 0.01). No differences in the impact of losartan between the II and DD groups were observed: Losartan 100 mg lowered systolic/diastolic blood pressure by 12/6 and 10/4 mm Hg, whereas albuminuria decreased by 55% (35 to 68) and 46% (28 to 61), in the II and DD groups, respectively (P = NS). CONCLUSION: Our data suggest that losartan offers similar short-term renoprotective and blood pressure lowering effects in albuminuric hypertensive type 1 diabetic patients with the ACE II and DD genotypes. However, the long-term renoprotective effects remain to be evaluated.

Adult↗