Lipoprotein metabolism of pregnant women is associated with both their genetic polymorphisms and those of their newborn children.

To explore whether the placenta contributes to the lipoprotein metabolism of pregnant women, we took advantage of the fact that placental proteins are encoded from the fetal genome and examined the associations between lipids of 525 pregnant women and the presence, in their newborns, of genetic polymorphisms of LPL and apolipoprotein E (APOE), two genes expressed in placenta. After adjustment for maternal polymorphisms, newborn LPL*S447X was associated with lower triglycerides (-21 +/- 9 mg/dl), lower LDL-cholesterol (LDL-C; -12 +/- 5 mg/dl), lower apoB (-14 +/- 4 mg/dl), higher HDL-C (5 +/- 2 mg/dl), and higher apoA-I (9 +/- 4 mg/dl) in their mothers; newborn LPL*N291S was associated with higher maternal triglycerides (114 +/- 31 mg/dl); and newborn APOE*E2 (compared to E3E3) was associated with higher maternal LDL-C (14 +/- 6 mg/dl) and higher maternal apoB (14 +/- 5 mg/dl). These associations (all P < 0.05) were independent of polymorphisms carried by the mothers and of lipid concentrations in newborns and were similar in amplitude to the associations between maternal polymorphisms and maternal lipids. Such findings support the active role of placental LPL and APOE in the metabolism of maternal lipoproteins and suggest that fetal genes may modulate the risk for problems related to maternal dyslipidemia (preeclampsia, pancreatitis, and future cardiovascular disease).

Lipoprotein concentrations in newborns are associated with allelic variations in their mothers.

BACKGROUND: Factors determining lipoprotein concentrations in the fetus are not yet fully understood. We postulated that an important factor is the genetic make-up of the mother. In the present study, we examined the associations between the cord blood concentrations of lipoproteins of 525 newborns and the polymorphisms present in their mothers on the genes of apolipoprotein E (APOE*E2, *E3, *E4), apolipoprotein C-III (APOC3*C3238G also called APOC3*S2) and lipoprotein lipase (LPL*S447X). RESULTS: Newborns born of mothers with APOE*E2 allele had significantly lower cord blood LDL-C (P < 0.01) and apoB (P < 0.01) and significantly higher cord blood HDL-C and apoA1 (all P-values < 0.03) compared to those born of mothers with APOE*E3E3 genotype. These associations were independent of the presence of APOE*E2 allele in the newborns. Similarly, APOC3*S2 in mothers was associated with significantly lower (all P < 0.001) cord blood LDL-C, apoB, HDL-C and apoA1. In contrast, LPL*S447X in mothers lowered significantly cord blood LDL-C and apoB only when LPL*S447X was present in newborns. Most of the effects of these maternal polymorphisms on the newborns were independent of the changes of maternal lipoproteins generated by these polymorphisms. CONCLUSIONS: This is the first evidence that maternal genetic variations influence fetal lipoprotein concentrations, independent of the genetic status of the fetus and of the variations of maternal lipoprotein concentrations generated by these genetic variants. It suggests that proteic components of maternal lipoproteins strongly control the metabolism of maternal lipoproteins carried out at the surface of the placenta to assure the cholesterol delivery to the fetus.

Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases.

The centrilobular liver cell necrosis observed in hypoxic hepatitis is generally attributed to failure of hepatic blood perfusion. Accordingly, this injury of the liver is commonly recognized under the terms "shock liver" or "ischemic hepatitis." During a 10-year period, 142 episodes of hypoxic hepatitis were consecutively identified in the intensive care unit of a general hospital, and the clinical, biological, and hemodynamic parameters were prospectively collected on individual files. We conducted the current study to assess retrospectively the role of the hemodynamic mechanisms of tissue hypoxia: ischemia, passive venous congestion, and hypoxemia. Among the 142 episodes of hypoxic hepatitis, 138 were separated in 4 main groups based on clinical features: decompensated congestive heart failure (80 cases), acute cardiac failure (20 cases), exacerbated chronic respiratory failure (19 cases), and toxic/septic shock (19 cases). An elementary hemodynamic evaluation, including blood pressure, central venous pressure, and arterial blood gas analysis, was carried out in every episode and a more complete hemodynamic assessment through pulmonary artery catheterization was performed in 61 episodes. The hemodynamic mechanisms responsible for hypoxic hepatitis were different in the 4 groups. In congestive heart failure and acute heart failure, the hypoxia of the liver resulted from decreased hepatic blood flow (ischemia) due to left-sided heart failure and from venous congestion secondary to right-sided heart failure. In chronic respiratory failure, liver hypoxia was mainly due to profound hypoxemia. In toxic/septic shock, oxygen delivery to the liver was not decreased but oxygen needs were increased, while the liver was unable to use oxygen properly. In all conditions underlying hypoxic hepatitis, except toxic/septic shock, a shock state was observed in only about 50% of the cases. Therefore, the expressions "shock liver" or "ischemic hepatitis" are misleading and should be replaced by the more general term "hypoxic hepatitis."

Silent ischaemia in familial hypercholesterolemia.

In a cohort of 66 FH-men (age 25-55) prospectively recruited during a 2-years period, we estimated the incidence of coronary heart disease to 52% (N=34). Thirty-two percent (N=21) had earlier history of symptomatic ischaemic disease whereas 20% (N=13) had significant ST/T changes during exercise stress test. Amongst the 8 patients with positive exercise stress test who underwent coronary angiography, six had severe coronary artery disease. Because of the severity of the stenotic lesions, 4 of these 6 patients underwent coronary angioplasty or surgical bypass. We concluded that a great proportion of FH men suffered from myocardial ischaemia, either asymptomatic or symptomatic, and that even the silent form is associated with severe coronary stenosis. This advocates to systematically perform exercise testing in asymptomatic FH men after age 25.

[Screening for hepatocarcinoma in a cohort with cirrhosis mainly of alcoholic origin]. / Dépistage du carcinome hépatocellulaire dans une cohorte de malades porteurs d'une cirrhose d'origine principalement alcoolique.

OBJECTIVES: To assess the feasibility and efficiency of the screening for hepatocarcinoma in a cohort of cirrhoseis mainly of alcoholic origin. PATIENTS AND METHODS: 293 patients with cirrhosis, among them 186 (63.5%) from alcoholic origin, were included in a surveillance programme for hepatocarcinoma by carrying out liver ultrasonography and alpha-foetoprotein dosage every 6 months. Results were analyzed with a mean follow-up of 60 months. Seventeen hepatocarcinoma discovered through the surveillance programme ("screened HCC") were compared with 40 hepatocarcinoma discovered outside the surveillance programme during the same period ("incidental HCC"). RESULTS: The alcoholic origin of the cirrhosis was a predictive factor of poor compliance to the surveillance programme. Among the 186 patients with alcoholic cirrhosis, 129 (69%) were lost during the surveillance programme due to lack of compliance (97 cases) or death (32 cases). By comparison, among the 65 patients with hepatitis C-related cirrhosis, 18 were lost by lack of compliance (11 cases) or death (7 cases) (P<0.001). Moreover, sustained or relapsing alcohol abuse after inclusion in the surveillance programme were also related to the quality of the compliance. Seventeen hepatocarcinoma were discovered through the surveillance giving an annual incidence of 2% for the emergence of hepatocarcinoma. The comparison between screened (n=17) and incidental (n=40) hepatocarcinoma showed that screened HCC were more often asymptomatic (P<0.01), were more often a solitary nodule less than 5 cms (P<0.001) and underwent more often curative treatment (P=0.02). However, the survival between screened and incidental hepatocarcinoma was not different. CONCLUSIONS: Screening for hepatocarcinoma in patients with alcoholic cirrhosis is a difficult task due to poor compliance and early death. According to our results, a surveillance every 6 months is sufficient to detect early lesions accessible to curative treatment by surgical resection or transcutaneous ablation.