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mercredi 12 mars 2014

One paper a day, LDL and atheroma: do patients with familial hypobetalipoproteinemia have better risk profile? Do they have less atheroma?



"Cardiovascular Risk

Numerous studies have established a strong correlation between levels of LDL cholesterol and progression of IMT.44 In the present study, however, we could not show an independent statistical difference in terms of carotid IMT values between FHBL subjects and controls. Nevertheless, data have accumulated recently that show the predictive value of the assessment of vascular function, such as arterial stiffness, for future cardiovascular events.23,45–48 Arterial stiffness is closely correlated with increasing age, smoking, and hypertension.31,32,49–51 The impact of these risk factors is augmented in the presence of hypercholesterolemia and can be reverted by statin therapy.52,53 In our FHBL group, we observed a significant decrease in arterial stiffness. Of note, this difference was observed despite the fact that traditional risk factors such as smoking and diabetes occurred more frequently in the FHBL group compared with controls. In earlier studies, apoB-containing lipoproteins have been put forward as a pivotal “permissive” factor for the development of atherogenic changes of the vessel wall. To evaluate a potential interaction between apoB-containing lipoproteins and other traditional risk factors, we constructed a cumulative risk index including age, smoking, and systolic blood pressure in FHBL subjects as well as controls. In both groups, there was a linear relationship between increased risk score and arterial stiffness. Interestingly, the increase in arterial stiffness, also in presence of these risk factors was decreased significantly in the FHBL group compared with controls. These data suggest that apoB-containing lipoproteins indeed have the ability to potentiate the impact of traditional risk factors on vascular function. Tentatively, these observations might suggest that lowering of apoB-containing lipoproteins should have a beneficial impact also in subjects with “noncholesterol” risk factors. Recent studies have validated the beneficial effects of statin therapy in normocholesterolemic subjects with nonlipid risk factors, such as hypertension.54

This study has some limitations. We used the less sensitive ultrasonography method to evaluate fatty liver disease rather than magnetic resonance spectroscopy. However, in view of the carefully standardized methodology and the fact that both patients and controls were evaluated using the same methodology, it is unlikely that the latter has affected our outcomes. With regard to the IMT measurement, we could not find a clear relationship between LDL cholesterol levels and carotid IMT. Several reasons may have attributed to the absence of a relation. First, we studied a relatively young cohort with an inherently low risk for cardiovascular disease and hence low IMT values. Second, we studied IMT in a case control design to show thinner IMTs compared with healthy controls. A priori, it is very difficult to demonstrate decreased IMT thickness in “low-risk” groups compared with healthy controls. We have estimated that inclusion of more than 1000 subjects per group would have been necessary to be able to detect significantly thinner IMTs compared with healthy controls with a “normal” risk factor distribution, as seen in western populations.

In summary, our study shows that subjects with FHBL are at increased risk of developing FLD. Whereas long-term sequelae of FLD in FHBL subjects remain to be established, it is prudent to give lifestyle advice in affected individuals. As is illustrated by decreased vascular wall stiffness, our findings suggest that the vessel wall in FHBL subjects is relatively protected by the (life-long) reduced levels of exposure to apoB-containing lipoproteins. The attenuated gradual increase in vascular stiffness in the presence of classical, nonlipid cardiovascular risk factors in FHBL subjects is of interest and suggests that apoB-containing particles constitute a central factor in atherogenesis, amplifying any risk mediated by nonlipid risk factors. Further confirmation of this finding is needed in larger cohorts to ascertain its impact on cardiovascular risk."


Figure 2. Arterial stiffness versus cumulative risk score in FHBL. The cumulative risk score is based on 3 variables: age, smoking, and systolic blood pressure (SBP). Results of each variable, except for smoking, were divided into tertiles. For age and SBP, patients received scores of 1, 2, or 3 with each increasing tertile. Smoking was scored as either 0 for nonsmoking or 3 for smoking. Minimal and maximal attainable scores were 2 and 9, respectively. The probability value indicates the difference in slope between the 2 regression lines.

The only conclusion we can draw from this paper is that ApoB 100 deficient humans have not more atheroma in the carotid than controls.
One can speculate that ApoB 100 is not the culprit and that at least it is not sufficient to have ApoB 100 lipoprotein (id est LDL particles) to build plaques in the artery wall.




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