Background:
Statin treatment exhibits a beneficial effect on non-alcoholic fatty liver disease (NAFLD)
and on cardiovascular disease (CVD) in patients with NAFLD.
Objective:
The aim of this review is to summarize the role of proprotein convertase subtilisin kexin type-
9(PCSK9) in the pathogenesis of NAFLD and discuss the effects of the new hypolipidaemic drugs PCSK9 inhibitors
on NAFLD.
Results:
Data indicates that high intrahepatic or circulating PCSK9 levels increase muscle and liver lipid storage,
adipose energy storage and hepatic fatty acids, as well as triglycerides storage and secretion, thus contributing to
the pathogenesis of NAFLD. The findings of animal and human studies, aiming to reduce PCSK9 with inhibitors
(human IGG antibodies, antisense particles against PCSK9 mRNA, and small anti PCSK9 antibodies) point towards
liver protection from NAFLD through inhibition of PCSK9 expression in the induction of degradation of
hepatic HNF1a protein, insulin resistance (IR), and other mechanisms.
Conclusions:
The use of PCSK9 inhibitors ameliorates NAFLD, aside from beneficial effects on CVD and independently
of low density lipoprotein cholesterol level reduction.
Background:Low density lipoprotein cholesterol (LDL-C) and low grade arterial inflammation are key pathogenic factors for atherosclerosis and its manifestation, cardiovascular disease (CVD).Objective:In this narrative review we assessed if decreasing LDL-C levels or inflammation or both is more effective in reducing CVD events.Results:In the Scandinavian Simvastatin Survival Study (4S), all statin trials of the 90s’ and the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) the benefit came from the LDL-C reduction. In the GREak and Atorvastatin Coronary heart disease Evaluation (GREACE), the Treating to New Targets (TNT), and the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trials both mechanisms in combination produced significant benefits. In the Atorvastatin for Reduction of MYocardial Damage during Angioplasty (ARMYDA) trials and the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) with a human antibody targeting IL-1β with no lipid lowering effect, the reduction in arterial inflammation played the only beneficial role because there was no change in lipids levels.Conclusion:Both LDL-C and inflammation reduction are beneficial to the reduction of CVD risk. However, canakinumab is a very expensive drug that only induced a 15% reduction in CVD events, thus drastically reducing the possibility for it to be used in clinical practice. Besides, canakinumab is associated with increased infections, some fatal. A potent statin with anti-inflammatory effects is probably the best choice for the majority of those needing hypolipidaemic drug therapy.
Arterial stiffness and central hemodynamics attract increasing scientific interest within the hypertensive community during the last decade. Accumulating evidence indicates that aortic stiffness is a strong and independent predictor of cardiovascular events and all-cause mortality in hypertensive patients, and its predictive value extends beyond traditional risk factors. The role of central hemodynamics and augmentation index (a marker of reflected waves), remains less established and requires further investigation. Several lines of evidence indicate that antihypertensive therapy results in significant reductions of pulse wave velocity and central hemodynamics. However, beta-blockers seem to be the only exception with significant within-class differences. Conventional beta-blockers, although equally effective in reducing pulse wave velocity, seem to be less beneficial on central hemodynamics and augmentation index than the other antihypertensive drug categories, whereas the newer vasodilating beta-blockers seem to share the benefits of the other antihypertensive drugs. In conclusion, aortic stiffness seems ready for 'prime-time' in the management of essential hypertension, while further research is needed for central hemodynamics and augmentation index.
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