Lipid Targets During Statin Treatment in Dyslipidemic Patients Affected by Nonalcoholic Fatty Liver Disease

Maroni, Lorenzo; Guasti, Luigina; Castiglioni, Luana; Marino, Franca; Contini, Sara; Macchi, Valentina; Leo, Alessandra De; Gaudio, Giovanni; Tozzi, Matteo; Grandi, Anna Maria; Cosentino, Marco; Venco, Achille

doi:10.1097/maj.0b013e318213e526

Cited by 18 publications

(16 citation statements)

References 32 publications

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“…We have several hypotheses for the under-prescription and suboptimal use of statin. 25 In our study, there was no significant difference in the serum ALT level and in the proportion of patients with elevated ALT among patients who should be on statin compared with patients who were rightly not on statin, and among patients who were not treated to target compared with patients who were treated to target. Several factors could have contributed to this, including lack of awareness of treatment targets according to cardiovascular risk, lack of proper assessment of cardiovascular risk, and assumption by gastroenterologists and hepatologists that dyslipidemia would be managed by physicians attending to the patients' other coexisting metabolic conditions.…”

Section: Discussioncontrasting

confidence: 47%

“…24 Another study on NAFLD patients with dyslipidemia showed that statin can be used to achieve LDL cholesterol treatment target without significant changes in liver enzyme levels between baseline and follow-up visits. 25 In our study, there was no significant difference in the serum ALT level and in the proportion of patients with elevated ALT among patients who should be on statin compared with patients who were rightly not on statin, and among patients who were not treated to target compared with patients who were treated to target. This suggests that serum ALT level should not have deterred the prescription of statins among patients who needed it or the treatment to LDL cholesterol target among patients who were already on statins.…”

Section: Discussioncontrasting

confidence: 47%

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Suboptimal treatment of dyslipidemia in patients with nonalcoholic fatty liver disease

Khoo

Wong

Goh

et al. 2019

J of Gastro and Hepatol

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Background and Aim Nonalcoholic fatty liver disease (NAFLD) patients often have dyslipidemia, and optimal treatment of dyslipidemia lowers the risk of cardiovascular disease and mortality. Our aim was to study the prescription of statin and low‐density lipoprotein cholesterol treatment targets in NAFLD patients. Methods Consecutive NAFLD patients attending five clinics in Asia were included in this study. The 10‐year cardiovascular disease risk was calculated based on the Framingham Heart Study, and patients were categorized as moderate, high, or very high risk for cardiovascular disease on the basis of the American Association of Clinical Endocrinologist 2017 Guidelines. The low‐density lipoprotein cholesterol treatment goal for each of the risk groups was 2.6, 2.6, and 1.8 mmol/L, respectively. Results The data for 428 patients were analyzed (mean age 54.4 ± 11.1 years, 52.1% male). Dyslipidemia was seen in 60.5% (259/428), but only 43.2% (185/428) were on a statin. The percentage of patients who were at moderate, high, and very high risk for cardiovascular disease was 36.7% (157/428), 27.3% (117/428), and 36.0% (154/428), respectively. Among patients who were on a statin, 58.9% (109/185) did not achieve the treatment target. Among patients who were not on a statin, 74.1% (180/243) should be receiving statin therapy. The percentage of patients who were not treated to target or who should be on statin was highest among patients at very high risk for cardiovascular disease at 79.6% (78/98) or 94.6% (53/56), respectively. Conclusion This study highlights the suboptimal treatment of dyslipidemia and calls for action to improve the treatment of dyslipidemia in NAFLD patients.

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Section: Discussioncontrasting

confidence: 47%

Section: Discussioncontrasting

confidence: 47%

Suboptimal treatment of dyslipidemia in patients with nonalcoholic fatty liver disease

Khoo

Wong

Goh

et al. 2019

J of Gastro and Hepatol

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“…Recent reports have shown that reduction of serum lipoprotein levels can prevent steatosis in LDLR −/− mice 36 and may help to prevent the development of hepatic dysfunction in humans with non-alcoholic steatohepatitis 37, 38 . To ascertain the impact of LDN-193189 on steatosis and associated hepatic function, liver histology and biochemical liver function tests were performed in these animals.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Bone Morphogenetic Protein Signaling Reduces Vascular Calcification and Atherosclerosis

Derwall

Malhotra

Lai

et al. 2012

ATVB

193

168

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Objective The expression of bone morphogenetic proteins (BMPs) is enhanced in human atherosclerotic and calcific vascular lesions. While genetic gain- and loss-of-function experiments in mice have supported a causal role of BMP signaling in atherosclerosis and vascular calcification, it remains uncertain whether BMP signaling might be targeted pharmacologically to ameliorate both of these processes. Methods and Results We tested the impact of pharmacologic BMP inhibition upon atherosclerosis and calcification in low density lipoprotein receptor-deficient (LDLR−/−) mice. LDLR−/− mice fed a high-fat diet developed abundant vascular calcification within twenty weeks. Prolonged treatment of LDLR−/− mice with the small molecule BMP inhibitor LDN-193189 was well-tolerated and potently inhibited development of atheroma, as well as associated vascular inflammation, osteogenic activity, and calcification. Administration of recombinant BMP antagonist ALK3-Fc replicated the anti-atherosclerotic and anti-inflammatory effects of LDN-193189. Treatment of human aortic endothelial cells with LDN-193189 or ALK3-Fc abrogated the production of reactive oxygen species (ROS) induced by oxidized LDL, a known early event in atherogenesis. Unexpectedly, treatment of mice with LDN-193189 lowered LDL serum cholesterol by 35% and markedly decreased hepatosteatosis without inhibiting HMG-CoA reductase activity. Treatment with BMP2 increased, whereas LDN-193189 or ALK3-Fc inhibited apolipoprotein B100 secretion in HepG2 cells, suggesting that BMP signaling contributes to the regulation of cholesterol biosynthesis. Conclusions These results definitively implicate BMP signaling in atherosclerosis and calcification, while uncovering a previously unidentified role for BMP signaling in LDL cholesterol metabolism. BMP inhibition may be helpful in the treatment of atherosclerosis and associated vascular calcification.

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“…Statins, in monotherapy and in combination with other lipid-lowering drugs or antioxidants, are beneficial in NAFLD patients by improving dyslipidemia (Athyros et al, 2011; Fon Tacer and Rozman, 2011). The inter-individual variability in the response to statins varies in NAFLD patients based on their risk for cardiovascular diseases (Maroni et al, 2011). Moreover, the CYP3A4 drug metabolizing activity is also a factor influencing inter-individual variability and hence, is relevant to NAFLD patients undergoing statin therapy.…”

Section: Nafld and Drug Dispositionmentioning

confidence: 99%

Molecular Interactions between NAFLD and Xenobiotic Metabolism

Belič¹,

Zanger²,

Rozman³

2013

Front. Gene.

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Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, is a complex multifactorial disease characterized by metabolic deregulations that include accumulation of lipids in the liver, lipotoxicity, and insulin resistance. The progression of NAFLD to non-alcoholic steatohepatitis and cirrhosis, and ultimately to carcinomas, is governed by interplay of pro-inflammatory pathways, oxidative stress, as well as fibrogenic and apoptotic cues. As the liver is the major organ of biotransformation, deregulations in hepatic signaling pathways have effects on both, xenobiotic and endobiotic metabolism. Several major nuclear receptors involved in the transcription and regulation of phase I and II drug metabolizing enzymes and transporters also have endobiotic ligands including several lipids. Hence, hepatic lipid accumulation in steatosis and NAFLD, which leads to deregulated activation patterns of nuclear receptors, may result in altered drug metabolism capacity in NAFLD patients. On the other hand, genetic and association studies have indicated that a malfunction in drug metabolism can affect the prevalence and severity of NAFLD. This review focuses on the complex interplay between NAFLD pathogenesis and drug metabolism. A better understanding of these relationships is a prerequisite for developing improved drug dosing algorithms for the pharmacotherapy of patients with different stages of NAFLD.

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Lipid Targets During Statin Treatment in Dyslipidemic Patients Affected by Nonalcoholic Fatty Liver Disease

Cited by 18 publications

References 32 publications

Suboptimal treatment of dyslipidemia in patients with nonalcoholic fatty liver disease

Suboptimal treatment of dyslipidemia in patients with nonalcoholic fatty liver disease

Inhibition of Bone Morphogenetic Protein Signaling Reduces Vascular Calcification and Atherosclerosis

Molecular Interactions between NAFLD and Xenobiotic Metabolism

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