Lipids in health and disease

2004 ◽  
Vol 32 (6) ◽  
pp. 1051-1056 ◽  
Author(s):  
J. Shepherd

The evidence linking cholesterol levels in the blood to vascular risk is now incontrovertible and the introduction of HMG CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitor (or statin) therapy into clinical practice has now revolutionized the management of lipid disorders and silenced at a stroke the critics of cholesterol control as a means to vascular disease prevention. Statins were the first lipid-lowering agents, which, within a framework of a clinical trial, actually extended life by mechanisms that probably go beyond cholesterol alone. Their benefits are so impressive that some enthusiasts have been emboldened to write that they ‘are to atherosclerosis what penicillin was to infectious disease’. But is Nature as easily tamed as we might imagine? Some individuals show a modest or even poor response to statin therapy. The recent discovery of ezetimibe, a highly efficient and precise cholesterol absorption inhibitor, has proven to be a very effective cholesterol lowering alternative for them and combining statins with ezetimibe, thereby inhibiting cholesterol absorption and endogenous synthesis, takes us to realms of cholesterol lowering capability that could not have been dreamt of a decade ago.

2007 ◽  
Vol 9 (1) ◽  
pp. 29-45 ◽  

The use of cardiovascular medications can have a variety of neuropsychiatric consequences. Many cardiovascular agents cause higher rates of fatigue and sedation than placebo, and case reports of medication-induced mood syndromes, psychosis, and cognitive disturbances exist for many cardiovascular drugs. Depression has been associated with P3-blockers, methyldopa, and reserpine, but more recent syntheses of the data have suggested that these associations are much weaker than originally believed. Though low cholesterol levels have been associated with depression and suicide, lipid-lowering agents have not been associated with these adverse effects. Finally, cardiovascular medications may have beneficial neuropsychiatric consequences; for example, the use of clonidine in patients with attention deficit-hyperactivity disorder, the use of prazosin for patients with post-traumatic stress disorder; and the use of propranolol for performance anxiety and akathisia.


2020 ◽  
Vol 5 (1) ◽  
Author(s):  
David T W Lui ◽  
Alan C H Lee ◽  
Kathryn C B Tan

Abstract Familial hypercholesterolemia (FH) is the most common monogenic disorder associated with premature atherosclerotic cardiovascular disease. Early diagnosis and effective treatment can significantly improve prognosis. Recent advances in the field of lipid metabolism have shed light on the molecular defects in FH and new therapeutic options have emerged. A search of PubMed database up to March 2020 was performed for this review using the following keywords: “familial hypercholesterolemia,” “diagnosis,” “management,” “guideline,” “consensus,” “genetics,” “screening,” “lipid lowering agents.” The prevalence rate of heterozygous FH is approximately 1 in 200 to 250 and FH is underdiagnosed and undertreated in many parts of the world. Diagnostic criteria have been developed to aid the clinical diagnosis of FH. Genetic testing is now available but not widely used. Cascade screening is recommended to identify affected family members, and the benefits of early interventions are clear. Treatment strategy and target is currently based on low-density lipoprotein (LDL) cholesterol levels as the prognosis of FH largely depends on the magnitude of LDL cholesterol-lowering that can be achieved by lipid-lowering therapies. Statins with or without ezetimibe are the mainstay of treatment and are cost-effective. Addition of newer medications like PCSK9 inhibitors is able to further lower LDL cholesterol levels substantially, but the cost is high. Lipoprotein apheresis is indicated in homozygous FH or severe heterozygous FH patients with inadequate response to cholesterol-lowering therapies. In conclusion, FH is a common, treatable genetic disorder, and although our understanding of this disease has improved, many challenges still remain for its optimal management.


2015 ◽  
Vol 18 (4) ◽  
pp. 344 ◽  
Author(s):  
Dhiaa A Taha ◽  
Ellen K Wasan ◽  
Kishor M Wasan ◽  
Pavel Gershkovich

Consumption of plant sterols/ stanols has long been demonstrated to reduce plasma cholesterol levels. The objective of this review is to demonstrate the lipid-lowering activity and anti-atherogenic effects of natural and semi-synthetic plant sterols/ stanols based on evidence from cell-culture studies, animal studies and clinical trials. Additionally, this review highlights certain molecular mechanisms by which plant sterols/ stanols lower plasma cholesterol levels with a special emphasis on factors that affect the cholesterol-lowering activity of plant sterols/stanols. The crystalline nature and the poor oil solubility of these natural products could be important factors that limit their cholesterol-lowering efficiency. Several attempts have been made to improve the cholesterol-lowering activity by enhancing the bioavailability of crystalline sterols and stanols. Approaches involved reduction of the crystal size and/or esterification with fatty acids from vegetable or fish oils. However, the most promising approach in this context is the chemical modification of plant sterols /stanols into water soluble disodium ascorbyl phytostanyl phosphates analogue by esterification with ascorbic acid. This novel semi-synthetic stanol derivative has improved efficacy over natural plant sterols/ stanols and can provide additional benefits by combining the cholesterol-lowering properties of plant stanols with the antioxidant potential of ascorbic acid. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Waleed Kadro ◽  
Maya Turkmani ◽  
Hussam Rahim ◽  
Oussama Beshir ◽  
Oussama Khatib ◽  
...  

Introduction: Cholesterol lowering is associated with a reduction in cardiovascular morbidity and mortality. Statins are the main drugs for cholesterol lowering. Ezetimibe when added to statins gives further reduction in cholesterol but its long-term effect on cardiovascular morbidity and mortality and ischemic events is not known. This study sought to determine whether further cholesterol lowering with ezitimibe will also results in a reduction of myocardial ischemia during daily life. Hypothesis: Further cholestrol with ezetimibe lowering may reduce silent ischemia. Methods: We enrolled 50 patients with proven stable coronary artery disease (CAD) and at least one episode of ST-segment depression on ambulatory ECG monitoring. All of them were receiving optimal therapy for CAD including statin therapy for cholesterol reduction. 25 patients were randomized to continue their statin therapy (Statin only group) and 25 to recieve statin plus Ezitimibe 10mg/day (ezitimibe group). Serum cholesterol and LDL cholesterol levels and ambulatory monitoring were repeated after 4 to 6 months of therapy. The two groups were comparable with respect to baseline characteristics, number of episodes of ST-segment depression, and baseline serum cholesterol levels. Holters were read by a blinded cardiologist. Results: The ezitimibe group had lower mean total and LDL cholesterol levels at study end and experienced a significant reduction in the number of episodes of ST-segment depression compared with the statin only group. ST-segment depression was completely resolved in 13 of 25 patients (52%) in the ezitimibe group versus 3 of 25 (12%) in the statin only group. The ezitimibe group exhibited a highly significant reduction in ambulatory ischemia (P<.001). By logistic regression, treatment with ezitimibe was an independent predictor of ischemia resolution. Conclusions: Further cholesterol lowering with ezitimibe can result in reduction or resolution of myocardial ischemia recorded as episodes of ST-segment depression in ambulatory monitoring of the ECG. A larger study is required to confirm this results. This may be translated into long term mortality reduction for CAD by adding ezetimibe.


2016 ◽  
Vol 157 (31) ◽  
pp. 1219-1223 ◽  
Author(s):  
György Paragh ◽  
István Karádi

Considerable evidence suggests that “the lower the better” is a reasonable approach for reducing cardiovascular risk by lowering LDL cholesterol levels. Despite the reduction in cardiovascular events and mortality achieved by statin therapy, significant residual risk remains, especially in severe hereditary hypercholesterolemia, such as familial hypercholesterolemia. Some new strategies to achieve even lower LDL levels are now available, including the addition of cholesterol absorption inhibitor ezetimibe, and the recently available Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies. In addition, new LDL drugs may be effectively administrated in those individuals who are unable to tolerate statins. The authors summarize the efficacy and clinical indications of these new agents and review the currently available guidelines. Orv. Hetil., 2016, 157(31), 1219–1223.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Akshyaya Pradhan ◽  
Monika Bhandari ◽  
Rishi Sethi

Low-density lipoprotein lowering with statins has convincingly and consistently proven to reduce cardiovascular events in both primary and secondary prevention. However, despite high-dose statin therapy, residual cardiovascular risk remains and many patients also do not tolerate statins. Ezetimibe was initially projected as a frontline alternative to statin. It is an intestinal cholesterol absorption inhibitor with modest LDL lowering effects. But, major studies failed to demonstrate any beneficial effect of CV outcomes, and the drug was relegated to oblivion. IMPROVE-IT, a contemporary, large, and well-designed trial, unequivocally demonstrated reduction in CV outcomes with ezetimibe when added to statin therapy. The benefits are seen in both sexes, elderly, CKD, diabetes mellitus, and in patients with prior CABG. It also reduces biomarkers and induces plaque regression like statins. The drug has now established itself as an add-on therapy to statin when monotherapy fails to achieve LDL goals and when it is not tolerated. The combination therapy has excellent safety and efficacy record. It has now been endorsed by major guidelines too in management of dyslipidemia. Yes, ezetimibe can indeed improve cardiovascular outcomes!


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