Therapies to Increase High-Density Lipoprotein Cholesterol and Their Effect on Cardiovascular Outcomes and Regression of Atherosclerosis

Venkatesh, Prasanna K.; Caskey, David; Reddy, Pratap

doi:10.1097/maj.0b013e31815d4419

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…39 Statins have been shown to decrease LDL levels, but the evidence for reduction of coronary artery disease risk with HDL-raising therapy is relatively thin, partly due to the scarcity of effective and safe drugs for increasing HDL levels. 3…”

Section: Ongoing Researchmentioning

confidence: 99%

“…1,2 Epidemiological studies have shown that low HDL is an independent risk factor for cardiovascular disease associated with diabetes mellitus and metabolic syndrome, even in patients having normal LDL levels. 3,4 This report highlights some of the therapeutic implications of the National Cholesterol Education Program -Adult Treatment Panel III guidelines report and various therapeutic approaches to lowering elevated LDL and triglycerides, as well as increasing low levels of HDL to optimize clinical event rate reduction in patients with coronary heart disease. 5 New insights into the basic science of HDL function and metabolism, such as the discovery of beta-chain adenosine triphosphate (ATP) synthase as a hepatic catabolic HDL receptor, are f urther characterizing the importance of HDL in atheroprotection and identifying novel targets of drug development.…”

Section: Introductionmentioning

confidence: 99%

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High-density lipoproteins: a novel therapeutic target for cardiovascular disease

Saleem¹,

Rani²,

Gauthaman³

2011

RRCC

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Cardiovascular disease has a high rate of mortality in both Western and developing countries. Atherosclerosis and generation of reactive oxygen species through oxidative stress is the major risk factor for cardiovascular disease. Atherothrombosis with low levels of high-density lipoprotein (HDL) and high levels of low-density lipoprotein is a major risk factor for atherosclerosis-induced cardiovascular disease. Lipid-lowering drugs like statins, niacin, fibrates, and some newer agents, ie, the apolipoprotein A-I mimetics and the cholesteryl ester transfer protein inhibitors, not only increase HDL levels but are also effective in reducing key atherogenic lipid components, including triglyceride-rich lipoproteins. The aim of this review is to discuss the accumulating evidence suggesting that HDL possesses a diverse range of biological actions, and that increasing HDL levels by drug treatment may be beneficial in the prevention of cardiovascular disease.

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Section: Ongoing Researchmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High-density lipoproteins: a novel therapeutic target for cardiovascular disease

Saleem¹,

Rani²,

Gauthaman³

2011

RRCC

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“…High Lp(a) levels were also correlated with CAD and HDL irrespective of the HDL concentration which is paradoxically supposed to yield a protective effect against CAD. 31 , 32 Our data showed that even in the presence of high HDL serum levels (≥35 mg/dL), high levels of Lp(a) (≥30 mg/dL) yielded increased number of patients with CAD, thus dampening the protective effect exerted by HDL on artery stenosis. Observational studies have demonstrated that HDL can be converted to a dysfunctional form in the presence of conditions associated with systemic and vascular inflammation and therefore the anti-atherosclerotic effects of normally functioning HDL can be frequently impaired.…”

Section: Discussionmentioning

confidence: 72%

Elevated Lp(a) Levels Correlate with Severe and Multiple Coronary Artery Stenotic Lesions

Hageh

Chacar

Ghassibe-Sabbagh

et al. 2023

VHRM

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Backgrounds and Aims The role of Lipoprotein(a) (Lp(a)) in increasing the risk of cardiovascular diseases is reported in several populations. The aim of this study is to investigate the correlation of high Lp(a) levels with the degree of coronary artery stenosis. Methods Two hundred and sixty-eight patients were enrolled for this study. Patients who underwent coronary artery angiography and who had Lp(a) measurements available were included in this study. Binomial logistic regressions were applied to investigate the association between Lp(a) and stenosis in the four major coronary arteries. The effect of LDL and HDL Cholesterol on modulating the association of Lp(a) with coronary artery disease (CAD) was also evaluated. Multinomial regression analysis was applied to assess the association of Lp(a) with the different degrees of stenosis in the four major coronary arteries. Results Our analyses showed that Lp(a) is a risk factor for CAD and this risk is significantly apparent in patients with HDL-cholesterol ≥35 mg/dL and in non-obese patients. A large proportion of the study patients with elevated Lp(a) levels had CAD even when exhibiting high HDL serum levels. Increased HDL with low Lp(a) serum levels were the least correlated with stenosis. A significantly higher levels of Lp(a) were found in patients with >50% stenosis in at least two major coronary vessels arguing for pronounced and multiple stenotic lesions. Finally, the derived variant (rs1084651) of the LPA gene was significantly associated with CAD. Conclusion Our study highlights the importance of Lp(a) levels as an independent biological marker of severe and multiple coronary artery stenosis.

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“…The clinical use of nicotinic acid is, however, hindered by harmless but unpleasant effect skin flushing seen in 70% of patients. Other adverse effects and their reported frequency include headaches, gastrointestinal symptoms, hepatoxicity (up to 7%), elevated fasting glucose levels (7%), elevated uric acid levels (9%) that may have clinical relevance in selected patients [26, 28, 29]. …”

Section: Existing Lipid-lowering Drugsmentioning

confidence: 99%

Cholesterol-metabolizing cytochromes P450: implications for cholesterol lowering

Pikuleva

2008

Expert Opinion on Drug Metabolism & Toxicology

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Cardiovascular disease (CVD) continues to be a leading cause of death worldwide. Elevated serum cholesterol is one of the classical risk factors for CVD which also include age, hypertension, smoking, diabetes mellitus, obesity and family history. A number of therapeutic drug classes have been developed to treat hypercholesterolemia, yet, an important percentage of patients do not reach their treatment goals. Therefore, new cholesterol-lowering medications, having a site of action different from that of currently available drugs need to be developed. This review summarizes new information about cytochrome P450 enzymes 7A1, 27A1, and 46A1, that play key roles in cholesterol elimination and that have potential to serve as targets for cholesterol-lowering.

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Therapies to Increase High-Density Lipoprotein Cholesterol and Their Effect on Cardiovascular Outcomes and Regression of Atherosclerosis

Cited by 7 publications

References 37 publications

High-density lipoproteins: a novel therapeutic target for cardiovascular disease

High-density lipoproteins: a novel therapeutic target for cardiovascular disease

Elevated Lp(a) Levels Correlate with Severe and Multiple Coronary Artery Stenotic Lesions

Cholesterol-metabolizing cytochromes P450: implications for cholesterol lowering

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