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Biomedical subjects

Emma A Meagher

Publications and source records attributed to Emma A Meagher.

5 recordsLinked to original sources

Addressing cardiovascular risk beyond low-density lipoprotein cholesterol: the high-density lipoprotein cholesterol story.

A large body of evidence from numerous, well-controlled, randomized trials demonstrates that treatment with statins reduce morbidity and mortality from cardiovascular disease (CVD). Although these observations are important and have resulted in the adoption of standard of care approaches to the management of CVD risk, they do not tell the whole story. When reviewing these landmark trials it is clear that on average two thirds of events are not prevented. This leads to the evaluation of risk beyond low-density lipoprotein cholesterol. This review focuses on the association of low high-density lipoprotein (HDL) cholesterol and increased CVD risk, the published trials that study the effect of raising HDL cholesterol on CVD outcomes, and the novel approaches toward HDL cholesterol raising that are on the horizon.

Cardiovascular Diseases↗

Cardiovascular and renovascular implications of COX-2 inhibition.

A group of chemical mediators, the eicosanoids, is critical players in a multitude of physiological processes. Generated by the action of the cyclooxygenase (COX) enzyme on arachidonic acid they are responsible for diverse and often opposing actions such as platelet function, vasomotor tone, gastric cytoprotection and inflammation. Since their discovery several decades ago, our knowledge concerning their synthesis, function as natural ligands and methods to manipulate their activity through drug development has expanded. Traditional Non Steroidal Anti-Inflammatory Drugs (NSAIDs) are nonselective inhibitors of the COX enzyme, of which two isoforms are known to exist - COX-1 and COX-2. NSAIDs have been the mainstay of treatment in the management of pain and inflammation associated with acute and chronic inflammatory conditions that affect more than 10 million Americans. Their efficacy in this regard is not questioned. However, gastrointestinal toxicity arising from chronic NSAID ingestion is common and limits their use in clinical practice. Gastrointestinal toxicity has been attributed to the blockade of the COX-1 mediated generation of the cytoprotective prostanoids, such as PGE(2) and PGI(2). Selective COX-2 inhibitors were designed to inhibit the production of COX-2 dependent inflammatory prostanoids and to leave intact the cytoprotective COX-1 products. The first of a new class of these selective COX-2 inhibitors - the coxibs- were introduced to the market in 1999. These compounds, while exhibiting similar efficacy to traditional NSAIDs, were associated with a reduced incidence of surrogate or actual indices of GI toxicity. Questions have been raised concerning the cardiovascular and renal profiles of these agents based on data from both small and large clinical studies. More recently, our increasing understanding of the relative contributions of both isoforms of the COX enzyme to individual components of vascular homeostais has allowed us to appreciate the cardiovascular and renovascular implications of selective COX-2 inhibition.

Animals↗

Balancing gastroprotection and cardioprotection with selective cyclo-oxygenase-2 inhibitors: clinical implications.

NSAIDs have been the mainstay of treatment in the management of pain and inflammation associated with chronic inflammatory disorders. They are effective. However, complications arising from chronic NSAID use are common and are primarily due to gastrointestinal (GI) toxicity in the form of gastritis, peptic erosions and ulceration and GI bleeds. GI toxicity has been attributed to the blockade of the cyclo-oxygenase (COX)-1-mediated generation of the cytoprotective prostanoids, such as prostaglandin (PG) E2 and PGI2 (prostacyclin). More recently, selective COX-2 inhibitors ('coxibs') were designed to inhibit the production of COX-2-dependent inflammatory prostanoids and to leave intact the cytoprotective COX-1 products. The coxibs, while exhibiting similar efficacy to traditional NSAIDs in controlled clinical trials of their efficacy in chronic inflammatory conditions, such as osteoarthritis and rheumatoid arthritis, have been associated with a reduced incidence of surrogate or actual indices of GI toxicity. However, concerns regarding cardiovascular safety in high-risk patients have evolved. These concerns were driven initially by the concept that inhibition of COX-2-derived endothelial PGI2 without concomitant inhibition of platelet thromboxane A2 would result in increased cardiovascular risk. This was borne out in the Vioxx Gastrointestinal Outcomes Research study of rofecoxib, but not demonstrated in the Celecoxib Long Term Arthritis Safety Study trial. Further elucidation of the relative roles of COX-1- and COX-2-generated prostanoids has enabled a greater understanding of the biology of these pathways. However, it is still not completely clear how this understanding may be appropriately translated into clinical medicine.

Anti-Inflammatory Agents, Non-Steroidal↗

Addressing cardiovascular disease in women: focus on dyslipidemia.

BACKGROUND: There is a need to better diagnose and treat women who may be at risk for cardiovascular disease. This is emphasized by the impending release of evidence-based guidelines for the prevention of cardiovascular disease in women. Dyslipidemia is one of the most important modifiable risk factors for coronary heart disease (CHD) and is the focus of the current literature review. METHODS: Medical literature on treating cardiovascular disease and cholesterol disorders in women was reviewed by searching Medline, including a selective search for randomized controlled clinical trials of lipid therapy. In addition, current dyslipidemia treatment guidelines were reviewed. RESULTS AND CONCLUSIONS: Subgroup analyses of both primary and secondary prevention trials have shown that lipid-modifying drugs offer benefits to women comparable with those seen in men. Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-modifying therapy for the reduction of coronary risk. However, there are differences between the sexes in the lipid profile that may have clinical implications. In women, changes in high-density lipoprotein cholesterol (HDL-C) and triglyceride levels are better predictors of coronary risk than LDL-C or total cholesterol. Thus, treatment beyond LDL-C may be of greater importance in women than in men. Furthermore, treatment options that provide improvement in all aspects of the lipid profile should be considered.

Adult↗