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Biomedical subjects

Peter H Jones

Publications and source records attributed to Peter H Jones.

29 records · Page 2Linked to original sources
PubMed2004

Pathophysiology of dyslipidemia and increased cardiovascular risk in HIV lipodystrophy: a model of 'systemic steatosis'.

PURPOSE OF REVIEW: This review addresses a syndrome of dyslipidemia and lipodystrophy that has emerged in HIV-infected patients receiving highly active antiretroviral therapy (HAART). The term 'HIV/HAART associated dyslipidemic lipodystrophy (HADL)' describes this syndrome. Although HAART increases patient survival rates, their increased longevity and dyslipidemias place them at risk for cardiovascular disease. Identification of rationally based therapies requires an understanding of the mechanistic basis of HADL. RECENT FINDINGS: A case definition for HIV lipodystrophy, based on age, gender, duration of HIV disease, serum HDL cholesterol and anthropometry, provides high diagnostic sensitivity and specificity. The dyslipidemias, mainly hypercholesterolemia, hypertriglyceridemia and low-plasma HDL cholesterol, among HIV-infected patients in the pre- and post-HAART eras are summarized. Clinical studies of HADL patients show increased lipolysis, which increases free fatty acid transfer to liver for incorporation into lipoprotein triglycerides that are secreted, and to skeletal muscle where they impair normal insulin signaling. A model of HADL that includes preferential lipolysis in femoral-gluteal fat depots is presented. Relevant therapies include those that inhibit lipolysis (niacin) or increase hepatic fatty acid oxidation (fibrates). SUMMARY: HADL is one of several disorders characterized by dyslipidemia, insulin resistance, and lipodystrophy. The relative acuteness of HADL should facilitate identification of the sequence of metabolic changes that gives rise to the syndrome. Current evidence suggests that deranged energy storage in femoral-gluteal and other peripheral sites is important; the molecular details for the derangement are unknown but are under scrutiny by many investigators.

Animals↗
PubMed2004

Adiponectin, inflammation, and the expression of the metabolic syndrome in obese individuals: the impact of rapid weight loss through caloric restriction.

Severe obesity increases the prevalence of the metabolic syndrome, and moderate acute weight loss with a very low-calorie diet in obese subjects with the metabolic syndrome leads to significant metabolic benefits. Adiponectin has been implicated in both the pathogenesis of obesity-related insulin resistance and increased inflammation. We analyzed the relationship of the adipocyte-derived hormone adiponectin with indices of inflammation, adiposity, and insulin resistance in obese subjects with (MS+, n = 40) and without (MS-, n = 40) the metabolic syndrome and examined the acute effects of rapid weight loss. MS+ subjects had significantly lower adiponectin (7.6 +/- 0.6 vs. 10.4 +/- 0.6 microg/ml; P = 0.003) and significantly higher TNF-alpha (3.3 +/- 0.2 vs. 2.8 +/- 0.3 pg/ml; P = 0.004) levels compared with MS- subjects matched for age and body mass index. Plasma adiponectin and TNF-alpha levels were inversely related to the number of metabolic syndrome factors in a stepwise manner. After 4-6 wk of weight loss, there was marked improvement in glucose, insulin, leptin, and triglycerides, whereas adiponectin and TNF-alpha concentrations did not change. Thus, increases in plasma levels of adiponectin or reductions in TNF-alpha are not required for marked improvements in glucose/insulin and lipid metabolism with acute weight loss.

Adiponectin↗
PubMed2003

Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial).

The primary objective of this 6-week, parallel-group, open-label, randomized, multicenter trial was to compare rosuvastatin with atorvastatin, pravastatin, and simvastatin across dose ranges for reduction of low-density lipoprotein (LDL) cholesterol. Secondary objectives included comparing rosuvastatin with comparators for other lipid modifications and achievement of National Cholesterol Education Program Adult Treatment Panel III and Joint European Task Force LDL cholesterol goals. After a dietary lead-in period, 2,431 adults with hypercholesterolemia (LDL cholesterol > or =160 and <250 mg/dl; triglycerides <400 mg/dl) were randomized to treatment with rosuvastatin 10, 20, 40, or 80 mg; atorvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; or pravastatin 10, 20, or 40 mg. At 6 weeks, across-dose analyses showed that rosuvastatin 10 to 80 mg reduced LDL cholesterol by a mean of 8.2% more than atorvastatin 10 to 80 mg, 26% more than pravastatin 10 to 40 mg, and 12% to 18% more than simvastatin 10 to 80 mg (all p <0.001). Mean percent changes in high-density lipoprotein cholesterol in the rosuvastatin groups were +7.7% to +9.6% compared with +2.1% to +6.8% in all other groups. Across dose ranges, rosuvastatin reduced total cholesterol significantly more (p <0.001) than all comparators and triglycerides significantly more (p <0.001) than simvastatin and pravastatin. Adult Treatment Panel III LDL cholesterol goals were achieved by 82% to 89% of patients treated with rosuvastatin 10 to 40 mg compared with 69% to 85% of patients treated with atorvastatin 10 to 80 mg; the European LDL cholesterol goal of <3.0 mmol/L was achieved by 79% to 92% in rosuvastatin groups compared with 52% to 81% in atorvastatin groups. Drug tolerability was similar across treatments.

Adult↗
PubMed2003

Comparing HMG-CoA reductase inhibitors.

The statins have proved to be some of the most potent therapies for reducing elevated low-density lipoprotein (LDL) cholesterol and lessening the risk of coronary heart disease (CHD) and related events. Nonetheless, there are still questions about the clinical relevance of individual drug characteristics, such as chemical derivation, solubility properties, and metabolic route, in terms of tolerability or therapeutic benefit. At the same time, no clear explanation has emerged for the significantly steeper reductions in LDL cholesterol levels achieved with atorvastatin versus lovastatin, simvastatin, pravastatin, or fluvastatin, or, more recently, with rosuvastatin versus atorvastatin, although possible mechanisms have been suggested. More studies are needed to characterize the effects of statins on high-density lipoprotein (HDL) in different patient groups. Clearly, though, several statins have yielded significant reductions in CHD risk and have shown to be well tolerated in both primary and secondary prevention trials. The possibility that statins exert pronounced effects beyond lowering blood lipids is opening other avenues of research into the benefits of these drugs.

Anticholesteremic Agents↗
PubMed2003

Comparison of the efficacy of rosuvastatin versus atorvastatin, simvastatin, and pravastatin in achieving lipid goals: results from the STELLAR trial.

In the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial, the efficacy of rosuvastatin calcium (Crestor) was compared with that of atorvastatin (Lipitor), simvastatin (Zocor), and pravastatin (Pravachol) for lowering plasma low-density lipoprotein cholesterol (LDL-C) after 6 weeks of treatment. In this multicenter, parallel-group, open-label trial, adults with hypercholesterolemia were randomized to treatments with rosuvastatin 10, 20, 40, or 80 mg, atorvastatin 10, 20, 40, or 80 mg, simvastatin 10, 20, 40, or 80 mg, or pravastatin 10, 20, or 40 mg. Efficacy and safety results from this trial have been previously published. The additional analyses included in this report show that 53% (83/156) to 80% (125/157) of patients in the rosuvastatin 10- to 40-mg groups achieved LDL-C levels < 100 mg/dl (< 2.6 mmol/l), compared with 18% (28/158) to 70% (115/165) of patients who received atorvastatin, 8% (13/165) to 53% (86/163) of patients who received simvastatin, and 1% (1/160) to 8% (13/161) of patients who received pravastatin. Other additional analyses showed that more patients in the rosuvastatin 10- to 40-mg groups than in the comparator groups who were at high risk of coronary heart disease according to National Cholesterol Education Program Adult Treatment Panel (ATP) III, Joint European Societies, or Canadian guidelines achieved the LDL-C goals of < 100 mg/dl (< 2.6 mmol/l) (55% to 77% compared with 0 to 64%), < 3.0 mmol/l (< 116 mg/dl) (76% to 94% compared with 6% to 81%), and < 2.5 mmol/l (< 97 mg/dl) (47% to 69% compared with 0 to 53%), respectively. Results favoring rosuvastatin versus the comparators were also reported for patients: (a) who had triglycerides > or = 200mg/dl (> or = 2.3 mmol/l), and achieved both ATP III LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) goals (80% to 84% versus 15% to 84%); (b) overall who achieved the Canadian LDL-C goals of < 2.5 (< 97 mg/dl) to < 5.0 mmol/l (< 193 mg/dl) (85% to 91% versus 44% to 86%); and (c) who achieved all 3 Canadian goals for LDL-C, triglycerides (< 3.0 mmol/l [< 266 mg/dl] to < 2.0 mmol/l [< 177 mg/dl]), and the total cholesterol/high-density lipoproteincholesterol ratio (< 4 to < 7) (70% to 83% versus 35% to 79%).

Anticholesteremic Agents↗
PubMed2003

Lipid-lowering: can ezetimibe help close the treatment gap?

Most patients who should be on lipid-lowering therapy are not receiving it, and most patients who are receiving it are not reaching their appropriate low-density lipoprotein (LDL) goals. This is in part because physicians and patients fear side effects of statins and other lipid-lowering agents. Ezetimibe (Zetia), a new lipid-lowering drug, may help physicians close this "treatment gap" in more patients, especially in combination with a statin.

Anticholesteremic Agents↗
PubMedDate not supplied

Dyslipidemia in older adults.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown in many large, randomized clinical trials to be safe and highly effective for decreasing low-density lipoprotein cholesterol, thus preventing cardiovascular events and decreasing mortality in patients both with and without prior cardiovascular disease. Statins are also appropriate agents for older adults, although they remain underutilized in this population. This article uses three typical case history presentations to review the most recent clinical trial data and guidelines on statin therapy to provide practical guidance on clinical decision making for lipid-lowering therapy in the geriatric population.

Aged↗
PubMedDate not supplied

Effectiveness and tolerability of adding ezetimibe to niacin-based regimens for treatment of primary hyperlipidemia.

OBJECTIVE: To determine the effectiveness and tolerability of adding ezetimibe, 10 mg daily, to niacin-based regimens for dyslipidemia. METHODS: We conducted a retrospective review of medical records of 53 patients in 2 lipid clinics who received ezetimibe as add-on therapy to stable doses of niacin and other lipid medications. Mean percentage changes of lipoprotein cholesterol and triglyceride levels were determined. Safety and tolerability measures included adverse events, serum hepatic transaminases, and hemoglobin A1c (in patients with diabetes). RESULTS: Most study subjects (81%) had established atherosclerotic disease. The niacin formulation was extended-release in 31 patients (58%), immediate-release in 17 (32%), and slow-release in 5 (9%). Most patients (75%) were also taking a statin. Add-on ezetimibe therapy yielded mean reductions of 18% for total cholesterol (P<0.001), 25% for low-density lipoprotein (LDL) cholesterol (P<0.001), and 17% for triglycerides (P<0.001). High-density lipoprotein (HDL) cholesterol did not change significantly (+2%). Only 7 patients (13%) met Adult Treatment Panel III (ATP III) LDL cholesterol goals before the addition of ezetimibe, but 24 (45%; P<0.001 compared with baseline) attained these goals after addition of ezetimibe to the therapeutic regimen. Ezetimibe effectiveness did not correlate with the baseline dose of niacin or the dose/efficacy of the statin used. The addition of ezetimibe to niacin-based therapy for dyslipidemia was well tolerated. No patient had clinically significant elevations in hepatic enzyme or hemoglobin A1c levels or discontinued the ezetimibe therapy permanently. CONCLUSION: In our study, the addition of ezetimibe to niacin-based regimens lowered the LDL cholesterol level by 25% and did not change the level of HDL cholesterol. This combination can be useful in multidrug regimens for high-risk patients with dyslipidemia who are not achieving ATP III treatment goals.

Aged↗