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Biomedical subjects

Peter H Jones

Publications and source records attributed to Peter H Jones.

At least 19 recordsLinked to original sources
PubMed2007

Statin therapy: is the percent reduction or the attained low-density lipoprotein cholesterol level more important?

Hyperlipidemia is a well-known risk factor for atherosclerosis. Several trials have demonstrated the importance of lowering low-density lipoprotein cholesterol (LDL-C) levels to reduce all-cause mortality, coronary ischemia, and cerebrovascular accidents. Although the optimal goal for LDL-C levels in patients with known coronary heart disease has been less than 100 mg/dL, more recent findings support achieving even lower LDL-C levels for very high-risk patients. As the target levels for LDL-C trend towards lower values, it is important to evaluate the status for optimal management with statin therapy. In this review article, we discuss the role of percent LDL-C reduction versus attained LDL-C levels as targets for statin therapy in order to maximize the preventive care provided to high-risk patients.

Atherosclerosis↗
PubMed2006

Effective use of combination lipid therapy.

Despite the benefits of statin therapy, low-density lipoprotein (LDL) cholesterol management remains suboptimal and many patients do not achieve their recommended target goals. The aim of combination lipid drug therapy in high-risk patients is to achieve LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol goals with a minimum of serious adverse effects. Although statins are the drug of first choice, statin monotherapy may be limited by intolerance of dose escalation or failure to attain non-HDL cholesterol goals in those with mixed hyperlipidemia. Statins plus bile acid resins or ezetimibe can achieve greater than 50% reduction in LDL cholesterol, with little or no increase in adverse effects. Fibrates, niacin, and omega-3 fatty acids, when added to statins, can reduce triglycerides, increase HDL cholesterol, and reduce non-HDL cholesterol to a greater extent than statin monotherapy. The safety profile of combination lipid therapy is acceptable if the global coronary heart disease risk of the patient is high, thus producing a favorable risk to benefit ratio. Careful surveillance of hepatic transaminases, avoidance of gemfibrozil in statin-fibrate combinations, and awareness of statin-concomitant drug interactions is key to safe and efficacious use of combination lipid drug therapy.

Journal Article↗
PubMed2006

Rationale for intensive statin treatment in high-risk patients.

Intensive lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is now an established regimen for patients at high risk for cardiovascular events, regardless of baseline low-density lipoprotein cholesterol levels. Treatment with statins to reduce low-density lipoprotein cholesterol levels significantly below 100 mg/dL has been shown to further reduce the risk of cardiovascular morbidity and mortality in high-risk patients and has provided the necessary data for an update to the National Cholesterol Education Program's Third Adult Treatment Panel (ATP III) guidelines. Intensive statin therapy is also well tolerated, with no increased risk of noncardiovascular adverse events and a low incidence of clinically significant liver or muscle enzyme abnormalities. Results of recent clinical and surrogate end point trials confirm that intensive lowering of low-density lipoprotein cholesterol is beneficial and safe in a majority of high-risk patients.

Adult↗
PubMed2005

Eotaxin and obesity.

CONTEXT: Asthma and obesity incidence is increasing worldwide, and asthma is often more severe in the obese. Eotaxin, a CC chemokine, is important in extrinsic asthma, an inflammatory disorder. OBJECTIVE: Our objective was to examine the relation between eotaxin and obesity. DESIGN: We conducted a comparison study of eotaxin in mice fed high-fat vs. standard chow diet for 26 wk, in obese vs. lean humans, in obese humans before and after 4-6 wk of weight loss, and in sc vs. visceral adipose tissue from patients undergoing bariatric surgery. SETTING: Our clinical study occurred in an outpatient weight loss program. PATIENTS: Patients were obese adults with metabolic syndrome (n = 40) and nine morbidly obese bariatric surgery patients. INTERVENTION: Intervention was a very-low-calorie diet. MAIN OUTCOME MEASURES: We assessed circulating eotaxin and eotaxin mRNA levels in adipose tissue. RESULTS: Serum eotaxin levels were significantly higher in obese mice, and adipose mRNA levels correlated positively with serum eotaxin levels. Adipose tissue explants from obese mice showed increased secretion of eotaxin compared with explants from lean mice. In obese patients, plasma eotaxin levels were significantly higher than in lean controls and significantly reduced after weight loss, and eotaxin mRNA levels were 4.7-fold higher in visceral than sc adipose tissue. CONCLUSIONS: Circulating eotaxin and eotaxin mRNA levels in visceral adipose tissue were increased in obesity in mice and humans. Adipose tissue explants secrete eotaxin, and the stromal/vascular component of adipose tissue seems to be the predominant source of eotaxin. Diet-induced weight loss in humans led to reduction in plasma eotaxin levels, demonstrating that clinical interventions that target obesity can modulate systemic eotaxin levels.

3T3 Cells↗
PubMed2005

Comparison of the instructional efficacy of Internet-based CME with live interactive CME workshops: a randomized controlled trial.

CONTEXT: Despite evidence that a variety of continuing medical education (CME) techniques can foster physician behavioral change, there have been no randomized trials comparing performance outcomes for physicians participating in Internet-based CME with physicians participating in a live CME intervention using approaches documented to be effective. OBJECTIVE: To determine if Internet-based CME can produce changes comparable to those produced via live, small-group, interactive CME with respect to physician knowledge and behaviors that have an impact on patient care. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial conducted from August 2001 to July 2002. Participants were 97 primary care physicians drawn from 21 practice sites in Houston, Tex, including 7 community health centers and 14 private group practices. A control group of 18 physicians from these same sites received no intervention. INTERVENTIONS: Physicians were randomly assigned to an Internet-based CME intervention that could be completed in multiple sessions over 2 weeks, or to a single live, small-group, interactive CME workshop. Both incorporated similar multifaceted instructional approaches demonstrated to be effective in live settings. Content was based on the National Institutes of Health National Cholesterol Education Program--Adult Treatment Panel III guidelines. MAIN OUTCOME MEASURES: Knowledge was assessed immediately before the intervention, immediately after the intervention, and 12 weeks later. The percentage of high-risk patients who had appropriate lipid panel screening and pharmacotherapeutic treatment according to guidelines was documented with chart audits conducted over a 5-month period before intervention and a 5-month period after intervention. RESULTS: Both interventions produced similar and significant immediate and 12-week knowledge gains, representing large increases in percentage of items correct (pretest to posttest: 31.0% [95% confidence interval {CI}, 27.0%-35.0%]; pretest to 12 weeks: 36.4% [95% CI, 32.2%-40.6%]; P<.001 for all comparisons). Chart audits revealed high baseline screening rates in all study groups (> or =93%) with no significant postintervention change. However, the Internet-based intervention was associated with a significant increase in the percentage of high-risk patients treated with pharmacotherapeutics according to guidelines (preintervention, 85.3%; postintervention, 90.3%; P = .04). CONCLUSIONS: Appropriately designed, evidence-based online CME can produce objectively measured changes in behavior as well as sustained gains in knowledge that are comparable or superior to those realized from effective live activities.

Education, Medical, Continuing↗
PubMed2005

Effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin on atherogenic dyslipidemia in patients with characteristics of the metabolic syndrome.

The metabolic syndrome (MS) is a constellation of coronary risk factors. Atherogenic dyslipidemia is an important factor in cardiovascular risk in these patients, and treatment of atherogenic dyslipidemia has been identified as an important goal of therapy in patients with MS. This post hoc analysis of data from a 6-week, randomized, open-label, parallel-group, comparative trial (Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin [STELLAR]) assessed the effects of rosuvastatin 10, 20, and 40 mg, atorvastatin 10, 20, 40, and 80 mg, simvastatin 10, 20, 40, and 80 mg, and pravastatin 10, 20, and 40 mg on plasma lipids in hypercholesterolemic patients (low-density lipoprotein cholesterol >/=160 and <250 mg/dl; triglycerides <400 mg/dl) who had >/=3 of the 5 National Cholesterol Education Program Adult Treatment Panel III criteria for MS (body mass index >30 kg/m(2) substituted for waist circumference). Of 2,268 patients, 811 met criteria for MS. Percent reductions in low-density lipoprotein cholesterol ranged from 20% in the pravastatin 10-mg group to 55% in the rosuvastatin 40-mg group. In patients with MS, triglyceride reductions were 22% to 34% with rosuvastatin, 23% to 33% with atorvastatin, 15% to 23% with simvastatin, and 12% to 15% with pravastatin. High-density lipoprotein cholesterol increased by 8% to 11% with rosuvastatin, 5% to 9% with atorvastatin, 8% to 10% with simvastatin, and 3% to 7% with pravastatin. Rosuvastatin, atorvastatin, simvastatin, and pravastatin treatment had favorable effects in hypercholesterolemic patients on the atherogenic dyslipidemia associated with MS. Rosuvastatin had the most favorable effect on the atherogenic lipid profile of MS overall.

Adult↗
PubMed2005

Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin.

There is an increasing trend among physicians to use 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in combination with other antilipidemic agents. The complementary lipid-altering effects of statins and fibric acid derivatives (fibrates) have led to an increasing use of statin/fibrate combination therapy, particularly for patients who have mixed dyslipidemia. Clinical experience indicates that there may be an increased risk of myotoxicity associated with statin/fibrate combination therapy. However, it is not known whether there are differences in the rate of myotoxicity between the use of fenofibrate and gemfibrozil in combination with statins. To evaluate this question, data from the United States Food and Drug Administration's Adverse Event Reporting System was reviewed to determine how many adverse events were reported for patients who were being treated concomitantly with statins and fibrates. The findings suggest that the use of fenofibrate in combination with statins results in fewer reports of rhabdomyolysis per million prescriptions dispensed than does the use of gemfibrozil.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Effective use of combination lipid therapy.

Despite the benefits of statin therapy, low-density lipoprotein cholesterol (LDL-C) management remains suboptimal and many patients do not achieve their recommended target goals. The aim of combination lipid drug therapy in high-risk patients is to achieve LDL-C and non-high-density lipoprotein cholesterol (HDL-C) goals with a minimum of serious adverse effects. Although statins are the drug of first choice, statin monotherapy may be limited by intolerance of dose escalation or failure to attain non-HDL-C goals in those with mixed hyperlipidemia. Statins plus bile acid resins or ezetimibe can achieve greater than 50% reduction in LDL-C, with little or no increase in adverse effects. Fibrates, niacin, and omega-3 fatty acids, when added to statins, can reduce triglycerides, increase HDL-C, and reduce non-HDL-C to a greater extent than statin monotherapy. The safety profile of combination lipid therapy is acceptable, if the global coronary heart disease risk of the patient is high, thus producing a favorable risk to benefit ratio. Careful surveillance of hepatic transaminases, avoidance of gemfibrozil in statin-fibrate combinations, and awareness of statin-concomitant drug interactions is key to safe and efficacious use of combination lipid drug therapy.

Anticholesteremic Agents↗
PubMed2005

Comparison of the efficacy and safety of atorvastatin initiated at different starting doses in patients with dyslipidemia.

BACKGROUND: The NASDAC study was designed to evaluate the safety and efficacy of atorvastatin at starting doses of 10, 20, 40, and 80 mg. METHODS: After an 8-week placebo washout period, 919 patients who were candidates for lipid-lowering therapy according to the National Cholesterol Education Program's Adult Treatment Panel III guidelines were randomized to 1 of 4 atorvastatin treatment groups: 10 mg (n = 229), 20 mg (n = 228), 40 mg (n = 231), and 80 mg (n = 231). RESULTS: Atorvastatin reduced low-density lipoprotein cholesterol (LDL-C) levels dose dependently across the 10- to 80-mg-dose range (35.7%-52.2%). Each of the 20-, 40-, and 80-mg doses provided significantly greater decreases in LDL-C than all lower doses (P < .01). All doses also reduced total cholesterol, the LDL-C/high-density lipoprotein cholesterol ratio, apolipoprotein B, and triglycerides from baseline. An increase in high-density lipoprotein cholesterol was observed in all dose groups. Most participants, regardless of their level of coronary heart disease risk, attained their National Cholesterol Education Program's Adult Treatment Panel III LDL-C goal by the end of the study. Patients in all risk groups were more likely to achieve the NCEP LDL-C goal at higher starting doses. Atorvastatin was well tolerated at all dose levels. CONCLUSIONS: Atorvastatin initiated at doses of 10, 20, 40, and 80 mg is effective and safe for the treatment of patients with dyslipidemia. Depending on the percentage reduction needed to achieve an LDL-C goal, patients with or at risk of coronary heart disease may benefit from starting therapy at a higher dose of atorvastatin.

Adult↗
PubMed2005

Multiplexed analysis of biomarkers related to obesity and the metabolic syndrome in human plasma, using the Luminex-100 system.

BACKGROUND: The complex pathology of disease has sparked the development of novel protein expression profiling techniques that require validation in clinical settings. This study focuses on multiplexed analyses of adipocytokines and biomarkers linked to the metabolic syndrome, diabetes, and cardiovascular disease. METHODS: Multiplexed immunoassays using fluorescent microspheres and the Luminex-100 system were performed on plasma from 80 obese patients (40 with the metabolic syndrome) before and after 6-8 weeks of diet-induced weight loss. Leptin, insulin, C-peptide, monocyte chemoattractant protein-1 (MCP-1), eotaxin, interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and IL-6 concentrations measured with multiplex panels from 3 different manufacturers were compared with results from commercial ELISAs. Detection limits and between- and within-run imprecision were determined for each analyte. Bland-Altman analysis was used to determine agreement between multiplexed immunoassays and ELISAs. RESULTS: Correlation between the Luminex multiplexed assays and ELISAs was good for leptin (Linco), insulin (Linco), MCP-1 (Biosource and Upstate), and eotaxin (Biosource) with correlation coefficients of 0.711-0.895; fair for eotaxin (Upstate) and C-peptide (Linco) with correlation coefficients of 0.496-0.582; and poor for TNF-alpha, IL-8, and IL-6 (Linco, Biosource, Upstate, and R&D) with correlation coefficients of -0.107 to 0.318. Within- and between-run imprecision values for the multiplex method were generally <15%. Relative changes in plasma leptin and insulin concentrations after diet-induced weight loss were similar whether assessed by multiplex assay or ELISA. CONCLUSION: Although this technology appears useful in clinical research studies, low assay sensitivity and poor correlations with conventional ELISA methods for some analytes with very low plasma concentrations should be considered when using the Luminex platform in clinical studies.

Adipose Tissue↗
PubMed2005

Safety of statins: effects on muscle and the liver.

Although statin drugs can have adverse effects on muscles and the liver, these effects are uncommon. Caution is warranted in patients at higher risk, ie, those who are elderly, frail, or small; have multisystem disease; are receiving immunosuppressive drugs or other medications that interact with statins; or are receiving higher doses of a statin.

Alanine Transaminase↗
PubMed2005

Statins: the case for higher, individualized starting doses.

If patients with hypercholesterolemia were started on higher doses of statins tailored to their lipid levels and risk, more of them would achieve their low-density lipoprotein cholesterol (LDL-C) goals, possibly leading to fewer cardiovascular events and deaths.

Coronary Disease↗
PubMed2004

Effectiveness and tolerability of ezetimibe add-on therapy to a bile acid resin-based regimen for hypercholesterolemia.

Combination lipid-reducing therapy is increasingly used, particularly for the management of severe or combined dyslipidemia in patients at high risk for coronary heart disease. To assess the potential additive effects of combining the cholesterol absorption inhibitor ezetimibe with a bile acid resin (BAR), a prospective chart review was performed of 40 patients in whom ezetimibe 10 mg/day was added to a stable regimen that included a BAR. At an average follow-up of 107 +/- 57 days, ezetimibe coadministration significantly reduced total cholesterol by 18%, triglycerides by 14%, and low-density lipoprotein cholesterol by 19% (all p < or =0.03), without significantly changing high-density lipoprotein cholesterol, and the combination was well tolerated.

Allylamine↗
PubMed2004

Low-density lipoprotein cholesterol reduction and cardiovascular disease prevention: the search for superior treatment.

Current US lipid-lowering guidelines indicate that optimal plasma levels of low-density lipoprotein cholesterol (LDL-C) are <100 mg/dL, and targeting global risk assessment has significantly increased the number of individuals who are candidates for intensive plasma lipid-lowering therapy. There is accumulating evidence that reduction of plasma LDL-C concentrations to targets even lower than those currently recommended may provide additional benefit in coronary heart disease (CHD) prevention. For example, the Heart Protection Study (HPS) found that statin treatment initiated at a baseline LDL-C plasma level of <100 mg/dL in patients at high risk provided a relative benefit in reducing the incidence of cardiovascular events that was similar to when it was initiated at higher LDL-C plasma levels. In addition, it is becoming clear that CHD risk, and the need for intensive lipid-lowering treatment, may be underestimated in some populations, including individuals with the metabolic syndrome. In the overall primary prevention population, high-sensitivity C-reactive protein measurement has been shown to identify individuals at high risk of cardiovascular events who would not be considered at high risk on the basis of current systems of risk assessment. The increasing focus on intensive plasma lipid lowering to reduce CHD risk has placed a premium on the development of therapies with improved ability to reduce plasma levels of LDL-C.

Cholesterol, HDL↗
PubMed2004

Statins as the cornerstone of drug therapy for dyslipidemia: monotherapy and combination therapy options.

Low-density lipoprotein (LDL) cholesterol reduction with statin treatment remains the cornerstone of lipid-lowering therapy to reduce risk of coronary heart disease. Combination therapy with a statin poses advantages in certain settings and may allow use of lower doses of multiple drugs rather than maximum doses of a single drug. Bile-acid sequestrants or the cholesterol-absorption inhibitor ezetimibe can be added to a statin to achieve greater LDL cholesterol reductions. Niacin or fenofibrate can be added to a statin for treatment of mixed dyslipidemia. Differences in statin efficacy in reducing LDL cholesterol and meeting recommended LDL cholesterol targets as well as differences among these agents in beneficial effects on other lipid parameters can affect whether and how these agents are prescribed in monotherapy and combination therapy.

Alanine Transaminase↗
PubMed2004

Effects of rosuvastatin versus atorvastatin, simvastatin, and pravastatin on non-high-density lipoprotein cholesterol, apolipoproteins, and lipid ratios in patients with hypercholesterolemia: additional results from the STELLAR trial.

BACKGROUND: Non-high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) B, and lipid and apolipoprotein ratios that include both atherogenic and antiatherogenic lipid components have been found to be strong predictors of coronary heart disease risk. OBJECTIVE: The goal of this study was to examine prospectively the effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin across dose ranges on non-HDL-C, apo B, apo A-I, and total cholesterol (TC):HDL-C, low-density lipoprotein cholesterol (LDL-C):HDL-C, non-HDL-C:HDL-C, and apo B:apo A-I ratios in patients with hypercholesterolemia (LDL-C > or =160 mg/dL and <250 mg/dL and triglycerides <400 mg/dL) in the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial. METHODS: In this randomized, Multicenter, parallel-group, open-label trial (4522IL/0065), patients > or =18 years of age received 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 for 6 weeks. Pairwise comparisons were prospectively planned and performed between rosuvastatin 10, 20, and 40 mg and milligram-equivalent or higher doses of comparators. RESULTS: A total of 2268 patients were randomized to the rosuvastatin 10- to 40-mg, atorvastatin, simvastatin, and pravastatin groups. Fifty-one percent of patients were women, the mean (SD) age was 57 (12) years, and 19% had a documented history of atherosclerotic disease. Over 6 weeks, rosuvastatin significantly reduced non-HDL-C, apo B, and all lipid and apolipoprotein ratios assessed, compared with milligram-equivalent doses of atorvastatin and milligram-equivalent or higher doses of simvastatin and pravastatin (all, P < 0.002). Rosuvastatin reduced non-HDL-C by 42.0% to 50.9% compared with 34.4% to 48.1% with atorvastatin, 26.0% to 41.8% with simvastatin, and 18.6% to 27.4% with pravastatin. Rosuvastatin reduced apo B by 36.7% to 45.3% compared with 29.4% to 42.9% with atorvastatin, 22.2% to 34.7% with simvastatin, and 14.7% to 23.0% with pravastatin. The highest increase in apo A-I (8.8%) was observed in the rosuvastatin 20-mg group, and this increase was significantly greater than in the atorvastatin 40-mg and 80-mg groups (both, P < 0.002). CONCLUSION: Rosuvastatin 10 to 40 mg was more efficacious in improving the lipid profile of patients with hypercholesterolemia than milligram-equivalent doses of atorvastatin and milligram-equivalent or higher doses of simvastatin and pravastatin.

Aged↗