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Biomedical subjects

Jennifer G Robinson

Publications and source records attributed to Jennifer G Robinson.

16 recordsLinked to original sources
PubMed2007

Update on PPAR agonists: the clinical significance of FIELD and PROACTIVE.

The peroxisome proliferator-activated receptor (PPAR) family of genes plays a major role in metabolic regulation. Unfortunately, the results of two recent, large event trials of PPAR agonists have been mixed. High rates of crossover to statin use confound the interpretation of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, which found a less than expected reduction in coronary and stroke events with fenofibrate. Of concern, nonsignificant increases in coronary and sudden deaths, thrombotic events, and pancreatitis occurred in the fenofibrate group. The PROspective pioglitAzone Clinical Trial In macroVascular Events (PROACTIVE) also found a reduction in coronary and stroke events with pioglitazone compared with placebo in a population with diabetes and cardiovascular disease, but this benefit was counterbalanced by an increase in congestive heart failure as well as symptomatic edema. Further research is needed to determine the role of PPAR agonists in the prevention of cardiovascular disease.

Coronary Disease↗
PubMed2006

Is it time for a cardiovascular primary prevention trial in the elderly?

BACKGROUND AND PURPOSE: Statins have been shown conclusively to reduce the risk of cardiovascular events in subjects with clinical cardiovascular disease or diabetes aged 65 to 80 years of age. However, few data are available for primary prevention of cardiovascular disease in those aged > or =70 years. SUMMARY OF REVIEW: A moderate-dose statin was of little benefit in a population aged 70 to 82 years when given for 3 years in the setting of suboptimally treated blood pressure. More evidence supports the use of blood pressure-lowering medications, but few data are available regarding the appropriate blood pressure target and most effective agents in the elderly. Some evidence also suggests that the elderly could experience higher mortality with antihypertensive treatment. These findings, along with greater safety concerns and an increasing number of competing risks and medical conditions with advancing age, make it imperative to carefully evaluate the risk/benefit balance from treating hypercholesterolemia and hypertension in persons aged > or =70 years. CONCLUSIONS: We propose a 5-year 2x2 factorial trial of primary prevention in the elderly that will (1) evaluate whether statin therapy will reduce the risk of cardiovascular events when added to the treatment of hypertension to achieve a blood pressure <140/90 mm Hg in most patients and (2) determine the most appropriate blood pressure regimen for the prevention of cardiovascular and renal events.

Aged↗
PubMed2006

Identifying patients for aggressive cholesterol lowering: the risk curve concept.

The National Cholesterol Education Program's 2004 report identified more aggressive optional low-density lipoprotein (LDL) cholesterol treatment goals of <70 mg/dl for secondary prevention patients and <100 mg/dl for moderately high risk, primary prevention patients. Although LDL cholesterol reduction is the first step in reducing cardiovascular risk, it may be difficult for clinicians to visualize the risk reduction benefit for patients from various risk interventions. The concept of a "risk curve," or the absolute risk of a patient for subsequent cardiovascular events over a range of LDL cholesterol values, is proposed. In conclusion, placing a patient on the appropriate risk curve may facilitate an individualized clinical management strategy that takes into account the patient's absolute benefit from further LDL cholesterol reduction as well as from shifting the risk curve downward through non-LDL cholesterol interventions.

Anticholesteremic Agents↗
PubMed2006

Impact of cyclooxygenase inhibitors in the Women's Health Initiative hormone trials: secondary analysis of a randomized trial.

OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women's Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials. DESIGN: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6. SETTING: The Women's Health Initiative hormone trials were conducted at 40 clinical sites in the United States. PARTICIPANTS: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. INTERVENTIONS: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. OUTCOME MEASURES: Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. RESULTS: Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified. CONCLUSIONS: Use of COX inhibitors did not significantly affect the Women's Health Initiative hormone trial results.

Journal Article↗
PubMed2006

Antiatherosclerotic and antithrombotic effects of omega-3 fatty acids.

Omega-3 fatty acids from both marine and plant sources have been shown to reduce the risk of coronary artery disease death. Although their beneficial cardiovascular effects are thought to be due to their antiarrhythmic properties, omega-3 fatty acids also have been shown to have a wide range of antiatherosclerotic and antithrombotic effects in animal and human studies. Review of the findings of randomized, controlled trials published through August 2005 shows that omega-3 fatty acids of marine origin consistently lower elevated plasma triglyceride levels in a dose-dependent fashion, with greater efficacy at higher triglyceride levels. Smaller effects on lowering blood pressure, improving endothelial function, and increasing plasma levels of high-density lipoprotein cholesterol were also found. No consistent effects on other lipid, hemostatic, inflammatory, glucose tolerance, or plaque stabilization parameters were found. Epidemiologic studies show more consistent reductions in the incidence of nonfatal myocardial infarction and ischemic stroke than do the clinical trials of increased omega-3 fatty acid intake, which suggests important confounding factors in observational studies. Ongoing clinical trials may clarify the non-antiarrhythmic benefits of omega-3 fatty acid supplementation.

Animals↗
PubMed2006

Elderly women diagnosed with nonspecific chest pain may be at increased cardiovascular risk.

BACKGROUND: Women are more likely than men to have nonspecific chest pain (NSCP) symptoms. The long-term outcomes in women discharged with a diagnosis of NSCP are unknown. METHODS: The Women's Health Initiative Observational Study enrolled postmenopausal women aged 50-79 years. After excluding those with prior cardiovascular disease (CVD), 83,622 women were studied. NSCP cases were defined as having an initial primary hospital discharge diagnosis of NSCP (ICD-9 codes 786.50, 786.51, 786.59) without a prior diagnosis of coronary heart disease (CHD). Risks of subsequent CHD events were estimated from Cox proportional hazard ratio (HR) models stratified by clinic and adjusted for baseline age, cardiovascular risk factors, and hormone use. RESULTS: Over an average of 8 years of follow-up, 11% (230 of 2,092) of women with NSCP experienced a cardiovascular event compared with 9.5% (7,724 of 81,530) who did not. Compared with women without a hospitalization for NSCP during follow-up, those with NSCP had a greater than 2-fold higher risk of a subsequent hospitalization for clinically diagnosed angina (HR 2.18, 95% CI 1.66-2.86) and at least a 1.5-fold higher risk of nonfatal myocardial infarction (MI) (HR 1.59, 1.10-2.31), revascularization (HR 1.67, 1.28-2.20), and congestive heart failure (HR 1.75, 1.27-2.41). Women with NSCP who subsequently experienced a CHD event were more likely to be over age 65 or to have cardiovascular risk factors. CONCLUSIONS: Older women discharged with a diagnosis of NSCP may be at increased risk of CHD morbidity. Further research is needed to replicate these findings in other populations.

Aged↗
PubMed2006

Lipid-lowering effects of statins: a comparative review.

The pharmacological regulation of lipid metabolism in patients with dyslipidaemia is unequivocally associated with significant reductions in risk for cardiovascular morbidity and mortality. There is strong clinical trial data to support of the use of statin therapies in the settings of both primary and secondary prevention. This paper addresses: i) the mechanisms of action of antilipidaemic medications; ii) dosing regimens and the pharmacokinetic differences among drugs of the same class; iii) risk for drug interactions; and iv) reviews the clinical trial evidence used to support the use of particular antilipidaemic medications in specific physiological settings.

Cytochrome P-450 CYP3A↗
PubMed2006

Combination therapy with ezetimibe and simvastatin to achieve aggressive LDL reduction.

A low-density lipoprotein (LDL) cholesterol goal of less than 100 mg/dl is recommended for patients at moderate to high risk of cardiovascular disease with an optional LDL goal of less than 70 mg/dl for patients at a very high risk of cardiovascular disease. Most patients will require reductions in LDL of more than 50% in order to achieve these more aggressive goals. Only a few agents will lower LDL by at least 50%. This review will focus on the efficacy and safety ezetimibe/simvastatin coadministered as a therapy with enhanced LDL-lowering efficacy, while minimizing the adverse effects of statins in a wide range of patients. Ezetimibe 10 mg/simvastatin 80 mg lowers LDL by approximately 60% and has been demonstrated to be superior to the highest doses of atorvastatin and rosuvastatin for lowering LDL and raising high-density lipoprotein.

Anticholesteremic Agents↗
PubMed2005

Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis.

OBJECTIVES: This study sought to determine whether statins reduce coronary heart disease (CHD) risk more than other interventions that also primarily lower low-density lipoprotein cholesterol (LDL-C). BACKGROUND: Statins have anti-inflammatory, immunomodulatory, antithrombotic, vascular, and other non-LDL-C-lowering effects. It is unclear whether these pleiotropic effects contribute to cardiovascular risk reduction beyond that expected from LDL-C reduction alone. METHODS: Trials published in English language journals were retrieved by searching Medline (1966 to October 2004), bibliographies, and the author's reference files. Randomized, placebo-controlled trials of interventions to primarily lower LDL-C of three or more years' duration in which clinical disease or death were primary outcomes were used. Information on sample size, treatment type and duration, participant characteristics at baseline, reduction in lipids, and outcome was independently abstracted by two authors (J.R. and N.M.) using a standardized protocol. Data from 5 diet, 3 bile acid sequestrant, 1 surgery, and 10 statin trials, with 81,859 participants, were included in the CHD meta-regression analysis. RESULTS: The regression lines for non-statin and statin trials were similar and consistent with a one-to-one relationship between LDL-C lowering and CHD and stroke reduction over five years of treatment. CONCLUSIONS: The pleiotropic effects of statins do not seem to contribute an additional cardiovascular risk reduction benefit beyond that expected from the degree of LDL-C lowering observed in other trials that primarily lowered LDL-C.

Cholesterol, LDL↗
PubMed2005

A "poly-portfolio" for secondary prevention: a strategy to reduce subsequent events by up to 97% over five years.

A "polypill" for the primary prevention of cardiovascular disease has been proposed. We estimated the projected benefit of a secondary prevention "poly-portfolio" strategy, including pharmacologic and lifestyle approaches for those with coronary heart disease (CHD) or stroke. Based on recent clinical trial results and clinical guidelines, combinations of a high-dose statin, low to standard doses of antihypertensive therapy, aspirin, omega-3 fish oil, cardiac rehabilitation, and diet were evaluated. Patients with CHD, post-myocardial infarction (MI), or stroke were projected to experience 84%, 91%, and 77% reductions, respectively, in CHD events from a pharmacologic approach. Numbers of those needed to treat (NNT) for 5 years were 9 to 11 to prevent 1 CHD event, and 21 to prevent 1 stroke. Post-MI patients were projected to experience a 93% reduction in the risk of CHD death (NNT 16) from a pharmacologic approach and a 97% reduction in the risk of CHD death (NNT 15) with the addition of lifestyle changes. A secondary prevention polyportfolio holds great promise for reducing the burden of cardiovascular disease in the highest risk patients.

Adrenergic beta-Antagonists↗
PubMed2004

Evidence-based public health: an evolving concept.

Evidence-based public health (EBPH) has been proposed as a practice model that builds upon the success of evidence-based medicine (EBM). EBM has been described as a more scientific and systematic approach to the practice of medicine. It has enhanced medical training and practice in many settings. Both EBM and EBPH systematically use data, information, and scientific principles to enhance clinical care and population health, respectively. In this paper, we review the evolution of EBPH, propose a new definition for EBPH, and discuss developments that may support its further advancement.

Evidence-Based Medicine↗
PubMed2001

A Comparison of NCEP and Absolute Risk Stratification Methods for Lipid-Lowering Therapy in Middle-Aged Adults: The ARIC Study. The ARIC Investigators.

Lipid-lowering therapy has been shown to reduce cardiovascular disease risk in individuals with low-density lipoprotein cholesterol (LDL-C) levels of at or above 130 mg/dL. Several methods have been developed for identifying those at highest risk for treatment. The objective was to compare the 1993 National Cholesterol Education Program guidelines to absolute risk assessment methods similar to those used by recently developed European and British cholesterol treatment guidelines. The design and setting was a population-based, prospective cohort study in four US communities. Among Atherosclerosis Risk in the Communities study participants aged 45-64 years followed for a mean of 7 years, 7314 women and 5762 men were included who had no evidence of clinical cardiovascular disease and were not receiving lipid-lowering drug therapy at entry. Main outcome measures were number meeting criteria for treatment, number of cardiovascular events expected to be prevented with treatment, number needed to treat to prevent one cardiovascular event, and sensitivity of criteria for detecting cases for the entire cohort and for those at or above the LDL-C treatment threshold (within-group). The 1993 National Cholesterol Education Program guidelines identified 16% of participants for treatment: n=2112; events expected to be prevented=77; number needed to treat=27; sensitivity=0.31 (0.28-0.35); sensitivity when LDL-C was greater-than-or-equal160 mg/dL=0.86. Use of a LDL-C treatment threshold of greater-than-or-equal130 mg/dL, a greater-than-or-equal20% 10-year absolute risk cut-point (similar to European guidelines) identified 13% for treatment: n=1701; events expected to be prevented=66; number needed to treat=26; sensitivity=0.29 (0.25-0.32); sensitivity when LDL-C was >130 mg/dL=0.43. A greater-than-or-equal15% risk cut-point (similar to British guidelines) identified 17% for treatment: n=2233; events expected to be prevented=82; number needed to treat=27; sensitivity=0.37 (0.33-0.40); sensitivity when LDL-C was greater-than-or-equal130 mg/dL=0.55. Modified National Cholesterol Education Program guidelines (LDL-C treatment threshold lowered from 160 to 130 mg/dL for those with greater-than-or-equal2 risk factors) identified 30% for treatment: n=3867; events expected to be prevented=120; number needed to treat=32; sensitivity=0.55 (0.52-0.59); sensitivity when LDL-C was 130 mg/dL=0.83. A hybrid strategy using greater-than-or-equal15% risk, or 10% to 14% risk with a parental history of premature coronary heart disease or treated, controlled hypertension, identified 20% for treatment: n=2646; events expected to be prevented=97; number needed to treat=27; sensitivity=0.44 (0.40-0.47); sensitivity when LDL-C was greater-than-or-equal130 mg/dL=0.66. Depending on the priorities of a health care system, higher absolute cut-points can be used for allocating health care resources to those at the highest risk. However, fewer cardiovascular events will be prevented and fewer patients who later experience cardiovascular events will be offered treatment despite acceptable numbers needed to treat to prevent one cardiovascular disease event. A hybrid absolute risk strategy incorporating family history and treated hypertension information appears to be superior to absolute risk strategies that do not include this information. Copyright 2001 CHF, Inc.

Journal Article↗