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Neil J Stone

Publications and source records attributed to Neil J Stone.

35 records · Page 2Linked to original sources
PubMed2004

Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.

The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.

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PubMed2004

Treatment of metabolic syndrome.

The metabolic syndrome is intended to identify patients who have increased risk of diabetes and/or a cardiac event due to the deleterious effects of weight gain, sedentary lifestyle, and/or an atherogenic diet. The National Cholesterol Education Program's Adult Treatment Panel III definition uses easily measured clinical findings of increased abdominal circumference, elevated triglycerides, low high-density lipoprotein-cholesterol, elevated fasting blood glucose and/or elevated blood pressure. Three of these five are required for diagnosis. The authors also note that other definitions of metabolic syndrome focus more on insulin resistance and its key role in this syndrome. This review focuses on how treatment might affect each of the five components. Abdominal obesity can be treated with a variety of lower calorie diets along with regular exercise. Indeed, all of the five components of the metabolic syndrome are improved by even modest amounts of weight loss achieved with diet and exercise. For those with impaired fasting glucose tolerance, there is good evidence that a high fiber, low saturated fat diet with increased daily exercise can reduce the incidence of diabetes by almost 60%. Of note, subjects who exercise the most, gain the most benefit. Metformin has also been shown to be helpful in these subjects. Thiazolidinedione drugs may prove useful, but further studies are needed. Although intensified therapeutic lifestyle change will help the abnormal lipid profile, some patients may require drug therapy. This review also discusses the use of statins, fibrates, and niacin. Likewise, while hypertension in the metabolic syndrome benefits from therapeutic lifestyle change, physicians should also consider angiotensin converting enzyme inhibitor drugs or angiotensin receptor blockers, due to their effects on preventing complications of diabetes, such as progression of diabetic nephropathy and due to their effects on regression of left ventricular hypertrophy. Aspirin should be considered in those with at least a 10% risk of a coronary event over 10 years. Finally, three related conditions, nonalcoholic fatty liver disease, polycystic ovary syndrome and protease inhibitor associated lipodystrophy improve with therapeutic lifestyle change. Although metformin is shown to be useful with polycystic ovary syndrome, the data supporting drug therapy for the other syndromes is less convincing. More robust studies are needed before any firm recommendations can be made.

Abdomen↗
PubMed2004

Improvement in the function of hibernating myocardium in a patient with heart failure due to coronary artery disease receiving high-dose simvastatin.

We report the case of a 70-year-old man with a history of myocardial infarction and coronary artery bypass grafting, presenting with signs and symptoms of heart failure. Cardiac magnetic resonance imaging demonstrated a small amount of scarring in the anteroseptal wall, moderate left ventricular enlargement, and a left ventricular ejection fraction of 26%. Patient was started on simvastatin 20 mg daily, gradually increased to 80 mg daily, which were maintained for another 4 weeks. Twelve weeks after the initial presentation, the patient experienced a marked improvement in his symptoms. Repeat cardiac magnetic resonance imaging showed global improvement in left ventricular contractility, with ejection fraction of 36% and end-diastolic volume decreasing from 230 to 153 ml. We speculate that high-dose statin therapy had a significant role in improving the ventricular function in our patient by improving the endothelial flow. This hypothesis is presently being tested in a larger prospective trial.

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PubMed2003

Effects of dietary modification to reduce vascular risks and treatment of obesity.

This article has considered a vast literature attesting to the efficacy of dietary intervention on risk factors for CHD and on vascular outcomes. Rather than relying solely on pharmacotherapy to improve risk factors and vascular outcomes, physicians, nurses, dietitians, pharmacists, and medical providers should emphasize the benefits of a well-balanced, nutritionally sound dietary program. The diet should be low in saturated fatty acids, controlled in calories to avoid (or reduce) obesity, and rich in fruits, vegetables, whole grain products, and good sources of protein. Emphasis on foods rich in n-3 fatty acids shows promise for reducing cardiovascular outcomes, particularly sudden death.

Cardiovascular Diseases↗
PubMed2002

Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve.

BACKGROUND: Despite the common occurrence of aortic stenosis, the cellular causes of the disorder are unknown, in part because of the absence of experimental models. We hypothesized that atherosclerosis and early bone matrix expression in the aortic valve occurs secondary to experimental hypercholesterolemia and that treatment with atorvastatin modifies this transformation. METHODS AND RESULTS: To test this hypothesis, we developed an experimental hypercholesterolemic rabbit model. New Zealand White rabbits (n=48) were studied: group 1 (n=16), normal diet; group 2 (n=16), 1% (wt/wt) cholesterol diet; and group 3 (n=16), 1% (wt/wt) cholesterol diet plus atorvastatin (3 mg/kg per day). The aortic valves were examined with hematoxylin and eosin stain, Masson trichrome, macrophage (RAM 11), proliferation cell nuclear antigen (PCNA), and osteopontin immunostains. Cholesterol and highly sensitive C-reactive protein (hsCRP) serum levels were obtained by standard assays. Computerized morphometry and digital image analysis were performed for quantifying PCNA (% area). Electron microscopy and immunogold labeling were performed for osteopontin. Semiquantitative RT-PCR was performed for the osteoblast bone markers [alkaline phosphatase, osteopontin, and osteoblast lineage-specific transcription factor (Cbfa-1)]. There was an increase in cholesterol, hsCRP, PCNA, RAM 11, and osteopontin and osteoblast gene markers (alkaline phosphatase, osteopontin, and Cbfa-1) in the cholesterol-fed rabbits compared with control rabbits. All markers except hsCRP were reduced by atorvastatin. CONCLUSIONS: These findings of increased macrophages, PCNA levels, and bone matrix proteins in the aortic valve during experimental hypercholesterolemia provide evidence of a proliferative atherosclerosis-like process in the aortic valve associated with the transformation to an osteoblast-like phenotype that is inhibited by atorvastatin.

Alkaline Phosphatase↗
PubMed2002

Therapeutic lifestyle change and Adult Treatment Panel III: evidence then and now.

The Third Report of the National Cholesterol Education Program's Adult Treatment Panel (ATP III) has an extensive section on nonpharmacologic therapy for those with abnormal blood lipids. ATP III focused on the high-saturated fat atherogenic diet, obesity, and sedentary lifestyle and recommended a program of therapeutic lifestyle change (TLC). This review discusses several issues, including 1) why ATP III changed from the Step I and Step II diets to TLC; 2) the benefits of keeping trans fatty acid intake low and the addition of viscous fiber and plant stanol/sterol esters to reduce low-density lipoprotein cholesterol beyond that seen with the Step II diet; 3) the de-emphasis on total fat and a sharper focus on the kinds of fat ingested in the new guidelines; 4) the endorsement of regular physical activity and weight loss as important first steps in reversing the unwanted metabolic effects of the metabolic syndrome; and 5) the emphasis of health-promoting aspects of the diet that include, among other things, fish and omega-3 fatty acids. At all stages of TLC, ATP III encourages the referral to registered dietitians or other qualified nutritionists for medical nutrition therapy. TLC and the ATP III guidelines should provide guidance to practitioners who wish to get low-density lipoprotein cholesterol to goal (whether or not drugs are used), prevent or treat the metabolic syndrome, and improve the overall health of the patient.

Coronary Disease↗
PubMed2002

Goals of statin therapy: three viewpoints.

The "lipid hypothesis" is now universally recognized as a law. Few issues in medicine are as completely resolved as the question of whether reducing serum cholesterol increases longevity. However, there are a few questions that remain, and the most important uncertainty is to what extent cholesterol should be reduced. The medical community, in partnership with government and industry, has contributed many excellent trials demonstrating the effects in patients with elevated cholesterol (above the mean). Where should our goal of therapy be? Until data is available from several large, ongoing trials, we do not have a final answer. We asked three investigators, Drs. Gilbert Thompson, Christopher Packard, and Neil Stone, who have all been integrally involved in the accumulation of our present database, to argue three different possible answers.

Goals↗
PubMedDate not supplied

Are statins indicated for the primary prevention of coronary heart disease in octogenarians? protagonist viewpoint.

Statins should be given to octogenarians for primary prevention of coronary heart disease. There is a substantial burden of disease and disability in this population that statin treatment can address in an effective manner. It has been shown that statin treatment is both effective and safe, and details of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial are reviewed. It may be useful to tease out those at particularly high risk who would benefit from statin treatment. In this regard, a low high-density lipoprotein cholesterol level, high-sensitivity C-reactive protein level, and subclinical measures of atherosclerosis may be particularly useful.

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