Showing papers by "Scott M. Grundy published in 2001"
TL;DR: The sex-specific Framingham CHD prediction functions perform well among whites and blacks in different settings and can be applied to other ethnic groups after recalibration for differing prevalences of risk factors and underlying rates of CHD events.
Abstract: Context The Framingham Heart Study produced sex-specific coronary heart disease (CHD) prediction functions for assessing risk of developing incident CHD in a white middle-class population. Concern exists regarding whether these functions can be generalized to other populations. Objective To test the validity and transportability of the Framingham CHD prediction functions per a National Heart, Lung, and Blood Institute workshop organized for this purpose. Design, Setting, and Subjects Sex-specific CHD functions were derived from Framingham data for prediction of coronary death and myocardial infarction. These functions were applied to 6 prospectively studied, ethnically diverse cohorts (n = 23 424), including whites, blacks, Native Americans, Japanese American men, and Hispanic men: the Atherosclerosis Risk in Communities Study (1987-1988), Physicians' Health Study (1982), Honolulu Heart Program (1980-1982), Puerto Rico Heart Health Program (1965-1968), Strong Heart Study (1989-1991), and Cardiovascular Health Study (1989-1990). Main Outcome Measures The performance, or ability to accurately predict CHD risk, of the Framingham functions compared with the performance of risk functions developed specifically from the individual cohorts' data. Comparisons included evaluation of the equality of relative risks for standard CHD risk factors, discrimination, and calibration. Results For white men and women and for black men and women the Framingham functions performed reasonably well for prediction of CHD events within 5 years of follow-up. Among Japanese American and Hispanic men and Native American women, the Framingham functions systematically overestimated the risk of 5-year CHD events. After recalibration, taking into account different prevalences of risk factors and underlying rates of developing CHD, the Framingham functions worked well in these populations. Conclusions The sex-specific Framingham CHD prediction functions perform well among whites and blacks in different settings and can be applied to other ethnic groups after recalibration for differing prevalences of risk factors and underlying rates of CHD events.
2,173 citations
TL;DR: Data support an anti-inflammatory effect of these drugs on levels of high-sensitive CRP in patients with combined hyperlipidemia, and there was no relationship between reductions in hs-CRP and LDL cholesterol.
Abstract: Background —Prospective studies indicate that baseline levels of C-reactive protein (CRP), the prototypic marker of inflammation, are associated with an increased risk for cardiovascular events. Limited studies have examined therapies that influence high-sensitive CRP (hs-CRP) levels, especially in hyperlipidemic patients. Thus, we tested the effects of 3 hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins), simvastatin (20 mg/d), pravastatin (40 mg/d), and atorvastatin (10 mg/d), on levels of hs-CRP in a randomized, double-blind, crossover trial of 22 patients with combined hyperlipidemia (LDL cholesterol >130 mg/dL and triglycerides of 200 to 600 mg/dL).
Methods and Results —After 6 weeks of an American Heart Association Step 1 diet, fasting blood samples were drawn at baseline and after 6 weeks of therapy with each drug. hs-CRP levels were significantly decreased after treatment with all 3 statins compared with baseline (median values: baseline, 2.6 mg/L; atorvastatin, 1.7 mg/L; simvastatin, 1.7 mg/L; and pravastatin, 1.9 mg/L; P <0.025). The reductions obtained with the 3 statins were similar. In addition, there was no significant effect on either plasma interleukin-6 or interleukin-6 soluble receptor levels. There was no relationship between reductions in hs-CRP and LDL cholesterol.
Conclusions —Pravastatin, simvastatin, and atorvastatin significantly decreased levels of hs-CRP. These data support an anti-inflammatory effect of these drugs.
750 citations
TL;DR: Since the original publication (in 1995) of the AHA consensus statement on secondary prevention, important evidence from clinical trials has emerged that further supports the merits of aggressive risk reduction therapies for patients with atherosclerotic cardiovascular disease.
Abstract: Since the original publication (in 1995) of the American Heart Association (AHA) consensus statement on secondary prevention, which was endorsed by the American College of Cardiology (ACC), important evidence from clinical trials has emerged that further supports the merits of aggressive risk reduction therapies for patients with atherosclerotic cardiovascular disease. As noted in that statement, aggressive risk factor management clearly improves patient survival, reduces recurrent events and the need for interventional procedures, and improves the quality of life for these patients.
The compelling evidence from recent clinical trials was the impetus …
741 citations
TL;DR: Since the original publication (in 1995) of the AHA consensus statement on secondary prevention, important evidence from clinical trials has emerged that further supports the merits of aggressive risk reduction therapies for patients with atherosclerotic cardiovascular disease.
Abstract: Since the original publication (in 1995) of the American Heart Association (AHA) consensus statement on secondary prevention, which was endorsed by the American College of Cardiology (ACC), important evidence from clinical trials has emerged that further supports the merits of aggressive risk reduction therapies for patients with atherosclerotic cardiovascular disease. As noted in that statement, aggressive risk factor management clearly improves patient survival, reduces recurrent events and the need for interventional procedures, and improves the quality of life for these patients.
The compelling evidence from recent clinical trials was the impetus …
649 citations
TL;DR: Key findings and recommendations of the AHA Prevention V conference are amplified, new research since the conference is highlighted, and an approach to the use of office-based testing and additional noninvasive procedures in selected patients to better define their coronary event risk is proposed.
Abstract: At least 25% of coronary patients have sudden death or nonfatal myocardial infarction without prior symptoms1 Therefore, the search for coronary patients with subclinical disease who could potentially benefit from intensive primary prevention efforts is critically important The American Heart Association’s (AHA) Prevention V Conference, “Beyond Secondary Prevention: Identifying the High Risk Patient for Primary Prevention,” addressed ways to identify more patients who are asymptomatic and clinically free of coronary heart disease (CHD) but at sufficiently high risk for a future coronary event to justify more intensive risk reduction efforts2 In this report, we amplify on key findings and recommendations of the AHA Prevention V conference, highlight new research since the conference, and propose an approach to the use of office-based testing and additional noninvasive procedures in selected patients to better define their coronary event risk The recommendations are concordant with the recently released approach to risk assessment and management from the third report of the Adult Treatment Panel of the National Cholesterol Education Program (ATP-III)3
Enthusiasm for primary prevention and risk assessment in asymptomatic people has been spurred by recent advances in prevention research Lipid-lowering trials demonstrated that primary prevention of coronary events is feasible, evidenced by the West of Scotland Coronary Primary Prevention Study (WOSCOPS) trial4 of hypercholesterolemic men and by the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) trial5 in average or typical risk men and women with only moderate lipid abnormalities Aspirin6 or ACE inhibitors7 can also reduce risk in selected asymptomatic, high-risk people Emerging coronary risk factors have been described including inflammatory, infectious, and thrombotic markers,8 and there has been a steady flow of reports that focus attention on potential new ways of predicting coronary risk9 In addition, noninvasive tests for subclinical atherosclerotic disease are available …
565 citations
Journal Article•
TL;DR: The embryonic lethality of Apex-null mice is confirmed and the phenotypic characterization of mice that are heterozygous mutants for the Apex gene (Apex+/-) is reported, which is consistent with a proposed role for this enzyme in protection against the deleterious effects of oxidative stress.
Abstract: Apurinic/apyrimidinic endonuclease is a key enzyme in the process of base excision repair, required for the repair of spontaneous base damage that arises as a result of oxidative damage to DNA. In mice, this endonuclease is coded by the Apex gene, disruption of which is incompatible with embryonic life. Here we confirm the embryonic lethality of Apex -null mice and report the phenotypic characterization of mice that are heterozygous mutants for the Apex gene ( Apex +/− ). We show that Apex heterozygous mutant cells and animals are abnormally sensitive to increased oxidative stress. Additionally, such animals manifest elevated levels of oxidative stress markers in serum, and we show that dietary supplementation with antioxidants restores these to normal levels. Apex +/− embryos and pups manifest reduced survival that can also be partially rescued by dietary supplementation with antioxidants. These results are consistent with a proposed role for this enzyme in protection against the deleterious effects of oxidative stress and raise the possibility that humans with heterozygous mutations in the homologous HAP1 gene may be at increased risk for the phenotypic consequences of oxidative stress in cells.
175 citations
TL;DR: This report was derived from a workshop on cardiovascular risk assessment, which addressed whether risk equations developed in the Framingham Heart Study for predicting new-onset coronary heart disease (CHD) apply to diverse population groups.
Abstract: This report was derived from a workshop on cardiovascular risk assessment sponsored by the National Heart, Lung, and Blood Institute, which addressed whether risk equations developed in the Framingham Heart Study (FHS) for predicting new-onset coronary heart disease (CHD) apply to diverse population groups. Preparation for the workshop included a reanalysis and comparison of prospective studies in several different populations in which risk factors were related to cardiovascular outcomes. Some studies included fatal and nonfatal CHD end points, whereas others contained only CHD mortality. Extensive collaboration provided as much uniformity as possible with respect to both risk factors and CHD end points.
The FHS has led in defining the quantitative impact of risk factors.1 Many potential risk factors were measured and related to cardiovascular outcomes. Several risk factors proved to be strong, largely independent predictors of cardiovascular disease (CVD). These factors—advancing age, cigarette smoking, blood pressure (particularly systolic), cholesterol in total serum and HDL, and diabetes—served as the basis for the development of risk prediction equations.1
If FHS risk estimates are to be widely used, they must apply widely in the US population. To document their transportability, they must be compared with prospective studies in other populations. Although the FHS is the longest running prospective study, there are other major studies. The cardiovascular end points of these other studies have varied. Some include cardiovascular morbidity and mortality; others have only cardiovascular mortality. Among the end points, CHD is the most extensively reported; for this reason, CHD was the primary focus of the workshop.
### Multivariate Relative Risk Comparisons
In preparation for the workshop, multivariate regression coefficients for each risk factor were compared in different populations with those of the FHS. Adjusted relative risk estimates make it possible to determine whether each independent risk factor confers a similar or different relative risk among different …
156 citations
TL;DR: The conference highlighted the progress that has been made in understanding the biological effects of fatty acids and also addressed the need to learn more about how different fatty acids affect the risk of chronic disease, within the context of refining dietary guidance to further enhance health.
Abstract: The objective of this Executive Summary is to provide a synopsis of the research findings presented at the American Heart Association conference “Dietary Fatty Acids and Cardiovascular Health—Dietary Recommendations for Fatty Acids: Is There Ample Evidence?” held on June 5–6, 2000, in Reston, Va. The conference was held to summarize the current understanding of the effects of fatty acids on risk of cardiovascular disease (CVD) and cancer, as well as to identify gaps in our knowledge base that need to be addressed. There is great interest in learning more about the biological effects of the individual fatty acids, their role in chronic disease risk, and their underlying mechanisms of action. As research advances are made, there is always the need to question how new findings may be translated into practice. There is a long history of research providing the basis for the modification of existing dietary guidelines. Research findings have been used to verify intake criteria and are considered along with practical issues of implementation to establish new guidelines. A substantive body of consistent evidence sufficient to defend a dietary recommendation or a change in existing dietary guidance is essential. The conference highlighted the progress that has been made in understanding the biological effects of fatty acids and also addressed the need to learn more about how different fatty acids affect the risk of chronic disease, within the context of refining dietary guidance to further enhance health.
As study designs have become increasingly rigorous, a number of megatrends have emerged from the data.1 2 There is increased emphasis on identifying the type of fat that best correlates with disease end points. The classic studies of Keys et al3 and Hegsted et al4 have shown that saturated fatty acids (ie, those with a carbon chain length of C12:0 …
138 citations
TL;DR: The degree of plaque burden could be used to replace age as a risk factor in Framingham scoring for risk prediction and this article describes a technique whereby such a replacement can be made.
Abstract: Risk assessment is assuming an increasing role for identification of high-risk persons for intensive medical intervention to reduce risk for coronary heart disease (CHD). Of particular importance is the need to identify those persons with CHD risk equivalents who can be managed with the same intensity as patients with established CHD. For example, the National Cholesterol Education Program (NCEP) recently classified diabetes as a CHD risk equivalent. The NCEP also recommended use of Framingham risk scoring in persons with multiple (2+) risk factors to uncover others without diabetes who have CHD risk equivalents. One limitation of Framingham risk scoring, however, is that age becomes the dominant risk factor after age 50. Age is a surrogate for coronary atherosclerotic plaque burden, which is the true risk factor. However, for individuals, coronary plaque burden can vary greatly at any given age. For this reason, if coronary plaque burden could be measured accurately with noninvasive techniques, the degree of plaque burden could be used to replace age as a risk factor in Framingham scoring for risk prediction. This article describes a technique whereby such a replacement can be made.
99 citations
TL;DR: The NAA Program constitutes a major new effort to enhance nutrition knowledge and skills among health care providers and to effectively apply the science of human nutrition to clinical medicine.
80 citations
TL;DR: Conference Planning and Writing Committee:Penny Kris-Etherton, PhD, Stephen R. Krauss, MD, Alice H. Lichtenstein, DSc, Frank Sacks,MD, Sachiko St. Jeor, PhD , Meir Stampfer, DrPH, For the American Heart Association Nutrition Committee Nutrition Committee Speakers and Discussants.
Abstract: Conference Planning and Writing Committee:Penny Kris-Etherton, PhD, Stephen R. Daniels, MD, PhD, Robert H. Eckel, MD, Marguerite Engler, PhD, RN, Barbara V. Howard, PhD, Ronald M. Krauss, MD, Alice H. Lichtenstein, DSc, Frank Sacks, MD, Sachiko St. Jeor, PhD, Meir Stampfer, MD, DrPH, For the American Heart Association Nutrition Committee Speakers and Discussants:, Robert H. Eckel, MD, Scott M. Grundy, MD, PhD, Lawrence J. Appel, MD, MPH, Tim Byers, MD, Hannia Campos, PhD, Greg Cooney, PhD, Margo A. Denke, MD, Barbara V. Howard, PhD, Eileen Kennedy, DSc, Ronald M. Krauss, MD, Penny Kris-Etherton, PhD, Alice H. Lichtenstein, DSc, Peter Marckmann, MD, DSc, Thomas A. Pearson, MD, PhD, Gabriele Riccardi, MD, Lawrence L. Rudel, PhD, Mike Rudrum, PhD, Frank Sacks, MD, Daniel T. Stein, MD, Russell P. Tracy, PhD, Virginia Ursin, PhD, Robert A. Vogel, MD, Peter L. Zock, PhD, AHA Members:, Terry L. Bazzarre, PhD and Julie Clark, AHA Staff
TL;DR: The new clinical guidelines of the US National Cholesterol Education Program (NCEP) were released in May 2001 as the NCEP's Adult Treatment Panel (ATP) III report, derived from an extensive review of the emerging literature so as to provide an evidence-based report.
Abstract: The new clinical guidelines of the US National Cholesterol Education Program (NCEP) were released in May 2001. These guidelines were published as the NCEP's Adult Treatment Panel (ATP) III report. They are derived from an extensive review of the emerging literature so as to provide an evidence-based report. Thanks to recent clinical trials of cholesterol-lowering therapy, it is possible to expand the scope of clinical management for both dietary and drug therapies. This expansion derives from a conclusive demonstration of efficacy, safety, and cost-effectiveness of therapies. This article will review briefly the major features of ATP III.
TL;DR: The novel observation that the LDL of chronic renal failure patients on HD and PD appears to be potentially more atherogenic, since it induces greater monocyte-endothelial cell adhesion is made.
Abstract: Premature atherosclerosis is a major cause of morbidity and mortality in chronic renal failure patients undergoing dialysis. In this study, we compared autoantibodies to oxidized low-density lipoprotein (OX-LDL), soluble cell adhesion molecules (CAMs), and the effect of both LDL and OX-LDL on monocyte endothelial cell adhesion in chronic renal failure patients on hemodialysis (HD, n = 16) and peritoneal dialysis (PD, n = 17) compared with matched healthy control subjects (C, n = 17). In addition, we studied the effect of supplementation with RRR-alpha-tocopherol (AT) 800 IU/d for 12 weeks on the above measures. LDL and OX-LDL induced adhesion of U937 cells to cultured endothelium, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin); autoantibodies to OX-LDL and markers of lipid peroxidation were determined before and after AT supplementation. Native LDL from PD patients induced greater monocyte-endothelial cell adhesion than LDL from C subjects (43.8% ± 17.0% v25.3% ± 17.7%, respectively, P = .0028). OX-LDL from chronic renal failure patients on both PD and HD stimulated greater adhesion than OX-LDL from the C subjects (68.0% ± 18.5% and 57.6% ± 15.1% v 40.9% ± 17.3%, respectively, P < .01); OX-LDL from PD patients induced greater adhesion than that from HD patients (P < .01). Plasma methylglyoxal levels were significantly increased in both HD and PD groups, with higher levels in the HD group. Chronic renal failure patients on HD and PD also had higher levels of plasma sVCAM-1 and sE-selectin than C subjects (P < .01), indicating endothelial activation. Titers of autoantibodies to OX-LDL were not elevated in renal failure patients. Supplementation with AT 800 IU/d for 12 weeks, while resulting in significant enrichment with AT in LDL, did not have a significant effect on any of the parameters studied. This study makes the novel observation that the LDL of chronic renal failure patients on HD and PD appears to be potentially more atherogenic, since it induces greater monocyte-endothelial cell adhesion.
TL;DR: The ability to measure the extent of subclinical atherosclerosis could be of value in the selection of persons for more intensive primary care patients as discussed by the authors, and the introduction of new imaging techniques offers the opportunity for identification of the presence of the subclinical plaque in asymptomatic persons.
TL;DR: Levels of atrial natriuretic peptide in hypertrophic cardiomyopathy, a more dependent on atrial filling volume than on filling pressure in chronic congestive heart failure.
Abstract: levels of atrial natriuretic peptide in hypertrophic cardiomyopathy. Am J Cardiol 1992;70:1502–1504. 2. Nishigaki K, Tomita M, Kagawa K, Noda T, Minatogichi S, Oda H, Watanabe S, Morita N, Nakao K, Fujiwara H. Marked expression of plasma brain natriuretic peptide is a special feature of hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 1996;28:1231–1242. 3. Hamada M, Shigematsu Y, Kawakami H, Minamino N, Kangawa K, Matsuo H, Hiwada K. Increased plasma levels of adrenomedullin in patients with hypertrophic cardiomyopathy: its relation to endothelin-1, natriuretic peptides and noradrenaline. Clin Sci 1997;94:21–28. 4. Levin ER, Gradner DG, Samson WK. Natriuretic peptides. N Engl J Med 1998;339:321–328. 5. Tsutamoto T, Wada A, Maeda K, Hisanaga T, Fukai D, Ohnishi M, Sugimoto Y, Kinoshita M. Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure. Circulation 1997;96:509–516. 6. Wilkins MR, Redondo J, Brown LA. The natriuretic-peptide family. Lancet 1997;349:1307–1310. 7. Yamada T, Fukunami M, Shimonagata T, Kumagai K, Ogita H, Asano Y, Hirata A, Hori M Hoki N. Prediction of paroxysmal atrial fibrillation in patients with congestive heart failure: a prospective study. J Am Coll Cardiol 2000;35: 405–413. 8. Rossi A, Enriquez-Sarano M, Burnett JC, Lerman A, Abel MD, Seward JB. Natriuretic peptide levels in atrial fibrillation. J Am Coll Cardiol 2000;35:1256– 1262. 9. Tuinenbrg AE, Van Veldhuisen DJ, Boomsma F, Van Den Berg MP, De Kam PJ, Crijns HJ. Comparison of plasma neurohormones in congestive heart failure patients with atrial fibrillation versus patients with sinus rhythm. Am J Cardiol 1998;81:1207–1210. 10. Globits S, Frank H, Pacher B, Huelsman M, Orgis E, Pacher R. Atrial natriuretic peptide release is a more dependent on atrial filling volume than on filling pressure in chronic congestive heart failure. Am Heart J 1997;135:592– 597. 11. Takemura G, Fujiwra H, Mukoyam M, Aito Y, Nakao K, Kawamura A, Ishida M, Kida M, Uegaito T, Tanaka M, Matsumori A, Fujiwara T, Imura H, Kawai C. Expression and distribution of atrial natriuretic peptide in human hypertrophic ventricle of hypertensive hearts and hearts with hypertrophic cardiomyopathy. Circulation 1991;83:181–190.
TL;DR: In his News Focus article, Gary Taubes discusses what he calls “The soft science of dietary fat”, which reviews the history of the diet-heart issue.
Abstract: The role of dietary fat in the causation of coronary heart disease (CHD) has long been a topic of interest and dispute. In his News Focus article, Gary Taubes discusses what he calls “The soft science of dietary fat” (30 Mar., p. [2536][1]). He reviews the history of the diet-heart issue and
Journal Article•