scispace - formally typeset
Search or ask a question

Showing papers by "Scott M. Grundy published in 1999"


Journal ArticleDOI
TL;DR: The most prevalent form of diabetes mellitus is type 2 diabetes as discussed by the authors, which typically makes its appearance later in life and is associated with other cardiovascular risk factors: dyslipidemia, hypertension, and prothrombotic factors.
Abstract: This statement examines the cardiovascular complications of diabetes mellitus and considers opportunities for their prevention. These complications include coronary heart disease (CHD), stroke, peripheral arterial disease, nephropathy, retinopathy, and possibly neuropathy and cardiomyopathy. Because of the aging of the population and an increasing prevalence of obesity and sedentary life habits in the United States, the prevalence of diabetes is increasing. Thus, diabetes must take its place alongside the other major risk factors as important causes of cardiovascular disease (CVD). In fact, from the point of view of cardiovascular medicine, it may be appropriate to say, “diabetes is a cardiovascular disease.” The most prevalent form of diabetes mellitus is type 2 diabetes. This disorder typically makes its appearance later in life. The underlying metabolic causes of type 2 diabetes are the combination of impairment in insulin-mediated glucose disposal (insulin resistance) and defective secretion of insulin by pancreatic β-cells. Insulin resistance develops from obesity and physical inactivity, acting on a substrate of genetic susceptibility.1 2 Insulin secretion declines with advancing age,3 4 and this decline may be accelerated by genetic factors.5 6 Insulin resistance typically precedes the onset of type 2 diabetes and is commonly accompanied by other cardiovascular risk factors: dyslipidemia, hypertension, and prothrombotic factors.7 8 The common clustering of these risk factors in a single individual has been called the metabolic syndrome. Many patients with the metabolic syndrome manifest impaired fasting glucose (IFG)9 even when they do not have overt diabetes mellitus.10 The metabolic syndrome commonly precedes the development of type 2 diabetes by many years11 ; of great importance, the risk factors that constitute this syndrome contribute independently to CVD risk. Recently, new criteria have been accepted for the diagnosis of diabetes.9 The upper threshold of fasting plasma glucose for the …

2,800 citations


Journal ArticleDOI
TL;DR: The approaches described in this statement can be used for guidance at several levels of primary prevention; however, the statement does not attempt to specifically link risk assessment to treatment guidelines for particular risk factors, but provides critical background information that could be used in the development of new treatment guidelines.

1,276 citations


Journal ArticleDOI
TL;DR: Various therapeutic approaches for the patient with the metabolic syndrome should be implemented to decrease the risk of cardiovascular disease events, including decreasing obesity, increasing physical activity, and managing dyslipidemia.
Abstract: The metabolic syndrome consists of a cluster of metabolic disorders, many of which promote the development of atherosclerosis and increase the risk of cardiovascular disease events. Insulin resistance may lie at the heart of the metabolic syndrome. Elevated serum triglycerides commonly associate with insulin resistance and represent a valuable clinical marker of the metabolic syndrome. Abdominal obesity is a clinical marker for insulin resistance. The metabolic syndrome manifests 4 categories of abnormality: atherogenic dyslipidemia (elevated triglycerides, increased small low-density lipoproteins, and decreased high-density lipoproteins), increased blood pressure, elevated plasma glucose, and a prothrombotic state. Various therapeutic approaches for the patient with the metabolic syndrome should be implemented to decrease the risk of cardiovascular disease events. These interventions include decreasing obesity, increasing physical activity, and managing dyslipidemia; the latter may require the use of pharmacotherapy with cholesterol-lowering and triglyceride-lowering drugs.

598 citations


Journal ArticleDOI
TL;DR: Results show that Asian Indian men are more insulin resistant than Caucasian men independently of generalized or truncal adiposity, which may account for the excessive morbidity and mortality from diabetes and coronary heart disease in this population.
Abstract: It has been proposed that excessive insulin resistance in Asian Indians living in urban areas or migrated to western countries is responsible for the higher incidence of type 2 diabetes and coronary heart disease observed in this population. To evaluate whether Asian Indians are more insulin resistant than Caucasians and to define the role of generalized and truncal adiposity, we performed hydrodensitometry, skinfold measurements, and euglycemic-hyperinsulinemic clamps in 21 healthy Asian Indian men and 23 Caucasian men of similar age and body fat content. The glucose disposal rate (Rd) was significantly lower in the Asian Indians than in the Caucasians (3.7+/-1.3 vs. 5.3+/-2.0 mg/min x kg lean body mass, respectively; P = 0.003). Despite similar total body fat content, Asian Indians had higher truncal adiposity than Caucasians (sum of truncal skinfolds, 117+/-37 and 92.4+/-38 mm, respectively). In both Asian Indians and Caucasians, the insulin sensitivity index (Rd/plasma insulin concentrations) was inversely correlated with both total body fat (r = -0.49; P<0.03 and r = -0.67; P<0.001, respectively) and sum of truncal skinfold thickness (r = -0.55; P<0.001 and r = -0.61; P<0.002, respectively). After adjustment for total body fat and truncal skinfold thickness, Asian Indians still had a significantly lower glucose disposal rate (P = 0.04). These results show that Asian Indian men are more insulin resistant than Caucasian men independently of generalized or truncal adiposity. The excessive insulin resistance in Asian Indians is probably a primary metabolic defect and may account for the excessive morbidity and mortality from diabetes and coronary heart disease in this population.

406 citations


Journal ArticleDOI
TL;DR: The purpose of this statement is to highlight risk factor management strategies that are appropriate for women with a broad range of CHD risk, and to highlight clinicians are missing opportunities to prevent CHD.
Abstract: Coronary heart disease (CHD) is the single leading cause of death and a significant cause of morbidity among American women.1 Risk factors for CHD in women are well documented.2 Compelling data from epidemiological studies and randomized clinical trials show that CHD is largely preventable. Assessment and management of several risk factors for CHD are cost-effective.3 Despite these facts, there are alarming trends in the prevalence and management of risk factors in women.2 Smoking rates are declining less for women than for men. The prevalence of obesity is increasing, and ≈25% of women report no regular sustained physical activity.4 Approximately 52% of women >45 years old have elevated blood pressure, and ≈40% of women >55 years old have elevated serum cholesterol.5 The purpose of this statement is to highlight risk factor management strategies that are appropriate for women with a broad range of CHD risk. A more detailed description, including the scientific basis for these recommendations, is available in the 1997 American Heart Association scientific statement “Cardiovascular Disease in Women.”2 Recently, the Centers for Disease Control and Prevention National Ambulatory Medical Care Survey6 showed clinicians are missing opportunities to prevent CHD. In this study of 29 273 routine office visits, women were counseled less often than men about exercise, nutrition, and weight reduction. In the multicenter Heart and Estrogen/progestin Replacement Study (HERS),7 only 10% of women enrolled with documented CHD had baseline LDL-cholesterol levels below a National Cholesterol Education Program (NCEP) target of 100 mg/dL. A recent national survey showed that women were significantly less likely than men to enroll in cardiac rehabilitation after an acute …

377 citations



Journal ArticleDOI
TL;DR: The area of primary prevention is complex and contentious; some of the issues will not be easily resolved; however, if the burden of CHD in industrialized and developing societies is to be substantially reduced, effective strategies for primary prevention must be put in place.
Abstract: The concept that coronary heart disease (CHD) can be prevented has increasingly become a driving force in cardiovascular medicine. For many years, the field gave lip service to prevention but neglected to take it seriously. The possibility of effective prevention was met with skepticism from many quarters. Gradually, however, the tide has turned, and prevention is getting the upper hand. Widespread acceptance of the benefits of prevention came first in the area of secondary prevention, ie, preventing recurrent coronary events in patients with established CHD.1 Secondary prevention stands at the boundary between prevention and treatment. Many cardiologists consider secondary prevention to be treatment of coronary artery disease; others see it as prevention of recurrent coronary events. There is a more uniform agreement that prevention of new-onset CHD should be called primary prevention. This article examines some of the major issues currently under scrutiny for primary prevention of CHD. Without question, the area of primary prevention is complex and contentious; some of the issues will not be easily resolved. However, if the burden of CHD in industrialized and developing societies is to be substantially reduced, effective strategies for primary prevention must be put in place. Major advances have recently been made in understanding the pathogenesis of acute coronary syndromes (unstable angina, myocardial infarction, and coronary death). Of great importance was the recognition that rupture of vulnerable plaques leading to coronary thrombosis accounts for most acute coronary syndromes.2 3 Equally important was the discovery that the risk of plaque rupture and its consequences can be substantially reduced by medical intervention. For example, cigarette smoking almost certainly predisposes to plaque rupture, and smoking cessation rapidly lowers risk for coronary thrombosis.4 Meta-analysis confirms that lowering blood pressure in hypertensive patients will reduce acute myocardial infarctions.5 Low-dose aspirin therapy likewise lowers …

291 citations


Journal ArticleDOI
TL;DR: Hepatic lipase catalyses the hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins as discussed by the authors, and genetic deficiency of this enzyme is associated with a unique plasma lipoprotein profile, characterized by hypertriglyceridemia and elevated concentrations of intermediate density lipopro
Abstract: Hepatic lipase catalyses the hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. Genetic deficiency of this enzyme is associated with a unique plasma lipoprotein profile, characterized by hypertriglyceridemia and elevated concentrations of intermediate density lipopro

151 citations




Journal ArticleDOI
TL;DR: The incidence of coronary heart disease (CHD) peaks in the elderly population, and cholesterol-lowering therapy reduces risk for CHD in both older and younger participants, so this benefit can be extended to the elderly.
Abstract: The incidence of coronary heart disease (CHD) peaks in the elderly population. In secondary and primary prevention trials, cholesterol-lowering therapy reduces risk for CHD in both older and younger participants. This benefit, therefore, can be extended to the elderly.

Journal ArticleDOI
TL;DR: Noninvasive assessment of subclinical atherosclerosis is a better measurement of plaque burden and can provide a better assessment of "arterial age" in patients with advancing age.
Abstract: Advancing age is a major risk factor for coronary heart disease and is an indicator of coronary plaque burden. Noninvasive assessment of subclinical atherosclerosis is a better measurement of plaque burden and can provide a better assessment of "arterial age."

Journal ArticleDOI
TL;DR: The hypothesis-based findings of 4S, CARE, and WOSCOPS support current clinical guidelines, and lowering LDL-C may reduce risk more substantially than might have been predicted, and lower cholesterol intervention should be target based, as current guidelines recommend.
Abstract: The benefit of cholesterol-lowering therapy in the prevention of coronary heart disease (CHD) is well established. The secondary prevention Scandinavian Simvastatin Survival Study (4S) and the primary prevention West of Scotland Coronary Prevention Study (WOSCOPS) demonstrated that lipid lowering with a statin can dramatically and cost-effectively reduce CHD morbidity and mortality with no increase in noncardiovascular mortality. The Cholesterol and Recurrent Events (CARE) trial extended benefit to CHD patients without high cholesterol. Post hoc analyses of data from these large trials are contributing to speculation, driven by subset analyses and meta-analyses, about whether cholesterol intervention should be target based, as current guidelines recommend. Whereas CARE data support the importance of baseline LDL cholesterol (LDL-C), with greatest clinical event risk reduction in the upper part of the LDL-C range in the trial, 4S found no difference in outcome according to baseline LDL-C in a quartile analysis, and WOSCOPS found no linear relation between decrease in LDL-C and decrease in relative risk for CHD. Furthermore, WOSCOPS showed no additional clinical benefit with LDL-C lowering beyond approximately 24%. Questions raised by such analyses require answers from prospective, hypothesis-based data, and at present there is no compelling argument for moving away from LDL-C targets. The hypothesis-based findings of 4S, CARE, and WOSCOPS support current clinical guidelines, and lowering LDL-C may reduce risk more substantially than might have been predicted.

Journal ArticleDOI
TL;DR: The role of physical activity in the prevention and treatment of obesity and its comorbidities and the AHA/ACC scientific statement on assessment of cardiovascular risk by use of multiple-risk-factor assessment equations are reviewed.
Abstract: 1. Physical activity in the prevention and treatment of obesity and its comorbidities. PMID: 10593519 [PubMed-indexed for MEDLINE]Related citations 2. Physical activity in the prevention and treatment of obesity and its comorbidities: evidence report of independent panel to assess the role of physical activity in the treatment of obesity and its comorbidities. 3. AHA/ACC scientific statement: Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology. [PubMed-indexed for MEDLINE]Related citations 4. Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology.

Journal ArticleDOI
TL;DR: Investigating the cause of low HDL-C levels in Turks found the elevation most likely has a genetic basis, as no dietary or behavioral factors have been identified in the Turkish population that account for increased hepatic triglyceride lipase activity.

Journal ArticleDOI
TL;DR: Genetic and pharmacological data indicate that variation in hepatic lipase activity has highly specific effects on the distribution of HDL subclasses in the circulation, particularly in normotriglyceridemic men.

Journal ArticleDOI
TL;DR: Clear evidence points to the need to reduce intakes of saturated and trans fatty acids in the diet, and a balanced ratio of unsaturated fatty acids to carbohydrate leading to fat intake of approximately 30% of total energy seems appropriate for the American public.
Abstract: A major issue in human nutrition is the optimal relation of carbohydrate-to-fat in the diet. According to some investigators, a high proportion of fat energy to total energy favors the development of several chronic diseases. Among these are obesity, coronary heart disease, diabetes, and cancer. The theory that a high proportion of fat relative to other nutrients promotes the development of obesity is founded on research with experimental animals and in human population surveys. This theory has been difficult to prove in prospective feeding studies in humans; therefore it remains a contentious issue. Regarding coronary heart disease, little evidence supports a claim that a high proportion of dietary fat predisposes to disease. On the other hand, strong evidence bolsters the claim that certain fatty acids raise the risk for coronary heart disease. These include saturated fatty acids and trans fatty acids, both of which raise serum cholesterol levels. In contrast, neither monounsaturated nor polyunsaturated fatty acids raise serum cholesterol levels and seemingly pose little risk for coronary disease. The relationship between dietary fat and type 2 diabetes is tied largely to the issue of obesity, because obesity is a major cause of diabetes. Although animal studies and epidemiological studies have implicated dietary fat as a factor in cancer, recent prospective epidemiological data in humans have cast doubt on the possibility of a strong relationship. In summary, clear evidence points to the need to reduce intakes of saturated and trans fatty acids in the diet. Beyond this change, a balanced ratio of unsaturated fatty acids to carbohydrate leading to fat intake of approximately 30% of total energy seems appropriate for the American public.

Journal ArticleDOI
TL;DR: The data indicate that a primary decrease in hepatic lipase activity of as much as 30% does not influence susceptibility to CAD in white men.
Abstract: Hepatic lipase is an important determinant of plasma HDL concentration and LDL subclass distribution and may therefore influence susceptibility to coronary artery disease (CAD). To assess the effect of genetic variation in hepatic lipase activity on CAD susceptibility, we determined the frequency of the -514T allele of hepatic lipase in white men with CAD and in controls who did not have CAD. In men with CAD, postheparin plasma hepatic lipase activity was 15% to 20% lower in heterozygotes and 30% lower in homozygotes for the -514T allele. Allele frequencies were similar in cases and controls, however, and were consistent with Hardy-Weinberg expectation in both groups. This finding was confirmed in a second group comprising cases with premature symptomatic CAD and controls who were free of disease. These data indicate that a primary decrease in hepatic lipase activity of as much as 30% does not influence susceptibility to CAD in white men.


Journal Article
TL;DR: Results of clinical trials confirm the efficacy and safety of statins for cholesterol lowering and open the door to new approaches to reducing low-density lipoprotein (LDL) cholesterol concentrations.
Abstract: Results of clinical trials confirm the efficacy and safety of statins for cholesterol lowering and open the door to new approaches to reducing low-density lipoprotein (LDL) cholesterol concentrations. Statins inhibit cholesterol synthesis, reduce hepatic cholesterol, enhance expression of LDL receptors and lower serum LDL cholesterol levels. Another way to increase LDL receptors is to inhibit cholesterol absorption, which reduces serum LDL cholesterol about one-half of that obtained by statin therapy. Although different agents inhibit cholesterol absorption (e.g. Olestra, neomycin, surformer [AOMA], acyl coenzyme A acyltransferase inhibitors, microsomal lipid transfer protein inhibitors, plant sterols and stanols), the latter are the most practical for widespread use. Stanols act entirely within the gastrointestinal tract, a feature that greatly increases their safety. Consequently, they are a useful adjunct to dietary therapy for LDL cholesterol lowering. Stanol esters have other characteristics of an ideal dietary adjunct for cholesterol lowering. They are well tolerated and seemingly are free from side-effects. Their potential utility as a dietary adjunct for lowering LDL cholesterol is considered in the context of preventive strategies, both secondary and short- and long-term primary prevention, in high-risk and low-risk persons.

Journal ArticleDOI
TL;DR: It was not possible to detect a significant decreased synthesis of cholesterol, either from balance studies or from urinary excretion of mevalonic acid, which raises the possibility that lifibrol activates the LDL‐receptor pathway through a different mechanisms which remains to be determined.
Abstract: Lifibrol is a powerful cholesterol-lowering drug of unknown mechanism of action This investigation was carried out to determine whether the major action of lifibrol is to enhance clearance of low density lipoproteins (LDL) through the LDL-receptor pathway, and if so, whether the drug exerts its action by altering the excretion of bile acids (acidic steroids), the absorption of cholesterol, or the synthesis of cholesterol In a first study, in two patients with complete absence of LDL receptors, lifibrol therapy had essentially no effect on plasma LDL concentrations; in two others who had a marked reduction in LDL-receptor activity, response to the drug was attenuated These findings suggest that lifibrol requires an intact LDL-receptor pathway to exert its action In a second study, in patients with primary moderate hypercholesterolemia, isotope kinetic studies showed that lifibrol enhanced the fractional catabolic rate of LDL-apolipoprotein B (apo B), but had no effect on transport rates of LDL; these observations likewise support the probability that lifibrol acts mainly to increase the activity of the LDL-receptor pathway However, in a third study in hypercholesterolemic patients, lifibrol therapy failed to increase acidic steroid excretion, inhibit cholesterol absorption, or reduce net cholesterol balance Furthermore, lifibrol treatment did not significantly reduce urinary excretion of mevalonic acid In contrast, in a parallel study, simvastatin therapy, which is known to inhibit cholesterol synthesis, gave the expected decrease in net cholesterol balance and reduction in urinary excretion of mevalonic acid Thus, lifibrol, like statins, appears to increase the activity of LDL receptors; but in contrast to findings with statins, it was not possible to detect a significant decreased synthesis of cholesterol, either from balance studies or from urinary excretion of mevalonic acid This finding raises the possibility that lifibrol activates the LDL-receptor pathway through a different mechanisms which remains to be determined