Thomas A. Pearson

Markers of Inflammation and Cardiovascular Disease Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association

In 1998, the American Heart Association convened Prevention Conference V to examine strategies for the identification of high-risk patients who need primary prevention. Among the strategies discussed was the measurement of markers of inflammation.1 The Conference concluded that “many of these markers (including inflammatory markers) are not yet considered applicable for routine risk assessment because of: (1) lack of measurement standardization, (2) lack of consistency in epidemiological findings from prospective studies with endpoints, and (3) lack of evidence that the novel marker adds to risk prediction over and above that already achievable through the use of established risk factors.” The National Cholesterol Education Program Adult Treatment Panel III Guidelines identified these markers as emerging risk factors,1a which could be used as an optional risk factor measurement to adjust estimates of absolute risk obtained using standard risk factors. Since these publications, a large number of peer-reviewed scientific reports have been published relating inflammatory markers to cardiovascular disease (CVD). Several commercial assays for inflammatory markers have become available. As a consequence of the expanding research base and availability of assays, the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly. Despite this, there has been no consensus from professional societies or governmental agencies as to how these assays of markers of inflammation should be used in clinical practice. On March 14 and 15, 2002, a workshop titled “CDC/AHA Workshop on Inflammatory Markers and Cardiovascular Disease: Applications to Clinical and Public Health Practice” was convened in Atlanta, Ga, to address these issues. The goals of this workshop were to determine which of the currently available tests should be used; what results should be used to define high risk; which patients should be tested; and the indications for which the tests would be most useful. These …

AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases

The initial Guide to the Primary Prevention of Cardiovascular Diseases was published in 1997 as an aid to healthcare professionals and their patients without established coronary artery disease or other atherosclerotic diseases.1 It was intended to complement the American Heart Association (AHA)/American College of Cardiology (ACC) Guidelines for Preventing Heart Attack and Death in Patients with Atherosclerotic Cardiovascular Disease (updated2) and to provide the healthcare professional with a comprehensive approach to patients across a wide spectrum of risk. The imperative to prevent the first episode of coronary disease or stroke or the development of aortic aneurysm and peripheral arterial disease remains as strong as ever because of the still-high rate of first events that are fatal or disabling or require expensive intensive medical care. The evidence that most cardiovascular disease is preventable continues to grow. Results of long-term prospective studies consistently identify persons with low levels of risk factors as having lifelong low levels of heart disease and stroke.3,4⇓ Moreover, these low levels of risk factors are related to healthy lifestyles. Data from the Nurses Health Study,5 for example, suggest that in women, maintaining a desirable body weight, eating a healthy diet, exercising regularly, not smoking, and consuming a moderate amount of alcohol could account for an 84% reduction in risk, yet only 3% of the women studied were in that category. Clearly, the majority of the causes of cardiovascular disease are known and modifiable. This 2002 update of the Guide acknowledges a number of advances in the field of primary prevention since 1997. Research continues to refine the recommendations on detection and management of established risk factors, including evidence against the safety and efficacy of interventions once thought promising (eg, antioxidant vitamins).6 This, in turn, has …

Trends and Disparities in Coronary Heart Disease, Stroke, and Other Cardiovascular Diseases in the United States Findings of the National Conference on Cardiovascular Disease Prevention

A workshop was held September 27 through 29, 1999, to address issues relating to national trends in mortality and morbidity from cardiovascular diseases; the apparent slowing of declines in mortality from cardiovascular diseases; levels and trends in risk factors for cardiovascular diseases; disparities in cardiovascular diseases by race/ethnicity, socioeconomic status, and geography; trends in cardiovascular disease preventive and treatment services; and strategies for efforts to reduce cardiovascular diseases overall and to reduce disparities among subpopulations. The conference concluded that coronary heart disease mortality is still declining in the United States as a whole, although perhaps at a slower rate than in the 1980s; that stroke mortality rates have declined little, if at all, since 1990; and that there are striking differences in cardiovascular death rates by race/ethnicity, socioeconomic status, and geography. Trends in risk factors are consistent with a slowing of the decline in mortality; there has been little recent progress in risk factors such as smoking, physical inactivity, and hypertension control. There are increasing levels of obesity and type 2 diabetes, with major differences among subpopulations. There is considerable activity in population-wide prevention, primary prevention for higher risk people, and secondary prevention, but wide disparities exist among groups on the basis of socioeconomic status and geography, pointing to major gaps in efforts to use available, proven approaches to control cardiovascular diseases. Recommendations for strategies to attain the year 2010 health objectives were made.

AHA/ACC Guidelines for Preventing Heart Attack and Death in Patients With Atherosclerotic Cardiovascular Disease: 2001 Update A Statement for Healthcare Professionals From the American Heart Association and the American College of Cardiology

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 …

How to Interpret a Genome-wide Association Study

Genome-wide association (GWA) studies use high-throughput genotyping technologies to assay hundreds of thousands of single-nucleotide polymorphisms (SNPs) and relate them to clinical conditions and measurable traits. Since 2005, nearly 100 loci for as many as 40 common diseases and traits have been identified and replicated in GWA studies, many in genes not previously suspected of having a role in the disease under study, and some in genomic regions containing no known genes. GWA studies are an important advance in discovering genetic variants influencing disease but also have important limitations, including their potential for false-positive and false-negative results and for biases related to selection of study participants and genotyping errors. Although these studies are clearly many steps removed from actual clinical use, and specific applications of GWA findings in prevention and treatment are actively being pursued, at present these studies mainly represent a valuable discovery tool for examining genomic function and clarifying pathophysiologic mechanisms. This article describes the design, interpretation, application, and limitations of GWA studies for clinicians and scientists for whom this evolving science may have great relevance.

Primary Prevention of Coronary Heart Disease: Guidance From Framingham A Statement for Healthcare Professionals From the AHA Task Force on Risk Reduction

The Framingham Heart Study has contributed importantly to understanding of the causes of coronary heart disease (CHD), stroke, and other cardiovascular diseases. Framingham research has helped define the quantitative and additive nature of these causes or, as they are now called, “cardiovascular risk factors.”1 The National Cholesterol Education Program (NCEP)2 3 has made extensive use of Framingham data in developing its strategy for preventing CHD by controlling high cholesterol levels. The NCEP guidelines2 3 adjust the intensity of cholesterol-lowering therapy with absolute risk as determined by summation of risk factors. The National High Blood Pressure Education Program (NHBPEP) has set forth a parallel approach for blood pressure control. In contrast to the NCEP,2 however, earlier NHBPEP reports issued through the Joint National Committee4 did not match the intensity of therapy to absolute risk for CHD. “Normalization” of blood pressure is the essential goal of therapy regardless of risk status. Blood pressure–lowering therapy is carried out as much for prevention of stroke and other cardiovascular complications as for reduction of CHD risk. Nonetheless, risk assessment could be important for making decisions about type and intensity of therapy for hypertension. Thus, the most recent Joint National Committee report5 gives more attention to risk stratification for adjustment of therapy for hypertension. Although Framingham data have already been influential in the development of national guidelines for risk factor management, the opportunity may exist for both cholesterol and blood pressure programs to draw more extensively from Framingham results when formulating improved risk assessment guidelines and recommending more specific strategies for risk factor modification. The American Heart Association has previously used Framingham risk factor data to prepare charts for estimating CHD risk. Framingham investigators of the National Heart, Lung, and Blood Institute prepared the original charts and have now revised …

Dietary guidelines for healthy American adults: A statement for health professionals from the Nutrition Committee, American Heart Association

In 1957 the American Heart Association proposed that modification of dietary fat intake would reduce the incidence of coronary heart disease (CHD), which had become the leading cause of disability and death in the United States and other industrialized countries.1 Since then the AHA has issued seven policy statements on diet and CHD as reliable new information has become available.2 3 4 5 6 7 8 In each of these statements emphasis was placed on consumption of total fat, saturated and certain unsaturated fatty acids, dietary cholesterol, and sodium because of their significant contribution to risk of CHD. Later, excessive alcohol intake was considered because of its association with hypertension, stroke, and other diseases. Such knowledge has encouraged other health organizations and the federal government to make similar recommendations. In May 1989 representatives of nine health organizations and governmental bodies met under the aegis of the AHA, reviewed the scientific evidence, and concluded that most Americans can improve their overall health and maintain it with a few specific but fundamental dietary changes.9 The following guidelines are consistent with those promoted by each organization: • Eat a nutritionally adequate diet consisting of a variety of foods. • Reduce consumption of fat, especially saturated fat, and cholesterol. • Achieve and maintain an appropriate body weight. • Increase consumption of complex carbohydrates and dietary fiber. • Reduce intake of sodium. • Consume alcohol in moderation, if at all. Children, adolescents, and pregnant women should abstain. Current AHA recommendations regarding diet and related lifestyle practices for the general population are based on evidence indicating that modification of specific risk factors will decrease incidence of CHD.8 These risk factors include cigarette smoking; elevated levels of plasma cholesterol, particularly low-density lipoprotein (LDL) cholesterol; low levels of high-density lipoprotein (HDL) cholesterol; increased blood …

Stroke following coronary artery bypass grafting: A ten-year study

To identify possible risk factors for the occurrence of stroke during coronary artery bypass grafting (CABG), the cases of 3,279 consecutive patients having isolated CABG from 1974 to 1983 were reviewed. During this period, the risk of death fell from 3.9% to 2.6%. The stroke rate, however, fell initially but then rose from 0.57% in 1979 to 2.4% in 1983. Adjustment of these data for age clearly demonstrated that the risk of stroke has increased largely because of an increase in the mean age of patients undergoing CABG procedures. A case-control study involving all 56 stroke victims and 112 control patients was used to identify those risk factors significantly associated with the development of stroke in univariate analysis: increased age (63 versus 57 years in stroke patients and controls, respectively; p less than 0.0001); preexisting cerebrovascular disease (20% versus 8%; p less than 0.03); severe atherosclerosis of the ascending aorta (14% versus 3%; p less than 0.005); protracted cardiopulmonary bypass time (122 minutes versus 105 minutes; p less than 0.005); and severe perioperative hypotension (23% versus 4%; p less than 0.0001). Other variables not found to correlate with postoperative stroke included previous myocardial infarction, hypertension, diabetes mellitus, lower extremity vascular disease, preoperative left ventricular function, and intraoperative perfusion techniques. Elderly patients who have preexisting cerebrovascular disease or severe atherosclerosis of the ascending aorta or who require extensive revascularization procedures have a significantly increased risk of postoperative stroke.

Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel.

There is abundant evidence that the risk of atherosclerotic vascular disease is directly related to plasma cholesterol levels. Accordingly, all of the national and transnational screening and therapeutic guidelines are based on total or LDL cholesterol. This presumes that cholesterol is the most important lipoprotein‐related proatherogenic risk variable. On the contrary, risk appears to be more directly related to the number of circulating atherogenic particles that contact and enter the arterial wall than to the measured concentration of cholesterol in these lipoprotein fractions. Each of the atherogenic lipoprotein particles contains a single molecule of apolipoprotein (apo) B and therefore the concentration of apo B provides a direct measure of the number of circulating atherogenic lipoproteins. Evidence from fundamental, epidemiological and clinical trial studies indicates that apo B is superior to any of the cholesterol indices to recognize those at increased risk of vascular disease and to judge the adequacy of lipid‐lowering therapy. On the basis of this evidence, we believe that apo B should be included in all guidelines as an indicator of cardiovascular risk. In addition, the present target adopted by the Canadian guideline groups of an apo B <90 mg dL−1 in high‐risk patients should be reassessed in the light of the new clinical trial results and a new ultra‐low target of <80 mg dL−1 be considered. The evidence also indicates that the apo B/apo A‐I ratio is superior to any of the conventional cholesterol ratios in patients without symptomatic vascular disease or diabetes to evaluate the lipoprotein‐related risk of vascular disease.

Guide to preventive cardiology for women

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 …