Long QT syndrome

Several mutations have been identified in the sodium or potassium channel genes responsible for long QT syndrome, which predisposes to ventricular arrhythmias and sudden death. The inherited form of long QT syndrome is caused by discrete mutations in genes that encode ion channels. Several mutations have been identified in the sodium channel gene SCN5A.11-13 The long QT associated mutations in SCN5A are associated with increased sodium flux and prolong depolarization. The mechanism believed to...

Elderly patients

Elderly patients constitute a high percentage of those with MI, CABG, and PTCA and are also at high risk of disability following a coronary event. Seven studies - one nonrandomized study and six observational studies - provide the evidence for this review.6 Also, the Surgeon General's report5 concludes that physical activity, including strength training (resistance) exercise, appears to be protective against falling and fractures among elderly people, probably by increasing muscle strength and...

Heart failure and cardiac transplantation

Twelve studies - five RCTs, three non-randomized, and four observational studies - provide evidence for the benefit of exercise training in the heart failure population. Exercise training in patients with heart failure and moderate to severe LV dysfunction improves functional capacity and symptoms, without changes in LV function. Exercise training is recommended in these patients to attain functional and symptomatic improvement but there is a potentially higher likelihood of adverse events. In...

P2 adrenergic receptor 2AR

Adrenergic receptors are members of a large family of receptors linked to guanine-nucleotide-binding proteins (G proteins). Recent studies in molecular biology have contributed to our understanding of the structure, function and regulation of adrenergic receptors,53 including their interaction with G-proteins in the heart.54-56 In a series of studies, Liggett and colleagues identified several polymorphisms in the (3-2 receptors and their functional and clinical consequences.57 Four of the nine...

Recommendations for adults

Recent recommendations for physical activity from the Centers for Disease Control (CDC) and National Institutes of Health (NIH) suggest that American adults should engage in physical activity at a level appropriate to their capacity, needs, and interests. Regular exercise is recommended, preferably daily, of at least 30-45 minutes of brisk walking (3mph), bicycling or working around the house or yard. Activities may include formal exercise such as walking or jogging or intermittent types of...

Info

Failure, and a very small likelihood of observing that it is superior to low-dose diuretics in reducing major coronary events (Table 14.5). The fact that excess cardiovascular events with doxazosin occurred despite BP reduction that was similar to the diuretic group points to the importance of drug selection in the treatment of hypertension. A meta-analysis of nine randomized comparative clinical trials of intermediate- and long-acting calcium-channel blockers (CCB) was recently published.32...

Infection and cardiovascular disease

Human atherosclerotic heart or cerebrovascular disease has been associated with previous exposure to the bacteria Chlamydia pneumoniae,68,69 Helicobacter pylori, or Porphyromonas gingivalis '11 and with the viruses cytomegalovirus,72 herpes simplex virus type 1 and 2,73 enteroviruses,74 or hepatitis A virus,73 but prospective studies remain limited for all but the first two infections. Overall, current data have not convincingly demonstrated an important role for infections in human CV disease....

Relationship between the glucose level and retinopathy nephropathy and peripheral neuropathy

In patients with diabetes, the risk of retinopathy, nephropathy, and neuropathy is highly correlated with various measures of glycemia including fasting plasma glucose, 2 hour postprandial plasma glucose (after a 75 g oral glucose load), and glycated hemoglobin level.10'16'17 For example, the risk of retinal and renal disease is very low below a fasting and 2 hour plasma glucose of 7-0mmol l or 11-1 mmol l respectively, and increases as these measures increase within the diabetic range....

Outcomes studies and processoutcome relationships

Researchers, clinicians, and administrators alike are also drawing on outcomes with increasing frequency as a means of assessing quality of care. To repeat a point made earlier, various biases threaten the validity of inferences drawn from these non-randomized studies but they have a useful role both in monitoring quality of care and as a source of evidence when randomization is not feasible or appropriate. Just as studies in the 1960s and 1970s showed geographic and institutional variations in...

O

Figure 3.1 Nomogram for predicting the probability of significant coronary artery disease (CAD) in men. ECG, electrocardiogram MI, myocardial infarction. (After Pryor et al.6) Example A 50 year old, white male with atypical angina and diabetes mellitus, but no ECG ST changes, previous MI, smoking, or hyperlipidemia. Point score on left scale 10 + 7 17. Appropriate reading line on right labeled no smoking or lipids. Connect age 50 on this reading line to point score of 17 with a straight edge....

Are there safety concerns regarding calcium antagonists and p blockers

A number of safety concerns have been raised in relation to calcium antagonists, and to some extent also to p blockers. Many of these are based on case-control or cohort studies, which are not a reliable source of information.7'9 There are major contradictions between the various studies. The question of cancer and gastrointestinal hemorrhage as possible side effects is reviewed by the WHO-ISH committee, and by Opie et al7 without a causative association being found.10 In the case of cancer,...

Current global burden of tobacco and future projections

Worldwide, the only two major causes of death whose effects are now increasing rapidly are HIV and tobacco. If current smoking patterns persist, there will be about one billion deaths from tobacco during the twenty-first century, compared to only about 0-1 billion (100 million) during the whole of the twentieth century. About half of these deaths will be in middle age (35 to 69) rather than old age, and those killed by tobacco in middle age lose, on average, more than 20 years of non-smoker...

Community interventions

Community- or population-based smoking cessation interventions have been implemented in a number of settings. Typically, they involve use of mass media to promote public awareness and education, to encourage health professionals to raise smoking as an issue in consultations with patients, and to offer self-help materials. Evaluation of the effectiveness of such programs is difficult and they are discussed in Chapter 10. Contented smokers Relapsing

Tobacco a risk factor for coronary heart disease

It is well established that prolonged smoking is an important cause of chronic disease. Prolonged smoking causes many diseases in addition to lung cancer, notably other cancers and chronic respiratory and cardiovascular diseases. However, the toll of death and disability from smoking outside the high income countries has yet to be felt. This is because the diseases caused by smoking can take several decades to develop. Even when smoking is common in a population, the damage to health may not...

Demographic changes due to the epidemiologic transition

A major public health challenge, identified by recent analyses of global health trends, is the projected rise in both proportional and absolute CVD mortality rates in the developing countries over the next quarter century. The reasons for this are many.4 In the second half of the 20th century, most developing countries experienced a major surge in life expectancy. This was principally as a result of a decline in deaths occurring in infancy, childhood and adolescence, and was related to more...

CVD related expenditure in developed countries

The management of CVD is often technology intensive and expensive. Procedures for diagnosis or therapy, drugs, hospitalization and frequent consultations with healthcare providers all contribute to high costs, both to those affected and to society. In developed countries they already account for about 10 of direct healthcare costs, equal to between 0-5 and 1 of a country's gross national product.2 As life expectancy increases and the duration of the therapy becomes prolonged, the costs may...

Dyslipidemia

Lipid abnormalities in overweight and obese individuals are typically characterized by high triglycerides, increased small LDL particles and low HDL cholesterol levels.61 In the presence of abdominal obesity, high serum triglycerides are commonly associated with a clustering of metabolic risk factors known as the metabolic syndrome (atherogenic lipopro-tein phenotype, hypertension, insulin resistance, glucose intolerance, prothrombotic and proinflammatory states). Thus, in obese patients...

Ethnic diversity

Although ethnic diversity in CVD rates, risk factor levels and risk factor interactions are evident from population studies, the extent to which genetic factors contribute is unclear. It is only after demographic profiles, environmental factors and possible programming factors are ascertained and adjusted for that differences in gene frequency or expression can be invoked as a probable explanation for interpopulation differences in CVD.39 The extent to which chronic diseases, including CVD,...

Diabetes

Overweight and obesity have long been recognized as important determinants of elevated blood glucose, and the vast majority of patients with type 2 diabetes are either overweight or obese. Both at a population and at an individual level, the prevalence and incidence of type 2 diabetes is dependent on the degree of obesity. Thus, in the 10 year follow up (1986-1996) of middle-aged women in the Nurses' Health Study and men in the Health Professionals Follow-up Study, the risk of developing...

Decision analysis evaluating new technologies

Over the past several years, investigators have attempted to calculate the cost effectiveness of the ICD in patients at high risk for sudden cardiac death. Recent evidence from the Antiarrhythmics versus Implantable Defibrillators Trial indicates a decrease of 27 in 2 year mortality with ICD.15 Kupersmith et al16 assessed ICD placement on an inpatient basis for patients with and without prior electrophysiologic (EP) studies. Grade A1c The investigators assumed an 84 improvement in life...

Carbohydrates

The relationship of dietary carbohydrates to CVD appears to be mediated through indirect mechanisms contribution to total energy and its effect on overweight and obesity influence on central obesity effects on plasma lipids, especially triglycerides and effects on glycemic control. The balance between carbohydrates and fat as sources of energy as well as the fiber component of the diet are also areas of interest while considering this relationship. In feeding experiments, an increase in dietary...

Specialist smoking cessation clinics

Specialist smoking cessation clinics have been shown to deliver effective interventions and can make a useful contribution to the provision of individual interventions, usually by providing regular group treatments. There is some evidence that they can achieve enhanced attendance and abstinence rates as high as 20 or more, but interpretation of their success should take account of the fact that they recruit widely and participants are generally highly motivated to stop, compared with the...

Measuring effectiveness

The effectiveness of an intervention in practice can be measured in a variety of ways, with different outcome measures most appropriate for specific applications. Physiologic end points are often used in clinical trials, with the result of therapy assessed by a laboratory measure such as millimeters of mercury for blood pressure or episodes of non-sustained ventricular tachycardia on an electrocardiographic monitor. Laboratory measures are useful in judging the physiologic effects of therapy...

Lifestyle intervention

With regard to dietary therapy, a review of 48 randomized controlled trials5 concluded that an average weight loss of 8 can be obtained over 3-12 months with a controlled energy low-calorie diet (LCD) aimed to reduce caloric intake by 500-1000 kcal day (2092-4184kJ day), and that this weight loss effects a decrease in abdominal fat. It also appears that lower-fat diets with energy reduction promote greater weight loss than energy reduction alone. Very low-calorie diets (VLCDs), generally...

Primary prevention

With the exception of the initial report from Framingham on this issue, all the observational studies of healthy postmenopausal women comparing hormone users with non-users described an association of hormone use (particularly current hormone use) with lower risk for CHD.19-24 However, as reviewed elsewhere, the consistency of these results may be due to powerful systematic biases in observational studies, which may lead to an overestimation of benefit and an underestimation of harm associated...

Practical aspects of smoking cessation in clinical practice

The essential features of individual smoking cessation interventions in medical practice are to assess in any medical consultation the smoking status of the patient, whether a non-smoker, smoker or ex-smoker advise all smokers about the desirability and importance of stopping smoking because of health hazards, especially those who already have smoking-related diseases assist smokers to stop smoking, particularly those with smoking-related diseases and especially if expressing interest to do so...

Addendum

On July 9, 2002, the National Heart, Lung, and Blood Institute announced that the WHI trial67 of estrogen plus progestin versus placebo in 16 608 healthy women with an intact uterus had been stopped early, after an average of 5-2 years of follow up rather than the planned 8-5 years. The reasons for stopping were that an increased risk for breast cancer started emerging at 4 years, which by 5 years had crossed the prespecified monitoring boundary. In addition, there was evidence of overall harm....

Clinical and physiologic outcomes in the coronary population

A comprehensive review by the Agency for Health Care Policy and Research6 provides consistent scientific evidence of the benefits of exercise training on a number of outcomes that include morbidity, mortality, exercise tolerance, and symptoms (see summary below). The evidence is less consistent for the benefit of reduced blood lipids, smoking cessation, psychological wellbeing, social adjustment and functioning, reduction in excess body weight, and a series of physiologic measures.

Review of cessation studies

Grade A In a comprehensive systematic review of 188 randomized controlled trials of the efficacy of a wide range of interventions aimed at helping people to stop smoking, it was concluded that simple advice, even on one occasion only, given by a doctor in general or family practice or in a hospital clinic to all smokers who consulted, resulted in sustained cessation of about 2 and that additional encouragement and support (additional visits, exhaled CO measurement, letters, etc.) further...

Evidence of benefits from smoking cessation

Many observational epidemiologic studies have investigated the effect of stopping smoking on smoking-related diseases, and there is a wealth of evidence that, not only is tobacco smoking a major risk factor for cardiovascular disease, but also stopping smoking reduces this risk. Grade B However, there is less agreement about the rate at which the risk attenuates after smoking cessation. In the 20 year follow up of the British Doctors Study, for example, excess risk was halved within 2 or 3...

Variations in the transition

There are, however, variations on this theme. Even within Europe, for example, northern Europe and the Mediterranean countries have differences in CVD mortality rates which are better explained by cultural differences in diet than by the level of economic development.21 Japan has so far avoided the CHD epidemic.6 Whether recent changes in diet, with a rise in mean plasma cholesterol levels in the population, combined with high smoking rates, will lead to a major CHD epidemic in the future...

High density lipoprotein cholesterol

There is an inverse association between HDL cholesterol (or apolipoprotein A1) and ischemic heart disease. An absolute increase corresponding to 0-12mmol l (about 10 of the average value) is associated with about a 15 decrease in the risk of ischemic heart disease at age 604'30 or a 20 decrease with adjustment for the regression dilution bias.30 The effect of alcohol in increasing HDL cholesterol is the major mechanism for the lower risk of heart disease in drinkers.31 The effect of smoking in...

The size of the effect

Cohort studies provide the best estimates because they cover a wide age range and have high statistical power, and because the serum cholesterol differences between individuals recorded on entry to a cohort study will have been present on average for decades beforehand (so cohort studies show long-term associations). Trials, on the other hand, show the effect of short-term differences. Cohort studies are subject to bias, but this can be corrected. The major bias is the so-called regression...

What is the transition

The health status and dominant disease profile of human societies have been historically linked to the level of their economic development and social organization at any given stage. The shift from nutritional deficiencies and infectious diseases as the major causes of death and disability, to degenerative disorders (chronic diseases such as CVD, cancer, diabetes) has marked the economic ascent of nations as they industrialized. This has been called the epidemiologic transition. The economic...

Inflammation and cardiovascular disease

There is increasing recognition of the involvement of inflammation in human atherosclerosis, although the clinical implications are unclear. Whether inflammation is a fundamental part of the process of atherosclerosis or a secondary phenomenon has yet to be determined. The destabilization of the lipid-rich, vulnerable thin-capped arterial plaque may involve activation of peripherally situated macrophages, leading to platelet activation and thrombosis.56 Chronic atherosclerotic lesions are...

Inflammation conclusions and recommendations

The role for measuring inflammatory markers is evolving, with a demonstrated utility of high-sensitivity CRP for risk stratification. Whether high CRP levels require treatment, and whether other inflammatory risk markers should be measured routinely, is not clear from the available evidence. Whether these inflammatory molecules play a causal role in atheroma formation also remains unknown. The beneficial effects of aspirin and of statins in CV prevention may be mediated in part by their...

Preface to the First edition

if a man declares to you that he has found facts that he has observed and confirmed with his own experience, be cautious in accepting what he says. Rather, investigate and weigh this opinion or hypothesis according to requirements of pure logic, without paying attention to this contention that he affirms empirically. Thus did the great physician Maimonides make a plea for an evidence-based approach to medicine by admonishing his followers to seek common ground between objectivism and...

Aboriginal populations

Although mortality rates for CVD among aboriginal populations appear to be lower than whites, CHD is the leading cause of death in North American Indian and Alaskan Native males and females.18 Although research in this ethnic group is limited, the Strong Heart Study,96 which was initiated in 1988, studied 4549 American Natives aged 45-74 years from 13 tribes in the Southern US. The prevalence estimates of definite MI in those aged 45-74 years was 2-8 in men without diabetes, and 5-3 in men with...

Preface to the Second

Where is the knowledge in all that information Where is the wisdom in all that knowledge The recent proliferation of carefully controlled large scale clinical trials, their meta-analyses and selective observational studies has contributed to the remarkable strides made in the management of cardiovascular disease. One of the prophesies stated in the first edition of this textbook has come to pass - namely, that management guided by external evidence is an evolving process as newer and more...

Definition of obesity

Definitions of overweight and obesity in adults have varied over time.7 Ideally, a health-oriented definition of obesity would be based on the amount of excess body fat that determines the presence of weight-responsive health risk in an individual.8 Body mass index (BMI), defined as weight in kilograms divided by height in meters squared (kg m2), is an easily obtained measure that is now widely used, as it has a high correlation with excess body fat or adiposity. However, BMI is not a measure...

Lipids as screening tests

Serum cholesterol reduction is important in reducing the risk of ischemic heart disease, but cholesterol and other lipids are poor population screening tests for ischemic heart disease. The reason for the apparent discrepancy is that the screening potential of a factor depends not only on the strength of its relationship with disease, but also on its variation in magnitude across individuals in a community. In the case of lipids, the high average values in western societies place everyone at...

Dietary fat and serum cholesterol

The relationship between dietary saturated fat and serum cholesterol is shown by the data from Japan and Britain in Table 12.3. This comparison is a useful one because dietary saturated fat differs greatly, yet dietary polyunsaturated fat and cholesterol are similar in the two countries. As in other situations (salt and blood pressure, for example) the size of the association varies with age, yet there has been a tendency to generalize to older age groups the results of studies conducted in...

Coronary artery disease

Overweight and obesity are now considered major independent risk factors for coronary artery disease 4 nevertheless, the impact of excess body fat and fat distribution in different populations (men and women, young and elderly, ethnic groups) remains to be fully determined. In a recent review of 11 independent studies, Anderson and Konz30 estimated an overall RR of 2-71 for women and 2-80 for men for a BMI of 33 v 23kg m2, respectively. This increased risk was partly (but not fully) accounted...

Peripheral arterial disease

Observational data show the expected association between peripheral arterial disease and serum cholesterol. In a large case-control study the association was equivalent in magnitude to an increase in risk of intermittent claudication of about 24 for a 0-6 mmol l increase in serum cholesterol22 (uncorrected for regression dilution bias), similar in magnitude to the association of serum cholesterol with ischemic heart disease. In the 4S trial (serum cholesterol reduction 1-8 mmol l) the incidence...

Primary prevention Grade A

Many observational studies (reviewed in Chapter 12) have established a strong dose-response relationship between cholesterol level and risk of coronary artery disease (CAD). These data suggest that therapies that reduce cholesterol the most should prevent the greatest number of coronary events. Trials evaluating the first generation of lipid-lowering agents (for example, Helsinki gemfibrozil , LRC-CPPT cholestyramine , and WHO clofibrate ) yielded modest reductions in cholesterol ( 10 ) and...

Clinical trials and metaanalysis

Although large effects on survival arising from certain treatments may occasionally be obvious from simple observation (as, for example, when cardioversion for ventricular fibrillation avoids otherwise certain death), the vast majority of interventions have only moderate effects on major outcomes and hence are impossible to evaluate without careful study. Enthusiasm for the biologic foundations of a particular therapeutic approach often leads to exaggerated hopes for the effects of treatment on...

Decision analysis in the evaluation of specific products

Decision analysis has been used extensively in the evaluation of specific clinical products, including contrast media and pharmaceutical products. Grade A1c Barrett etal18 developed a decision analytic model to assess the economic impact of low- and high-osmo-lality contrast media for cardiac angiography. Investigators assumed that low-osmolality contrast media reduced the risk of myocardial infarction and stroke. Reduction in the risk of specific clinical events with low-osmolality contrast...

Data sources and collection

Health services researchers use both primary and secondary data sources. Primary data are collected by design to answer specific research questions, whereas secondary data are used for multiple purposes and their use for research purposes may be unplanned. Administrative databases designed for purposes of health service funding and administration are among the most common secondary data sources used in assessing clinical practice. Databases specifically constructed for ongoing epidemiologic...

Coronary heart disease

20-24 25-34 35-44 45-54 55-64 65-74 75-84 85+ Age Figure 20.2 Annual mortality rates for CHD by age for US men and women on a semi-logarithmic scale 20-24 25-34 35-44 45-54 55-64 65-74 75-84 85+ Age Figure 20.2 Annual mortality rates for CHD by age for US men and women on a semi-logarithmic scale a decrease in fibrinogen level7-9) while others are potentially unfavorable (for example, an increase in factor VII8'9), and the net effect of estrogen on coagulation is uncertain. Similarly, some...

Mechanisms relating hyperglycemia to cardiovascular disease

Possible explanations for a glucose-cardiovascular disease relationship include direct toxic effects of glucose on cell function and structure indirect effects owing to insufficient insulin secretion to maintain normoglycemia a long history of insulin resistance and hyperinsulinemia prior to glucose elevations an association of dysglycemia with other recognized and unrecognized risk factors for cardiovascular disease, including dyslipidemia, hypertension, abdominal obesity, renal damage, and...

Dietary fat and coagulation

Dietary fat increases blood levels of coagulation factor VII and hence increases the risk of thrombosis, myocardial infarction and cerebral thrombosis.28,29 Saturated and unsat-urated fat increase factor VII equally, and the increase appears directly related to the extent of postprandial lipemia. The importance of this effect in increasing the risk of cardiovascular death is difficult to quantify. However, analyses of differences in serum cholesterol and ischemic heart disease mortality between...

Single gene cardiovascular disorders

Several cardiovascular disorders have been shown to have a familial basis. These diseases cover a wide spectrum, from structural defects such as familial atrial septal defects to functional defects such as long QT syndrome (Table 23.1). For most of these diseases the chromosomal location (locus) has been mapped but the gene has not yet been identified. However, diseases such as the cardiomyopathies, particularly hypertrophic cardiomyopathy, have undergone major investigations, with elucidation...

The nature of tobacco smoking

Before individual smoking interventions and cessation methods are considered, it is helpful to review briefly the nature of tobacco smoking and the consequent implications for interventions. Tobacco smoking is a complex behavior to which psychologic, social, and pharmacologic factors contribute.14 Its acquisition is almost invariably in adolescence, as the result of desire for experimental rebellious behavior, which is perceived as adult and encouraged by peer group pressure. However,...

Gender and cardiovascular disease

In the United States the number of women who die annually from cardiovascular disease is higher than men. The cardiovascular disease burden is particularly high in older women. In women aged 55 and older, major cardiovascular diseases (ICD 390-448-9) accounted for 473569 deaths in 1997 compared to 402310 deaths in older men.1 Major cardiovascular diseases accounted for 44 of all deaths in older women and 40 of all deaths in older men. The number of deaths from coronary heart disease (CHD) was...

Acute myocardial infarction

John A Cairns and Bernard J Gersh, Editors 30 Acute non-ST-segment elevation coronary syndromes unstable angina and 397 non-ST-segment elevation myocardial infarction 31 Fibrinolytic therapy 426 James S Zebrack, Jeffrey L Anderson 32 Mechanical reperfusion strategies in patients presenting with acute myocardial infarction 444 Sanjaya Khanal, W Douglas Weaver 33 Adjunctive antithrombotic therapy for ST-elevation acute myocardial infarction 456 John K French, Harvey D White 34 Pain relief,...

Patient selection and cost effectiveness

Drugs and procedures in medicine are applied to different patient groups for different clinical indications. The medical effectiveness of therapies varies considerably according to patient selection. Cholesterol lowering therapy, for instance, will extend the life expectancy of a patient with multiple cardiac risk factors more than it will for a patient with the same cholesterol level and no other cardiac risk factors. Coronary bypass surgery provides greater life extension to a patient with...

A critical appraisal of the cardiovascular history and physical examination

Akbar Panju, Brenda Hemmelgarn, Jim Nishikawa, Deborah Cook, Allan Kitching There have been numerous technological advances made in the diagnosis and treatment of cardiovascular disease. In spite of this, a carefully conducted clinical examination remains the cornerstone in the initial assessment of the patient with known or suspected cardiovascular disease. Before conducting further laboratory or radiologic diagnostic tests, clinicians implicitly consider each piece of historical information...

Sleep apnea and obesity hypoventilation syndrome

Obesity is the most common precipitating factor for obstructive sleep apnea and is a requirement for the obesity hypoventilation syndrome, both of which are associated with substantial morbidity and increased mortality.78 Numerous case reports and non-controlled trials document substantial improvement in sleep apnea and the obesity hypoventilation syndrome, particularly with surgically induced weight loss. In a recent Cochrane review of lifestyle modification for obstructive sleep apnea, the...

Cost effectiveness analysis

The cost of providing a particular medical service can be measured, but determination of whether the service provides good value for the money spent is a more difficult judgment. Cost effectiveness analysis is a method of weighing the cost of a service in light of the health effects it confers in an attempt to facilitate the ultimate value judgment about whether the service is worth the cost. Cost effectiveness analysis is one of several alternative analytic methods, each with its own strengths...

Myocardial infarction and other nonfatal end points

Registry studies have suggested a favorable effect on late myocardial infarction only among the highest risk subsets, such as patients with three vessel disease and severe angina pectoris.12 In the meta-analysis, no overall effect of CABG on subsequent infarction could be demonstrated, primarily because of an excess of infarction in the perioperative period (10-3 incidence of death or myocardial infarction at 30 days) among those assigned to surgery.7 Although the risk of subsequent myocardial...

David Naylor David A Alter

Research into cardiovascular clinical practice has grown early enormously in volume and sophistication since the early twentieth century, driven by the worldwide prominence of atherosclerotic vascular diseases. The sheer volume of research literature has made it virtually impossible for even a subspecialist to stay abreast of her his field. There is insufficient time for any evidence-oriented practitioner to critically appraise the full array of individual studies relevant to practice, and a...

Blacks of African origin

CVD mortality data from countries in Sub-Saharan Africa (SSA) are limited, as only 1-1 of all deaths are registered with a central agency.10 Data from other sources such as sample registries and small scale population studies in 1990 indicate that the prevalence of acute MI in males and females of all ages was 4-5 million DALY, and that the CHD mortality was 41 100 000.105 These rates are considerably lower than those of whites and South Asians who live in Africa, as well as rates of most...

Statins as potential antiischemic drugs

Statins have made a considerable difference to the mortality of patients with ischemic heart disease in several studies. In the West of Scotland Coronary Prevention Study (WESCOPS), pravastatin was able to reduce hard end points in middle-aged hypercholesterolemic men without prior MI. In this group, the occurrence of angina pectoris was highly correlated (P < 0-0001) with the primary end point, which was definite coronary heart disease death or non-fatal MI.73 Therefore, in...

International perspectives

With the advent of large multicenter clinical trials that enroll patients from several countries, interest has developed in cost comparisons between countries for the same service. Cost estimation as part of large randomized trials will enhance clinical decision making, for the randomized design is the strongest way to compare all outcomes of therapeutic alternatives, including cost. Extension of cost comparisons across national borders introduces a number of technical and conceptual issues...

Pharmacotherapy of obesity

Strong evidence indicates that the use of appropriate weight loss drugs can augment diet, physical activity and behavior therapy in weight loss.5,15 Orlistat is gastrointestinal lipase inhibitor that reduces enteral fat absorption by around 30 .81 Sibutramine is a centrally active serotonin and norepinephrine uptake inhibitor that reduces hunger, increases satiety, and which may have a small thermogenic effect.82 Both compounds have been approved by licensing authorities in most countries for...

Safety of cholesterol reduction

The uncertainty concerning the excess mortality from hem-orrhagic stroke at low serum cholesterol concentrations is unresolved, as discussed above. This apart, there are no material grounds for concern about hazard. Trials of statin drugs, particularly informative on safety because of the large reduction in serum cholesterol that they achieve, have resolved the issue of safety because they show no excess mortality from non-circulatory causes.1'7-11 The excess mortality from cancer and accidents...

Use of decision analysis in treatment strategies

Tosteson efa 56 used a decision analytic model to identify cost effective guidelines for admission to a coronary care unit (CCU) for uncomplicated patients without other indications for intensive care. The probabilities of death, and minor, major and life-threatening complications were based on 12139 emergency department patients who were enrolled in a multicenter chest pain study. Cost data were available from a subset of patients in the study admitted to one study center. Under the assumption...

AJ Marian Robert Roberts

The sequencing of the human genome is likely to be a landmark study of millennium proportions. The implications for cardiology of knowing the sequence of the human genome are many, among which the most obvious is identifying the gene responsible for familial disorders. Abnormalities of the heart and blood vessels are the most common of human birth defects, occurring in about 1 of live births.1'2 Genetic diagnosis and management are expected to be routinely incorporated into the practice of...

Treatment recommendations

Based on current evidence, postmenopausal hormone therapy is not recommended for prevention or treatment of CHD or stroke.64 For primary prevention, the American Heart Association (AHA) states that firm recommendations should await the results of ongoing randomized clinical trials, and that there are currently insufficient data to suggest that hormone therapy should be initiated for the sole purpose of primary prevention of cardiovascular disease.64 The AHA makes a stronger statement that...

Venous thromboembolism

Early observational studies did not suggest an increased risk for venous thromboembolism (deep vein thrombosis or pulmonary embolism) in postmenopausal hormone users however, as reviewed elsewhere, several more recent studies have found a two- to fourfold increased risk in hormone users.61 The studies are consistent in showing an increased relative risk for current but not past use of hormones. Recent onset of current use conferred higher risk than long duration of use, consistent with an...

Serum total and low density lipoprotein cholesterol

Typical values of serum total and low density lipoprotein (LDL) cholesterol in western countries are high in comparison to those in agricultural and hunter-gatherer communities, because of the high saturated fat content of the western diet. Average serum cholesterol concentration (in men aged 45-60) is about 3-3-5 mmol l in hunter-gatherer societies and rural China (where heart disease is rare), 5-0 mmol l in Japan, 5-5 mmol l in Mediterranean populations and a little higher in the USA, and 6...

Secondary prevention Grade A

The National Cholesterol Education Program May 2001 update identifies an LDL level of < 100mg dl as optimal in patients with established CAD.14 Several major clinical trials have demonstrated significant clinical benefit for statin ther apy as secondary prevention. The Scandinavian Simvastatin Survival Study (4S) was a double-blind placebo-controlled trial of adjusted-dose simvastatin in 4444 men and women between the ages of 35 and 60 with a history of angina or prior MI and total...

Speed of reversal and consistency of observational and trial data

Trial Speed Healthcare

Data have been analyzed from the old generation of 28 randomized trials in which the average serum cholesterol reduction was about 0-6 mmol l (10 ).6 Figure 12.2 shows the reduction in incidence of ischemic heart disease in all trials combined according to time since entry. In the first 2 years there was little reduction in risk. From 2 to 5 years the average reduction in risk was 22 , and after 5 years the reduction was 25 . The ischemic heart disease events in these trials mostly occurred at...

Arya M Sharma

The worldwide prevalence of obesity is increasing at an alarming rate. Recent estimates indicate that 40-60 of the population in industrialized countries and a substantial proportion of the population in developing countries must now be considered overweight or obese.1 In the United States, the prevalence of adult obesity (defined as body mass index > 30kg m2), based on self-reported weight and height, increased from 12-0 in 1991 to 18-9 in 1999, and it is estimated that this trend is likely...

Diabetic patients

Although aggressive control of blood glucose levels in type 2 diabetic patients reduces microvascular clinical outcomes, its effect on macrovascular disease outcomes remains unknown. Other traditional CHD risk factors are believed to increase dramatically the risk for clinical CHD events in these patients. Inherent in the diabetic disease process is an abnormality of lipoprotein lipase activity that is partially but not completely corrected by optimal glucose control. Any additional lipid and...

Diabetes Grade A

Diabetes leads to many long-term complications, including retinopathy, neuropathy, nephropathy and atherosclerosis. However, only recently has control of glucose level been demonstrated to reduce these complications. The DCCT (Diabetes Control and Complications Trial) randomized 1441 insulin-dependent diabetic patients to intensive insulin therapy versus conventional therapy, with a mean follow up of 6-5 years.51 The intensive therapy arm showed significant reductions in retinopathy, neuropathy...

Hyperinsulinemia

In non-diabetic people, fasting and 2 hour postload insulin levels rise with fasting and 2 hour glucose levels.58,59 Thus even mildly hyperglycemic patients have higher levels of insulin than normoglycemic controls. Moreover, hyperinsu-linemia is associated with coronary heart disease,60,61 and many other cardiovascular risk factors including hyperten-sion,62 left ventricular hypertrophy,63 elevated levels of triglyceride,64-66 fibrinogen, von Willebrand factor-related antigen, factor VIII...

Risk of cardiovascular disease in patients with diabetes

As noted above, diabetes is an independent risk factor for cardiovascular disease.2 People with diabetes have a two- to fourfold higher risk of coronary, cerebrovascular, and peripheral vascular disease than non-diabetic people.1 The relative risk is greater for women than for men.1,19 Diabetes is also a poor prognostic factor post myocardial infarction (MI) diabetic patients have a higher inhospital mortality, and postdischarge mortality than non-diabetic patients, and a higher risk of...

Glucose levels and the risk for cardiovascular disease in nondiabetic patients

Many prospective studies have consistently showed that the relationship between glucose levels and the subsequent risk of cardiovascular disease extends well below the diabetic threshold. For example, after 10 years of follow up in the Whitehall study of 18050 non-diabetic male civil servants, there was up to a twofold increase in coronary heart disease and stroke mortality in subjects whose 2 hour postload capillary glucose value was greater than 5-4 mmol l compared to those with lower glucose...

Conclusions revascularization in patients with diabetes

In both trials and observational data sets, diabetes mellitus is clearly a marker for high risk and, in comparison with non-diabetic patients, the prognosis is worse after either PTCA or CABG. In the largest randomized trial of PTCA versus CABG, patients with diabetes who received internal mammary artery grafts had better outcomes than those treated with PTCA. However, large non-randomized registry data suggest equivalent outcomes after either procedure as long as the sicker patients are...

Diagnostic tests and cost effectiveness

Cost effectiveness analysis has been applied primarily to assess specific therapies or therapeutic strategies, for which it is natural to measure effectiveness in terms of patient outcome. The principles of cost effectiveness can be extended to analyze screening tests and diagnostic strategies as well, but some additional factors must also be considered. Therapies are expected to improve patient outcome directly, by intervening in the pathophysiology of disease processes. In contrast, a...

Growth and hypertension and type 2 diabetes

There is now a substantial body of evidence showing that people who were small at birth remain biologically different to people who were larger. The differences include an increased susceptibility to hypertension and type 2 diabetes, two disorders closely linked to CHD.14-17 Table 22.4 is based on 698 patients being treated for type 2 diabetes and 2997 patients being treated for hypertension. It again shows odds ratios according to birthweight and quarters of BMI at age 11 years. The two...

Treatment of hypertension Grade A

Hypertension is an ideal disease for preventive therapy. It is a highly prevalent disorder, with more than 60 million Americans (one in four adults) estimated to have the disease.1 If untreated, hypertension leads to significant morbidity and mortality, with coronary disease, heart failure and strokes being the main cardiovascular complications. Finally, numerous interventions capable of lowering the blood pressure are available, including a wide spectrum of antihyper-tensive pharmacologic...

Obtaining incremental information from diagnostic tests

A 75 year old male presents with a history of exertional chest pain. The patient describes substernal chest pain that he perceives as a pressure sensation occurring when he walks too fast, uphill, or in the cold. It is relieved by rest within a few minutes. On two recent occasions, he tried a friend's nitroglycerin tablets, and obtained even more rapid relief of his symptoms. His symptoms have never occurred at rest. The patient has a history of diabetes...

General considerations

Practices clearly change over time in response to published evidence. At times, these changes can be rapid and dramatic, particularly when an innovation is associated with overwhelmingly positive risk-benefit ratios and is feasible for large numbers of practitioners to adopt. This model of knowledge-based practice change is termed passive diffusion. Its impact is heightened by the extent to which the mass media pick up major medical advances, and by the marketing initiatives of drug and device...

Prevention of hypertension

Despite the established benefits of antihypertensive treat ment, concerns are often raised about the prospect of use of antihypertensive drugs over decades by 20 or more of the adult population. All drugs have adverse effects and the cost of medical care for hypertension is considerable. Also, the 12 year follow up of approximately 350000 middle-aged men screened for the Multiple Risk Factor Intervention Trial shows that 32 of the CHD deaths related to elevated BP occurred below the level at...

CVD profile at different stages of the epidemiologic transition

The model of epidemiologic transition originally described by Omran,18 with three phases (the age of pestilence and famine the age of receding pandemics the age of degenerative and manmade diseases), was later modified to include a fourth phase, the age of delayed degenerative diseases.19 Life expectancy increases progressively from around 30 years in the first phase to over 70 years in the fourth phase. The shift to a dominant chronic disease profile occurs in the third phase. As the average...

Key points

Cardinal issues for using lipid altering agents 1. Is the diagnosis of hyperlipidemia certain 2. Are there currently medications in the patient's regimen that cause dyslipidemia or offer the potential for drug interactions with hypolipidemic therapy 3. ALWAYS start the therapeutic regimen with diet and other lifestyle modifications. Grade A 4. The statins act as a class of agents, but possess different dose response curves. Some may have substantial levels of adverse effects. Grade A 5. The...

Nicotine replacement therapy NRT

The advent of nicotine chewing gum in the 1970s provided the first specific pharmacologic treatment for smoking cessation. Grade B Subsequent development of transdermal nicotine patches, nicotine nasal sprays, and nicotine oral inhalers has increased the range of products available. The objective in using these nicotine replacement products is to provide a temporary alternative source of nicotine to allay withdrawal symptoms and so enhance the potential for smoking cessation. Large...

Genetics of hypertension

Hypertension is among the top three or four most common diseases worldwide. It is an independent risk factor for cardiac morbidity and mortality and a major stimulus for cardiac hypertrophy, which itself significantly increases susceptibility for sudden cardiac death. Hypertension, as indicated previously, is primarily a polygenic disease. It is expected that there are several genes that increase susceptibility to developing hypertension. These genes interact with the environment, and the onset...

Genetics hypertension and some potential druggene interactions

The phenotype of high BP represents a complex trait influenced by both genes and environment.38-40 While behavioral factors such as obesity and physical inactivity are clearly important in the etiology, family studies and twin studies suggest that about 30 of the variation in levels of BP can be attributed to genetic factors.39 Several monogenic forms of high BP have been identified, and they include, for instance, glucocorticoid-remediable aldosteronism and Liddle's syndrome.38,39 These...

Prevention of cardiovascular diseases89

9 Global perspective on cardiovascular disease 91 K Srinath Reddy 10 Tobacco global burden and community solutions 103 Terry F Pechacek, Samira Asma, Nicole Blair, Michael P Eriksen 11 Tobacco and cardiovascular disease achieving smoking cessation 114 Godfrey H Fowler 12 Lipids and cardiovascular disease 121 Malcolm Law 13 Use of lipid lowering agents in the prevention of cardiovascular disease 130 Jeffrey L Probstfield 14 Blood pressure and cardiovascular disease 146 Curt D Furberg, Bruce M...

Conclusion

There are a number of direct and indirect biologic pathways linking dysglycemia to cardiovascular disease. Similar to dyslipidemia, in which ongoing studies are continuing to show the therapeutic value of reducing even minimally elevated lipid levels,81 dysglycemia may be a continuous modifiable cardiovascular disease risk factor therapies that reduce elevated glucose levels may reduce the risk of cardiovascular disease. A number of ongoing studies will address this issue. These include the...

DASH diets

The effects of composite dietary interventions on blood pressure levels, in normotensive and hypertensive individuals were studied in well designed clinical trials.80'100 The initial dietary intervention, used in the Dietary Approaches to Stop Hypertension (DASH) trial, involved a diet that emphasized fruit, vegetables, and low fat dairy products, and included whole grains, poultry, fish, and nuts while reducing the amounts of red meat, sweets, and sugar-containing beverages. Two variants of...

Arabs

The term Arab refers to Semitic people who originate from the Middle East. Included in this region are the countries of Egypt, Saudi Arabia, Jordan, Iran, Iraq, and the United Arab Emirates. CVD is the leading cause of death among Arabs living in the Middle East.11 This is primarily caused by the rapid socioeconomic development, urbanization, and improved survival over the past several decades. The Global Burden of Disease report estimates that the acute myocardial infarction (AMI) rate among...

Calculation of cost effectiveness

After the costs of therapy and the medical effectiveness of therapy have been assessed, cost effectiveness (CE) can be calculated as where Costj and Cost2 represent the costs of program 1 and program 2, respectively, and QALY1 and QALY2 represent the effectiveness of programs 1 and 2, respectively. There are several implications of using this formula. First, cost effectiveness ratios that are positive (that is, > 0) result if and only if one alternative has both higher cost and greater...

Alcohol

The relationship of alcohol to overall mortality and cardiovascular mortality has generally been J-shaped, when studied in Western populations in whom the rates of atherothrombotic vascular disorders are high.120-124 The protective effect of moderate ethanol consumption is primarily mediated through its effect on the risk of coronary heart disease (CHD), as supported by more than 60 prospective studies.121 A consistent coronary protective effect has been observed for consumption of one to two...

Godfrey H Fowler

Worldwide, there are about one billion current smokers and about three million die annually from their smoking, half before the age of 70 this includes about 150000 annually in the UK and half a million in the USA.1 Even in countries where the health hazards of smoking are widely acknowledged, it remains a common behavior in the USA and Canada, for example, about a quarter of all adults smoke, and, in the UK, the situation is worse with about one third of adults smoking. Cardiovascular disease,...

Issues related to diet as an independent variable

These relate to the association of dietary behaviors with other behaviors which influence cardiovascular risk and the impact of diet on several cardiovascular risk factors which may partly or wholly be in the causal pathway to CVD as intermediate variables. Unhealthy dietary behaviors often occur in association with other unhealthy behaviors such as physical inactivity and smoking. Furthermore, unhealthy dietary practices such as high consumption of saturated fats, salt and refined...

Serum cholesterol and ischemic heart disease

Evidence from genetics, animal studies, experimental pathology, epidemiologic studies and clinical trials indicates conclusively that increasing serum cholesterol is an important cause of ischemic heart disease and that lowering serum cholesterol reduces the risk,5,6 and the results of six large randomized trials of statins have ensured that this is now widely accepted.1,7-11 Three important practical questions arise the nature of the dose-response relationship, the size of the effect, and the...