1 / 39

Chapter 05

Chapter 05. Coronary Heart Disease. Coronary Heart Disease Mortality History and Magnitude of the Problem Heart Disease has been the #1 cause of death in the US since 1920.

akamu
Download Presentation

Chapter 05

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Chapter 05 Coronary Heart Disease

  2. Coronary Heart Disease Mortality • History and Magnitude of the Problem • Heart Disease has been the #1 cause of death in the US since 1920. • CHD remains the number-one cause of death in the United States, costing an estimated $177 billion in 2010, more than one-third of the costs of all cardiovascular diseases. • Mortality Rates have decreased since 1950 • Smoking has decreased • Better hypertension medications • Increased public awareness on dietary intervention • Better medical treatment for heart attacks

  3. Coronary Heart Disease • Magnitude of the Problem • Currently (2010), an estimated 17.6 million persons aged 20 years and older in the United States have CHD. • It is estimated that approximately every 25 seconds, an American will suffer a coronary event and that approximately every minute, one American will die from such an event. • About half of American men and a third of American women will develop CHD. The average age at first MI for men is about 65 years; for women, it’s 70 years.

  4. Coronary Heart Disease Risk Factors • Genetic Susceptibility (Family History) • Sex (Male) • Age • Hypercholesterolemia • Low HDL-cholesterol • Cigarette Smoking • Uncontrolled Hypertension • Obesity • Diabetes • Physical Inactivity

  5. Major Modifiable Risk Factors for CHD • Hypercholesterolemia • Hypertension • Hyperlipidemia • Physical Inactivity • Smoking • Diabetes • Obesity • Stress • Alcohol abuse

  6. CHD – Etiology (Study of causation) Video • CHD is caused by Atherosclerosis • Atherosclerosis (plaque formation ) is a form of Arteriosclerosis (hardening of the artery) is characterized by fatty deposits called atheromas. Atherosclerosis is a disease affecting arterial blood vessels. It is a chronic inflammatory response in the walls of arteries, in large part to the deposition of lipoproteins (plasma proteins that carry cholesterol and triglycerides). It is commonly referred to as a "hardening" or "furring" of the arteries. It is caused by the formation of multiple plaques within the arteries.

  7. Pathologically, the atheromatous plaque is divided into three distinct components: • The atheroma ("lump of porridge", from Athera, porridge in Greek,) is the nodular accumulation of a soft, flaky, yellowish material at the center of large plaques, composed of macrophages nearest the lumen of the artery. • Underlying areas of cholesterol crystals. • Calcification at the outer base of older/more advanced lesions.

  8. The atheromatous plaques, eventually lead to plaque ruptures and stenosis (narrowing) of the artery and, therefore, an insufficient blood supply (ischemia) to the organ it feeds. • An ischemic event in the myocardium can cause a heart attack • Tearing of the plaque can cause a thrombus formation also causing a heart attack • A second problem occurs if the compensating artery enlargement process is excessive, a net aneurysm results.

  9. The atherosclerotic process begins in childhood. (see Progression of Atherosclerosis – next slide) • Severity is related to an increase in LDL-cholesterol, and conversely (retards atheroma growth) to HDL-cholesterol. HDL is believed to transport cholesterol from atheromas back to the liver. • Cigarette smoking, high blood pressure, and dietary intake of saturated fat and cholesterol also contribute to atherosclerosis. • LDL-cholesterol readily enters the artery wall by crossing the endothelial membrane. Once in the arterial wall, if LDL accumulates, it is subject to modification. The modification of LDL-cholesterol accelerates the genesis of atheromas.

  10. Progression of Atherosclerosis • Stages • Initial Lesion • Fatty Streak Formation • Intermediate Lesion • Atheroma • Fibroatheroma • Complicated Lesion

  11. Atherogenesis • Begins with lesions of the artery intima (inner lining) The intima includes the surface endothelial cells and the underlying connective tissue. • Lesions occur from elevated lipoprotein levels (cholesterol), toxic effects of chemicals in cigarettes, and elevated homocysteine levels. • Atherogenesis is a staged process that begin with the circulating blood platelets and the in endothelium • Staged process of atherosclerosis (atherogenesis) follows..

  12. Staged Process of Atherogenesis 1) Platelets adhere to the connective tissue beneath the damaged endothelial cells

  13. 2) Platelet adhesion activates fibrinogen 3) Fibrinogen enhances platelet aggregation (positive feedback) 4) Fibrinogen releases a growth factor that stimulates smooth proliferation (chemotactic) and fibroblasts (Fibroblasts provide a structural framework for many tissues, and play a critical role in wound healing. They are the most common cells of connective tissue ) 5)Smooth muscle cells and fibroblasts migrate into the intima and cause fibrosis (hardening) by the production of collagen, elastin (both connective tissue) ** LDL-cholesterol continues to collect in the damaged area.

  14. LDL and Atherogenesis • Oxidized LDL occurs via combining with a free radical of oxygen created from cellular respiration ( A free radical is an atom or group of atoms that transiently exists in an unstable state by carrying an unpaired electron until an electron can be stolen from another atom.) • Oxidized LDL secretions attract macrophages which become foam cells (Oxidized LDL stimulates secretion of monocyte chemo-attractant protein-1 (MCP-1), which results in a fatal attraction for immune cells known as macrophages, already drawn to the arterial lesion to ingest the debris of injured endothelial cells) • Oxidized leads to further injury of the endothelial cells (cytotoxic).

  15. Inflammation and Atherogenesis • The atherosclerotic disease involves an inflammatory process. • Major risk factors for CVD including hyperlipidemia, hypertension, diabetes, and obesity all have pro-inflammatory features as do viral and bacterial infections • Inflammatory responses can be measured via C-reactive protein. Associated with the presence of C-reactive protein includes the uptake of LDL by marcophages, and attraction of the monocytes to the endothelium, and the production of MCP-1. • In healthy men and women with normal LDL cholesterol levels but elevated C-reactive protein a drug (rosuvastatin) that lowered both LDL cholesterol (by 50%) and C-reactive protein levels (by 37%), resulted in a 44% reduction in the occurrence of a first cardiovascular event • Other inflammatory markers include elevated white blood cell counts and elevated levels of circulating fibrinogen • The anti-inflammatory effect of physical activity may be mediated through beneficial changes in body weight.

  16. Hemostasis • Hemostatic (blood clotting) factors are risk factors for CVD. • Coagulation or clotting of blood involves platelet aggregation and fibrinogenesis. Blood Coagulation 1. Blood coagulation is the most effective means of hemostasis. 2. Blood coagulation is very complex and uses clotting factors. 3.Damaged tissues release a chemical called tissue thromboplastin, which activates the first in a series of factors leading to the production of prothrombin activator.

  17. 4.Prothrombin activator converts prothrombin in the plasma into thrombin. This in turn, catalyzes a reaction that converts fibrinogen into fibrin. 5. The major event in blood clot formation is the conversion of soluble fibrinogen into net like insoluble fibrin (fibrinogenesis)causing the blood cells to catch. • The amount of prothrombin activator formed is proportional to the amount of tissue damage. • Once a blood clot forms, it promotes still more clotting through a positive feedback system. 8. After a clot forms, fibroblasts invade the area and produce fibers throughout the clots. 9. A clot that forms abnormally in a vessel is a thrombus; if it dislodges, it is an embolus.

  18. Process of Hemostasis

  19. Thus, the concentration of fibrinogen in the blood also is a risk factor for MI and stroke due to hemostasis. A high level of fibrinogen in blood plasma doubles the risk of developing CVD, and increases recurrent MI and ischemic stroke by 8%, independently of overall CVD risk status, smoking, and age • Fibrinogen levels increase with age, smoking, waist to hip ratios, and LDL cholesterol levels. • Plasmin is formed in the blood from plasminogen by tissue-type plasminogen activator (tPA), which is released from endothelial cells in blood vessels or by drugs such as streptokinase and trypsin. • A major contributor to impaired fibrinolysis is a high blood level of plasminogen activator inhibitor-1 (PAI-1), which also is released by blood vessel endothelial cells and inhibits tPA. High PAI-1 is a risk factor for first heart attack or stroke, a recurrent heart attack among heart attack survivors, and cardiac death among people reporting angina.

  20. Homocysteine • A natural intermediate amino acid formed during the metabolism of methionine (essential amino acid) • Elevated levels of homocysteine in the blood are associated with a higher risk of developing CVD, although whether this link is causal is unclear. Recent research diminishes the association with homocysteine and CVD (2008). • The homocysteine hypothesis of CVD is credited to physician Kilmer McCully (1969), who observed that children with the genetic condition homocystinuria (which leads to abnormally high levels of homocysteine because of deficiencies in metabolic enzymes) usually died from arteriosclerosis at an early age. • It is hypothesized that homocysteine damages the endothelial cells which results in platelet aggregation and blood clotting • Increasing dietary levels of B6 and B12 and Folic Acid (B9)deters homocysteine formation.

  21. Physical Activity and CHD: The Evidence • Occupational Activity and CHD Risk • London Bus Conductors (Morris) • Conductors at lower risk than drivers • If conductors developed CHD, it was less severe • BP was lower in conductors, if BP was the same between conductors and drivers, the conductors had fewer heart related problems than the drivers • Bus drivers rate of coronary death was higher independent of body mass

  22. Occupational Activity and CHD Risk • San Francisco Longshoremen (Dock Workers) • Active group had death rates 50% of the inactive group • Active group had sudden death rates 66% lower than the inactive group • Other early studies of Occupational Activity • Most studies report active workers have 33 to 75% fewer fatal CHD events than least active workers • Many studies did not control for confounding factors such as smoking and dietary habits, between workers with different occupational activity levels.

  23. Leisure-Time Physical Activity and CHD Risk • Retrospective Cohort and Case-Control Studies • The Netherlands • A significant inverse relationship between heart attack and walking, cycling, and gardening, if performed more than eight months per year. • King County Washington • Risk of cardiac death was 55-65% lower in men and women in higher intensity physical activity compared to those who did not engage in any higher intensity physical activity.

  24. Leisure-Time Physical Activity and CHD Risk • Retrospective Cohort and Case-Control Studies • Health Insurance Plan of New York • Incidence of MI in heavy and moderate activity groups was about 50% of the light activity group • Least active men had mortality rate 4.5x greater than the most active men following an MI.

  25. Prospective Studies • 26 Study Meta-analysis = The relative risk of CHD associated with a moderate, compared with a low, level of leisure-time physical activity was 0.88 (95% CI: 0.83-0.93) (Sofi et al. 2008). For high compared with low level of leisure-time physical activity, the relative risk was 0.73 (0.66-0.80) • Additional Meta-analysis findings that 150 min/week had 14% reduction in RR; whereas 300 min/week = 20% reduction in RR. • British Civil Servants Study • CHD death rate twice as high in the non-vigorous vs. vigorous group • Higher rates of CHD found in those who stopped activity • Vigorous sport activities protective for younger, lower intensity exercise protective for older men. Thus, the dose-response effect of exercise may vary with age.

  26. Prospective Studies • Harvard Alumni Study • Men who expended < 2000 kcal/wk were at 64% higher risk of CHD – There is a consistent dose-response relationship for optimal reductions in CHD morbidity and mortality at/around 2000 kcal expenditure/wk • Athletes did not have any risk reduction in later years if they discontinued exercise • Framingham • Relative Risk for CHD in least active men 1.3x that of the most active men.

  27. Prospective Studies • Seven Countries Study • Three of seven countries showed inverse relationship between physical inactivity and CHD. Note relatively few of the men in the study were classified as sedentary • Finnish Cohorts • CHD was clearly associated with sedentary habits • Puerto Rico Heart Health Program • Inverse association between the incidence of CHD and physical activity • Physical inactivity independently contributes to the risk of CHD

  28. Prospective Studies • Multiple Risk Intervention Trials (MRFIT) • CHD mortality in the most active 67% of the least active • Daily caloric threshold between 75-200kcal has a protective effect • Greater than 220, up top 640 kcal/day further decreases mortality rates. • A modest amount (20 min/day) of exercise decreases risk of CHD in middle-aged and older men.

  29. Prospective Studies • Nurses Health Study • Strong, Graded, and Inverse relationship between CHD risk and physical activity • Those women who exercised vigorously 1.5 hours per week had the greatest protective effect of exercise (adjusting for other risk factors) • Women’s Health Initiative Observational Study • Postmenopausal women • Women in the top three quintiles (most active) had significantly lower risk (equivalent of 2.5h of brisk walking/week)

  30. Prospective Studies • Health Professionals Follow-up Study • Total physical activity, running, weight training, and rowing were each inversely and linearly related to risk of CHD • Running for an hour or more per week was associated with a 42% risk reduction • Weight training for 30 min or more per week was associated with a 23% risk reduction • Rowing for 1 h or more per week was associated with an 18% risk reduction • A half hour per day or more of brisk walking was associated with an 18% risk reduction

  31. Physical Fitness and Coronary Heart Disease Risk ** The true size of the protective effect of physical activity against CHD is probably underestimated. • Los Angeles Public Safety Workers • Below average fitness = 2.2 RR (relative risk) of MI ; increasing to 6.6 with two additional risk factors (hypercholesterolemia, systolic hypertension, cigarette smoking) • Lipid Research Clinics Prevalence Study • CHD mortality RR in least fit was 6.5x for CVD death • See figure 5.8, p.108, and next slide for dose response

  32. Physical Fitness and Coronary Heart Disease Risk • Lipid Research Clinics Prevalence Study Cumulative rates of death from cardiovascular diseases in healthy men according to quartiles of exercise test heart rate. Men who were most active (first quartile) had the lowest CVD death rate. Divergence of mortality curves over follow-up indicates that the effect on cardiovascular mortality is unlikely to be due to bias.

  33. Physical Fitness and Coronary Heart Disease Risk • Aerobics Center Longitudinal Study • Mortality rate for highly fit 50% of the moderately fit, and the rate of the least fit 3x that of the moderately fit men • In women, mortality rate 3.6x in the moderately fit compared to the highly fit, and the low fit mortality rate was 2.5x that of the moderately fit • St James Women Take Heart Project • The relative risks for cardiac death among high-, medium-, and low-fit women were 1.00 (referent), 2.02 (95% CI: 0.46-8.82), and 4.27 (1.0317.6), respectively *** A review of the physical fitness studies show a causal relationship between regular physical activity and a reduced risk of CHD.

  34. Population Attributable Risk (PAR) for Physical Inactivity • PAR = a estimate of the reduction in mortality rate that might occur if all individuals with a particular risk factor (inactivity) were to eliminate that risk factor. • Estimate Reports • PAR U.S. Sedentary Lifestyle = 16% CHD Mortality • PAR Sedentary Lifestyle = 13% All Cause Mortality (similar to cigarette smoking, hypertension, and overweight) • Longitudinal Studies PAR for sedentary behavior show that low fitness had a PAR Mortality that was similar to , if not larger than the other risk factors. • Summary – Sedentary behavior substantially contributes to the public health burden, and eliminating this behavior would have as great, or greater, impact on reducing excess mortality as eliminating other major CHD risk factors.

  35. Strength of the Association between Physical Activity in All Cause and CHD Mortality • Strength of the Evidence • Temporal Sequence • Prospective Cohort designs in physical activity measure the independent variables before the outcome occurs, thus demonstrating the appropriate temporal sequence. • Strength of the Association • Review of literature on CHD and Mortality show that the RR of mortality is almost 2x as great for sedentary when compared to active persons

  36. Strength of the Association between Physical Activity in All Cause and CHD Mortality • Strength of the Evidence • Consistency of Results • Results are consistent about the association of physical activity with all-cause CHD mortality in both men and women • Biological Plausibility • Exercise decreases coronary atherosclerosis, and thus, increase myocardial oxygen demand • Exercise decreases the risk of coronary thrombosis reducing the risk for clotting in the coronary vessels • Acute bouts of exercise promotes fibrinolysis (decrease in blood clotting activity) • Chronic exercise decreases plasma fibrinogen and increases tissue plasminogen when compared to sedentary counterparts.

  37. Strength of the Association between Physical Activity in All Cause and CHD Mortality • Strength of the Evidence • Biological Plausibility (cont.) • Exercise decreases myocardial irritability, reducing the rate of ventricular fibrillation • Dose Response • Review of 31 studies show that physical activity has a causal, dose-response relationship with reduced CHD morbidity and mortality. • There is a threshold where the RR of CHD Mortality tends to plateau, possibly around 2-3,000 kcal/wk, with a tendencey to see reduction in risk around 500kcal/week • The accumulation of caloric expenditure is more closely associated with the overall risk reduction in CVD.

  38. Summary of Findings • Activity for CHD risk reduction should ideally require 150 min/week of moderate-intensity aerobic activity, or 75 min/week of vigorous-intensity physical activity, or the equivalent energy expenditure in a combination of moderate and vigorous activities. Physical activity can be accumulated in bouts of at least 10 min in duration to count toward the total. • For persons willing to do more, additional amounts of physical activity beyond that confer additional risk reductions.

  39. END OF PRESENTATION

More Related