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EARLY PREVENTION OF CORONARY HEART DISEASE

EARLY PREVENTION OF CORONARY HEART DISEASE. BY Jameel A. Al-ata, MD Consultant & Assistant Professor of Pediatrics & Pediatric Cardiology K.A.A.U.H & KFSH-RC JED. INTRODUCTION.

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EARLY PREVENTION OF CORONARY HEART DISEASE

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  1. EARLY PREVENTION OF CORONARY HEART DISEASE BY Jameel A. Al-ata, MD Consultant & Assistant Professor of Pediatrics & Pediatric Cardiology K.A.A.U.H & KFSH-RC JED.

  2. INTRODUCTION • Atherosclerosis leading to coronary heart disease is complexin origin. Involved in the pathogenesis of atherosclerosis arehemodynamic, thrombotic, and carbohydrate–lipid metabolicvariables, along with intrinsic characteristics of the arterialwall. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362:801-809.

  3. Morbidity due to coronary artery disease is generallyrelated to the extent of vascular lesions. In this regard,clinical risk factors are considered to be useful in predictingthe severity of atherosclerosis. Roberts WC. Am J Cardiol 1989;64:324-328. Solberg LA, Strong JP. Arteriosclerosis 1983;3:187-198.

  4. Environmental factorssuch as smoking or a sedentary lifestyle also contribute tothis process. The progression of atherosclerotic disease andthe increasing severity of atherosclerosis relate not only tothe presence and extent of cardiovascular risk factors but alsoto the persistence of risk factors over time. Dawber TR. The Framingham Study: the epidemiology of atherosclerotic disease. Cambridge, Mass.: Harvard University Press, 1980. Stamler J. Cardiology 1993;82:191-222.

  5. INTRDUCTION • Hypercholsterolemia is a proven risk for premature atherosclerosis & M.I. • Each 1% reduction in cholesterol reduces MI. incidence 2% in adult males. • Hypertriglyceridemia is a less significant risk, But also known to be associated with premature atherosclerosis.

  6. INTRODUCTION • ONE THIRD of ist MI. patients ( men under 50 & women under 60 years ) have hyperlipoprotienemia, HALF have an inherited lipoprotien disorder. • In Philadelphia childrens hosp. 75% of children have hyperlipidemia& strongly +ve Fmhx. Of premature CHD. • 21% ( FH ), 67% ( FCHL ), 11% ( hyperapobetalipoprotienemia ) & 1% (FHTG )

  7. INTRODUCTION • The understanding of the molecular basis of inborn errors of LDL metabolism - such as familial hypercholesterolemia due to a defect of the LDL receptor - provided us new insights in physiology and pathophysiology of LDL metabolism. • Most recently we have learned much about the vasoprotective HDL cholesterol. HDL is the major player in reverse cholesterol transport and some of its receptors such as ABCA1 and SR-BI were identified. This knowledge gives us a deeper understanding of the complex system which performs reverse cholesterol transport from peripheral tissue and the vessel wall back to the liver.

  8. INTRODUCTION • Fetal programming of coronary heart disease ; • People who develop coronary heart disease grow differently from other people both in utero and during childhood. Slow growth during fetal life and infancy is followed by accelerated weight gain in childhood. • Two disorders that predispose to coronary heart disease, type 2 diabetes and hypertension, are preceded by similar paths of growth.

  9. INTRODUCTION • Mechanisms underlying this are thought to include the development of insulin resistance in utero, reduced numbers of nephrons associated with small body size at birth and altered programming of the micro-architecture and function of the liver. • Slow fetal growth might also heighten the body's stress responses and increase vulnerability to poor living conditions in later life.

  10. INTRODUCTION • Coronary heart disease appears to be a developmental disorder that originates through two widespread biological phenomena, developmental plasticity and compensatory growth.

  11. INTRODUCTION • Clustering of coronary heart disease risk factors among obese children; • Recent secular trends have resulted in large numbers of very overweight children who are at increased risk for type 2 diabetes mellitus and for various coronary heart disease risk factors, including adverse levels of lipids, insulin, and blood pressure. All are associated with the initial stages of atherosclerosis. • The difficulties in preventing and reversing obesity, along with the frequent non-adherence of adolescents to lifestyle changes and medical treatment, will complicate treatment and prevention efforts.

  12. Epidemiologic studies have established that multiple risk factorsincrease the probability of cardiovascular events, since risk factors tend to reinforce each other in their influenceon morbidity and mortality. Kannel WB, National Heart, Lung, and Blood Institute, 1987. (NIH publication no. 87-2703.)

  13. Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (The Bogalusa Heart Study).

  14. Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (The Bogalusa Heart Study). • Race and sex differences in aorta and coronary atherosclerotic lesions were studied in 150 persons aged 6 to 30 years. • The intimal surface involvement with aorta fatty streaks was extensive, 0 to 71%, and greater in blacks than in whites (32 vs 20%, p less than 0.001). • Coronary artery fatty streaks were more extensive in male than in female subjects (range 0 to 22%).

  15. BHS • Fibrous plaque lesions were present but not extensive in either the aorta (0 to 12%) or the coronary artery (0 to 24%) specimens. Lesions were more prevalent in male than in female persons, particularly white male subjects. • The relation of fatty streaks to fibrous plaques was greater in the coronary vessels than in the aorta. In male subjects, aorta fatty streaks were strongly related to antemortem levels of total cholesterol, low-density lipoprotein cholesterol and ponderal index in white male subjects.

  16. BHS • Coronary artery fatty streaks in white male persons were significantly associated with serum triglycerides, very low density lipoprotein cholesterol, systolic and diastolic blood pressure and ponderal index. • These results link antemortem risk factors to the development of atherosclerotic lesions and emphasize the need for preventive cardiology in early life. Am J Cardiol 1992 Oct1;70(9):8518

  17. Furthermore, since clustering of risk factors is evident inchildhood and persists into young adulthood, the presenceof multiple risk factors could indicate the acceleration ofatherosclerosis in young people. The Bogalusa Heart Study. Prev Med 1979;8:407-418. Khoury P, Am J Epidemiol 1980;112:524-538. Smoak CG, Am J Epidemiol 1987;125:364-372. Bao W, Arch Intern Med 1994;154:1842-1847

  18. Association between Multiple Cardiovascular Risk Factors and Atherosclerosis in Children and Young Adults • Autopsy datafrom epidemiologic studies have shown a relation between coronaryartery disease and cardiovascular risk factors; for example,high serum total cholesterol concentrations and cigarette smokingare important contributors to the development of coronary atherosclerosis.

  19. Autopsy studies from the Bogalusa Heart Study have demonstrateda strong association of specific antemortem risk factors withvascular lesions in children and young adults. • These observationshave been extended by the findings in a larger, multicenterpostmortem study, Pathobiological Determinants of Atherosclerosisin Youth.

  20. The extent of fatty streaks and fibrous plaques in theaorta and coronary arteries increased with age. The associationbetween fatty streaks and fibrous plaques was much strongerin the coronary arteries (r=0.60, P<0.001) than in the aorta(r=0.23, P=0.03

  21. Among the cardiovascular risk factors, body-massindex, systolic and diastolic blood pressure, and serum concentrationsof total cholesterol, triglycerides, low-density lipoproteincholesterol, and high-density lipoprotein cholesterol, • as agroup, were strongly associated with the extent of lesions inthe aorta and coronary arteries (canonical correlation [a measureof the association between groups of variables]: r=0.70; P<0.001).

  22. cigarette smoking increased the percentage of theintimal surface involved with fibrous plaques in the aorta (1.22percent in smokers vs. 0.12 percent in nonsmokers, P=0.02) andfatty streaks in the coronary vessels (8.27 percent vs. 2.89percent, P=0.04).

  23. Subjects with 0,1, 2, and 3 or 4 risk factors had, respectively, 19.1 percent,30.3 percent, 37.9 percent, and 35.0 percent of the intimalsurface covered with fatty streaks in the aorta (P for trend=0.01). • The comparable figures for the coronary arteries were 1.3 percent,2.5 percent, 7.9 percent, and 11.0 percent, respectively, forfatty streaks (P for trend=0.01) and 0.6 percent, 0.7 percent,2.4 percent, and 7.2 percent for collagenous fibrous plaques(P for trend=0.003).

  24. Conclusions; These findings indicate that as the number of cardiovascularrisk factors increases, so does the severity of asymptomaticcoronary and aortic atherosclerosis in young people.

  25. Pathobiological Determinantsof Atherosclerosis in Youth (PDAY),

  26. Relation of a Postmortem Renal Index of Hypertension to Atherosclerosis in Youth • In a cooperative multicenter study, Pathobiological Determinantsof Atherosclerosis in Youth, of 1164 young men 15 through 34years of age who died of external causes and were autopsiedin forensic laboratories. • They measured atherosclerosis of theaorta and the right coronary artery.

  27. CONT, ( PDAY ) • Using the ratio of intimalthickness to outer diameter of the small renal arteries to predictmean arterial pressure (MAP) during life. Cases were classifiedas either normotensive (MAP <110 mm Hg) or hypertensive (MAP 110mm Hg).

  28. CONT, ( PDAY ) • By this criterion, the prevalence of hypertension in blackswas 16%; in whites, 12%. Hypertension was associated directly withblood level of glycohemoglobin (an indicator of blood glucose concentration)and with body mass index (BMI) but inversely with thicknessof the panniculus adiposus.

  29. CONT, ( PDAY) • Among hypertensive compared with normotensive cases, the extentof raised lesions (mainly fibrous plaques) was greater in the aortasof 30- to 34-year-old men and in the right coronary arteriesof 25- to 34-year-old men. • The prevalence of raised lesionsinvolving 5% or more of the intimal surface was twofold greaterin the aortas and right coronary arteries of hypertensive menthroughout the 15-to-34–year age span of the study cases.

  30. The prevalence of raised lesionsinvolving 5% or more of the intimal surface was twofold greaterin the aortas and right coronary arteries of hypertensive menthroughout the 15-to-34–year age span of the study cases.

  31. Althoughhypertension is associated with elevated blood glycohemoglobinand adiposity, the effect of hypertension on atherosclerosisis not accounted for by those variables.

  32. Relation of Glycohemoglobin and Adiposity to Atherosclerosis in Youth ( PDAY ) • In a cooperative multicenter study (Pathobiological Determinantsof Atherosclerosis in Youth, PDAY) of 1532 young persons 15through 34 years of age who died of external causes and were autopsiedin medical examiners' laboratories

  33. They quantified atherosclerosisof the aorta and the right coronary artery and analyzed postmortemblood cells for glycohemoglobin and postmortem serum for lipoproteincholesterol and thiocyanate (as an indicator for smoking). • They measured the thickness of the panniculus adiposus and the bodymass index (weight per height squared) as indicators of adiposity

  34. Glycohemoglobinlevels exceeding 8% were associated with substantially moreextensive fatty streaks and raised lesions in the right coronary arteryin persons more than 25 years of age and with more extensive raisedlesions in the aorta in persons more than 30 years of age. • Both thicknessof the panniculus adiposus and body mass index were associatedwith more extensive fatty streaks and raised lesions in the rightcoronary artery.

  35. The associations of atherosclerotic lesionswith glycohemoglobin and adiposity were not explained by a lessfavorable lipoprotein profile or smoking. • The results show thatatherosclerosis in young adults is associated with the prediabeticor early diabetic state, as indicated by elevated glycohemoglobinlevels, and with obesity.

  36. Several recent articles reviewed the potential mechanisms bywhich diabetes, hyperinsulinemia, and hyperglycemia augment atherogenesis. • Of the many mechanisms suggested, two seem most likelyto be involved in the association of glycohemoglobin concentrationin these young adults: • 1 ) the effects of dyslipoproteinemia andhyperinsulinemia in the prediabetic state, as suggested by Haffner etal, and , • 2 ) a direct effect of glycosylation of proteins on atherogenesis.

  37. The glycohemoglobin effect is not accounted for by serum lipoproteincholesterol levels (VLDL+LDL-C and HDL-C), and there is littlecorrelation between glycohemoglobin levels and serum lipoprotein levels. • However, the possibilityremains that individuals with elevated glycohemoglobin levelsmay have had abnormal lipoprotein profiles and hyperinsulinemia.

  38. A process similar to the glycosylation of hemoglobin occursin other proteins. Subsequently, the carbohydrate-protein complex undergoeschemical rearrangement to form irreversible advanced glycosylationend products, which have a variety of deleterious effects oncells and tissues.

  39. ConclusionsThe observations reported here suggest that both elevated glycohemoglobinlevels, possibly associated with the prediabetic state, andobesity are associated with accelerated atherogenesis in thethird and fourth decades of life. • The results provide hope thatearly detection and control of obesity and hyperglycemia inyoung persons will reduce the risk of atherosclerotic diseasein later life.

  40. Obesity and Atherosclerosis;The health effects of obesity have been difficult to study because (1)body weight and composition are influenced by many different conditions(eg, caloric intake, physical activity, smoking, and genetic factors),(2) its definition is not precise, (3) fat distribution may beas important as total fat, (4) duration of exposure and ageof the subject influence its effects, and (5) obesity is associatedwith a variety of health risks (hypertension, coronary heartdisease, stroke, non–insulin-dependent diabetes, cholelithiasis,and some forms of cancer).

  41. Obesity enhances three otherestablished risk factors for coronary heart disease; • hypertension, dyslipoproteinemia,and diabetes mellitus. • and is inversely related to anothermajor risk factor, smoking. • In many instances, when obesityis associated with coronary heart disease in univariate analyses,multivariate analyses including the other risk factors do not showan independent effect. • but several long-term longitudinal studies havefound an independent effect after controlling for other risk factors.

  42. Effects of Serum Lipoproteins and Smoking on Atherosclerosis in Young Men and Women ( PDAY ) • Atherosclerosis begins in childhood and progresses from fattystreaks to raised lesions in adolescence and young adulthood. • A cooperative multicenter study (Pathobiological Determinantsof Atherosclerosis in Youth [PDAY]) examined the relation ofrisk factors for adult coronary heart disease to atherosclerosisin 1079 men and 364 women 15 through 34 years of age, both blackand white, who died of external causes and were autopsied inforensic laboratories.

  43. They quantitated atherosclerosis of theaorta and right coronary artery as the extent of intimal surfaceinvolved by fatty streaks and raised lesions and analyzed postmortemserum for lipoprotein cholesterol and thiocyanate (as an indicatorof smoking).

  44. The extent of intimal surface involved with bothfatty streaks and raised lesions increased with age in all arterialsegments of all sex and race groups. • Women had a greater extentof fatty streaks in the abdominal aorta than men, but womenand men had about an equal extent of raised lesions.

  45. Women andmen had a comparable extent of fatty streaks in the right coronaryartery, but women had about half the extent of raised lesions.Blacks had a greater extent of fatty streaks than whites, butblacks and whites had a similar extent of raised lesions. • VLDLplus LDL cholesterol concentration was associated positivelyand HDL cholesterol was associated negatively with the extentof fatty streaks and raised lesions in the aorta and right coronaryartery.

  46. Smoking was associated with more extensive fatty streaksand raised lesions in the abdominal aorta. All three risk factorsaffected atherosclerosis to about the same degree in both sexesand both races. • Primary prevention of atherosclerosis by controllingthese adult coronary heart disease risk factors is applicableto young men and women and to young blacks and whites.

  47. The effects of VLDL+LDL-C and HDL-C concentrations andsmoking are similar in men and women and are similar in blacksand whites. Race and sex differences in atherosclerotic lesionsare not explained by differences in lipoprotein cholesterollevels or smoking. • These results are similar to those reported previously resultsare including those reported from the Bogalusa Heart Study.

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