early prevention of coronary heart disease by jameel a. al-ata, md consultant & assistant...

EARLY PREVENTION OF EARLY PREVENTION OF CORONARY HEART DISEASECORONARY HEART DISEASE

BYBY

Jameel A. Al-ata, MDJameel A. Al-ata, MD

Consultant & Assistant Professor of Consultant & Assistant Professor of Pediatrics & Pediatric CardiologyPediatrics & Pediatric Cardiology

K.A.A.U.H & KFSH-RC JED.K.A.A.U.H & KFSH-RC JED.

INTRODUCTIONINTRODUCTION

Atherosclerosis leading to coronary heart disease Atherosclerosis leading to coronary heart disease is complexis complex in origin. Involved in the in origin. Involved in the pathogenesis of atherosclerosis arepathogenesis of atherosclerosis are

hemodynamic, thrombotic, and carbohydrate–hemodynamic, thrombotic, and carbohydrate–lipid metaboliclipid metabolic variables, along with intrinsic variables, along with intrinsic characteristics of the arterialcharacteristics of the arterial wall.wall.

Ross R. The pathogenesis of atherosclerosis: a Ross R. The pathogenesis of atherosclerosis: a

perspective for the 1990s. Nature 1993;362:801-perspective for the 1990s. Nature 1993;362:801-809.809.

Morbidity due to coronary artery disease is Morbidity due to coronary artery disease is generallygenerally related to the extent of vascular related to the extent of vascular lesions. In this regard,lesions. In this regard, clinical risk factors clinical risk factors are considered to be useful in predictingare considered to be useful in predicting the the severity of atherosclerosis. severity of atherosclerosis.

Roberts WC. Am J Cardiol 1989;64:324-328.Roberts WC. Am J Cardiol 1989;64:324-328.

Solberg LA, Strong JP. Arteriosclerosis Solberg LA, Strong JP. Arteriosclerosis 1983;3:187-198.1983;3:187-198.

Environmental factorsEnvironmental factors such as smoking or a such as smoking or a sedentary lifestyle also contribute tosedentary lifestyle also contribute to this process. this process. The progression of atherosclerotic disease andThe progression of atherosclerotic disease and the the increasing severity of atherosclerosis relate not increasing severity of atherosclerosis relate not only toonly to the presence and extent of cardiovascular the presence and extent of cardiovascular risk factors but alsorisk factors but also to the persistence of risk to the persistence of risk factors over time.factors over time.

Dawber TR. The Framingham Study: the epidemiology of Dawber TR. The Framingham Study: the epidemiology of

atherosclerotic disease. Cambridge, Mass.: Harvard atherosclerotic disease. Cambridge, Mass.: Harvard University Press, 1980. University Press, 1980.

Stamler J. Cardiology 1993;82:191-222.Stamler J. Cardiology 1993;82:191-222.

INTRDUCTIONINTRDUCTION

Hypercholsterolemia is a proven risk for Hypercholsterolemia is a proven risk for premature atherosclerosis & M.I.premature atherosclerosis & M.I.

Each 1% reduction in cholesterol reduces Each 1% reduction in cholesterol reduces MI. incidence 2% in adult males.MI. incidence 2% in adult males.

Hypertriglyceridemia is a less significant Hypertriglyceridemia is a less significant risk, But also known to be associated with risk, But also known to be associated with premature atherosclerosis.premature atherosclerosis.


ONE THIRD of ist MI. patients ( men under 50 & ONE THIRD of ist MI. patients ( men under 50 & women under 60 years ) have hyperlipoprotienemia, women under 60 years ) have hyperlipoprotienemia, HALF have an inherited lipoprotien disorder.HALF have an inherited lipoprotien disorder.

In Philadelphia childrens hosp. 75% of children In Philadelphia childrens hosp. 75% of children have hyperlipidemia& strongly +ve Fmhx. Of have hyperlipidemia& strongly +ve Fmhx. Of premature CHD.premature CHD.

21% ( FH ), 67% ( FCHL ), 11% 21% ( FH ), 67% ( FCHL ), 11% ( hyperapobetalipoprotienemia ) & 1% (FHTG ) ( hyperapobetalipoprotienemia ) & 1% (FHTG )


The understanding of the molecular basis of inborn errors The understanding of the molecular basis of inborn errors of LDL metabolism - such as familial hypercholesterolemia of LDL metabolism - such as familial hypercholesterolemia due to a defect of the LDL receptor - provided us new due to a defect of the LDL receptor - provided us new insights in physiology and pathophysiology of LDL insights in physiology and pathophysiology of LDL metabolism. metabolism.

Most recently we have learned much about the Most recently we have learned much about the vasoprotective HDL cholesterol. HDL is the major player in vasoprotective HDL cholesterol. HDL is the major player in reverse cholesterol transport and some of its receptors such reverse cholesterol transport and some of its receptors such as ABCA1 and SR-BI were identified. This knowledge as ABCA1 and SR-BI were identified. This knowledge gives us a deeper understanding of the complex system gives us a deeper understanding of the complex system which performs reverse cholesterol transport from which performs reverse cholesterol transport from peripheral tissue and the vessel wall back to the liver.peripheral tissue and the vessel wall back to the liver.


Fetal programming of coronary heart disease ;Fetal programming of coronary heart disease ;

People who develop coronary heart disease grow People who develop coronary heart disease grow differently from other people both in utero and during differently from other people both in utero and during childhood. Slow growth during fetal life and infancy is childhood. Slow growth during fetal life and infancy is followed by accelerated weight gain in childhood.followed by accelerated weight gain in childhood.

Two disorders that predispose to coronary heart Two disorders that predispose to coronary heart disease, type 2 diabetes and hypertension, are preceded disease, type 2 diabetes and hypertension, are preceded by similar paths of growth. by similar paths of growth.


Mechanisms underlying this are thought to include Mechanisms underlying this are thought to include the development of insulin resistance in utero, the development of insulin resistance in utero, reduced numbers of nephrons associated with reduced numbers of nephrons associated with small body size at birth and altered programming small body size at birth and altered programming of the micro-architecture and function of the liver.of the micro-architecture and function of the liver.

Slow fetal growth might also heighten the body's Slow fetal growth might also heighten the body's stress responses and increase vulnerability to poor stress responses and increase vulnerability to poor living conditions in later life. living conditions in later life.


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


Clustering of coronary heart disease risk factors among Clustering of coronary heart disease risk factors among obese children; obese children;

Recent secular trends have resulted in large numbers of very Recent secular trends have resulted in large numbers of very overweight children who are at increased risk for type 2 diabetes overweight children who are at increased risk for type 2 diabetes mellitus and for various coronary heart disease risk factors, mellitus and for various coronary heart disease risk factors, including adverse levels of lipids, insulin, and blood pressure. including adverse levels of lipids, insulin, and blood pressure. All are associated with the initial stages of atherosclerosis. All are associated with the initial stages of atherosclerosis.

The difficulties in preventing and reversing obesity, along with The difficulties in preventing and reversing obesity, along with the frequent non-adherence of adolescents to lifestyle changes the frequent non-adherence of adolescents to lifestyle changes and medical treatment, will complicate treatment and prevention and medical treatment, will complicate treatment and prevention efforts.efforts.

Epidemiologic studies have established Epidemiologic studies have established that multiple risk factorsthat multiple risk factors increase the increase the probability of cardiovascular events, since probability of cardiovascular events, since risk factors tend to reinforce each other in risk factors tend to reinforce each other in their influencetheir influence on morbidity and mortality.on morbidity and mortality.

Kannel WB, National Heart, Lung, and Blood Institute, Kannel WB, National Heart, Lung, and Blood Institute,

1987. (NIH publication no. 87-2703.)1987. (NIH publication no. 87-2703.)

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

Atherosclerosis of the aorta and coronary arteries Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 and cardiovascular risk factors in persons aged 6

to 30 years and studied at necropsy (The to 30 years and studied at necropsy (The Bogalusa Heart Study).Bogalusa Heart Study).

Race and sex differences in aorta and coronary Race and sex differences in aorta and coronary atherosclerotic lesions were studied in 150 persons atherosclerotic lesions were studied in 150 persons aged 6 to 30 years. aged 6 to 30 years.

The intimal surface involvement with aorta fatty The intimal surface involvement with aorta fatty streaks was extensive, 0 to 71%, and greater in streaks was extensive, 0 to 71%, and greater in blacks than in whites (32 vs 20%, p less than 0.001).blacks than in whites (32 vs 20%, p less than 0.001).

Coronary artery fatty streaks were more extensive Coronary artery fatty streaks were more extensive in male than in female subjects (range 0 to 22%).in male than in female subjects (range 0 to 22%).

BHSBHS

Fibrous plaque lesions were present but not extensive in Fibrous plaque lesions were present but not extensive in either the aorta (0 to 12%) or the coronary artery (0 to either the aorta (0 to 12%) or the coronary artery (0 to 24%) specimens. Lesions were more prevalent in male 24%) specimens. Lesions were more prevalent in male than in female persons, particularly white male subjects. than in female persons, particularly white male subjects.

The relation of fatty streaks to fibrous plaques was The relation of fatty streaks to fibrous plaques was greater in the coronary vessels than in the aorta. In male greater in the coronary vessels than in the aorta. In male subjects, aorta fatty streaks were strongly related to subjects, aorta fatty streaks were strongly related to antemortem levels of total cholesterol, low-density antemortem levels of total cholesterol, low-density lipoprotein cholesterol and ponderal index in white male lipoprotein cholesterol and ponderal index in white male subjects.subjects.

BHSBHS

Coronary artery fatty streaks in white male persons Coronary artery fatty streaks in white male persons were significantly associated with serum were significantly associated with serum triglycerides, very low density lipoprotein triglycerides, very low density lipoprotein cholesterol, systolic and diastolic blood pressure cholesterol, systolic and diastolic blood pressure and ponderal index.and ponderal index.

These results link antemortem risk factors to the These results link antemortem risk factors to the development of atherosclerotic lesions and development of atherosclerotic lesions and emphasize the need for preventive cardiology in emphasize the need for preventive cardiology in early life.early life. Am J Cardiol 1992 Oct1;70(9):8518 Am J Cardiol 1992 Oct1;70(9):8518

Furthermore, since clustering of risk factors is Furthermore, since clustering of risk factors is evident inevident in childhood and persists into young childhood and persists into young adulthood, the presenceadulthood, the presence of multiple risk factors of multiple risk factors could indicate the acceleration ofcould indicate the acceleration of atherosclerosis atherosclerosis in young people.in young people.

The Bogalusa Heart Study. Prev Med 1979;8:407-418.The Bogalusa Heart Study. Prev Med 1979;8:407-418.

Khoury P, Am J Epidemiol 1980;112:524-538.Khoury P, Am J Epidemiol 1980;112:524-538.

Smoak CG, Am J Epidemiol 1987;125:364-372.Smoak CG, Am J Epidemiol 1987;125:364-372.

Bao W, Arch Intern Med 1994;154:1842-1847Bao W, Arch Intern Med 1994;154:1842-1847

Association between Multiple Association between Multiple Cardiovascular Risk Factors and Cardiovascular Risk Factors and

Atherosclerosis in Children and Young Atherosclerosis in Children and Young AdultsAdults

Autopsy dataAutopsy data from epidemiologic studies from epidemiologic studies have shown a relation between coronaryhave shown a relation between coronary

artery disease and cardiovascular risk artery disease and cardiovascular risk factors; for example,factors; for example, high serum total high serum total cholesterol concentrations and cigarette cholesterol concentrations and cigarette smokingsmoking are important contributors to the are important contributors to the development of coronary atherosclerosis.development of coronary atherosclerosis.

Autopsy studies from the Bogalusa Heart Study Autopsy studies from the Bogalusa Heart Study have demonstratedhave demonstrated a strong association of specific a strong association of specific antemortem risk factors withantemortem risk factors with vascular lesions in vascular lesions in children and young adults. children and young adults.

These observationsThese observations have been extended by the have been extended by the findings in a larger, multicenterfindings in a larger, multicenter postmortem study, postmortem study, Pathobiological Determinants of AtherosclerosisPathobiological Determinants of Atherosclerosis

in Youth.in Youth.

The extent of fatty streaks and fibrous The extent of fatty streaks and fibrous plaques in theplaques in the aorta and coronary aorta and coronary arteries increased with age. The arteries increased with age. The associationassociation between fatty streaks and between fatty streaks and fibrous plaques was much strongerfibrous plaques was much stronger in in the coronary arteries (r=0.60, P<0.001) the coronary arteries (r=0.60, P<0.001) than in the aortathan in the aorta (r=0.23, P=0.03(r=0.23, P=0.03

Among the cardiovascular risk factors, body-Among the cardiovascular risk factors, body-massmass index, systolic and diastolic blood index, systolic and diastolic blood pressure, and serum concentrationspressure, and serum concentrations of total of total cholesterol, triglycerides, low-density lipoproteincholesterol, triglycerides, low-density lipoprotein

cholesterol, and high-density lipoprotein cholesterol, and high-density lipoprotein cholesterol,cholesterol,

as aas a group, were strongly associated with the group, were strongly associated with the extent of lesions inextent of lesions in the aorta and coronary the aorta and coronary arteries (canonical correlation [a measurearteries (canonical correlation [a measure of the of the association between groups of variables]: association between groups of variables]: r=0.70; P<0.001).r=0.70; P<0.001).

cigarette smoking increased the cigarette smoking increased the percentage of thepercentage of the intimal surface intimal surface involved with fibrous plaques in the involved with fibrous plaques in the aorta (1.22aorta (1.22 percent in smokers vs. 0.12 percent in smokers vs. 0.12 percent in nonsmokers, P=0.02) andpercent in nonsmokers, P=0.02) and

fatty streaks in the coronary vessels fatty streaks in the coronary vessels (8.27 percent vs. 2.89(8.27 percent vs. 2.89 percent, P=0.04). percent, P=0.04).

Subjects with 0,Subjects with 0, 1, 2, and 3 or 4 risk factors had, 1, 2, and 3 or 4 risk factors had, respectively, 19.1 percent,respectively, 19.1 percent, 30.3 percent, 37.9 30.3 percent, 37.9 percent, and 35.0 percent of the intimalpercent, and 35.0 percent of the intimal surface surface covered with fatty streaks in the aorta (P for covered with fatty streaks in the aorta (P for trend=0.01).trend=0.01).

The comparable figures for the coronary arteries The comparable figures for the coronary arteries were 1.3 percent,were 1.3 percent, 2.5 percent, 7.9 percent, and 2.5 percent, 7.9 percent, and 11.0 percent, respectively, for11.0 percent, respectively, for fatty streaks (P for fatty streaks (P for trend=0.01) and 0.6 percent, 0.7 percent,trend=0.01) and 0.6 percent, 0.7 percent, 2.4 2.4 percent, and 7.2 percent for collagenous fibrous percent, and 7.2 percent for collagenous fibrous plaquesplaques (P for trend=0.003).(P for trend=0.003).

Conclusions;Conclusions; These findings indicate These findings indicate that as the number of cardiovascularthat as the number of cardiovascular

risk factors increases, so does the risk factors increases, so does the severity of asymptomaticseverity of asymptomatic coronary and coronary and aortic atherosclerosis in young people.aortic atherosclerosis in young people.

Pathobiological DeterminantsPathobiological Determinants of of Atherosclerosis in Youth (PDAY),Atherosclerosis in Youth (PDAY),

Relation of a Postmortem Renal Index of Relation of a Postmortem Renal Index of Hypertension to Atherosclerosis in Youth Hypertension to Atherosclerosis in Youth

In a cooperative multicenter study, In a cooperative multicenter study, Pathobiological DeterminantsPathobiological Determinants of of Atherosclerosis in Youth, of 1164 young Atherosclerosis in Youth, of 1164 young men 15 through 34men 15 through 34 years of age who died of years of age who died of external causes and were autopsiedexternal causes and were autopsied in in forensic laboratories.forensic laboratories.

They measured atherosclerosis of theThey measured atherosclerosis of the aorta aorta and the right coronary artery. and the right coronary artery.

CONT, ( PDAY )CONT, ( PDAY )

Using the ratio of intimalUsing the ratio of intimal thickness to outer thickness to outer diameter of the small renal arteries to diameter of the small renal arteries to predictpredict mean arterial pressure (MAP) during mean arterial pressure (MAP) during life. Cases were classifiedlife. Cases were classified as either as either normotensive (MAP <110 mm Hg) or normotensive (MAP <110 mm Hg) or hypertensive (MAP 110hypertensive (MAP 110 mm Hg).mm Hg).

CONT, ( PDAY )CONT, ( PDAY )

By this criterion, the prevalence of By this criterion, the prevalence of hypertension in blackshypertension in blacks was 16%; in whites, was 16%; in whites, 12%. Hypertension was associated directly 12%. Hypertension was associated directly withwith blood level of glycohemoglobin (an blood level of glycohemoglobin (an indicator of blood glucose concentration)indicator of blood glucose concentration)

and with body mass index (BMI) but and with body mass index (BMI) but inversely with thicknessinversely with thickness of the panniculus of the panniculus adiposus.adiposus.

CONT, ( PDAY)CONT, ( PDAY)

Among hypertensive compared with normotensive Among hypertensive compared with normotensive cases, the extentcases, the extent of raised lesions (mainly fibrous of raised lesions (mainly fibrous plaques) was greater in the aortasplaques) was greater in the aortas of 30- to 34-of 30- to 34-year-old men and in the right coronary arteriesyear-old men and in the right coronary arteries of of 25- to 34-year-old men. 25- to 34-year-old men.

The prevalence of raised lesionsThe prevalence of raised lesions involving 5% or involving 5% or more of the intimal surface was twofold greatermore of the intimal surface was twofold greater in in the aortas and right coronary arteries of the aortas and right coronary arteries of hypertensive menhypertensive men throughout the 15-to-34–year throughout the 15-to-34–year age span of the study cases.age span of the study cases.

The prevalence of raised lesionsThe prevalence of raised lesions involving involving 5% or more of the intimal surface was 5% or more of the intimal surface was twofold greatertwofold greater in the aortas and right in the aortas and right coronary arteries of hypertensive mencoronary arteries of hypertensive men

throughout the 15-to-34–year age span of throughout the 15-to-34–year age span of the study cases.the study cases.

AlthoughAlthough hypertension is associated with hypertension is associated with elevated blood glycohemoglobinelevated blood glycohemoglobin and and adiposity, the effect of hypertension on adiposity, the effect of hypertension on atherosclerosisatherosclerosis is not accounted for by those is not accounted for by those variables.variables.

Relation of Glycohemoglobin and Adiposity to Relation of Glycohemoglobin and Adiposity to Atherosclerosis in Youth Atherosclerosis in Youth

( PDAY )( PDAY )

In a cooperative multicenter study In a cooperative multicenter study (Pathobiological Determinants(Pathobiological Determinants of of Atherosclerosis in Youth, PDAY) of 1532 Atherosclerosis in Youth, PDAY) of 1532 young persons 15young persons 15 through 34 years of age through 34 years of age who died of external causes and were who died of external causes and were autopsiedautopsied in medical examiners' laboratoriesin medical examiners' laboratories

They quantified atherosclerosisThey quantified atherosclerosis of the aorta and of the aorta and the right coronary artery and analyzed postmortemthe right coronary artery and analyzed postmortem

blood cells for glycohemoglobin and postmortem blood cells for glycohemoglobin and postmortem serum for lipoproteinserum for lipoprotein cholesterol and thiocyanate cholesterol and thiocyanate (as an indicator for smoking). (as an indicator for smoking).

They measured the thickness of the panniculus They measured the thickness of the panniculus adiposus and the bodyadiposus and the body mass index (weight per mass index (weight per height squared) as indicators of adiposityheight squared) as indicators of adiposity

GlycohemoglobinGlycohemoglobin levels exceeding 8% were levels exceeding 8% were associated with substantially moreassociated with substantially more extensive fatty extensive fatty streaks and raised lesions in the right coronary streaks and raised lesions in the right coronary arteryartery in persons more than 25 years of age and in persons more than 25 years of age and with more extensive raisedwith more extensive raised lesions in the aorta in lesions in the aorta in persons more than 30 years of age.persons more than 30 years of age.

Both thicknessBoth thickness of the panniculus adiposus and of the panniculus adiposus and body mass index were associatedbody mass index were associated with more with more extensive fatty streaks and raised lesions in the extensive fatty streaks and raised lesions in the rightright coronary artery. coronary artery.

The associations of atherosclerotic lesionsThe associations of atherosclerotic lesions with with glycohemoglobin and adiposity were not glycohemoglobin and adiposity were not explained by a lessexplained by a less favorable lipoprotein profile or favorable lipoprotein profile or smoking.smoking.

The results show thatThe results show that atherosclerosis in young atherosclerosis in young adults is associated with the prediabeticadults is associated with the prediabetic or early or early diabetic state, as indicated by elevated diabetic state, as indicated by elevated glycohemoglobinglycohemoglobin levels, and with obesity.levels, and with obesity.

Several recent articles reviewed the potential Several recent articles reviewed the potential mechanisms bymechanisms by which diabetes, hyperinsulinemia, and which diabetes, hyperinsulinemia, and hyperglycemia augment atherogenesis.hyperglycemia augment atherogenesis.

Of the many mechanisms suggested, two seem most Of the many mechanisms suggested, two seem most likelylikely to be involved in the association of to be involved in the association of glycohemoglobin concentrationglycohemoglobin concentration in these young adults:in these young adults:

1 ) the effects of dyslipoproteinemia and1 ) the effects of dyslipoproteinemia and

hyperinsulinemia in the prediabetic state, as suggested hyperinsulinemia in the prediabetic state, as suggested by Haffner etby Haffner et al, and ,al, and ,

2 ) a direct effect of glycosylation of proteins on 2 ) a direct effect of glycosylation of proteins on atherogenesis.atherogenesis.

The glycohemoglobin effect is not accounted for The glycohemoglobin effect is not accounted for by serum lipoproteinby serum lipoprotein cholesterol levels cholesterol levels (VLDL+LDL-C and HDL-C), and there is little(VLDL+LDL-C and HDL-C), and there is little

correlation between glycohemoglobin levels and correlation between glycohemoglobin levels and serum lipoprotein levels.serum lipoprotein levels.

However, the possibilityHowever, the possibility remains that individuals remains that individuals with elevated glycohemoglobin levelswith elevated glycohemoglobin levels may have may have had abnormal lipoprotein profiles and had abnormal lipoprotein profiles and hyperinsulinemia.hyperinsulinemia.

A process similar to the glycosylation of A process similar to the glycosylation of hemoglobin occurshemoglobin occurs in other proteins. in other proteins. Subsequently, the carbohydrate-protein Subsequently, the carbohydrate-protein complex undergoescomplex undergoes chemical rearrangement chemical rearrangement to form irreversible advanced glycosylationto form irreversible advanced glycosylation

end products, which have a variety of end products, which have a variety of deleterious effects ondeleterious effects on cells and tissues.cells and tissues.

ConclusionsConclusionsThe observations reported here suggest that both The observations reported here suggest that both elevated glycohemoglobinelevated glycohemoglobin levels, possibly levels, possibly associated with the prediabetic state, andassociated with the prediabetic state, and obesity obesity are associated with accelerated atherogenesis in are associated with accelerated atherogenesis in thethe third and fourth decades of life. third and fourth decades of life.

The results provide hope thatThe results provide hope that early detection and early detection and control of obesity and hyperglycemia incontrol of obesity and hyperglycemia in young young persons will reduce the risk of atherosclerotic persons will reduce the risk of atherosclerotic diseasedisease in later life.in later life.

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

Obesity enhances three otherObesity enhances three other established risk factors for established risk factors for coronary heart disease;coronary heart disease;

hypertension, dyslipoproteinemia,hypertension, dyslipoproteinemia, and diabetes mellitus.and diabetes mellitus. and is inversely related to anotherand is inversely related to another major risk factor, major risk factor,

smoking. smoking. In many instances, when obesityIn many instances, when obesity is associated with is associated with

coronary heart disease in univariate analyses,coronary heart disease in univariate analyses,

multivariate analyses including the other risk factors do multivariate analyses including the other risk factors do not shownot show an independent effect.an independent effect.

but several long-term longitudinal studies havebut several long-term longitudinal studies have found found an independent effect after controlling for other risk an independent effect after controlling for other risk factors.factors.

Effects of Serum Lipoproteins and Smoking on Effects of Serum Lipoproteins and Smoking on Atherosclerosis in Young Men and Women Atherosclerosis in Young Men and Women

( PDAY )( PDAY )

Atherosclerosis begins in childhood and Atherosclerosis begins in childhood and progresses from fattyprogresses from fatty streaks to raised lesions in streaks to raised lesions in adolescence and young adulthood.adolescence and young adulthood.

A cooperative multicenter study (Pathobiological A cooperative multicenter study (Pathobiological DeterminantsDeterminants of Atherosclerosis in Youth of Atherosclerosis in Youth [PDAY]) examined the relation of[PDAY]) examined the relation of risk factors for risk factors for adult coronary heart disease to atherosclerosisadult coronary heart disease to atherosclerosis in in 1079 men and 364 women 15 through 34 years of 1079 men and 364 women 15 through 34 years of age, both blackage, both black and white, who died of external and white, who died of external causes and were autopsied incauses and were autopsied in forensic laboratories. forensic laboratories.

They quantitated atherosclerosis of theThey quantitated atherosclerosis of the aorta aorta and right coronary artery as the extent of and right coronary artery as the extent of intimal surfaceintimal surface involved by fatty streaks and involved by fatty streaks and raised lesions and analyzed postmortemraised lesions and analyzed postmortem

serum for lipoprotein cholesterol and serum for lipoprotein cholesterol and thiocyanate (as an indicatorthiocyanate (as an indicator of smoking).of smoking).

The extent of intimal surface involved with The extent of intimal surface involved with bothboth fatty streaks and raised lesions fatty streaks and raised lesions increased with age in all arterialincreased with age in all arterial segments of segments of all sex and race groups. all sex and race groups.

Women had a greater extentWomen had a greater extent of fatty streaks of fatty streaks in the abdominal aorta than men, but in the abdominal aorta than men, but womenwomen and men had about an equal extent and men had about an equal extent of raised lesions. of raised lesions.

Women andWomen and men had a comparable extent of fatty men had a comparable extent of fatty streaks in the right coronarystreaks in the right coronary artery, but women had artery, but women had about half the extent of raised lesions.about half the extent of raised lesions. Blacks had a Blacks had a greater extent of fatty streaks than whites, butgreater extent of fatty streaks than whites, but blacks blacks and whites had a similar extent of raised lesions. and whites had a similar extent of raised lesions.

VLDLVLDL plus LDL cholesterol concentration was plus LDL cholesterol concentration was associated positivelyassociated positively and HDL cholesterol was and HDL cholesterol was associated negatively with the extentassociated negatively with the extent of fatty streaks of fatty streaks and raised lesions in the aorta and right coronaryand raised lesions in the aorta and right coronary

artery. artery.

Smoking was associated with more extensive fatty Smoking was associated with more extensive fatty streaksstreaks and raised lesions in the abdominal aorta. and raised lesions in the abdominal aorta. All three risk factorsAll three risk factors affected atherosclerosis to affected atherosclerosis to about the same degree in both sexesabout the same degree in both sexes and both and both races. races.

Primary prevention of atherosclerosis by Primary prevention of atherosclerosis by controllingcontrolling these adult coronary heart disease risk these adult coronary heart disease risk factors is applicablefactors is applicable to young men and women and to young men and women and to young blacks and whites.to young blacks and whites.

The effects of VLDL+LDL-C and HDL-C The effects of VLDL+LDL-C and HDL-C concentrations andconcentrations and smoking are similar in men and smoking are similar in men and women and are similar in blackswomen and are similar in blacks and whites. Race and whites. Race and sex differences in atherosclerotic lesionsand sex differences in atherosclerotic lesions are are not explained by differences in lipoprotein not explained by differences in lipoprotein cholesterolcholesterol levels or smoking.levels or smoking.

These results are similar to those reported These results are similar to those reported previously resultspreviously results are including those reported are including those reported from the Bogalusa Heart Study.from the Bogalusa Heart Study.

These findings from the PDAY study strongly These findings from the PDAY study strongly support modificationsupport modification of the risk factors in young of the risk factors in young people to retard the developmentpeople to retard the development of early of early atherosclerotic lesions, particularly raised lesions.atherosclerotic lesions, particularly raised lesions.

They anticipate that risk factor modification would They anticipate that risk factor modification would delay thedelay the development of lesions, an effect that in development of lesions, an effect that in turn would delay correspondinglyturn would delay correspondingly the onset of the onset of clinical coronary heart disease later in life.clinical coronary heart disease later in life.

Persistent Elevation of Plasma Insulin Levels Is Persistent Elevation of Plasma Insulin Levels Is Associated With Increased Cardiovascular Risk Associated With Increased Cardiovascular Risk

in Children and Young Adults in Children and Young Adults The Bogalusa Heart Study The Bogalusa Heart Study

Hyperinsulinemia has been considered to be Hyperinsulinemia has been considered to be a potenta potent cardiovascular risk factor. cardiovascular risk factor.

community-based populationcommunity-based population over an 8-year over an 8-year period: 1606 individuals (39% were black) period: 1606 individuals (39% were black) agedaged 5 to 23 years participated in the first 5 to 23 years participated in the first survey.survey.

ComparedCompared with subjects with levels of insulin consistently with subjects with levels of insulin consistently in the lowestin the lowest quartile, those with levels always in the highest quartile, those with levels always in the highest quartile showedquartile showed higher (higher (PP<.001) levels of body mass index <.001) levels of body mass index (+9 kg/m(+9 kg/m22), ),

triglyceridestriglycerides (+58 mg/dL), LDL cholesterol (+11 mg/dL), (+58 mg/dL), LDL cholesterol (+11 mg/dL),

VLDL cholesterol (+8VLDL cholesterol (+8 mg/dL), glucose (+9 mg/dL),mg/dL), glucose (+9 mg/dL),

systolic blood pressure (+7 mm Hg),systolic blood pressure (+7 mm Hg), and diastolic blood and diastolic blood pressure (+3 mm Hg); lower (pressure (+3 mm Hg); lower (PP<.001) levels<.001) levels of HDL of HDL cholesterol (-4 mg/dL); and higher (cholesterol (-4 mg/dL); and higher (PP<.05) prevalence<.05) prevalence of of parental history of diabetes (3.3-fold) and hypertensionparental history of diabetes (3.3-fold) and hypertension (1.2-(1.2-fold). fold).

There were 739 young adults aged 20 to 31 yearsThere were 739 young adults aged 20 to 31 years

at follow-up.at follow-up.

As adults, individuals with consistently elevatedAs adults, individuals with consistently elevated

insulin versus those with consistently decreased insulin versus those with consistently decreased insulin hadinsulin had increased (increased (PP<.05) prevalence of <.05) prevalence of obesity (36-fold), hypertension (2.5-fold),obesity (36-fold), hypertension (2.5-fold), and and dyslipidemia (3-fold), which was attributed to dyslipidemia (3-fold), which was attributed to both baselineboth baseline insulin and change of insulin from insulin and change of insulin from baseline to follow-upbaseline to follow-up

. In. In addition, clustering of these risk factors addition, clustering of these risk factors was stronger (was stronger (PP<.05)<.05) in adults with in adults with persistent insulin elevation.persistent insulin elevation.

Conclusions; Conclusions; Elevated insulin levels persist Elevated insulin levels persist from childhood throughfrom childhood through young adulthood, young adulthood, resulting in a clinically relevant adverse resulting in a clinically relevant adverse cardiovascularcardiovascular risk profile in young adults.risk profile in young adults.

HOW TO PRVENT HOW TO PRVENT ATHEROSCLEROSISATHEROSCLEROSIS

Begin with childrenBegin with children

ScreeningScreening

Comperhensive Treatment ProgramComperhensive Treatment Program

SCREENINGSCREENING

Selective, children above 2y.Selective, children above 2y. Crieteria ;Crieteria ; 1) Parent OR grandparents with premature IHD.1) Parent OR grandparents with premature IHD. 2) Parent with hypercholest.( 6 mmol/L )2) Parent with hypercholest.( 6 mmol/L ) 3) Unavailable family history.3) Unavailable family history. 4) Associated risk factors ( DM, OBESITY, High 4) Associated risk factors ( DM, OBESITY, High

BP. ).BP. ). 5) ALL adults 20 y or above, check 5) ALL adults 20 y or above, check

CHOLESTEROLCHOLESTEROL

TREATMENTTREATMENT

1.1. A diet aimed at reducing fat intake to 30% of A diet aimed at reducing fat intake to 30% of total calories, saturated fat to less than 7% and total calories, saturated fat to less than 7% and cholesterol to less than 200 mg/day. The cholesterol to less than 200 mg/day. The expertise of a dietitian is highly recommended in expertise of a dietitian is highly recommended in counseling families.counseling families.

2.2. The national Cholesterol Education Program The national Cholesterol Education Program Consensus Panel recommended drug therapy Consensus Panel recommended drug therapy after the age of 10 years if diet therapy has n0ot after the age of 10 years if diet therapy has n0ot lowered the lipid levels sufficiently. The only lowered the lipid levels sufficiently. The only drugs currently approved for children are the drugs currently approved for children are the bile acid binding resins, cholestyramine and bile acid binding resins, cholestyramine and colestipol.colestipol.

TREATMENTTREATMENT

3.3. Lifestyle habits modification of the children and Lifestyle habits modification of the children and adolescents such as weight control, not smoking adolescents such as weight control, not smoking and daily exercise.and daily exercise.

Treatment Recommendations

Repeat within 5 years; general dietary recommendations.

Repeat and average with previous measurement; if average is < 170 mg/dL, then repeat within 5 years; if < 170 mg/DL, then do fasting lipoprotein profile.

Do fasting lipoprotein profile.

If fasting lipoprotein profile obtained Measure twice and average calculated LDL cholesterol with previous measurement.

Repeat profile within 5 years; general recommendations.

Risk factor counseling and dietary recommendations; re-evaluate in 1 year.

Clinical assessment to evaluate for primary and secondary causes of hyperlipidemia; greater restriction of dietary saturated fatty acids and cholesterol; if primary or familial hyperlipidemia suspected, screen other family members; after at least a 6-month trial of dietary intervention, evaluate for drug treatment.

CONCLUSIONCONCLUSION

4.4. Although selective screening criteria will not Although selective screening criteria will not identify all the children with identify all the children with hypercholesterolemia it will identify many. hypercholesterolemia it will identify many. Hopefully focusing on prevention of Hopefully focusing on prevention of cardiovascular disease in children and cardiovascular disease in children and adolescents will make a difference in the future adolescents will make a difference in the future of health care.of health care.

early prevention of coronary heart disease by jameel a. al-ata, md consultant & assistant...

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