Histological changes and risk factor associations in type 2 atherosclerotic lesions (fatty streaks) in young adults.

OBJECTIVES: The purpose of this study was to investigate which histological changes associated with risk factors could contribute to the progression from the initial atherosclerotic lesions including fatty streaks to the advanced lesions. METHODS: We examined the associations of histomorphometric findings in the determined anatomical sites of mid-thoracic aortas (TAs) and left anterior descending coronary arteries (LADs) with major risk factors for atherosclerosis, using a young autopsied series from the the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. The histological classification by the American Heart Association was graded for 1013 TAs and 1009 LADs. Histometric study, including immunohistochemistry, was performed in type 2 lesions (fatty streaks) of TAs from 59 subjects and LADs from 45 ones. RESULTS: For the progression from the initial lesions into the advanced atherosclerotic lesions, the most effective lipid profiles were low plasma HDL-C in TA and elevated serum non-HDL-C in LAD. This lipid profile of each artery correlated with number or density of intimal smooth muscle cell-derived foam cells, respectively. The serum concentration of non-HDL-C correlated with macrophage foam cells in TAs. Hypertension and hyperglycemia were associated with increase of intimal area and/or collagen content in both arteries, but not with either types of foam cell proliferation. Smoking correlated with increased collagen content in TAs. CONCLUSION: There were histologically different ways of progressing from fatty streaks to advanced atherosclerotic lesions depending on the risk factors. For the atherosclerosis progression from type 2 lesions to advanced lesions, increase in number of smooth muscle cell-derived foam cells could be an important indicator.

Common variants in the periostin gene influence development of atherosclerosis in young persons.

OBJECTIVE: We investigated the influence of genetic variants (rare and common) in the gene encoding periostin (POSTN) on atherosclerosis as measured in arterial specimens from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. METHODS AND RESULTS: A comprehensive survey of common POSTN variants (87 single-nucleotide polymorphisms [SNPs]) in PDAY subjects (n = 2527) identified numerous SNPs associated with raised lesions in abdominal aorta and with fatty streaks in thoracic aorta. These SNPs belonged to a small number of correlation bins that spanned the entire locus. To examine effects of rare variants, we resequenced POSTN functional regions in PDAY cases with raised lesions (n = 291) and controls with no raised lesions (n = 294). However, we found no significant associations with case-control status for carriers of POSTN rare variants using the weighted-sum method for rare variant analysis. CONCLUSIONS: We identified common variants in POSTN that are associated with arterial lesions in young persons from the PDAY study. This finding strongly supports a role for periostin in atherogenesis, as suggested by recent proteomics analysis that found abundant expression of periostin in atherosclerotic lesions. Genetic variation may influence atherosclerosis via periostin's known involvement in multiple relevant pathways, including angiogenesis, vascular remodeling, and stimulation of migration and differentiation of vascular smooth muscle cells.

Heparin cofactor II in atherosclerotic lesions from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study.

Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been shown to be a predictor of decreased atherosclerosis in the elderly and protective against atherosclerosis in mice. HCII inhibits thrombin in vitro and HCII-thrombin complexes have been detected in human plasma. Moreover, the mechanism of protection against atherosclerosis in mice was determined to be the inhibition of thrombin. Despite this evidence, the presence of HCII in human atherosclerotic tissue has not been reported. In this study, using samples of coronary arteries obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we explore the local relationship between HCII and (pro)thrombin in atherosclerosis. We found that HCII and (pro)thrombin are co-localized in the lipid-rich necrotic core of atheromas. A significant positive correlation between each protein and the severity of the atherosclerotic lesion was present. These results suggest that HCII is in a position to inhibit thrombin in atherosclerotic lesions where thrombin can exert a proatherogenic inflammatory response. However, these results should be tempered by the additional findings from this, and other studies, that indicate the presence of other plasma proteins (antithrombin, albumin, and alpha(1)-protease inhibitor) in the same localized region of the atheroma.

Associations of arterial tissue lipids with coronary heart disease risk factors in young people.

OBJECTIVE: To examine the associations of the coronary heart disease (CHD) risk factors with lipid composition of arterial tissue in 397 autopsied subjects 15-34 years of age from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. METHODS AND RESULTS: We measured esterified cholesterol, free cholesterol, and phospholipid in the left circumflex coronary artery and two segments of the abdominal aorta, one of which is more susceptible to advanced atherosclerosis than the other, and also measured the major CHD risk factors. Non-HDL cholesterol concentration was positively associated, and HDL cholesterol concentration was negatively associated, with tissue lipids in the left circumflex coronary artery and the abdominal aorta. Hypertension was positively associated with tissue lipids in both arteries. Hyperglycemia was associated with tissue lipids in the left circumflex coronary artery and smoking with lipids in the abdominal aorta. PDAY risk scores summarize the effects of the CHD risk factors on advanced atherosclerosis. These risk scores, computed from the mutable risk factors, were associated with tissue lipids in the left circumflex coronary artery and both segments of the abdominal aorta. CONCLUSIONS: The CHD risk factors are associated with lipids in arterial tissue just as they are associated with gross and microscopic lesions. These results support the proposal that early control of risk factors is likely to prevent or delay progression of atherosclerosis and prevent or delay the onset of CHD.

Histological topographical comparisons of atherosclerosis progression in juveniles and young adults.

BACKGROUND: The histologically topographic comparisons on atherosclerosis progression among three anatomical sites, mid-thoracic and lower abdominal aorta and left anterior descending coronary artery (LAD) were performed using a young population (age 15-34 years) from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. METHODS AND RESULTS: The histological classification based on the American Heart Association grading scheme showed that in the thoracic aorta type 2 lesions (numerous macrophage foam cells with fine particles but no pools of extracellular lipid) appeared in the first 10-year age group, with no significant change in prevalence in the next 10 years. Lesions greater than type 2 were rarely seen in the thoracic aorta. Although type 2 lesions appeared later in the LAD than in the aorta, the lesions within the LAD progressed rapidly to more advanced lesions (types 4 and 5) or atheroma. Lesion development in the abdominal aorta was intermediate to lesion development in the thoracic aorta and the LAD. CONCLUSIONS: The most striking topographic difference on lesion progression among the three anatomical sites was the vulnerability of type 2 lesions to progress into advanced lesions. The histology study, including immunohistochemistry limited to the type 2 lesions suggested that lesion progression was related to the intimal thickness and the amount of collagen but not to the number of macrophage foam cells.

Comparison of coronary heart disease risk factors in autopsied young adults from the PDAY Study with living young adults from the CARDIA study.

BACKGROUND: Disease is sometimes best studied by examination of tissue obtained from autopsied individuals. Results derived from autopsied persons are considered biased because many factors influence the decision to perform an autopsy, and variables measured postmortem may be affected by changes immediately prior to death and emergency medical treatment. METHODS: The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study measured coronary heart disease risk factors postmortem in autopsied young adults 23-34 years of age dying from external causes (accidents, homicides, suicides). The Coronary Artery Risk Development in Young Adults (CARDIA) study measured risk factors in living subjects of similar ages. RESULTS: Within sex, race, and age groups, the differences in body mass index between PDAY and CARDIA were significant but small. The prevalences of hyperglycemia/diabetes within sex, race, and age groups were similar in PDAY and CARDIA; overall, blacks in PDAY, but not in CARDIA, had a higher prevalence than whites. Serum lipoprotein concentrations were slightly and significantly higher and significantly more variable in PDAY subjects than in CARDIA subjects; the greater variability was interpreted as due primarily to emergency medical treatment. Prevalences of smoking and hypertension were substantially higher in PDAY subjects. CONCLUSIONS: Although there were statistically significant differences, the overall similarity of the risk factors in the two studies supports the validity of investigating associations of risk factors measured postmortem with anatomically determined arterial lesions in autopsied young adults dying from external causes. The greater variability in postmortem serum measurements attenuates but does not obscure associations.

PDAY risk score predicts advanced coronary artery atherosclerosis in middle-aged persons as well as youth.

A risk score formula to estimate the probability of advanced atherosclerosis using coronary heart disease (CHD) risk factors was developed for persons 15-34 years of age by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. We applied the PDAY risk score to autopsied individuals from the Community Pathology Study (CPS), a different population that included middle-aged as well as young subjects. The PDAY risk score was associated with extent of raised lesions in the coronary arteries of CPS cases 15-34 years of age. The PDAY risk score computed from only the modifiable risk factors was associated with extent of raised lesions in the coronary arteries of subjects 35-54 years of age. The association of the PDAY risk score with lesions in 15-34 year old CPS subjects validates the PDAY risk score. The associations in both younger (15-34 years) and older (35-54 years) subjects suggest a seamless progression of the effects of the modifiable risk factors on atherosclerosis from 15 to 54 years of age. These results support the proposal that early control of risk factors is likely to prevent or delay the onset of CHD.

Aortic rhythmic wrinkling in youth: the PDAY study.

Transverse, white-streak 'wrinkles' in the aorta were first described as Querlinien (cross lines) or Wellenlinien (wave lines) in the German literature in the early 20th century. These rhythmic structures were previously thought to be artifacts of stretching and shrinkage of the aorta. Not until the 1970s was it proposed that the areas of rhythmic wrinkling (RW) might be part of the process of atherosclerosis. We analyzed 2,650 aortas from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study for prevalence, extent, and topographical distribution of these areas of RW. Furthermore, we investigated the possible relationship of RW to atherosclerotic sudanophilic stained 'fatty streaks' and elevated intimal lesions called 'raised lesions' (RL). This study provides evidence that (1) the prevalence of RW is fairly high in the aorta and occurs in a specific distribution in both the thoracic and abdominal aorta; (2) RW seems to precede the development of RL, with RL occurring in the same topographical areas as RW; and (3) RW may be associated with the subsequent development of advanced atherosclerosis, particularly raised lesions.

Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis.

OBJECTIVES: Atherosclerosis begins in childhood and progresses during adolescence and young adulthood. The Pathobiological Determinants of Atherosclerosis in Youth Study previously reported risk scores to estimate the probability of advanced atherosclerotic lesions in young individuals aged 15 to 34 years using the coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia). In this study we investigated the relation of these risk scores to the early atherosclerotic lesions. METHODS: We measured atherosclerotic lesions in the left anterior descending coronary artery, right coronary artery, and abdominal aorta and the coronary heart disease risk factors in persons 15 to 34 years of age who died as a result of external causes and were autopsied in forensic laboratories. RESULTS: Risk scores computed from the modifiable risk factors were associated with prevalence of microscopically demonstrable lesions of atherosclerosis (American Heart Association grade 1) in the left anterior descending coronary artery and with the extent of the earliest detectable gross lesion (fatty streaks) in the right coronary artery and abdominal aorta. Risk scores computed from the modifiable risk factors also were associated with prevalence of lesions of higher degrees of microscopic severity (intermediate as well as advanced) in the left anterior descending coronary artery and with extent of lesions of higher degrees of severity (intermediate and raised lesions) in the right coronary artery and abdominal aorta. CONCLUSIONS: Risk scores calculated from traditional coronary heart disease risk factors to identify individual young persons with high probability of having advanced atherosclerotic lesions also are associated with earlier atherosclerotic lesions, including the earliest anatomically demonstrable atherosclerotic lesion. These results support lifestyle modification in youth to prevent development of the initial lesions and the subsequent progression to advanced lesions and, thereafter, to prevent or delay coronary heart disease.

Adipose tissue triglyceride fatty acids and atherosclerosis in Alaska Natives and non-Natives.

Essential polyunsaturated fatty acids (PUFA) of the omega-3 family are believed to protect against cardiovascular disease. A rich source of omega-3 PUFA is found in fish and marine mammals (seal, walrus, whale), which are a large part of the traditional diet of Alaska Natives (Eskimo, American Indians, Aleuts), a group that has been reported to have a lower mortality rate from cardiovascular disease than non-Natives. An autopsy study using standardized methods to evaluate the extent of atherosclerosis and its risk factors, and analyses of stored triglyceride fatty acids was conducted in a sample of Alaska Native subjects and non-Native subjects living in Alaska. Findings indicate that Alaska Natives had less advanced atherosclerosis in coronary arteries, along with higher proportions of omega-3 and lower proportions of omega-6 PUFA in adipose tissue, than did non-Natives. We conclude that high dietary intake of omega-3 PUFA may account for the lower extent of coronary artery atherosclerosis, contributing to the reported lower heart disease mortality among Alaska Natives.

Elevated serum C-reactive protein levels and advanced atherosclerosis in youth.

OBJECTIVE: To determine the associations among serum C-reactive protein (CRP) concentration, age, sex, risk factors for coronary heart disease (CHD), and atherosclerosis in young people. METHODS AND RESULTS: In 1244 subjects 15 to 34 years of age, we measured gross atherosclerotic lesions in the right coronary artery (RCA) and abdominal aorta (AA) and American Heart Association (AHA) lesion grade in the left anterior descending (LAD) coronary artery; serum CRP, lipoprotein cholesterol, and thiocyanate (for smoking) concentrations; intimal thickness of renal arteries (for hypertension); glycohemoglobin (for hyperglycemia); and body mass index (for obesity). Serum CRP levels increased with age, were higher in women than in men, and were positively related to obesity and hyperglycemia. Serum CRP > or =10 mg/L was associated with more extensive gross raised lesions in the RCA after age 25 and in the AA after age 30. Serum CRP > or =3 was associated with a greater prevalence of AHA grade 5 lesions in the proximal LAD coronary artery after age 25. The associations of CRP with lesions were independent of the traditional CHD risk factors. CONCLUSIONS: Serum CRP level is independently associated with advanced atherosclerosis in young persons.

Smoking is associated with advanced coronary atherosclerosis in youth.

Smoking is linked to atherosclerosis and coronary heart disease (CHD) in older adults. However, evidence that smoking affects coronary atherosclerosis in young people is incomplete. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study collected arteries, blood, and other tissues from persons 15 to 34 years of age dying of external causes and autopsied in forensic laboratories. Lesions in the proximal left anterior descending coronary arteries (LAD) from 1127 subjects were graded microscopically according to the American Heart Association criteria. Among individuals with advanced lesions (Grade 4 or 5), smokers had a greater prevalence of Grade 5 lesions than non-smokers (odds ratio 9.61, 95% confidence interval 2.34-39.57), a difference suggesting that smoking accelerates the transition from Grade 4 to Grade 5 lesions. This association occurred among both men and women, and among persons with and without other CHD risk factors. The difference in qualities of advanced lesions suggests that smoking possibly accelerates the transition from Grade 4 to Grade 5 lesions by promoting thrombosis and accretion on the intimal surface of the plaque.

Comparison of coronary and aortic atherosclerosis in youth from Japan and the USA.

This paper reports the results of the largest autopsy-based comparative study of atherosclerotic lesions between young Japanese and Americans, aged 15-34 years and autopsied between 1987 and 1995, by analyzing the data from the Japanese second nation-wide study of atherosclerosis and Pathobiological Determinants of Atherosclerosis in Youth study in the USA. In the right coronary arteries, in Japanese, fatty streaks were well established in the second decade of life with very little increase in the remaining age groups up to age of 34 years. In contrast, in American subjects, the average percentage of surface involvement of fatty streaks and raised lesions proceeded steadily with age without an obvious plateau throughout the 20-year period. The extent and prevalence of the raised lesions was much greater in Americans than in Japanese in 25-29 and 30-34-year age groups. Moreover, the rate of progression of raised lesions was much more rapid in Americans. These findings are in keeping with the fact that coronary heart disease (CHD) death rates are much higher in the USA than in Japan. In light of data showing that the risk factor profiles for CHD have become very similar between the two countries, these differences need to be explained.

Risk scores predict atherosclerotic lesions in young people.

BACKGROUND: Atherosclerosis begins in childhood and progresses through young adulthood to form the lesions that cause coronary heart disease. These preclinical lesions are associated with coronary heart disease risk factors in young persons. METHODS: The Pathobiological Determinants of Atherosclerosis in Youth study collected arteries and samples of blood and other tissues from persons aged 15 to 34 years who died of external causes and underwent autopsy in forensic laboratories. We measured the coronary heart disease risk factors and atherosclerotic lesions in the coronary arteries (CAs) (n = 1117) and the abdominal aorta (n = 1458). RESULTS: We developed risk scores, normalized so that a 1-unit increase was equivalent to a 1-year increase in age, to estimate the probability of advanced atherosclerotic lesions in the CAs and the abdominal aorta from age, sex, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia. Odds ratios for a 1-unit increase in the risk scores were 1.18 (95% confidence interval, 1.14-1.22) for the CAs and 1.29 (95% confidence interval, 1.23-1.35) for the abdominal aorta. These risk scores had good discrimination (c-indexes: 0.78 for the CAs and 0.84 for the abdominal aorta) and were calibrated. The presence of abdominal aortic lesions increased the likelihood of having CA lesions. CONCLUSION: Risk scores calculated from traditional coronary heart disease risk factors provide a tool for identifying young individuals with a high probability of having advanced atherosclerotic lesions.

MMP13 promoter polymorphism is associated with atherosclerosis in the abdominal aorta of young black males.

Previous studies suggested that remodeling of connective tissue is important in progression of atherosclerosis. We investigated the importance of matrix metalloproteinase 13 (MMP13), in the pathogenesis of atherosclerosis using 995 samples from the Pathobiological Determinants of Atherosclerosis in Youth collection in an association study. We identified two new MMP13 promoter polymorphisms. The genotype for one of the MMP13 polymorphisms was associated with fibrous plaque (P=0.024) in black males. Immunohistochemistry using antibodies for MMP13 showed that MMP13 is expressed in all layers of the aorta. In-vitro transfection experiments with reporter gene constructs and electrophoretic mobility-shift assays showed that the MMP13 polymorphism was a functional variant. MMP13 is therefore, a genetic risk factor for extent of fibrous plaque in the abdominal aorta in young black males. Elucidation of the currently unknown mechanism of the MMP13 polymorphism's action may provide for pharmacological intervention to reduce the severity of atherosclerotic changes in susceptible individuals.

Obesity accelerates the progression of coronary atherosclerosis in young men.

BACKGROUND: Obesity is a risk factor for adult coronary heart disease and is increasing in prevalence among youths as well as adults. Results regarding the association of obesity with atherosclerosis are conflicting, particularly when analyses account for other risk factors. METHODS AND RESULTS: The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study collected arteries, blood, and other tissue from approximately 3000 persons aged 15 to 34 years dying of external causes and autopsied in forensic laboratories. We measured gross atherosclerotic lesions in the right coronary artery (RCA), American Heart Association (AHA) lesion grade in the left anterior descending coronary artery (LAD), serum lipid concentrations, serum thiocyanate (for smoking), intimal thickness of renal arteries (for hypertension), glycohemoglobin (for hyperglycemia), and adiposity by body mass index (BMI) and thickness of the panniculus adiposus. BMI in young men was associated with both fatty streaks and raised lesions in the RCA and with AHA grade and stenosis in the LAD. The effect of obesity (BMI>30 kg/m(2)) on RCA raised lesions was greater in young men with a thick panniculus adiposus. Obesity was associated with non-HDL and HDL (inversely) cholesterol concentrations, smoking (inversely), hypertension, and glycohemoglobin concentration, and these variables accounted for approximately 15% of the effect of obesity on coronary atherosclerosis in young men. BMI was not associated with coronary atherosclerosis in young women although there was trend among those with a thick panniculus adiposus. CONCLUSIONS: Obesity is associated with accelerated coronary atherosclerosis in adolescent and young adult men. These observations support the current emphasis on controlling obesity to prevent adult coronary heart disease.

Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with different pathologies.

BACKGROUND: Elevations in serum C-reactive protein measured by high-sensitivity assay (hs-CRP) have been associated with unstable coronary syndromes. There have been no autopsy studies correlating hs-CRP to fatal coronary artery disease. METHODS AND RESULTS: Postmortem sera from 302 autopsies of men and women without inflammatory conditions other than atherosclerosis were assayed for hs-CRP. There were 73 sudden deaths attributable to atherothrombi, 71 sudden coronary deaths with stable plaque, and 158 control cases (unnatural sudden deaths and noncardiac natural deaths without conditions known to elevate CRP). Atherothrombi were classified as plaque ruptures (n=55) and plaque erosion (n=18); plaque burden was estimated in each heart. Total cholesterol, high-density lipoprotein cholesterol, diabetes, smoking history, and body mass index were also determined. Immunohistochemical stains for CRP and numbers of thin cap atheromas per heart were quantitated in coronary deaths with hs-CRP in the highest and lowest quintiles. The median hs-CRP was 3.2 microg/mL in acute rupture, 2.9 microg/mL in plaque erosion, 2.5 microg/mL in stable plaque, and 1.4 microg/mL in controls. Mean log hs-CRP was higher in rupture (P<0.0001), erosion (P=0.005), and stable plaque (P=0.0003) versus controls. By multivariate analysis, atherothrombi (P=0.02), stable plaque (P=0.003), and plaque burden (P=0.03) were associated with log hs-CRP independent of age, sex, smoking, and body mass index. Mean staining intensity for CRP of macrophages and lipid core in plaques was significantly greater in cases with high hs-CRP than those with low CRP (P=0.0001), as were mean numbers of thin cap atheromas (P<0.0001). CONCLUSIONS: hs-CRP is significantly elevated in patients dying suddenly with severe coronary artery disease, both with and without acute coronary thrombosis, and correlates with immunohistochemical staining intensity and numbers of thin cap atheroma.

Natural history and risk factors of atherosclerosis in children and youth: the PDAY study.

The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study was organized to document the natural history of athersclerosis and to determine the relation of cardiovascular risk factors to atherosclerosis in young subjects. Pathology laboratories in 15 centers collected coronary arteries, aortas, and other tissues from over 3,000 subjects age 15 to 34 who died of external causes between 1987 and 1994. The extent, prevalence, and topography of arterial lesions were evaluated and risk factors were analyzed in a central laboratory. Postmortem risk factors included serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin (diabetes), thickness of panniculus adiposus and body mass index (obesity), changes in small renal arteries (hypertension), and apoprotein isoforms. The PDAY study confirmed the origin of atherosclerosis in childhood, showed that progression toward clinically significant lesions may occur in young adulthood and demonstrated that the progression of atherosclerosis is strongly influenced by coronary heart disease (CHD) risk factors. Recent PDAY studies have shown that a significant number of advanced coronary artery lesions have microscopic qualities associated with susceptibility to rupture and that CHD risk factors are associated with the development of these characteristic microscopic qualities. The PDAY archive continues to provide an important resource for new investigators throughout the world that contribute to the understanding of atherosclerosis, the underlying cause of most cardiovascular disease and the leading cause of debilitating illness and death in this country. The PDAY findings emphasize the need to modify risk factors in young people to retard the development of atherosclerotic lesions, particularly clinically significant lesions. Thus, true primary prevention of atherosclerosis must being in childhood or early adolescence.

Early inflammatory-immunological lesions in juvenile atherosclerosis from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY)-study.

The Pathobiological Determinants of Atherosclerosis in Youth (PDAY)-study gave insight into the correlation between the classical risk factors for atherosclerosis development, such as hypercholesterolemia, hyperglycemia, high blood pressure and smoking in young Americans. We now present immunohistochemical data showing that immunological-inflammatory signs represent the first step towards atherosclerosis development in the arteries of young adults. In previous publications, we coined the term 'vascular-associated lymphoid tissue' (VALT) for the accumulation of mononuclear cells at regions of the arterial wall in healthy children and adolescents that are predisposed to the development of atherosclerotic lesions later in life if risk factors are present. In the present communication, we intended to close the gap between data from atherosclerotic arteries and those of healthy young children studied previously by our group. The PDAY-study comprising 15-34-year-old Americans who had no clinical symptoms of cardiovascular diseases offered a good basis for our intention. We document that inflammatory activity was found in all specimens, represented by activated T-lymphocytes, dendritic cells, macrophages and aberrant MHC class II expression in the intima. We therefore demonstrated that immunological-inflammatory cells are present in the earliest stages of atherogenesis in 15-34-year-old subjects, arguing in favour of an initiating role of the immune system in atherosclerosis development.

Traditional risk factors and the incidence of sudden coronary death with and without coronary thrombosis in blacks.

BACKGROUND: Blacks have a high rate of sudden coronary death (SCD). We determined the rate of SCD in men and women 30 to 69 years of age in a 6-year period recorded at a state Medical Examiner's Office. METHODS AND RESULTS: In a subset of 327 whites and 130 blacks, hearts were systematically studied to determine the extent of coronary disease, presence and type of thrombus (acute rupture, acute erosion, stable plaque), and heart weight. These parameters were correlated with the presence of conventional risk factors. The estimated rate of SCD in blacks was similar to that in whites under the age of 40 years but increased compared with whites with advancing age, becoming 1.5 times the rate for whites in the 7th decade (95% of the increase in the 6th decade was due to sudden death with stable plaque). Among the autopsied group with severe coronary atherosclerosis, HDL cholesterol was higher and hypertension more prevalent in blacks, but there was no difference in the prevalence of healed infarcts, plaque burden, heart weight, acute thrombi, or rates of diabetes, cigarette smoking, and total cholesterol. CONCLUSIONS: When compared with a control autopsy group of 568 deaths, multivariate analysis showed a significant association in blacks between stable plaque and left ventricular hypertrophy (risk ratio, 7.6), type 1 diabetes (risk ratio, 3.6), hypertension (risk ratio, 3.5), elevated total cholesterol (risk ratio, 3.1) and type 2 diabetes (risk ratio, 2.9). Because these risk factors are associated with SCD in blacks, they may be important targets for reducing the disparately high rate of SCD in blacks as compared with whites.