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Biomedical subjects

G T Malcom

Publications and source records attributed to G T Malcom.

At least 37 records · Page 2Linked to original sources
PubMed1999

Plaque rupture and sudden death related to exertion in men with coronary artery disease.

CONTEXT: Exertion has been reported to acutely increase the risk of sudden coronary death, but the underlying mechanisms are unclear. OBJECTIVE: To determine the frequency of plaque rupture in sudden deaths related to exertion compared with sudden deaths not related to exertion. DESIGN: Autopsy survey. Coronary arteries were perfusion fixed and segments with more than 50% luminal narrowing were examined histologically. Ruptured plaques were defined as intraplaque hemorrhage with disruption of the fibrous cap and luminal thrombus. Exertion before death was determined by the investigator of the death. SETTING: Medical examiner's office. PATIENTS: A total of 141 men with severe coronary artery disease who died suddenly, including 116 whose deaths occurred at rest (mean [SD] age, 51 [11] years) and 25 who died during strenuous activity or emotional stress (age, 49 [9] years). MAIN OUTCOME MEASURES: The frequency and morphology of plaque rupture was compared in men dying at rest vs those dying during exertion. Independent association of risk factors (total cholesterol, high-density lipoprotein cholesterol, glycosylated hemoglobin, cigarette smoking) in addition to acute exertion with plaque rupture were determined. RESULTS: The mean (SD) number of vulnerable plaques in the coronary arteries of men in the exertional-death group was 1.6 (1.5) and in the at-rest group was 0.9 (1.2) (P=.03). The culprit plaque in men dying during exertion was plaque rupture in 17 (68%) of 25 vs 27 (23%) of 116 men dying at rest (P<.001). Hemorrhage into the plaque occurred in 18 (72%) of 25 men in the exertional-death group and 47 (41%) of 116 men in the rest group (P=.007). Histological evidence of acute myocardial infarction was present in 0 of 25 in the exertion group and in 15 (13%) of 116 in the rest group. Men dying during exertion had a significantly higher mean (SD) total cholesterol-high-density lipoprotein cholesterol ratio (8.2 [3.0]) than those dying at rest (6.2 [ 2.7]; P=.002), and the majority (21/25) were not conditioned. In multivariate analysis, both exertion (P=.002) and total cholesterol-high-density lipoprotein cholesterol ratio (P=.002) were associated with acute plaque rupture, independent of age and other cardiac risk factors. CONCLUSION: In men with severe coronary artery disease, sudden death related to exertion was associated with acute plaque rupture.

Autopsy↗
PubMed1999

Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study.

CONTEXT: Atherosclerosis, the underlying cause of coronary heart disease, has been shown to be present even in young adults. OBJECTIVE: To document the extent and severity of atherosclerosis in adolescents and young adults in the United States. DESIGN AND SETTING: The Pathobiological Determinants of Atherosclerosis in Youth Study, a multi-institutional autopsy study conducted in US medical centers. Subjects A total of 2876 study subjects, between 15 and 34 years old, black and white, men and women, who died of external causes and underwent autopsy between June 1, 1987, and August 31, 1994. MAIN OUTCOME MEASURES: Extent, prevalence, and topography of atherosclerotic lesions. RESULTS: Intimal lesions appeared in all the aortas and more than half of the right coronary arteries of the youngest age group (15-19 years) and increased in prevalence and extent with age through the oldest age group (30-34 years). Fatty streaks were more extensive in black subjects than in white subjects, but raised lesions did not differ between blacks and whites. Raised lesions in the aortas of women and men were similar, but raised lesions in the right coronary arteries of women were less than those of men. The prevalence of total lesions was lower in the right coronary artery than in the aorta, but the proportion of raised lesions among total lesions was higher in the right coronary artery than in the aorta. CONCLUSIONS: Atherosclerosis begins in youth. Fatty streaks and clinically significant raised lesions increase rapidly in prevalence and extent during the 15- to 34-year age span. Primary prevention of atherosclerosis, as contrasted with primary prevention of clinically manifest atherosclerotic disease, must begin in childhood or adolescence.

Adolescent↗
PubMed1999

Apolipoprotein E and atherosclerosis in Greenland Inuit.

Arterial, liver, and serum specimens were collected from Greenland Inuit at autopsy and apolipoprotein E genotyping was done on 42 females (mean age = 61.3 years) and 56 males (mean age = 56.8 years). Estimates of the allele frequencies of the apo E, derived from the observed frequencies of the six common apolipoprotein E genotypes, are E2: 0.015+/-0.009; E3: 0.776+/-0.030; and E4: 0.209+/-0.029. No significant difference was found between these frequencies and those previously reported for Greenland Inuit, Canadian Inuit, or Alaska natives; however, differences were observed in comparison with frequencies reported for Japan, Norway, Sweden, USA-Blacks and USA-Whites. Anthropometric data (body mass index, panniculus adiposus thickness), blood analyte levels (total serum cholesterol, HDL-cholesterol, LDL + VLDL-cholesterol, and glycohemoglobin), and prevalence and extent of atherosclerotic lesions in the aorta and coronary arteries were analyzed for any associations with apolipoprotein E genotype. The occurrence of apolipoprotein E2 alleles are very rare and the E4 alleles are slightly more frequent in the Greenland Inuit population as compared to other populations. No significant association between apolipoprotein E genotypes and the extent of atherosclerotic lesions in the aorta and coronary arteries were found, and there does not appear to be any strong evidence for an association of either serum lipids, glycohemoglobin levels, or adiposity measurements to apolipoprotein E genotype in Greenland Inuit.

Adult↗
PubMed1999

Arterial remodeling in the left coronary system: the role of high-density lipoprotein cholesterol.

OBJECTIVES: We sought to evaluate the plaque and patient variables related to arterial remodeling responses of early, de novo atherosclerotic lesions involving the left coronary artery. BACKGROUND: Coronary artery remodeling is a lesion-specific process involving either enlargement or shrinkage of atherosclerotic coronary arteries. There are little histologic data available correlating plaque morphologic and patient clinical characteristics with the degree and type of arterial remodeling in early atherosclerosis. METHODS: We studied 736 serial arterial sections from the left coronary system of 97 autopsy cases (mean age 33 +/- 11 years) by correlating the arterial remodeling response to plaque with demographic, serologic and histologic variables. Using the most proximal section as a reference, and considering the expected degree of internal elastic lamina tapering, remodeling was classified as positive (including neutral remodeling or compensatory enlargement) or negative. RESULTS: Remodeling was classified as positive in 84.3% (compensatory in 30.6%) and negative in 15.7% of sections with an overall mean luminal stenosis of 10.4 +/- 9.9%. In the lesions with the greatest arterial cross-sectional narrowing from each case, compensatory enlargement was associated with higher high-density lipoprotein (HDL) cholesterol (59.4 +/- 27.2 mg/dl) compared with either neutral (49.3 +/- 15.5 mg/dl) or negative remodeling (30.4 +/- 5.2 mg/dl; p = 0.019). In subjects with advanced atherosclerosis (maximum American Heart Association histologic grade 5 atherosclerosis), there was a modest linear relationship between higher HDL cholesterol and the propensity for positive remodeling (r2 = 0.37; p = 0.025). On multivariate analysis, only HDL cholesterol was related to the arterial remodeling response. CONCLUSIONS: Negative arterial remodeling occurs in early atherosclerosis. Higher HDL cholesterol may favor positive remodeling.

Adolescent↗
PubMed1999

Lipid and apolipoprotein predictors of atherosclerosis in youth: apolipoprotein concentrations do not materially improve prediction of arterial lesions in PDAY subjects. The PDAY Research Group.

We compared serum lipid and apolipoprotein predictors of atherosclerosis in cases from the multicenter study, Pathobiological Determinants of Atherosclerosis in Youth (PDAY). The lipid measures included HDL cholesterol (HDL-C) and non-HDL-C, and the apolipoprotein measures included concentrations of apoA1, apoB, and Lp(a), and sizes of the apo(a) proteins. We tested whether the apolipoprotein measures predicted atherosclerotic lesions as well as the more traditional lipid measures. We estimated extent of lesions as fatty streaks or raised lesions (fibrous plaques, complicated or calcified lesions) in 3 sites: thoracic aorta, abdominal aorta, and right coronary artery. Neither apoA1 nor apoB measures were as strongly or consistently correlated with extent of lesions as the corresponding lipid measure (HDL-C and non-HDL-C, respectively). Beyond the basic model that included sex, age, race, smoking status, hypertension, and the lipid measures, apoA1 and apoB added only an average 1.3% increased explanatory ability to the model, whereas HDL-C plus non-HDL-C added an average 2.5%. The results suggest that the traditional lipid measures are more useful than apolipoprotein measures for detecting young persons at high risk of precocious atherosclerosis. Because of large racial differences, the two Lp(a)-related measures, Lp(a) concentrations and apo(a) size, were evaluated in blacks and whites separately. Under these circumstances, neither of the Lp(a)-related measures was strongly or consistently correlated with extent of lesions.

Adolescent↗
PubMed1998

Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women.

BACKGROUND: Traditional risk factors have been linked to atherosclerotic heart disease in women. However, the effect of risk factors and menopausal status on the mechanism of sudden coronary death is unknown. METHODS AND RESULTS: We examined 51 cases of sudden coronary death and 15 hearts from women who died of trauma. Coronary deaths were divided into four mechanisms of death: ruptured plaque with acute thrombus (n = 8), eroded plaque with acute thrombus (n = 18), stable plaque with healed infarct (n = 18), and stable plaque without infarction (n = 7). Vulnerable plaques prone to rupture were defined as those with a thin, fibrous cap infiltrated by macrophages and were quantitated in coronary deaths and control subjects. Total cholesterol (TC), HDL cholesterol, glycosylated hemoglobin, cigarette smoking, and hypertension were determined in each case. Compared with control subjects, women with plaque ruptures had elevated TC (270 +/- 55 versus 194 +/- 44 mg/dL, P = 0.002), and those with erosions were more likely to be smokers (78% versus 33%, P = 0.01). Women with stable plaque and healed infarct had elevated glycosylated hemoglobin (10.2 +/- 5.0% versus 6.4 +/- 0.4% in control subjects, P = 0.001) and were more likely to be hypertensive (50% versus 15% in control subjects, P = 0.03). By multivariate analysis, cigarette smoking was associated with plaque erosion (P = 0.03, odds ratio [OR] 21), glycoslyated hemoglobin with stable plaque and healed infarct (P = 0.03, OR 41), TC with plaque rupture (P = 0.02, OR 7), and hypertension with stable plaque with healed infarct (P = 0.02, OR 15). Seven of 8 plaque ruptures occurred in women > 50 years of age versus 3 of 18 erosions (P = 0.001). In cases of coronary death, vulnerable plaques were associated with elevated cholesterol (P = 0.002) and age > 50 years (P = 0.002), independent of other risk factors. CONCLUSIONS: In women, traditional risk factors have distinct effects on the mechanisms of sudden coronary death, which vary by menopausal status. Effective risk factor modification may therefore differ between younger and older women and may be targeting different mechanisms of plaque instability.

Acute Disease↗
PubMed1998

Arterial calcification as a marker for atherosclerosis in three Arctic populations.

Accumulation of calcification in the arterial wall in the course of the atherogenic process is considered to be a manifestation of advanced atherosclerosis. In this study of autopsy specimens from Alaska non-Natives, Alaska Natives, and Greenland Natives, comparisons were made of the prevalence and extent of arterial calcification with that of all raised (advanced) lesions in the thoracic aorta, abdominal aorta, right coronary artery, and left anterior descending coronary artery, to determine the degree to which calcified lesions track the development of advanced lesions. Calcification was determined quantitatively from radiograph images of the fixed specimens; advanced lesion data on these specimens were available from prior studies. Findings show that the prevalence and extent of calcified lesions closely follows the pattern of prevalence and extent of advanced lesions among the groups. We conclude that calcification is a good marker for comparisons of the prevalence and may also provide a good measure of the extent of atherosclerosis in these populations.

Adolescent↗
PubMed1997

Coronary risk factors and plaque morphology in men with coronary disease who died suddenly.

BACKGROUND: Cigarette smoking and abnormal serum cholesterol concentrations are risk factors for acute coronary syndromes, but the underlying mechanisms are poorly understood. We studied whether cigarette smoking and abnormal cholesterol values may precipitate acute coronary thrombosis and sudden death resulting from either rupture of vulnerable coronary plaques or erosion of plaques. METHODS: We examined the hearts of 113 men with coronary disease who had died suddenly and also analyzed their coronary risk factors. We found an acute coronary thrombus in each of 59 men, and severe narrowing of the coronary artery by an atherosclerotic plaque without acute thrombosis (stable plaque) in 54. Cases of acute thrombosis were divided into two groups: 41 resulting from rupture of a vulnerable plaque (a thin fibrous cap overlying a lipid-rich core), and 18 resulting from the erosion of a fibrous plaque rich in smooth-muscle cells and proteoglycans. Vulnerable plaques that had not ruptured were counted in each heart. RESULTS: Cigarette smoking was a risk factor in 44 (75 percent) of the men with acute thrombosis, as compared with 22 (41 percent) of the men with stable plaques (P<0.001). The mean (+/-SD) ratio of serum total cholesterol to high-density lipoprotein (HDL) cholesterol was markedly elevated in the men who died of acute thrombosis with plaque rupture (mean, 8.5+/-4.0) but only mildly elevated in the men without acute thrombosis (5.5+/-2.4; P<0.001) and in the men with thrombi overlying eroded plaques (5.0+/-1.8; P<0.001). Multivariate analysis showed an association between an elevated ratio of serum total cholesterol to HDL cholesterol and the presence of vulnerable plaques (P<0.001). CONCLUSIONS: Among men with coronary disease who die suddenly, abnormal serum cholesterol concentrations - particularly elevated ratios of total cholesterol to HDL cholesterol - predispose patients to rupture of vulnerable plaques, whereas cigarette smoking predisposes patients to acute thrombosis.

Acute Disease↗
PubMed1997

Atherosclerosis in youth: are hypertension and other coronary heart disease risk factors already at work?

The purposes of this review were to describe the natural history of atherosclerosis in youth, discuss the role of adult coronary heart disease (CHD) risk factors in the development of atherosclerosis-particularly in the young- and present the relationship between atherosclerosis and hypertension. Evidence is presented that, by age 15 years, 100% of the youth have aortic atherosclerosis and about one-half have coronary atherosclerosis. Risk factors for adult CHD, including lipoproteins, smoking, glycohemoglobin (a marker for diabetes), obesity, and hypertension, are associated with extent and prevalence of atherosclerosis in young people. Hypertension seems to play its role mainly by converting early atherosclerotic lesions (fatty streaks) to more advanced lesions (raised lesions).

Adolescent↗
PubMed1997

Effects of serum lipoproteins and smoking on atherosclerosis in young men and women. The PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth.

Atherosclerosis begins in childhood and progresses from fatty streaks to raised lesions in adolescence and young adulthood. A cooperative multicenter study (Pathobiological Determinants of Atherosclerosis in Youth [PDAY]) examined the relation of risk factors for adult coronary heart disease to atherosclerosis in 1079 men and 364 women 15 through 34 years of age, both black and white, who died of external causes and were autopsied in forensic laboratories. We quantitated atherosclerosis of the aorta and right coronary artery as the extent of intimal surface involved by fatty streaks and raised lesions and analyzed postmorterm serum for lipoprotein cholesterol and thiocyanate (as an indicator of smoking). The extent of intimal surface involved with both fatty streaks and raised lesions increased with age in all arterial segments of all sex and race groups. Women had a greater extent of fatty streaks in the abdominal aorta than men, but women and men had about an equal extent of raised lesions. Women and men had a comparable extent of fatty streaks in the right coronary artery, but women had about half the extent of raised lesions. Blacks had a greater extent of fatty streaks than whites, but blacks and whites had a similar extent of raised lesions. VLDL plus LDL cholesterol concentration was associated positively and HDL cholesterol was associated negatively with the extent of fatty streaks and raised lesions in the aorta and right coronary artery. Smoking was associated with more extensive fatty streaks and raised lesions in the abdominal aorta. All three risk factors affected atherosclerosis to about the same degree in both sexes and both races. Primary prevention of atherosclerosis by controlling these adult coronary heart disease risk factors is applicable to young men and women and to young blacks and whites.

Adolescent↗
PubMed1996

Renovasculopathies of nephrosclerosis in relation to atherosclerosis at ages 25 to 54 years.

Renovasculopathies of hypertension include arteriolar hyalinization and arterial intimal fibroplasia. Atherosclerotic features of coronary arteries and aorta include fatty streaks and raised lesions. Data were obtained from a series of 573 autopsies of black and Caucasian males and females aged 25 to 54 years, who died of violent and natural causes unrelated to atherosclerosis. Analysis showed positive correlations of coronary and aortic raised lesions with arteriolar hyalinization. Arterial intimal fibroplasia correlated positively with raised lesions in the aorta but only weakly and inconsistently in the coronary arteries. The extent of fatty streaks in the coronaries, as in the aorta, did not correlate with either form of renovasculopathy. These results provide evidence that hyalinization of renal arterioles may be a marker for young people who have the most advanced coronary atherosclerosis, and who therefore have an early start upon a course toward coronary heart disease later in life.

Adult↗
PubMed1996

The Inuit diet. Fatty acids and antioxidants, their role in ischemic heart disease, and exposure to organochlorines and heavy metals. An international study.

Traditional food is culturally, economically and nutritionally important for the Greenlandic Inuit people. In the 1970s the preventive effect of marine fat on cardiovascular disease, thrombosis and atherosclerosis was described. The low incidence of ischemic heart disease among Greenlanders has been related to the high intake of marine food. Since 1990 routine autopsies have taken place in two towns in Greenland, Nuuk and Ilulissat. The autopsies represent 26% of the total number of deaths in these two towns. Samples have been collected from 104 autopsies. International cooperative studies have analysed specimens in relation to ischemic heart disease as a benefit related to diet, as well as the level of heavy metals and organochlorine in organs as a risk related to diet. High amounts of mono-unsaturated and Omega-3 poly-unsaturated fatty acid were found in adipose tissue. Liver analyses of selenium have confirmed the expected high intake among Greenlanders. Reduced atherosclerotic lesions were found in the coronary arteries. Blood pressure levels calculated from renovascholopathia of hypertension indicate prevailing levels similar to those in industrialized countries. Some factors in Greenland may be protecting the coronary arteries, thereby of setting the expected effect of hypertension. The level of methyl mercury in organs is generally high. PCB concentrations found in organs of Greenlanders are higher than among other populations. Health and risk effects of the traditional foods need further investigation.

Adipose Tissue↗