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Biomedical subjects

Henry C McGill

Publications and source records attributed to Henry C McGill.

14 recordsLinked to original sources
PubMed2006

Prediction of coronary artery calcium in young adults using the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) risk score: the CARDIA study.

BACKGROUND: Using data from autopsied young people aged 15 to 34 years, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study developed a risk score based on age, sex, smoking status, high-density lipoprotein and non-high-density lipoprotein cholesterol levels, and the presence of obesity, hyperglycemia, and hypertension to predict advanced coronary artery atherosclerosis. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study assessed coronary artery calcium (CAC) by computed tomography in young adults participating in the 15-year examination. The PDAY risk score was calculated from risk factors measured at the CARDIA examinations at years 0, 5, 10, and 15. RESULTS: Odds ratios for amount of CAC (6 ordinal categories) for a 1-point increase in risk score computed from the modifiable risk factors ranged from 1.10 to 1.16 (all statistically significant). Odds ratios for presence of any amount of CAC ranged from 1.09 to 1.15 (all statistically significant), with the highest odds ratio for the risk score at year 0. An increase in risk score between years 0 and 15 increased the odds of CAC, and a decrease in risk score decreased the odds of CAC. A positive family history of cardiovascular disease increased the odds of CAC. The c statistics ranged from 0.752 to 0.770, with the highest discrimination based on the year 0 revised PDAY risk score that included family history and increased the points for the sex differential. CONCLUSION: The PDAY risk score predicts CAC up to 15 years before its assessment, and risk score change during 15 years affects the risk of CAC.

Adolescent↗
PubMed2006

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.

Adolescent↗
PubMed2006

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.

Adolescent↗
PubMed2005

Expression levels of ACAT1 and ACAT2 genes in the liver and intestine of baboons with high and low lipemic responses to dietary lipids.

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) 1 and ACAT2 play an important role in cellular cholesterol esterification and thus modulate intestinal cholesterol absorption and hepatic lipoprotein secretion. The relative expression levels of ACAT1 and ACAT2 in human tissues differ from those in other animals, including nonhuman primates. The present study compared the relative expression levels of ACAT1 and ACAT2 in baboons with high and low lipemic responses to dietary lipids. We isolated RNA and prepared cDNA from frozen liver and small intestine from high- and low-responding pedigreed baboons necropsied after consuming a high-cholesterol and high-fat diet for 18 months. The expression of ACAT1 and ACAT2 was measured by TaqMan real-time quantitative PCR normalized to 18s ribosomal RNA. The expression of ACAT1 was higher than that of ACAT2 in the liver, whereas the expression of ACAT2 was higher than that of ACAT1 in the duodenum and jejunum. There was no difference in the expression of ACAT1 or ACAT2 in the liver and intestine between high- and low-responding baboons except that the expression of ACAT1 was higher in the duodenum of high responders than in that of low responders. Western blot analysis also showed a higher level of ACAT1 protein in the duodenum of high responders than in that of low responders. There was a significant correlation between duodenal ACAT expression levels and total plasma cholesterol concentration in baboons. These results suggest that differences in ACAT1 expression may affect plasma cholesterol concentration and partly affect diet-induced hyperlipidemia.

Animals↗
PubMed2005

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.

Adolescent↗
PubMed2005

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.

Adolescent↗
PubMed2005

ACE insert/delete polymorphism and atherosclerosis.

We report on the results of a large autopsy study focusing upon the hypothesis that deletion of the Alu insert in the angiotensin converting enzyme (ACE) gene is associated with: (a) greater prevalence or extent of atherosclerosis in the aorta and coronary arteries; and (b) microscopic qualities of established atherosclerotic plaques in the coronary arteries. This study was conducted in young US black (n=290) and white (n=379) males using available materials and data from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, a multi-center cooperative autopsy study organized in 1985 to explore the relationships of known cardiovascular risk factors to atherosclerosis in victims of accidents, homicides, or suicides in the age range of 15-34 years. The results provide strong evidence that ACE genotype may not be a predictor of either the prevalence or the extent of the lesions of atherosclerosis in the right coronary artery or the aorta of young adults, an observation that confirms previous studies that estimated the prevalence and extent of atherosclerosis using coronary angiography. In addition, the results suggest that ACE genotype does not contribute to the formation of atherosclerotic lesions that have the characteristics of vulnerable plaques in the left anterior descending coronary artery of young adults.

Adolescent↗
PubMed2005

Expression levels of genes for ATP-binding cassette transporters and sterol 27-hydroxylase in liver and intestine of baboons with high and low cholesterolemic responses to dietary lipids.

Baboons with high and low lipemic responses to dietary lipids differ in intestinal cholesterol absorption and hepatic cholesterol metabolism. ATP-binding cassette (ABC) transporters play an important role in cholesterol absorption and hepatic cholesterol metabolism. Using frozen tissues from high- and low-responding baboons maintained on the cholesterol and fat-enriched diet, we determined the relative expression of ABCA1, ABCG5, ABCG8, and 27-hydroxylase genes in the liver and intestine using TaqMan real-time polymerase chain reaction. There was no consistent difference in the expression of ABC-transporters and 27-hydroxylase in the intestine between high- and low-responding baboons. However, hepatic expression of sterol 27-hydroxylase, ABCG5, and ABCG8 was higher in low-responding baboons than in high-responding baboons. There was also a significant correlation between the expression of sterol 27-hydroxylase and ABCG5, and ABCG8 in both the liver and the intestine. These results suggest that differences in hepatic lipid metabolism but not in cholesterol absorption between high- and low-responding baboons observed previously may be mediated by the differences in the expression levels of 27-hydroxylase, ABCG5, and ABCG8.

ATP-Binding Cassette Transporters↗
PubMed2004

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.

Adolescent↗
PubMed2004

Effect of Synthetic Truncated Apolipoprotein C-I Peptide on Plasma Lipoprotein Cholesterol in Nonhuman Primates.

The present studies were conducted to determine whether a synthetic truncated apoC-I peptide that inhibits CETP activity in baboons would raise plasma HDL cholesterol levels in nonhuman primates with low HDL levels. We used 2 cynomolgus monkeys and 3 baboons fed a cholesterol- and fat-enriched diet. In cynomolgus monkeys, we injected synthetic truncated apoC-I inhibitor peptide at a dose of 20 mg/kg and, in baboons, at doses of 10, 15, and 20 mg/kg at weekly intervals. Blood samples were collected 3 times a week and VLDL $+$ LDL and HDL cholesterol concentrations were measured. In cynomolgus monkeys, administration of the inhibitor peptide caused a rapid decrease in VLDL $+$ LDL cholesterol concentrations (30%-60%) and an increase in HDL cholesterol concentrations (10%-20%). VLDL $+$ LDL cholesterol concentrations returned to baseline levels in approximately 15 days. In baboons, administration of the synthetic inhibitor peptide caused a decrease in VLDL $+$ LDL cholesterol (20%-60%) and an increase in HDL cholesterol (10%-20%). VLDL $+$ LDL cholesterol returned to baseline levels by day 21, whereas HDL cholesterol concentrations remained elevated for up to 26 days. ApoA-I concentrations increased, whereas apoE and triglyceride concentrations decreased. Subcutaneous and intravenous administrations of the inhibitor peptide had similar effects on LDL and HDL cholesterol concentrations. There was no change in body weight, food consumption, or plasma IgG levels of any baboon during the study. These studies suggest that the truncated apoC-I peptide can be used to raise HDL in humans.

Journal Article↗
PubMed2002

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.

Adipose Tissue↗
PubMed2002

Genetic determination of HDL variation and response to diet in baboons.

We fed 634 baboons three diets to assess the separate effects of increasing dietary fat and cholesterol intakes on three independent measures of HDL phenotype: concentrations of HDL cholesterol and apoAI, and size distributions of HDL cholesterol. Increasing dietary fat significantly increased concentrations of HDL cholesterol and apoAI (both, P<0.0001), but did not affect HDL particle sizes, whereas increasing dietary cholesterol increased HDL cholesterol (P<0.0001) concentrations and HDL particle sizes (P=0.08), but did not affect apoAI concentrations. A substantial proportion of variation in each of the HDL traits was influenced by genes (heritabilities ranged from 25 to 61%) and a common set of genes influenced HDL variation on each of the diets (genetic correlations ranged from 0.64 to 1.0). However, genes exerted a smaller effect on HDL response to changes of dietary fat and of dietary cholesterol. Therefore, dietary fat and cholesterol alter HDL levels and characteristics, but the dietary responses are not strongly mediated by additive genetic effects.

Animals↗
PubMed2002

A major gene influences variation in large HDL particles and their response to diet in baboons.

Some baboons accumulate appreciable amounts of large apoE-rich HDLs (HDL(1)) which are similar to those reported in humans with several different dyslipoproteinemias. We estimated HDL(1) cholesterol concentrations by gradient gel electrophoresis of serum samples obtained from 634 pedigreed baboons fed with three diets differing in levels of fat and cholesterol. The HDL(1) trait was highly heritable on each diet (0.390< or =h(2)< or =0.528). Segregation analyses yielded significant evidence that a single major gene plus polygenes affected HDL(1) on a high-fat low-cholesterol diet. The major gene explained approximately 56% of total trait variance and 90% of the additive genetic variance in HDL(1) levels in these baboons. Bivariate one-locus segregation analyses indicated that this major gene exerts significant pleiotropic effects on a number of traditional HDL traits on all three diets, including HDL size distributions, and concentrations of HDL-C, apoAI, and apoE. Linkage analyses showed that this major gene was not located in chromosomal regions that contain six candidate genes whose protein products are important to HDL metabolism (LCAT, CETP, APOA1, APOE, ABCA1, LIPC). Our results suggest this major gene in baboons plays a pivotal role in HDL metabolism, but is unlikely to code for any of the proteins previously implicated in studies of human HDL(1).

Animals↗