Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Risk Score in Young Adults Predicts Coronary Artery and Abdominal Aorta Calcium in Middle Age: The CARDIA Study.

Background: We explored whether, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary and abdominal risk scores measured at 18 to 30 years of age and changes in these scores would more strongly predict coronary artery calcium (CAC) and abdominal aortic calcium (AAC) assessed 25 years later, than scores measured 25 years later.

Methods And Results: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, 3008 participants had measurements of risk score components at 5-year intervals beginning at 18 to 30 years of age. CAC and AAC were assessed at 43 to 55 years of age.

Use of a direct-fed microbial product as a supplement during the transition period in dairy cattle.

Two studies were conducted. The objective of the first study was to assess the effects of a direct-fed microbial (DFM) product on dry matter intake, milk yield, milk components, disease incidence, and blood metabolites in dairy cattle. The objective of the second study was to assess the effects of DFM on apparent total-tract nutrient digestibility (ATTD).

Are pediatricians responsible for prevention of adult cardiovascular disease?

Atherosclerosis begins in childhood with fatty streaks, which progress seamlessly to fibrous plaques in adulthood. These plaques, in turn, might rupture and cause thrombotic arterial occlusion and ischemic damage to vital organs. The earliest stages and progression of atherosclerosis in youth are influenced by the same major established risk factors for this condition in adults-dyslipidemia, hypertension, smoking, obesity, and diabetes mellitus.

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.

Coronary heart disease risk factors and atherosclerosis in young people.

Atherosclerosis begins in childhood or adolescence and progresses during the young adult years to cause clinical coronary heart disease (CHD) in middle-aged and older individuals. This article reviews evidence regarding the association of the major established CHD risk factors with atherosclerosis in adolescents and young adults, with emphasis on the findings of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Age, non-high-density lipoprotein cholesterol concentration, smoking, hypertension, obesity, and hyperglycemia are positively associated with atherosclerotic lesions, whereas female gender and high-density lipoprotein cholesterol concentration are negatively associated with lesions.

Association of Pathobiologic Determinants of Atherosclerosis in Youth risk score and 15-year change in risk score with carotid artery intima-media thickness in young adults (from the Cardiovascular Risk in Young Finns Study).

The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study of autopsy findings in subjects 15 to 34 years of age developed a risk score using coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia) to estimate the probability of advanced atherosclerotic lesions in the coronary arteries. The Cardiovascular Risk in Young Finns Study measured coronary heart disease risk factors in a population-based cohort in 1986 and 2001 and measured carotid artery intima-media thickness (IMT) with ultrasonography in 2001. We computed the PDAY risk score from risk factors measured in 1,279 subjects who were 12 to 24 years of age in 1986 and 27 to 39 years of age in 2001.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Atherosclerosis in youth.

Background: Coronary heart disease (CHD) and the related diseases due to atherosclerosis continue to be major public health problems in the industrialized countries and are likely to become serious problems in the developing countries. Treatment of end stage disease has improved, and risk factor modification has succeeded in reducing risk among adults. However, the age at which to begin risk factor control for long-range primary prevention is controversial.

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.

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.

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.

Caution on the use of saliva measurements to monitor absorption of progesterone from transdermal creams in postmenopausal women.

Objectives: To determine the levels of progesterone in plasma, red cells and saliva as well as pregnanediol-3-glucuronide excretion in postmenopausal women using transdermal progesterone creams.

Methods: A double-blind placebo controlled study was carried out using 24 postmenopausal women. Creams (placebo, 20 or 40 mg progesterone/g) were applied twice daily for 3 weeks followed by 1 week without before a further 3-week treatment.

Effects of nonlipid risk factors on atherosclerosis in youth with a favorable lipoprotein profile.

Background: The strong association between coronary heart disease and dyslipoproteinemia has often overshadowed the effects of the nonlipid risk factors-smoking, hypertension, obesity, and diabetes and impaired glucose tolerance-and even led to questioning the importance of these risk factors in the presence of a favorable lipoprotein profile.

Methods And Results: A cooperative multicenter study, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY), examined the relation of the nonlipid risk factors to atherosclerosis in 629 men and 227 women 15 to 34 years of age who died of external causes and who had a favorable lipoprotein profile (non-HDL cholesterol <4.14 mmol/L [<160 mg/dL] and HDL cholesterol >/=0.