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Biomedical subjects

Samuel S Gidding

Publications and source records attributed to Samuel S Gidding.

At least 19 recordsLinked to original sources
PubMed2026

Monogenic ALB Variants as Determinants of Severe Hypercholesterolemia: A Population-Based Cohort Study.

BACKGROUND: Hypoalbuminemia is associated with several risk factors for myocardial infarction, including hypercholesterolemia, liver disease, kidney disease, and diabetes. Homozygosity of loss-of-function (LoF) variants in the ALB gene, which encodes albumin, is a known cause of congenital hypoalbuminemia. Studies have also shown that heterozygous ALB LoF variants are associated with increases in low-density lipoprotein cholesterol (LDL-C), comparable to those seen in familial hypercholesterolemia. OBJECTIVES: This study examined the effect of ALB LoF variants and other causes of low albumin on LDL-C levels in 2 population biobanks. METHODS: This study used data from 2 large cohorts with linked electronic health record and genetic information: Geisinger's MyCode Community Health Initiative, a health care population based in Pennsylvania, USA; and the National Institutes of Health All of Us Research Program, a nationwide epidemiologic cohort. LDL-C values were adjusted for lipid-lowering medication use. Myocardial infarction diagnoses were extracted from electronic health records using International Classification of Diseases codes. A polygenic score for serum albumin was calculated for participants of European ancestry. Linear regression models were used to estimate associations, and results were meta-analyzed across cohorts using fixed-effects models. RESULTS: Among 155,530 MyCode and 405,701 All of Us adult participants, 77 individuals (1 of 7,289) carried an ALB LoF variant. Among noncarriers, a 1 g/dL decrease in serum albumin was associated with a 10.9 mg/dL (95% CI:, 10.4-11.4) decrease in LDL-C. In contrast, ALB LoF variants were associated with a 0.69 g/dL (95% CI: 0.60-0.78) reduction in serum albumin and a 38.3 mg/dL (95% CI: 28.2-48.5) increase in LDL-C. Paradoxically, whereas monogenic determinants of hypoalbuminemia were associated with increased LDL-C, polygenic determinants of lower albumin were associated with a 0.22 mg/dL (95% CI: 0.17-0.26) decrease in LDL-C per decile. CONCLUSIONS: ALB LoF variants represent a previously underrecognized monogenic cause of elevated LDL-C, with effect sizes slightly less than canonical familial hypercholesterolemia variants. The divergent effects of ALB-mediated vs polygenic or physiological reductions in albumin on LDL-C suggest distinct underlying mechanisms.

Humans↗
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

Cardiovascular risk factors in adolescents.

Most children who are normal weight for height and otherwise healthy have risk factor levels associated with the absence of heart disease (ie, they do not smoke, do not have diabetes, are physically active, have low-density lipoprotein levels < 110 mg/dL, and have blood pressure < 120/80 mm Hg). However, by adolescence, the earliest lesions in the atherosclerotic process, fatty streaks and raised lesions, are present in the coronary arteries and the abdominal aorta. The severity of early atherogenesis is related to the coexistence of the major cardiovascular risk factors. Most commonly, the associated risk disturbances are mild: borderline hypertension, mild dyslipidemia, insulin resistance, overweight, physical inactivity, and initiation of tobacco use. Rarely, more severe risk factors are present: familial hypercholesterolemia (a genetic disorder of lipid metabolism), diabetes mellitus, secondary hypertension of long standing, or risk factors associated with chronic conditions such as end-stage renal disease. Thus, cardiovascular risk management in this age group has two components: primordial prevention (the prevention of the development of cardiovascular risk in the first place) and primary prevention (more aggressive treatment of identified risk factors in high-risk individuals either through behavioral or pharmacologic means). Trials beginning in adolescence of the primary prevention of atherosclerosis-related diseases have not been undertaken; thus, the decision to initiate pharmacologic management in high-risk adolescents requires careful thought.

Journal Article↗
PubMed2006

Fontan completion in infants.

BACKGROUND: Since the implementation of the Fontan procedure, several clinical factors have been linked to outcome. A study of the outcome after Fontan completion was undertaken with particular attention to the influence of age and cardiac diagnosis. METHODS: Review of all patients (n = 107) undergoing Fontan completion between January 1998 and July 2005 to identify predictors of outcome: early death, prolonged effusions, and prolonged hospital stay. RESULTS: Median age was 13 months (range, 11 to 35) and median weight was 9.4 kgs (6.7 to 15.1). Hypoplastic left heart syndrome was present in 61 patients, and stage I Norwood was the initial palliation in 69. An interim superior cavopulmonary connection was performed in all. A lateral tunnel was used, and a deliberate right to left shunt was created in 99 patients. Mean transpulmonary gradient and pulmonary artery pressure were 5.7 +/- 1.5 mm Hg and 11.6 +/- 2.2 mm Hg, respectively. Median time to extubation was 5 hours (range, 2.5 to 184). Median duration of pleural effusion was 3 days (1 to 58) and was greater or equal to 14 days in 13 patients (12%). Overall mortality was 4.5% (5 of 107). Variables associated with poor outcome included associated noncardiac diagnosis (p < 0.05), elevated transpulmonary gradient (p = 0.03), and pulmonary artery pressure (p < 0.02). Hypoplastic left heart syndrome was the only variable associated with prolonged effusive complications. CONCLUSIONS: Fontan completion can be performed with good results in the first year of life independent of anatomic diagnosis. Significant noncardiac pathology, and a higher pulmonary artery pressure were predictive of worse outcome. Hypoplastic left heart syndrome was associated with prolonged effusions.

Abnormalities, Multiple↗
PubMed2006

The relationship of body mass index and blood pressure in primary care pediatric patients.

OBJECTIVE: To determine whether an association of overweight, or risk of overweight, and blood pressure can be detected in children in the pediatric primary care practice setting. STUDY DESIGN: We examined electronic medical record (EMR) data from primary care practices on 18,618 children age 2 to 19 years. Each child was classified on the basis of age- and sex-specific body mass index (BMI) percentile as normal weight (BMI < 85th percentile), at risk for overweight (BMI > or = 85th and < 95th percentile), or overweight (BMI > or = 95th percentile). BMI Z-score and height Z-score were computed. Systolic and diastolic blood pressures were compared among age-sex-BMI groups. RESULTS: Among children in primary care pediatric practices, 16.7% were at risk of overweight and 20.2% were overweight. With increasing BMI status there was a significant increase in both systolic blood pressure (P < .001) and diastolic blood pressure (P < .001). The association of higher blood pressure with increasing BMI status was present in all age groups. CONCLUSIONS: Clinical data from pediatric primary care practices verify the high prevalence of childhood overweight. The effect of overweight on blood pressure is present in childhood and can be detected even in children as young as 2 to 5 years.

Adolescent↗
PubMed2006

Dietary recommendations for children and adolescents: a guide for practitioners.

Since the American Heart Association last presented nutrition guidelines for children, significant changes have occurred in the prevalence of cardiovascular risk factors and nutrition behaviors in children. Overweight has increased, whereas saturated fat and cholesterol intake have decreased, at least as percentage of total caloric intake. Better understanding of children's cardiovascular risk status and current diet is available from national survey data. New research on the efficacy of diet intervention in children has been published. Also, increasing attention has been paid to the importance of nutrition early in life, including the fetal milieu. This scientific statement summarizes current available information on cardiovascular nutrition in children and makes recommendations for both primordial and primary prevention of cardiovascular disease beginning at a young age.

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↗
PubMed2006

Higher self-reported physical activity is associated with lower systolic blood pressure: the Dietary Intervention Study in Childhood (DISC).

OBJECTIVE: Children participating in a dietary clinical trial were studied to (1) assess physical activity patterns in boys and girls longitudinally from late childhood through puberty and (2) determine the association of level of physical activity on systolic blood pressure, low-density lipoprotein cholesterol, and BMI. PATIENTS AND METHODS: In the Dietary Intervention Study in Childhood, a randomized clinical trial of a reduced saturated fat and cholesterol diet in 8- to 10-year-olds with elevated low-density lipoprotein, a questionnaire that determined time spent in 5 intensity levels of physical activity was completed at baseline and at 1 and 3 years. An estimated-metabolic-equivalent score was calculated for weekly activity; hours per week were calculated for intense activities. We hypothesized that weekly self-reported physical activity would be associated with lower systolic blood pressure, low-density lipoprotein, and BMI over 3 years. Longitudinal data analyses were performed for each outcome (systolic blood pressure, low-density lipoprotein, and BMI) by using generalized estimating equations with estimated-metabolic-equivalent score per week as the independent variable adjusted for visit, gender, and Tanner stage (BMI was included in models for systolic blood pressure and low-density lipoprotein). RESULTS: The initial study cohort comprised 663 youths (362 boys [mean age: 9.7 years] and 301 girls [mean age: 9.0 years], of whom 623 (94%) completed the 3-year visit. For every 100 estimated-metabolic-equivalent hours of physical activity, there was a decrease of 1.15 mmHg of systolic blood pressure. There was a 1.28 mg/dL decline in low-density lipoprotein for a similar energy expenditure. For BMI, an analysis of intense physical activity showed that for every 10 hours of intense activity, there was a trend toward significance with a 0.2 kg/m2 decrease. CONCLUSIONS: Children with elevated cholesterol levels who lead a more physically active lifestyle have lower systolic blood pressure and a trend toward lower low-density lipoprotein over a 3-year interval. Long-term participation in intense physical activity may reduce BMI as well.

Blood Pressure↗
PubMed2005

Dietary recommendations for children and adolescents: a guide for practitioners: consensus statement from the American Heart Association.

Since the American Heart Association last presented nutrition guidelines for children, significant changes have occurred in the prevalence of cardiovascular risk factors and nutrition behaviors in children. Overweight has increased, whereas saturated fat and cholesterol intake have decreased, at least as percentage of total caloric intake. Better understanding of children's cardiovascular risk status and current diet is available from national survey data. New research on the efficacy of diet intervention in children has been published. Also, increasing attention has been paid to the importance of nutrition early in life, including the fetal milieu. This scientific statement summarizes current available information on cardiovascular nutrition in children and makes recommendations for both primordial and primary prevention of cardiovascular disease beginning at a young age.

Adolescent↗
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

Overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment.

The prevalence of overweight among children and adolescents has dramatically increased. There may be vulnerable periods for weight gain during childhood and adolescence that also offer opportunities for prevention of overweight. Overweight in children and adolescents can result in a variety of adverse health outcomes, including type 2 diabetes, obstructive sleep apnea, hypertension, dyslipidemia, and the metabolic syndrome. The best approach to this problem is prevention of abnormal weight gain. Several strategies for prevention are presented. In addition, treatment approaches are presented, including behavioral, pharmacological, and surgical treatment. Childhood and adolescent overweight is one of the most important current public health concerns.

Adolescent↗
PubMed2005

A longitudinal study of physical activity and heart rate recovery: CARDIA, 1987-1993.

PURPOSE: Autonomic nervous system function may be a mechanism by which frequent physical activity is associated with better coronary heart disease outcomes. In a diverse, population-based sample, we tested whether physical activity participation was associated with higher parasympathetic function. METHODS: Participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study underwent symptom-limited graded exercise testing at baseline (1985-1986; N=3446) and at 7 yr follow-up (N=1627). Heart rate recovery (HRR), the difference between maximum heart rate (HR) and HR 2 min after test cessation, was used to estimate parasympathetic activity. RESULTS: Participants who self-reported in the highest tertile of total physical activity (the sum of moderate- and heavy-intensity activities) had significantly faster HRR than participants in the lowest tertile (45.1 vs 41.8 beats.min, P<0.01), and the odds of having abnormal HRR (<or=22 beats.min) were 1.9 (95% confidence interval: 1.1, 3.4) times greater in the lowest versus the highest tertile after adjustment for age, race, gender, body mass index, smoking status, and diastolic blood pressure. Findings were consistent across strata of covariates. On average, HRR declined 2.5 beats.min over 7 yr. HRR declined the least among participants whose physical activity increased (-1.3 beats.min) or remained stable (-1.8 beats.min), compared with participants whose physical activity decreased (-3.6 beats.min; P<0.01 vs increase or stable). CONCLUSIONS: In this diverse, population-based sample, physical activity was associated with faster HRR from an exercise treadmill test. Regular physical activity may blunt age-related declines in autonomic nervous system function.

Adult↗
PubMed2004

Cardiovascular complications in pediatric end-stage renal disease.

Mortality from end-stage renal disease (ESRD) is often due to cardiac causes. Although cardiovascular complications of ESRD have long been recognized, only recently has the presence of traditional cardiovascular risk factors been associated with late cardiovascular complications. This review presents a history of cardiac involvement in ESRD, the pathophysiology of accelerated atherosclerosis and left ventricular hypertrophy, and a summary of the literature on cardiovascular risk assessment in children. Techniques for non-invasive assessment of cardiac end-organ injury are also discussed. Recommendations for monitoring of risk factors and treatment in the pediatric ESRD population are presented.

Adolescent↗
PubMed2004

Severe obesity associated with cardiovascular deconditioning, high prevalence of cardiovascular risk factors, diabetes mellitus/hyperinsulinemia, and respiratory compromise.

OBJECTIVE: To determine the extent and severity of obesity-related cardiorespiratory morbidity in children with body mass index (BMI) >or=40 kg/m(2). STUDY DESIGN: Cross-sectional analysis of a cohort comprised of 48 boys and girls aged 8 to 17 years with BMI >or=40 kg/m(2). Cardiorespiratory fitness (graded cycle exercise test), left ventricular (LV) mass (echocardiography), blood pressure, fasting lipid profile, fasting insulin, fasting glucose, HbA1c, and pulmonary function (spirometry and sleep studies) were measured. RESULTS: The cohort averaged 14.2 +/- 2 years of age with mean BMI of 45.5 kg/m(2). Only 2 patients had normal fitness; 37 of 48 had peak oxygen consumption <20 mL O(2)/minute. Hypertension was present in 10 of 48 patients. Mean lipid values were: triglycerides 103 +/- 48 mg/dL, HDL cholesterol 41 +/- 10 mg/dL, and LDL cholesterol 108 +/- 26 mg/dL. Type II diabetes mellitus was diagnosed in 6 patients. Mean fasting insulin was 31 +/- 19 microU/mL. Asthma treatment, small airways disease by pulmonary function testing, or both were present in 35 of 48 patients; upper airway obstruction was present in 7 patients. LV hypertrophy was present in 8 patients, with a mean LV mass of 43 +/- 11 g/m(2.7). CONCLUSIONS: Children and adolescents with BMI >or=40 kg/m(2) have substantial cardiorespiratory morbidity including severe physical deconditioning.

Adolescent↗