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Biomedical subjects

R R Fabsitz

Publications and source records attributed to R R Fabsitz.

At least 73 records · Page 4Linked to original sources
PubMed1991

The NHLBI Twin Study: heritability of apolipoprotein A-I, B, and low density lipoprotein subclasses and concordance for lipoprotein(a).

Heritability of plasma apolipoprotein (apo) A-I, apo B, and low density lipoprotein (LDL) subclasses and concordance for lipoprotein(a) excess were assessed in 109 monozygotic (MZ) and 113 dizygotic (DZ) twin pairs participating in the third examination of the National Heart, Lung, and Blood Institute Twin Study. The intraclass correlation coefficient for apo A-I was significantly greater in MZ twins (0.56) than in DZ twins (0.37, P less than 0.05); however, apo A-I showed an unequal distribution in the two groups, with significantly greater total variance in DZ twins. Therefore the among-component estimate of genetic variance was applied, and the results indicated no significant heritability for apo A-I (P = 0.59). MZ and DZ twins had equal apo B variance. The intraclass correlation coefficient for apo B in MZ twins (0.71) was significantly higher than in DZ twins (0.25) (P less than 0.0001), indicating significant heritability for apo B. Plasma apo A-I levels were significantly correlated with alcohol intake (P less than 0.0001), body mass index (BMI, P less than 0.0001), and physical activity, while apo B levels were significantly correlated only with BMI (P less than 0.05). After plasma apo A-I and apo B concentrations were adjusted for all of these variables and for cigarette smoking, the analysis of variance and intraclass correlation coefficients remained virtually unchanged. The LDL type intraclass correlation coefficient was higher in MZ twins (0.58) than in DZ twins (0.32, P less than 0.005); however, greater total variance for this parameter in DZ twins was observed and after applying the among component estimate of genetic variance, no significant heritability of LDL type was observed. After adjustment for covariate effects the conclusions were not changed. Only 8.4% of MZ twin pairs, as compared with 26.7% of DZ twin pairs, were discordant for elevated lipoprotein(a) on gradient gels (P less than 0.0001). Our data indicate that there is a strong heritability for plasma apo B and lipoprotein(a), with only weak evidence for heritability of LDL type or plasma apo A-I levels within this population sample.

Aged↗
PubMed1991

Concordance of ischemic heart disease in the NHLBI twin study after 14-18 years of follow-up.

Morbidity and mortality were assessed in the NHLBI twin study at the end of 1987. Deaths were greater in DZ twins (58/520, 11.2%) than MZ twins (38/508, 7.5%). Ischemic heart disease concordances were 2.3 times higher in MZ pairs and 2.8 times higher in DZ pairs than expected based on the prevalence of ischemic heart disease in the cohort. Family history scores for heart disease, calculated 14-18 years earlier at entry to the study, were significantly higher in DZ pairs where one or both members later developed ischemic heart disease and in corcordant MZ pairs than in twin-pairs without any subsequent heart disease. Concordance rates were not significantly different between MZ and DZ pairs. The results agree with previous suggestions that selection at enlistment into the armed services over 40 years ago, as well as later volunteering for the NHLBI twin study, resulted in a decline in the number of concordant MZ pairs.

Cause of Death↗
PubMed1991

Genetic effects on cardiovascular responses to cold and mental activity in late adulthood.

The purpose of the present investigation was to examine the genetic contributions to cardiovascular reactivity in an adult cohort of male twins. A total of 47 monozygotic (MZ) twin pairs and 54 dizygotic (DZ) twin pairs, aged 59 to 69 years, were laboratory tested at four sites as part of the third examination of the National Heart, Lung, and Blood Institute Twin Study. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded during two tasks, a mental arithmetic task involving serial subtraction and the cold pressor test. Significant cardiovascular responsivity was observed during both tasks as measured by substantial elevations in SBP, DBP, and HR from resting periods to task periods. Heritability estimates were statistically significant for SBP and DBP but not HR levels during pretask baseline periods and during both tasks. Genetic variance was maintained for blood pressure reactivity to the mental arithmetic task after adjustments for baseline and performance. No genetic variance for SBP or DBP reactivity to the cold pressor test was evident.

Aged↗
PubMed1991

Relation of risk factor levels in young adulthood to parental history of disease. The CARDIA study.

BACKGROUND: The relation between self-reported parental disease and risk factor levels was examined in 2,637 black and 2,478 white men and women aged 18-30 years at the Coronary Artery Risk Development in Young Adults (CARDIA) Study baseline examination (1985-1986). METHODS AND RESULTS: The prevalence of parental disease (at least one parent) in white versus black participants was 44% and 56% for hypertension, 47% and 44% for obesity, 16% and 13% for myocardial infarction, 11% and 17% for diabetes, and 6% and 10% for stroke, respectively. Among these young adults, parental hypertension was associated with higher sex- and age-adjusted systolic and diastolic blood pressure levels. Parental myocardial infarction was associated with higher plasma cholesterol, higher blood pressure levels, and lower high density lipoprotein cholesterol levels in white participants. Parental diabetes was associated with higher fasting blood glucose and insulin levels in all race-sex groups and with higher triglycerides and lower high density lipoprotein cholesterol in black participants only. Parental history of obesity was related to less favorable age- and sex-adjusted lipid levels in white participants and higher blood pressure levels in black participants. Parental history of stroke was associated with higher systolic blood pressure levels in black participants. In general, these differences across family history were predicted only in part by obesity. The prevalence of more than one disease reported in parents occurred more frequently than would have been expected due to chance alone. CONCLUSIONS: These associations between parental disease and risk factors in their adult children probably reflects the impact of both environmental and genetic factors. Parental history may be a useful marker for high risk individuals.

Adult↗
PubMed1990

Heritability of cognitive performance in aging twins. The National Heart, Lung, and Blood Institute Twin Study.

The genetic contribution to performance on scales designed to measure mild to moderate decrements in cognitive functioning in a population at risk is unknown. In the present analysis, 134 monozygotic and 133 dizygotic male twin pairs (mean age, 63 years) were given three cognitive tests: the Mini-Mental State examination, the Iowa Screening Battery for Mental Decline, and, for comparison, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale. The primary objective of the analysis was to test for a significant heritable component to performance on these measures. A secondary objective was to determine the extent to which shared variance with significant confounders such as education, age, and depression affects the outcome of the heritability analysis. Results indicate that performance on tests intended to measure cognitive decline in the elderly does have a significant genetic component and that these estimates tend to increase after adjustment for covariates. Heritability estimates adjusted for covariates were 30% for the Iowa Screening score, 60% for the Mini-Mental State score, and 67% for the Digit Symbol Substitution score.

Age Factors↗
PubMed1990

Family history of ischemic heart disease with respect to mean twin-pair cholesterol and subsequent ischemic heart disease in the NHLBI twin study.

This study examines the independent and interactive effects of family history scores (FHxS) for the prevalence of ischemic heart disease with plasma lipids and subsequent morbidity and mortality from ischemic heart disease. FHxS were calculated for 514 sets of middle aged male twins who participated in the entry examination of the NHLBI Veteran twin study in 1969-1973. Comparison of the FHxS with the level of plasma total cholesterol and HDL cholesterol (HDLc) paralleled earlier reported findings in young adults; individuals with high total cholesterol in two exams 8-12 years apart had significantly (P less than .01) higher FHxS. The same relationship was noted when using the mean twin-pair cholesterol level at the initial exam when the twins were in their 40s. Using the pair means over two exams as the cotwins aged into their 50s, the association of FHxS with total cholesterol declined and pairs with HDLc persistently in the highest quintile at both exams had significantly (P less than .01) lower FHxS. The changes in the pattern of association of lipid fractions with FHxS with age parallel the reported age decline of total cholesterol as a risk factor for heart disease. Assessment of ischemic heart disease events up to January 1988 revealed a highly significant association (P less than .0001) of later ischemic heart disease events with FHxS. At each level of lipid categorization pairs who later had events had higher FHxS than those without any subsequent heart disease; these differences were significant in all but the low risk lipid groups (low total cholesterol, high HDLc, and low total cholesterol/HDLc ratio). We conclude that FHxS is related to total cholesterol and HDLc but also is an independent predictor of subsequent ischemic heart disease after 14-18 years of follow-up.

Adult↗
PubMed1990

Dietary protein and blood pressure in monozygotic twins.

Cross-sectional studies relating blood pressure to dietary intake have shown equivocal results, in part due to the inability to take into account the strong genetic component of blood pressure. Intervention studies, using the same subject as his own control, often encounter additional problems when subjects are asked to adhere to an alternate diet. The National Heart, Lung, and Blood Institute Twin Study of middle-aged men provided information concerning the possible relationship of food-frequency-estimated nutrient intake to blood pressure while controlling for genetic effects in a free-living group of subjects. Using differences in monozygotic twins, a direct association of dietary protein intake and diastolic blood pressure was identified and persisted after adjustment for known covariates of blood pressure. Adjusting for known covariates and holding total calories constant, a 9-g difference in daily protein intake was directly associated with a 1 mm Hg difference in diastolic blood pressure. For protein intake as a percentage of total calories, a 2.18% difference was directly associated with a 1 mm Hg difference in diastolic blood pressure. The co-twin-control method provides a powerful design to address the interrelationships between nutrients and blood pressure in an observational as well as an experimental setting.

Adult↗
PubMed1990

Smoking and alcohol consumption in adult male twins: genetic heritability and shared environmental influences.

This paper examines the heritability of cigarette smoking and alcohol consumption in 360 adult, male twin pair participants (176 monozygotic and 184 dizygotic pairs) in the second exam of the National Heart, Lung, and Blood Institute's Twin Study. Heritability estimates for smoking and alcohol use were calculated both before and after adjustment for shared variance between these behaviors and other characteristics, including coffee consumption, contact between twins, and two psychological traits: anger and activity. The purpose of the analysis was to determine the impact of adjustment for covariates on heritability estimates of smoking and alcohol use. Before adjustment, heritability of both smoking and alcohol use was highly significant and accounted for 52% and 60% of the variance, respectively. After adjustment for covariates, the heritability of smoking remained at 52% while that for alcohol use decreased to 43%. The fact that these estimates remained significant after adjustment for covariates leads to increased confidence about the role of genetics in both smoking and alcohol consumption.

Aged↗
PubMed1990

Heritability of substance use in the NAS-NRC Twin Registry.

This study examines the heritability of cigarette smoking, alcohol, and coffee consumption in 4,960 adult, male twin pairs (2,390 MZ and 2,570 DZ pairs) participants in an epidemiologic survey of the NAS-NRC Twin Registry conducted in the USA during 1972-73. Heritability estimates for smoking, alcohol and coffee use were calculated both before and after adjustment for shared variance between these behaviors and other demographic characteristics including socioeconomic status and an occupational adjustment score. The objective of the analysis was to determine the impact of adjustment for covariates on heritability estimates of smoking, alcohol and coffee use. Before adjustment, genetic effects in smoking, alcohol and coffee use accounted for 53%, 36%, and 45% of the variance, respectively. After adjustment, the corresponding estimates were 35%, 29%, and 36%. The fact that these estimates remained significant after adjustment for covariates leads to increased confidence about the role of genetic factors in substance use behaviors.

Alcoholic Beverages↗
PubMed1990

Nongenetic influences of obesity on other cardiovascular disease risk factors: an analysis of identical twins.

The importance of genetic influences on obesity has been emphasized recently. We conducted matched co-twin analyses of 250 pairs of White, male, monozygotic twins from the National Heart, Lung, and Blood Institute (NHLBI) Twin Study. Entirely in the absence of genetic influences, obesity was significantly associated with systolic and diastolic blood pressures; one-hour, post-load glucose; total, LDL-, and HDL-cholesterol; and triglycerides among these 42-55 year old men. Similar results were obtained in longitudinal analyses of weight change during adulthood (from mean age of 20 to mean age of 48 years) and risk factor status at middle-age. These results indicate that behaviors and environmental exposures that occur later in life are responsible, at least in part, for the associations between adult obesity and cardiovascular disease risk, supporting the appropriateness of weight reduction efforts during adulthood.

Adult↗
PubMed1990

Genetic and behavioral influences on body fat distribution.

Genetic and environmental influences on four measures of body fat distribution - subscapular/triceps ratio (STR), waist/hip ratio (WHR), and regression-adjusted subscapular skinfold and waist circumference indices - were examined in 265 pairs of white male twins, ages 59 to 70 years, who participated in the third examination of the National Heart, Lung, and Blood Institute's Twin Study. Skinfold indices of fat distribution were not highly correlated with indices based on body circumferences (r = 0.26-0.37 for the four possible correlations). After adjustment for overall obesity, the heritability of the adjusted subscapular skinfold index was substantial (h2 = 0.60, P less than 0.001), as were estimates for both subscapular and tricep skinfolds individually. By contrast, heritability of the STR was low and of borderline statistical significance (h2 = 0.24, P = 0.06). Heritability for the WHR (h2 = 0.31, P = 0.07) was also low. Although higher estimates were observed for the adjusted waist circumference index (h2 = 0.46, P = 0.02) and for the component circumferences, these were not clearly due to genetic influences. Among behavioral influences, cigarette smoking was strongly related to the WHR and adjusted waist circumference index (P less than 0.0001). A crude measure of total physical activity was weakly, inversely related to WHR (P = 0.06), and slightly more strongly related to the adjusted waist circumference index (P = 0.01). Skinfold indices were unrelated to either behavior. We conclude that: (1) skinfold indices measure a different dimension of fat distribution than circumference indices; (2) there is evidence for a genetic influence on subcutaneous fat distribution, but less evidence for such an influence on the WHR; (3) behavioral factors appear to be more important in determining the WHR than subcutaneous fat patterning.

Adipose Tissue↗
PubMed1989

HLA associations with obesity.

A subgroup of 351 subjects with human leukocyte antigen (HLA) typing were available from the Framingham Heart Study for analyses to identify associations with obesity. The subjects consisted of 143 males and 208 females aged 58-88 years at the 15th biennial examination in 1978. The obese classification was based on maximum body mass index (BMI) over the 16 available biennial examinations of the Framingham Heart Study. The subjects were classified as obese if they exceeded the 95th percentile of BMI for 20- to 29-year-old subjects as described in the NHANES II study; males were obese if BMI greater than 31.1 and females were obese if BMI greater than 32.3. There were 27 obese males (18.9%) and 44 obese females (21.2%) in the sample. Gene frequencies were compared between the nonobese and obese groups for the pooled sample as well as by sex. Among alleles previously shown to be related to obesity, HLA Bw35 appeared to be more frequent in obese females but these data did not confirm a difference for the B18 or Cw4 alleles. More importantly, HLA Aw30 was found to be significantly higher among the obese subjects in both males and females. Further analyses adjusting for potential confounding variables reduced the estimated relative risk for obesity for subjects with the Bw35 allele to approximately 1.30 and no longer significant for this sample size. In contrast, the relative risk for Aw30, while reduced, remained significant after adjustment for confounding variables. Based on these data, individuals with the Aw30 allele have a relative risk of 2.61 for obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Evidence of genetic influence on central body fat in middle-aged twins.

The heritability of centrally and peripherally deposited subcutaneous body fat, as measured by thickness of subscapular and triceps skinfolds respectively, was examined in 173 monozygotic and 178 dizygotic pairs of white male twins, ages 54 to 65 years, who participated in the second examination of the National Heart, Lung, and Blood Institute's Twin Study. The heritability of two indices of body fat distribution (subscapular/triceps ratio and subscapular-triceps difference) and two indices of overall obesity (body mass index and sum of skinfolds) were also assessed. Evidence for a genetic influence on central deposition of body fat was suggested in that the classical estimate of heritability for subscapular skinfold thickness was 0.77 (p less than 0.0001). After adjusting subscapular skinfold for the overall level of obesity, heritability was reduced but remained highly significant (0.40, p = 0.003). Heritability estimates for triceps skinfold thickness and for the two fat distribution indices were substantially lower and were not statistically significant after adjustment for overall obesity. High classical estimates of heritability were also observed for both measures of overall obesity: 0.70 for BMI and 0.73 for sum of skinfolds. However, these two estimates were biased upward because of lower total variances among monozygotic compared to dizygotic twins in this sample. The more conservative and unbiased among-component estimates also suggested substantial heritability for each measure (0.35, p = 0.08 and 0.53, p = 0.01, respectively). The heritability of overall obesity emphasizes the importance of adjusting measures of fat distribution for overall obesity before assessing its heritability.

Adipose Tissue↗
PubMed1988

Characteristics of participants and nonparticipants in the NHLBI Twin Study.

The NHLBI Twin Study is a longitudinal study of cardiovascular disease risk factors in 514 pairs of white, middle aged, male, veteran twins. The initial examination took place between 1969-1973. Ten years later, 81% of the living cohort returned for a second examination. Data collected up to 30 years prior to recruitment for the initial examination were used to characterize participants and nonparticipants; data from the initial examination were used to characterize returnees and nonreturnees to the second examination. Participants had significantly lower diastolic blood pressure and higher socioeconomic status than nonparticipants as measured thirty years earlier. Between the first and second examinations, the mortality of participants was less than 50% of the mortality of nonparticipants. Returnees to the second examination had a better health profile at the initial examination than nonreturnees, with significantly lower levels of cigarette smoking, glucose intolerance, hypertension, and diabetes and higher levels of pulmonary function. However, returnees were more obese than nonreturnees. Thus, this study of cardiovascular disease risk factors in twins appears to be affected by response bias in a way similar to studies of individuals. Additional analyses of biases that may affect the genetic component of the study indicated that factors related to classical twin analyses were relatively unaffected by selection.

Analysis of Variance↗
PubMed1985

Drinking water source and mortality in US cities.

An apparent excess risk of all-cancer mortality among 473 of the largest US cities was found in relation to surface drinking water supplies. The increased risk for 100% surface water versus 100% ground water use was slight, about 2%, but statistically significant. This finding agrees with reports from several earlier studies in smaller geographical regions of the US, Great Britain and Canada. A relationship was further supported by the replication of this association within the larger of the 11 independent regions studied. Our data suggest that the association with surface water may be specific to cancer mortality. The increased risk would be expected to be greater than 2% if analyses were restricted to cancers of sites previously related to the use of surface drinking water.

Carcinogens, Environmental↗
PubMed1983

Weight and hypertension.

Both excess weight and hypertension may contribute independently to increased risk of cardiovascular disease. Weight and blood pressure have been found to be associated in most studies in diverse populations. The increase or decrease of blood pressure with weight gain or loss suggests a causal relation, although the mechanism is uncertain. A correlation between blood pressure and weight can be identified early in life. This correlation coefficient increases to approximately 0.4 in young adults and then begins to decrease at older ages. It is likely that weight interacts with various factors controlling blood pressure at different points over a lifetime. The implications for prognosis or control of blood pressure at different ages may vary as well. Attention to minimizing weight gain at a particular period of life, such as in young adulthood, might have long-term beneficial effects in preventing subsequent hypertension or excess blood pressure increase with aging.

Adolescent↗
PubMed1982

Genetic and environmental influences on pulmonary function in adult twins.

As part of the NHLBI Twin Study, pulmonary function tests were successfully administered to 127 monozygotic and 141 dizygotic white male twin pairs 42 to 56 yr of age. Values for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were obtained using a standardized protocol for spirometry. Initial twin analyses showed significant genetic variance (p less than 0.001) for both FVC and FEV1, whether or not adjustments were made for individual differences in age and body size. After adjustment, heritability estimates were 0.91 and 0.77 for FVC and FEV1, respectively. Further analyses indicated that the observed heritability of FVC resulted from the effects of pack-years of smoking as well as from genetic factors related to body size. These findings suggest that there were no other significant genetic determinants of FVC. In contrast, heritability of FEV1 could not be explained by constitutional factors, such as height and weight, or by cigarette smoking or propensity for cardiopulmonary disease symptoms. Additional analyses were done based on frequency of twin contact, which served as an indirect measure of environmental similarity between cotwins. Results suggested that there was a shared environmental variation in FEV1, as well as genetic variation, that could not be attributed to subpopulation differences in measured characteristics. The findings of this study are consistent with theories of genetic influences on alveolar and airway development and argue in favor of early as well as adult environmental influences on pulmonary function.

Adult↗