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The National Heart, Lung and Blood Institute (NHLBI) twin study is a collaborative, longitudinal study of the role of genetic risk factors on subsequent cardiovascular disease processes in 514 pairs of white, male World War II and Korean veteran twins born between 1917 and 1927. This paper describes the sampling procedures and zygosity determination at the initial examination, participation by the cohort members at later examinations, and a summary of the variables provided for Genetic Analysis Workshop 8 (GAW8).

The Strong Heart Study is a study of cardiovascular disease and its risk factors among diabetic and nondiabetic Native Americans. The study includes 12 tribes in Arizona, Oklahoma, and North and South Dakota. Phase I, initiated in October 1988, included a mortality survey to determine CVD death rates in individuals 35-74 yr old between 1984 and 1988, and a medical record review to determine rates of myocardial infarction and stroke for individuals ages 45-74 during the same time. In addition, a physical examination was performed on persons 45-74 yr old to measure the prevalence of cardiovascular and peripheral vascular diseases and known and suspected risk factors. In Phase II, CVD mortality and morbidity rates will be determined in the examined cohort by surveillance. CVD risk factors, changes in risk factors over time, and the relationship between risk factors and CVD incidence will be assessed longitudinally. This study provides data on the relative importance of cardiovascular risk factors in nondiabetic and diabetic Native Americans and will provide insight into possible variations in the quantitative or qualitative importance of CVD risk factors among diverse population groups.

The National Heart, Lung, and Blood Institute (NHLBI) Twin Study provided longitudinal data on a cohort of 514 pairs of adult male twin pairs who were examined at approximate ages of 48, 57, and 63 years. Because the sample was selected from military veterans, height and weight data were also available from their induction physical examinations when they were approximately 20 years of age. From the total NHLBI Twin Study cohort, 124 monozygotic and 119 dizygotic male twin pairs had complete data available for both members of the pair at induction and three examinations spanning 43 years of adult life. Using these data, the contributions of genetics and shared and non-shared environmental factors to BMI over the 43 year period were estimated by model fitting procedures. Model fitting included both a factor decomposition of these effects as well as a developmental path model. Results from the decomposition procedure indicate significant genetic effects at each examination cycle. Fitting a developmental path model, two independent genetic contributions to the variability of BMI were found: one at, or prior to, the induction examination about age 20, and a second between ages 20 and 48. Significant non-shared environmental contributions at each examination were also indicated, but shared environmental effects were not significant. We conclude that cumulative genetic effects explain most of the tracking in obesity over time; non-shared environmental effects, although significant at each age, are relatively short-lived and make only a minor contribution to tracking.

The present study examined the contribution of genetic factors to Digit Symbol performance and its decline in 23 monozygotic twin pairs (mean age at examination 1, 57.1 years) and 21 dizygotic twin pairs (mean age at examination 1, 56.3 years). These men were assessed twice during a 5-year interval as part of the National Heart, Lung, and Blood Institute Twin Study. The prevalence of decline (a change, greater than 1 SD) during the 5-year interval was 35% and 39% for monozygotic and dizygotic twins, respectively. The pairwise concordance for decline was 45% in monozygotic and 8% in dizygotic twin pairs, suggesting a possible role for genetic factors in the decline in Digit Symbol performance in this sample. A comparison of baseline biologic and behavioral characteristics within monozygotic twin pairs discordant for decline in Digit Symbol performance revealed that decliners had higher initial systolic blood pressures, lower serum cholesterol levels, and lower heart rates than nondecliners.

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.

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.

Maximal grip strength was measured in kilograms using a hand dynamometer on 344 unrelated males between the ages of 59 and 70 participating in the third examination of the NHLBI Twin Study. There was a significant linear decline in mean grip strength over this age range. Mean grip strength and grip strength per kilogram weight are presented for age 59, ages 60-64 and 65-69. Genetic analysis using 127 pairs of identical (MZ) twins and 130 pairs of fraternal (DZ) twins indicated significant genetic effects for absolute grip strength and grip strength per kilogram weight. The largest estimate of heritability (65%) was obtained for grip strength adjusted for significant effects of weight, height, age, and various anthropometric measures of fatness, muscle mass, and frame size.

Sixty cases of dyslipidemic hypertension were identified in the 1028 middle-aged, white, male twin participants in the first examination of the National Heart, Lung, and Blood Institute Twin Study (1969 to 1973). The prevalence of dyslipidemic hypertension was similar by zygosity but proband concordance was three times greater in monozygotic than dizygotic twins (0.44 [seven concordant and 18 discordant pairs] vs 0.14 [two concordant and 24 discordant pairs]), suggesting a genetic effect on the condition. Low high-density lipoprotein cholesterol level was the most common lipid abnormality in concordant pairs. Mortality from ischemic heart disease was significantly higher in individuals with dyslipidemic hypertension. Obesity and glucose intolerance were closely associated with the syndrome. Moreover, within the 18 discordant monozygotic twin pairs, the twins with dyslipidemic hypertension had gained significantly more weight as adults and were significantly heavier than their unaffected cotwins. Thus, although genetic factors may influence development of dyslipidemic hypertension, nongenetic, potentially modifiable aspects of obesity are also closely related to expression of this clinically important syndrome.

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.

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.

In the National Heart, Lung, and Blood Institute Twin Study, body mass index (BMI) was studied at military induction and at three subsequent examinations spanning five decades in a cohort of white, male World War II veterans. At military induction (1940s) and again at the first clinical examination of this study (1969-1973), there was close agreement of three commonly used estimates of heritability (range 0.72 to 0.80), and no evidence of a difference in total variance of BMI between the zygosities. However, at the last two examinations (1980s), the total variance in dizygotic (DZ) twins was significantly greater than that of monozygotic (MZ) twins (P less than 0.01) and these same heritability estimates varied widely. The among-pair estimate of heritability fell to unrealistic negative values, the within-pair estimate rose to values of 1.0 or greater, and the intraclass correlation coefficient estimate was slightly lower than in the entire cohort at baseline. The cause of the unequal zygosity total variance appears to have been nonparticipation at later examinations of MZ twins with extreme values of BMI, with no evidence of a similar selection process influencing DZ twins. This selection process biased the three estimates of heritability, making it difficult to determine which estimate is the most appropriate. Despite these biases, it remains clear that genetic factors contribute substantially to BMI in this population.

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.

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.

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.

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.

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.

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.

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.

Prehospital delay is considered to be an important cause of out-of-hospital coronary mortality. Behavior of patients and physicians in response to the symptoms of myocardial infarction (MI) or impending out-of-hospital death (OHD) was studied for 107 consecutive acute coronary events in Framingham, Mass. Delay due to inappropriate patient behavior was the most important component of total delay. Delay related to patient-physician contact occurred in two thirds of MI cases and was more than 30 minutes in half of these. Office visits and inappropriate triage by nurses and receptionists were important factors in physician delay. However, 60% to 75% of OHDs occur so rapidly that their prevention by reduction of prehospital delay seems impossible. A strategy for reduction of delay that might be of benefit in preventing some of the remaining OHDs is described.

In the NHLI Twin Study MZ twins are shown to "get together" substantially more often than DZ twins. With this result as an indicator of differences in shared environment, the assumption of equal shared environmental variation for MZ and DZ twins is assessed using nutritional data calculated from a food frequency questionnaire. Six nutrients show significant genetic variance for the total sample. However, when stratified on the basis of how frequently twins see each other, none of the nutrients shows significant genetic variance for both strata. A similar pattern is seen for several individual items from the questionnaire. In addition, four of the nutrients show significant correlation between the absolute difference in the nutrient intake of MZ twin pairs and how often they "get together." These data appear to show that unequal environmental effects may lead to falsely high estimates of genetic variance for nutrient intake.

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)

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.

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.

The Framingham Cardiovascular Disease Survey was undertaken to test the hypothesis that a short-term surveillance study of a defined population could yield incidence data comparable to those obtained by an elaborate longitudinal study of the same population, at a fraction of the cost. New cases of coronary heart disease (CHD), congestive heart failure (CHF) and stroke occurring from June 15, 1970 through June 14, 1971, were detected by monitoring admissions to hospitals and nursing homes, reporting of new events by local physicians and perusal of death certificates, Necessary data on each case were collected and reviewed by a panel of physicians using strict diagnostic criteria. Incidence rates based on 332 CHD or CHF events were calculated and were found to be consistent with findings of the Framingham Heart Study. A one-year community surveillance study is an economical and reasonably accurate method of determining the incidence of CHD and CHF.

Olfactory sensitivity to acetic acid, isobutyric acid, and 2-sec-butyl-cyclohexanone was tested in 97 adult male twin pairs to determine the extent to which variation in odor perception was genetically determined. Analysis of the data revealed no evidence for heritability of olfactory sensitivity. However, factors significantly associated with odor perception included cigar, pipe, and cigarette smoking; body fatness; alcohol consumption; and diabetes mellitus.

Fasting plasma triglycerides and cholesterol, as well as cholesterol in very low density, low density and high density lipoproteins, were measured in 250 MZ and 264 DZ adult male twin pairs. A new method was used to choose an estimate of genetic variance. This includes an estimate of genetic variance for use when the total variances of MZ and DZ twins are unequal. DZ twins had greater total variance for cholesterol. When genetic variance was estimated by subtracting the within-MZ-sets mean square from the within-DZ-sets mean square, all of the lipids had significant estimates of genetic variance; however, when genetic variance was estimated by a method designed to correct bias due to unequal total variances of MZ and DZ twins, only triglycerides had significant genetic variance. The heritability of plasma triglycerides was calculated to be 0.68.

Mortality trends from 1950 to 1970 were studied for 473 cities in the United States with populations of 25,000 or more in 1950, according to fluoridation status of their water supplies. Findings showed no relationship between fluoridation and observed changes in general mortality over the 20-year period. Also, no relationship was found between fluoridation and heart or cancer death rate trends.

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.

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.

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.