Alcohol consumption and risk of intermittent claudication in the Framingham Heart Study.

BACKGROUND: Intermittent claudication (IC) is associated with an increased risk of cardiovascular disease morbidity and mortality. The relation of alcohol consumption to the risk of IC remains controversial. The purpose of this study was to assess the relation of alcohol consumption and type of beverage to the development of IC among participants in the Framingham Heart Study. METHODS AND RESULTS: Alcohol consumption was categorized as 0, 1 to 6, 7 to 12, 13 to 24, and >/=25 g/d. During a mean follow-up of 6.8 years, 414 subjects developed IC. From the lowest to the highest category of alcohol intake, the age-standardized incidence rates of IC were 5.3, 4.1, 4.2, 3.2, and 4.6 cases/1000 person-years for men and 3.4, 2.5, 1.5, 1.9, and 2.5, respectively, for women. A multivariate Cox regression model demonstrated an inverse relation, with the lowest IC risk at levels of 13 to 24 g/d for men and 7 to 12 g/d for women compared with nondrinkers; the hazard ratio (95% CI) was 0.67 (0.42 to 0.99) for men and 0.44 (0.23 to 0.80) for women. This protective effect was seen mostly with wine and beer consumption. CONCLUSIONS: Our data are consistent with a protective effect of moderate alcohol consumption on IC risk, with lowest risk observed in men consuming 13 to 24 g/d (1 to 2 drinks/d) and in women consuming 7 to 12 g/d (0.5 to 1 drink/d).

Alcohol consumption and hemostatic factors: analysis of the Framingham Offspring cohort.

BACKGROUND: Moderate alcohol consumers have lower rates of cardiovascular disease than abstainers. One proposed mechanism is a beneficial effect on hemostatic parameters, but previous studies have provided conflicting results. METHODS AND RESULTS: We measured levels of fibrinogen, plasma viscosity, von Willebrand factor, factor VII, plasminogen activator inhibitor antigen-1, and tissue plasminogen activator antigen in a cross-sectional analysis of 3223 adults free of cardiovascular disease enrolled in the Framingham Offspring Study. We assessed their alcohol consumption with a standardized questionnaire. Light-to-moderate alcohol consumption was associated with lower levels of fibrinogen, plasma viscosity, von Willebrand factor, and factor VII. This association was most pronounced for consumers of 3 to 7 drinks weekly for viscosity and 7 to 21 drinks weekly for the other hemostatic measures. Alcohol intake of 7 to 21 drinks weekly or more was associated with impaired fibrinolytic potential, reflected by higher levels of plasminogen activator inhibitor antigen-1 and tissue plasminogen activator antigen. Wine drinkers had lower plasminogen activator inhibitor antigen-1 levels than other drinkers, particularly at 3 to 21 drinks weekly, but beverage type did not otherwise consistently affect the results. CONCLUSIONS: Light-to-moderate alcohol consumption is associated with lower levels of coagulatory factors, but higher intake is associated with impaired fibrinolytic potential. These findings are consistent with the hypothesis that a balance between hemostatic and fibrinolytic activity may contribute to the complex relation of alcohol use with coronary heart disease.

Lack of association between skin tags and colon polyps in a primary care setting.

Cutaneous skin tags (acrochordons) have recently been proposed as markers for adenomatous polyps of the colon among symptomatic patients referred for colonoscopy. To ascertain the utility of skin tags as a predictor of colonic polyps in a primary care setting, 492 patients, with a mean age of 58 +/- 13.3 years (241 with signs or symptoms and 251 for screening), were evaluated for the presence of skin tags and then examined using a 60-cm fiberoptic sigmoidoscope by an examiner "blinded" to the skin findings. Among patients with skin tags, 23 (10.2%) of 226 had polyps, whereas among patients without skin tags, 20 (7.5%) of 266 had polyps. The predictive value of the presence of a skin tag was 10.2%. Contrary to studies done in more selected populations with a higher prevalence of adenomatous polyps, the results using a 60-cm flexible sigmoidoscope in a primary care population suggest that cutaneous skin tags are not a marker for adenomatous polyps of the colon.

Physician attitudes toward cost containment. The missing piece of the puzzle.

A survey of 720 physicians practicing in central and western Massachusetts was undertaken to examine their attitudes toward cost-containment measures. The majority of physicians felt that major techniques (58%), major procedures (57%), inappropriate ordering of diagnostic tests (48%), and malpractice concerns (47%) were very important contributors to increasing health care costs. Physician age, practice affiliation, and specialty area were related to the perceived importance of these factors. In addition, while there was a uniform lack of prior training in cost-containment measures, 48% of all physicians felt that courses in cost-containment techniques would be worthwhile. These results suggest a variety of concerns and issues that need to be considered when attempting to modify the cost-containment attitudes and practices of physicians.

Obesity, sodium intake, and blood pressure in adolescents.

It has been postulated that increased dietary sodium associated with greater food intake by obese people is a mechanism for the relationship between obesity and blood pressure (BP). We have evaluated this hypothesis by exploring the interrelationships of measures of obesity, sodium intake, and BP in 248 "normal" adolescents, 16 to 17 years of age. As an index of sodium intake, the sodium excretion in three overnight urine collections was used. As a more specific index of saltiness of diet, we used a ratio of sodium excretion to calorie intake, with calories estimated from 3-day diet records and dietary interview. Body weight and other measures of obesity showed a positive relationship with systolic blood pressure (SBP), but not with diastolic (K5) blood pressure (DBP5). Measures of overnight sodium excretion were positively correlated with body weight and calculated body fat percentage, suggesting that heavier people indeed ingest more sodium. This may result not from increased intake of food per se, but from increased saltiness of diet, since calorie intake did not increase with body weight. No significant relationships were found between BP and concurrent measures of sodium excretion or diet saltiness.

Glycosylated hemoglobins and long-term blood glucose control in diabetes mellitus.

The glycosylated minor hemoglobin components Hb A1a+b and HbA1c are elevated in insulin-dependent juvenile diabetic patients, 3.2+/-0.7 (+/-1 SD) and 10.0+/-1.9% of total hemoglobin respectively, versus 2.1+/-0.4 and 4.9+/-0.7% in a normal non-diabetic control population. Total glycosylated hemoglobin components, Hb A1a+b+c, correlated with the degree of diabetic blood glucose regulation as measured by antecedent 24-h urinary glucose excretion determined in 220 diabetic patients immediately before, 1, 2, and 3 months prior to the HB A1a+b+c measurement. This assay for long-term blood glucose regulation was utilized to determine the effect of hyperglycemia on plasma cholesterol levels in 112 diabetic patients. Hb A1a+b+c levels correlated with plasma cholesterol levels, suggesting that long-term hyperglycemia is associated with hypercholesterolemia. It is suggested that glycosylated hemoglobin measurement is a good index of long-term blood glucose levels in diabetic patients.

Alcohol in the Mediterranean diet.

Alcohol consumption clearly reduces risk of cardiovascular disease (CVD) in populations throughout the world and may contribute to lower rates of CVD among residents of Mediterranean countries. In addition, overall mortality rates are generally slightly lower among moderate drinkers than among abstainers. However, several studies have linked alcohol consumption (even amounts equivalent to two drinks daily) to increased rates for certain cancers, especially breast cancer in women. A Mediterranean diet, which is high in fruit, vegetables, and grains, also typically includes one to two drinks per day. Whether one to two drinks adversely affect cancer incidence in the presence of a Mediterranean diet has not been fully explored. With the evidence currently available, we conclude that alcohol, when consumed responsibly in most populations, is an important component of the Mediterranean diet and a component of a healthy lifestyle.

Relation between dietary fiber consumption and fibrinogen and plasminogen activator inhibitor type 1: The National Heart, Lung, and Blood Institute Family Heart Study.

Considerable evidence suggests that high plasma concentrations of plasminogen activator inhibitor type 1 (PAI-1) and fibrinogen increase the risk of cardiovascular disease. Recent studies report beneficial effects of dietary fiber on coronary artery disease, although the mechanisms by which high fiber intake reduces the risk of heart disease are not well understood. This study examined the relation of dietary fiber intake to PAI-1 and fibrinogen concentrations in 883 men and 1116 women aged 50.4 +/- 13.8 and 52.1 +/- 13.7 y, respectively, in the National Heart, Lung, and Blood Institute Family Heart Study. Diet was assessed with a semiquantitative food-frequency questionnaire. The natural logarithm was used to transform PAI-1 because of a skewed distribution. In the first through fifth age- and energy-specific quintiles of fiber intake, mean (ln)PAI-1 was 6.09, 5.91, 5.88, 5.82, and 5.67 pmol/L, respectively, for men and 5.50, 5.37, 5.39, 5.23, and 5.18 pmol/L, respectively, for women. Multiple regression showed that when the lowest was compared with the second, third, fourth, and fifth age- and energy-specific quintiles of fiber intake, (ln)PAI-1 was 0.21, 0.25, 0.22, and 0.32 pmol/L lower in men (P for trend = 0.009) and 0.08, 0.06, 0.14, and 0.20 pmol/L lower in women (P for trend = 0.037), respectively, with anthropometric, lifestyle, and metabolic factors adjusted for. No significant association was found between fiber intake and fibrinogen. Waist-hip ratio did not modify the relation of fiber intake to PAI-1 (P for interaction = 0.39 for men and 0.36 for women). These data suggest that higher fiber intake is inversely associated with PAI-1, but not with fibrinogen concentration.

Relation between dietary linolenic acid and coronary artery disease in the National Heart, Lung, and Blood Institute Family Heart Study.

BACKGROUND: Epidemiologic studies suggest that a higher consumption of eicosapentaenoic acid and docosahexaenoic acid is associated with a reduced risk of cardiovascular disease. Studies in humans and animals also reported an inverse association between alpha-linolenic acid and cardiovascular disease morbidity and mortality. OBJECTIVE: We examined the relation between dietary linolenic acid and prevalent coronary artery disease (CAD). DESIGN: We studied 4584 participants with a mean (+/-SD) age of 52.1 +/- 13.7 y in the National Heart, Lung, and Blood Institute Family Heart Study in a cross-sectional design. Participants' diets were assessed with a semiquantitative food-frequency questionnaire. For each sex, we created age- and energy-adjusted quintiles of linolenic acid, and we used logistic regression to estimate prevalent odds ratios for CAD. RESULTS: From the lowest to the highest quintile of linolenic acid, the prevalence odds ratios of CAD were 1.0, 0.77, 0.61, 0.58, and 0.60 for the men (P for trend = 0.012) and 1.0, 0.57, 0.52, 0.30, and 0.42 for the women (P for trend = 0.014) after adjustment for age, linoleic acid, and anthropometric, lifestyle, and metabolic factors. Linoleic acid was also inversely related to the prevalence odds ratios of CAD in the multivariate model (0.60 and 0.61 in the second and third tertiles, respectively) after adjustment for linolenic acid. The combined effect of linoleic and linolenic acids was stronger than the individual effects of either fatty acid. CONCLUSIONS: A higher intake of either linolenic or linoleic acid was inversely related to the prevalence odds ratio of CAD. The 2 fatty acids had synergistic effects on the prevalence odds ratio of CAD.

Parent-child relationships in nutrient intake: the Framingham Children's Study.

Nutrient intake affects many of the identified risk factors for coronary heart disease (CHD). Although CHD risk factors have been shown to aggregate within families, less is known about the familial aggregation of nutrient intake. We analyzed diet records for an average of 9 d per subject on 87 mothers, 83 fathers, and 91 children aged 3-5 y. A statistically significant but modest correlation (r less than 0.50) was found between parents' and children's intakes for most nutrients. The intake of nutrients was more strongly related between mothers and children than between fathers and children, and there was a stronger association with children's values for parents consuming more meals at home. The results of this study confirm that parents' eating habits have an impact on the nutrient intake of their preschool children; the study furnishes indirect support for dietary-intervention programs targeting families for the primary prevention of CHD.

Effects of alterations in fatty acid intake on the blood pressure of adolescents: the Exeter-Andover Project.

To judge the effect on blood pressure, the ratio of polyunsaturated to saturated fatty acids (P:S) of foods served to students at two boarding high schools was modified alternately at each school for one school year. The average P:S of the diet of males increased from 0.53 to 0.93 during the intervention whereas among females it increased from 0.64 to 0.98. Comparison of repeated systolic and diastolic blood pressure measurements near the end of the school year did not demonstrate a beneficial effect of the dietary fat changes on the blood pressure of these normotensive adolescents. Compared with the blood pressure patterns during control years, the dietary intervention resulted in slightly higher systolic (+0.88 mm Hg; 95% CI -0.66, +2.42) and diastolic (+1.23 mm Hg; 95% CI = +0.04, +2.42) blood pressure readings among males. Among females the intervention resulted in slightly lower systolic (-0.54 mm Hg; 95% CI = -1.95, +0.88) and diastolic (-0.80 mm Hg (95% CI -2.18, +0.58) blood pressure readings.

Plasma homocysteine and its association with carotid intimal-medial wall thickness and prevalent coronary heart disease: NHLBI Family Heart Study.

Mildly elevated plasma total homocysteine (tHcy) levels have been associated with increased risk of coronary heart disease (CHD). Carotid artery intimal-medial wall thickening is a predictor of cardiovascular disease and has been previously shown to be positively associated with plasma tHcy in studies of asymptomatic subjects. In the current study we examined 1467 subjects with regard to their fasting plasma tHcy levels and intimal-medial wall thickness as measured by B-mode ultrasound and early onset CHD. The results showed that there is a significant positive association between plasma tHcy levels and carotid-artery wall thickness in participants 55 years or older even after the tHcy levels are adjusted for age, smoking and anti-hypertensive medication. The direction and magnitude of the relationship is similar although the result was not statistically significant in younger participants ( < 55 years). Early onset CHD at any age was not significantly different across the tHcy quintiles. The lack of an association of tHcy and CHD in the presence of a positive association with intimal-medial wall thickening may be a reflection of increased statistical power of quantitative versus qualitative traits. We conclude that the present finding of a positive association between tHcy and intimal-medial wall thickness strengthens the in vitro finding of the stimulating effect of homocysteine on vascular smooth muscle cell growth. Vascular smooth muscle cell proliferation may be an important mechanism through which mildly elevated plasma tHcy promotes atherosclerosis.

Post-methionine load hyperhomocysteinemia in persons with normal fasting total plasma homocysteine: initial results from the NHLBI Family Heart Study.

Hyperhomocysteimia, either fasting or after oral methionine loading, appears to be an independent risk factor for coronary heart disease (CHD). It remains unclear whether fasting total homocysteine determination alone adequately detects the full spectrum of hyperhomocysteinemic individuals. We measured fasting and 4-h post methionine loading (0.1 g L-methionine/kg body weight) total plasma homocysteine in 274 participants in The NHLBI Family Heart Study, a population-based investigation of genetic and non-genetic determinants of CHD. Of the total number (n = 47) of hyperhomocysteinemic persons, 43% (20/47) were identified only by methionine loading, while 32% (15/47) of the total number, and 75% of those with post-methionine loading hyperhomocysteinemia only (15/20), had fasting total homocysteine concentrations below the 75th percentile (10.7 mumol/l). We conclude that fasting total plasma homocysteine determination alone fails to identify a sizable percentage (> 40%) of persons who may have clinically relevant hyperhomocysteinemia post methionine loading.

Influence of leisure time physical activity and television watching on atherosclerosis risk factors in the NHLBI Family Heart Study.

Physical activity favorably influences atherosclerosis risk factors but only a few studies in adults considered the time watching television (TV) as a measure of physical inactivity. We therefore determined in a population-based sample of 1778 subjects from the NHLBI Family Heart Study (FHS) whether leisure time physical activity and TV watching have independent or interactive associations with cardiovascular disease risk factors and carotid artery intima-media wall thickness (IMT). Subjects were free from diabetes mellitus and clinically-ascertained coronary artery disease and did not take lipid-lowering or antihypertensive drugs. Only 0.7 and 1.3% of the variance in leisure time physical activity in women and men, respectively, was explained by the amount of TV watching. Leisure time physical activity had a clearly favorable, and TV watching an unfavorable association with anthropometric measurements (BMI (body mass index), waist girth, waist-hip ratio, subscapular and triceps skinfold thickness). The odds ratio (95% CI) of being overweight was 0.41 (0.28-0.62) in women and 0.69 (0.46-1.04) in men in the highest quartile of leisure time physical activity compared to the lowest quartile. The odds ratio increased for increasing quartiles of TV watching to 2.12 (1.45-3.10) in women and 1.61 (1.07-2.43) in men. Watching TV only 1 h per day in women with a BMI of 30 kg/m2 and doing about 75 min of moderate exercise per week was associated with a BMI 1.8 kg/m2 lower than in women watching TV 3 h per day and doing the same amount of exercise. Those with twice the amount of moderate exercise and watching TV 1 h per day had a BMI 0.45 kg/m2 lower. Furthermore, leisure time physical activity was negatively associated with concentrations of triglycerides and positively with HDL cholesterol in both genders. TV watching was significantly positively associated with triglycerides and slightly negatively with HDL cholesterol in men. The observed associations of leisure time physical activity and TV watching with atherosclerosis risk factors were independent from each other. Finally, we analyzed the relation between leisure time physical activity, TV watching and the degree of IMT of the carotid arteries. Neither of these two measures was significantly associated with IMT. In summary, TV watching, in addition to leisure time physical activity, shows an independent association with obesity-related anthropometric measurements, HDL and triglycerides. Decreasing the amount of TV watching might be effective as a first step in reducing atherosclerosis risk factors, especially overweight.

Risk factors for retrolental fibroplasia: experience with 3,025 premature infants. National Collaborative Study on Patent Ductus Arteriosus in Premature Infants.

The rate of retrolental fibroplasia in relation to prenatal and neonatal characteristics was explored on the basis of a cohort of 3,025 neonates with birth weight less than 1,750 g. The overall rate of retrolental fibroplasia of any degree at hospital discharge was 11%, varying from 43% for those with birth weight between 500 and 749 g to 3% for those in the 1,500- to 1,750-g category. Among the potential determinants, the main interest was in nonhyperoxic characteristics, conditional on measures of prematurity and oxygen supplementation. Maternal diabetes and antihistamine use during the last 2 weeks of pregnancy were associated with significantly higher rates of retrolental fibroplasia, whereas toxemia was associated with lower rates. Frequent apneic spells, bronchopulmonary dysplasia, and sepsis in the neonate were also associated with significantly higher rates. On the other hand, the data indicate no independent role of low Apgar score, intraventricular hemorrhage, exchange transfusion, patent ductus arteriosus, or certain other characteristics previously postulated as risk factors.

Electrocardiogram of the premature infant at 1 year of age.

ECGs were examined from 461 premature infants at 1 year of age. Data from those without a history of bronchopulmonary dysplasia were generally similar to published norms for healthy 1-year old infants. History and persistence of residual lung disease were reflected in the ECG by a high prevalence of findings suggestive of right ventricular hypertrophy. Clinically significant patent ductus arteriosus during the neonatal period did not influence the 1-year ECG findings. The data expand the published experience with follow-up ECGs from premature infants and suggest that the ECG may be a useful tool in follow-up of chronic residual lung disease in this population.

Evaluation of the preterm infant for patent ductus arteriosus.

As a first step in a multicenter, collaborative project to study the role of indomethacin in the management of patent ductus arteriosus in premature infants, a diagnostic scheme was developed, on an a priori basis, by a consensus of the participating neonatologists and pediatric cardiologists. The scheme, which utilizes clinical and noninvasive findings, was designed to detect infants with a "hemodynamically significant" patent ductus arteriosus (PDA). Among 1,689 infants with birth weight less than 1,750 g who were monitored during the first year of the study, 342 (20.2%) met the criteria for PDA. Rates were higher for smaller infants (42% with birth weight less than 1,000 g) than for larger infants (7% with birth weight 1,500 to 1,750 g). Although study protocol did not require a direct procedure to confirm the diagnosis of PDA, a marked decrease in the presence of most criteria was noted following surgical ligation of the ductus. Although the echocardiographic criterion (ratio of left atrium to aorta [LA/Ao] greater than or equal to 1.15) proved to have a low specificity for PDA, the data suggest that the overall scheme led to a very low rate of false-positive diagnosis. Following the application of the scheme for 1 year at 13 clinical centers, it has been shown to be a highly acceptable means of detecting infants with PDA.

Echocardiographic characteristics of premature infants with patient ductus arteriosus.

As part of a multicenter collaborative study, M-mode echocardiograms were obtained shortly after birth on 3,559 premature infants with birth weight less than or equal to 1,750 g. Of these infants, 1,496 did not develop a cardiac murmur or other signs of a "hemodynamically significant" patent ductus arteriosus (PDA). Echocardiographic parameters from this "normal" group were compared with results obtained from 415 infants in whom PDA was diagnosed on the basis of clinical findings alone, irrespective of the echocardiogram (PDA group). The best discrimination between the two groups, when considering a single parameter, was provided by a left atrial to aortic root ratio (LA/AO) of 1.40, a left ventricular to aortic root ratio (LV/AO) of 2.10, or a left ventricular systolic time interval ratio (LPEP/LVET) of 0.27. Multivariate analysis demonstrated that better separation between the two groups occurred when the left atrial to aortic root ratio and the left ventricular systolic time interval ratio were considered jointly. Because of a large degree of overlap of all echocardiographic variables between the normal group and the group with PDA, the echocardiogram alone was not a good indicator of PDA. However, when used in conjunction with a priori estimates of the probability of PDA (based, for example, on birth weight and degree of respiratory disease), use of echocardiographic data was found to improve the detection of hemodynamically significant patent ductus arteriosus in premature infants.

Lewis blood group phenotype as an independent risk factor for coronary heart disease (the NHLBI Family Heart Study).

In the Copenhagen Male Study, men with Lewis blood group phenotype Le(a-b-) were found to have increased risk for coronary heart disease (CHD); such a relation has not been confirmed in men, and has not been evaluated in women. In the NHLBI Family Heart Study, we determined the Lewis blood type of 1,620 white subjects (790 male and 830 female subjects). The Lewis(a-b-) phenotype was found in 142 subjects (8.8%), 6.3% of subjects from randomly chosen families and 9.7% of subjects from families found to be at high risk for CHD. A history of CHD was present in 39.1% of men with Le(a-b-) versus 27.2% of men with other Lewis types; for women, the corresponding numbers were 12.3% versus 9.4%, respectively. In multivariate analysis, adjusting for age, sex, and risk group, the odds ratio for CHD was 2.0 (95% confidence interval = 1.2 to 3.1) for Le(a-b-) versus other Lewis groups. Mean values for body mass index, blood pressure, total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol, glucose, insulin, homocysteine, and fibrinogen were not significantly different between Le(a-b-) subjects and others, but triglycerides (p = 0.002) were higher in the Le(a-b-) subjects. However, inclusion of all risk factors in multivariate analysis did not diminish the increased risk for CHD associated with the Le(a-b-) phenotype. We conclude that the Le(a-b-) phenotype is associated with an increased risk for CHD; its effect does not appear to act predominantly through conventional cardiovascular risk factors. At present, mechanisms of effect are unknown.

Hostility, social support, and coronary heart disease in the National Heart, Lung, and Blood Institute Family Heart Study.

This cross-sectional study investigated the association of hostility and social support to coronary heart disease (CHD) in 2 groups of men and women: those with a familial predisposition for CHD (high-risk sample) and a randomly selected group. The hypothesis was that hostility and low social support would be associated with CHD, and would have a greater effect in the high-risk group. The random sample contained 2,447 individuals (47.1% male) from 576 families, and the high-risk sample consisted of 2,300 people (45.5% male) from 542 families. Odds ratios (OR) and their 95% confidence intervals were calculated using generalized estimating equations (GEE) for logistic regression. Family was specified as the clustering variable, and robust SEEs were obtained to account for dependence of the data within families. After controlling for age, education, body mass index, exercise, smoking history, drinking history, and drinking >5 drinks a day, hostility was associated with a history of coronary bypass surgery or coronary angioplasty in high-risk men (OR 1.21) and a history of myocardial infarction in high-risk women (OR 1.39). High-risk women with high social support had reduced odds of a previous myocardial infarction (OR 0.76), whereas women with high network adequacy in the random sample had reduced risk of myocardial infarction (OR 0.41) and angina (OR 0.49). A ratio of high hostility to low social support was associated with past myocardial infarction in high-risk women (OR 2.47) and a history of angina (OR 2.02) in the random sample men. These results suggest that high hostility and low social support are associated with some manifestations of CHD after controlling for adverse health behaviors.