Tumor-associated antigen levels (carcinoembryonic antigen, human chorionic gonadotropin, and alpha-fetoprotein) antedating the diagnosis of cancer in the Framingham study.

Determinations of carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), and alpha-fetoprotein (AFP) were done by use of frozen serum samples antedating the diagnosis of cancer for 9 pancreatic and 8 gastric carcinoma patients from the Framingham Heart Study. The longest intervals for elevated antigens before cancer diagnosis were 10 months for CEA and 26 months for HCG. (The single elevated AFP was found in a sample 10 days before clinical diagnosis.) Samples from 31 controls matched with the cancer subjects by age, sex, vital capacity, and smoking status showed over 20% "false" positive CEA elevations (all smokers with low vital capacities) and over 20% borderline false positive HCG elevations in postmenopausal females. Although 10-26 months' lead time could infer some potential for use of these tumor-associated antigens to help detect malignant neoplasms at an earlier stage, a serious problem of frequent false positives prevents CEA and HCG levels from being useful as cancer-screening tests at this time.

Subarachnoid and intracerebral hemorrhage: natural history, prognosis, and precursive factors in the Framingham Study.

No uniformly accepted hypothesis explains the genesis and rupture of intracranial aneurysms. We followed 5,184 men and women prospectively for 26 years; 36 cases of aneurysmal subarachnoid hemorrhage (SAH) accounted for 62% of all intracranial hemorrhages. Blood pressure before SAH was higher in these patients than in controls. Definite hypertension (greater than or equal to 160 mm Hg and/or greater than or equal to 95 mm Hg) at entry to the study or at closest exam before SAH was more frequent than in controls. Cigarette smoking, particularly heavy smoking, was also more frequent among cases.

Cigarette smoking and HDL cholesterol: the Framingham offspring study.

High density lipoproteins were measured on fasting blood samples from 4107 men and women. Control for reported alcohol consumption and subscapular skinfold thickness using multiple regression analysis allowed an examination of the relationship between cigarette smoking and HDL cholesterol. Cigarette smoking was found to be associated with an average difference in HDL cholesterol of about 4 mg/dl in men and 6 mg/dl in women. Furthermore, when heavy alcohol drinkers were eliminated a significant negative association between number of cigarettes smoked and HDL cholesterol was demonstrable in both men and women. There was no evidence that former cigarette smokers, with the exception of those who switched to cigars or pipes or had quit less than one year, had lower HDL levels. Cigar or pipe smokers who had never smoked cigarettes had alcohol- and skinfold-adjusted HDL cholesterol comparable to the non-smoker. These observations indicate another possible link between inhaled tobacco smoke and the atherosclerotic process and suggest the need for further studies and experiments that might clarify the mutual relationship of HDL cholesterol, cigarette smoking and the atherosclerotic process.

Association of hyperestrogenemia and coronary heart disease in men in the Framingham cohort.

The serum levels of estradiol and testosterone as well as established risk factors for coronary heart disease were estimated in 61 men (mean age 70.0 +/- 6.4 [SD] years) with coronary heart disease and in 61 matched control subjects enrolled in the Framingham Heart Study. The mean serum estradiol level was significantly higher in the subjects with coronary disease (p = 0.011). This difference in estradiol level increased with the exclusion of subjects older than 75 years (p less than 0.001). The mean serum testosterone level was not significantly different. None of the established risk factors for coronary heart disease was different between subjects with coronary disease and control subjects except blood glucose level, which was higher in the subjects with coronary disease (p = 0.025). We conclude that hyperestrogenemia is an important correlate of coronary heart disease in men.

Risk factors for pulmonary embolism. The Framingham Study.

To assess potential long-term risk factors for major pulmonary embolism, 46 subjects from the Framingham Heart Study with autopsy-confirmed and clinically significant pulmonary embolism were identified in whom age, systolic blood pressure, cholesterol level, cigarette use, glucose level, Metropolitan relative weight, and varicose veins were ascertained at entry into the Study. These variables were compared among these 46 subjects, all 3,470 subjects in whom these variables were measured at the inception of the Study, and the 998 of these subjects who died within 26 years of follow-up. In multivariate analysis of subjects with autopsy-confirmed major pulmonary embolism and all subjects who died, only Metropolitan relative weight was significantly and independently associated with pulmonary embolism and only among women (p less than 0.001). These findings indicate that, in this cohort, increased adiposity in women is an important long-term factor for significant pulmonary embolism at autopsy. This raises the possibility that weight reduction in obese women may decrease the chances of pulmonary embolism.

Prognosis after initial myocardial infarction: the Framingham study.

During 20 years of follow-up of 5,127 men and women initially free of coronary heart disease in the Framingham cohort, 193 men and 53 women had one or more recognized, symptomatic myocardial infarctions. An additional 45 men and 28 women had unrecognized myocardial infarctions. Subsequent mortality and morbidity including angina, reinfarction, congestive failure and sudden death were ascertained. One in five men who had a first myocardial infarction died within 1 year, a mortality rate 14 times that of those free of coronary heart disease. In men who survived the 1st year, a recognized myocardial infarction increased risk of death over the next 5 years to 23 percent, four times that of the general population. The next 5 years carried a 25 percent mortality (three times that of the general population). The prognosis was distinctly worse in women than in men chiefly because of a higher (45 percent) early mortality rate in women. Patients with recognized and unrecognized myocardial infarctions had similar survival rates after 3 years. A second myocardial infarction occurred in 13 percent of the men and in 40 percent of the women within 5 years of the first infarction. Thus, women were more prone to death and reinfarction than men. Congestive heart failure occurred as commonly as reinfarction, affliction 14 percent of the men within 5 years of the initial infarction. Once congestive failure ensued, half of the affected patients were dead within 5 years. Angina developed in one third of the patients within 5 years of their first infarction.

Clinical-electrocardiographic correlates of newly acquired left bundle branch block: the Framingham Study.

To determine whether any associated electrocardiographic findings in persons with newly acquired complete left bundle branch block (LBBB) correlate with the prevalence of associated clinically apparent cardiovascular abnormalities, electrocardiograms (ECGs) from all 55 members of the Framingham Study cohort in whom LBBB developed during 18 years of routine prospective biennial examinations were reviewed. A QRS axis left of or equal to 0 degrees, left atrial conduction delay and an inverted T wave in lead V6 on the first ECG with LBBB, and an abnormal ECG in the Framingham examination preceding the appearance of LBBB each correlated with the prevalence of systemic hypertension, cardiomegaly, coronary heart disease and congestive heart failure. However, neither the PR interval nor the duration of the QRS complex on the first ECG with LBBB correlated with the prevalence of any of the associated cardiovascular abnormalities. The 8 patients with neither left atrial conduction delay nor a QRS axis left of or equal to 0 degrees on the first Framingham ECG with LBBB nor an abnormal ECG on the examination preceding the appearance of LBBB were 6 times more likely to remain free of all of the clinical cardiovascular abnormalities than the 47 patients with 1 or more of these 3 electrocardiographic findings (p less than 0.001).

Prevalence of submitral (anular) calcium and its correlates in a general population-based sample (the Framingham Study).

To obtain epidemiologic information on submitral calcium, 2,069 subjects in the original Framingham Study cohort (mean age 70 +/- 7 years) and 3,625 of the offspring of the cohort and their spouses (mean age 44 +/- 10 years) with adequate echocardiograms were evaluated. Submitral calcium was detected in 162 (2.8%) of the 5,694 subjects; greater than 90% of the subjects with such calcium came from the 40% of the study group greater than 59 years of age. Women were more than twice as likely to have such calcium as men. Age in both sexes, systolic blood pressure in men, and obesity in women were significantly and independently associated with submitral calcium. There was a 12-fold excess of atrial fibrillation in subjects with (20 of 162, 12%) compared with those without (53 of 5,532, 1%) submitral calcium.

Comparative features of newly acquired left and right bundle branch block in the general population: the Framingham study.

Cardiovascular abnormalities were prospectively identified in all 55 persons who acquired left bundle branch block and all 70 persons who acquired right bundle branch block during 18 years of follow-up of the Framingham Study cohort. Those with left and right bundle branch block did not differ from each other in the overall prevalence of either hypertension, clinical coronary disease or diabetes. In men, but not in women, left bundle branch block was associated with a significantly greater prevalence of cardiac enlargement and congestive failure than was right bundle branch block. A trend suggesting a higher mortality rate from cardiovascular disease in those with left than in those with right bundle branch block was more apparent in men than in women. It is concluded that in the general adult population, men who acquire left bundle branch block are more likely to have or subsequently acquire advanced cardiovascular abnormalities than are men who acquire right bundle branch block. In women, however, the clinical correlates of the two conduction abnormalities are similar.

Prevalence of coronary heart disease in the Framingham Offspring Study: role of lipoprotein cholesterols.

Forth-three of 1,312 men aged 35 to 54 years in the Framingham Offspring Study had clinically recognized coronary heart disease at the initial examination. Twenty-six men in this group had previously had a myocardial infarction. Of 1,296 women in the same age range, only 11 had coronary disease and 3 a prior myocardial infarction. The prevalence of coronary heart disease in men was strongly associated with age, smoking, high density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol using univariate analyses. When multivariate logistic regression analysis was used, age, smoking and HDL and LDL cholesterol retained their significant associatin with coronary heart disease. The total cholesterol/HDL cholesterol ratio was also strongly associated with coronary heart disease in the multivariate analysis. It is concluded that both HDL and LDL cholesterol are strongly and independently associated with the prevalence of coronary heart disease, whereas the level of very low density lipoprotein cholesterol makes no statistically significant independent contribution.

Validity of serum total cholesterol level obtained within 24 hours of acute myocardial infarction.

The relation of a serum cholesterol level obtained during acute myocardial infarction (AMI) to the patient's usual baseline level is unclear. Many physicians tend to ignore cholesterol levels measured during AMI and will wait several months before obtaining a repeat cholesterol measurement; in many instances this delays interventional programs. Using the Framingham study cohort of patients, the records of all persons sustaining AMI were reviewed. Eighty-three patients were identified who had total cholesterol (TC) levels recorded within 2 years of AMI, within 24 hours of hospitalization for AMI and within 2 years after hospital discharge. In these persons, there was no statistically significant difference in the TC values measured at these 3 times. Thus, TC levels drawn within the first 24 hours of AMI accurately reflect a baseline level and can be used in instituting intervention programs.

Obesity and lipoprotein cholesterol in the Framingham offspring study.

This study examines the relationship between obesity and low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and very-low-density lipoprotein (VLDL) cholesterol in 4260 young adult men and women. The strongest association between obesity and LDL cholesterol was found in 20-29 yr-old males, the weakest in 40-49-yr-old males. Conversely, in women the relationship between LDL cholesterol and obesity was modest except in the oldest (40-49 yr) age group. An inverse relationship between obesity and HDL cholesterol was of similar shape and strength in all sex and age-specific groups. When the ratio of total cholesterol (TCHOL) to HDL cholesterol was compared in lean and grossly obese 20-29-yr-old males, substantial differences were found. Since other data show this index of the lipoprotein profile to be the single best indicator of CHD risk, it would appear that the atherogenic potential of obesity is greater than would be suggested by the relatively weak association between obesity and TCHOL or any single lipoprotein cholesterol. These data also suggest that the impact of obesity as a risk factor for CHD may have been underestimated. The paucity of lean males 40-49-yr-old prevents firm conclusions about the CHD risk in such a group. Indirect evidence indicates that lean 40-49-yr-old men would have a markedly more favorable lipoprotein profile and consequently a much lower risk of CHD.

Monitoring accountability of a clinical nutrition service.

The first step in the effort to establish a stronger link between nutrition care intervention and health status is to identify actual services provided. This study examined the accountability of a clinical dietetic staff by using an explicit procedure that made it possible for performance to be measured. Data were gathered at an urban teaching hospital to determine the nutrition care provided as compared with stated standards. Using the Policy and Procedure Manual as the written standard, the authors analyzed data from medical record audit, time utilization studies, staff interviews, and monthly reports. The level of accountability was very high, with less than 1 discrepancy in 10, for all the data collected. The dietetic staff members at the hospital verified the attainment of established standards by clearly and specifically documenting their services. It would appear that a decision about priorities and responsibilities had been made that was well supported by staff and institution. The establishment of a nutrition care team, in which clinical dietitians assumed a supervisory role that promoted and supported delegation to dietetic technicians and dietetic assistants, also contributed to good performance.