Do cardiovascular risk factors confer the same risk for cardiovascular outcomes in rheumatoid arthritis patients as in non-rheumatoid arthritis patients?

OBJECTIVE: To compare the frequency of traditional cardiovascular (CV) risk factors in rheumatoid arthritis (RA) compared to non-RA subjects, and examine their impact on the risk of developing selected CV events (myocardial infarction (MI), heart failure (HF) and CV death) in these two groups. METHODS: We examined a population-based incidence cohort of subjects with RA (defined according to the 1987 American College of Rheumatology criteria), and an age- and sex-matched non-RA cohort. All subjects were followed longitudinally through their complete community medical records, until death, migration, or 1 January 2001. Clinical CV risk factors and outcomes were defined using validated criteria. The chi2 test was used to compare the frequency of each CV risk factor at baseline. Person-years methods were used to estimate the rate of occurrence of each CV risk factor during follow-up. Cox models were used to examine the influence of CV risk factors on the development of CV outcomes. RESULTS: A total of 603 RA and 603 non-RA subjects (73% female; mean age 58 years) were followed for a mean of 15 and 17 years (total: 8842 and 10,101 person-years), respectively. At baseline, RA subjects were significantly more likely to be former or current smokers when compared to non-RA subjects (p<0.001). Male gender, smoking, and personal cardiac history had weaker associations with CV events among RA subjects, compared to non-RA subjects. There was no significant difference between RA and non-RA subjects in the risk imparted with respect to the other CV risk factors (ie, family cardiac history, hypertension, dyslipidaemia, body mass index, or diabetes mellitus). CONCLUSION: While some traditional CV risk factors imparted similar risk among RA compared with non-RA subjects, others (ie, male gender, smoking and personal cardiac history) imparted significantly less risk for the development of CV disease. These differences in the overall impact of traditional CV risk factors suggest that strategies to prevent CV disease and mortality focused solely on controlling traditional CV risk factors may be relatively less beneficial in RA subjects than in the general population. Further research is needed to determine optimal approaches to reducing CV morbidity and mortality in persons with RA.

Dietary calcium intake and rates of bone loss in women.

We measured bone mineral density (BMD) at the midradius and lumbar spine in 106 normal women, ages 23-84 yr (61 were postmenopausal). Three to nine measurements (median, four) were made over 2.6 to 6.6 yr (mean, 4.1 yr). The correlation between calcium intake (range, 260-2,035 mg/d) and rate of change in BMD was not significant at the midradius (r = 0.06) or lumbar spine (r = 0.08), even after adjusting for age, menopausal status, and serum estrogen levels by multiple regression analysis. Women in the lower (mean, 501 mg/d) and in the upper (mean, 1,397 mg/d) quartiles of dietary intake had similar rates of change in BMD (%/yr [mean +/- SE], at midradius, -0.78 +/- 0.24 and -0.91 +/- 0.17 for lower and upper quartiles, respectively; at lumbar spine, -1.06 +/- 0.24 and 0.98 +/- 0.24). These data do not support the hypothesis that insufficient dietary calcium is a major cause of bone loss in women.

Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men.

Young adult males who cannot produce or respond to estrogen (E) are osteopenic, suggesting that E may regulate bone turnover in men, as well as in women. Both bioavailable E and testosterone (T) decrease substantially in aging men, but it is unclear which deficiency is the more important factor contributing to the increased bone resorption and impaired bone formation that leads to their bone loss. Thus, we addressed this issue directly by eliminating endogenous T and E production in 59 elderly men (mean age 68 years), studying them first under conditions of physiologic T and E replacement and then assessing the impact on bone turnover of withdrawing both T and E, withdrawing only T, or only E, or continuing both. Bone resorption markers increased significantly in the absence of both hormones and were unchanged in men receiving both hormones. By two-factor ANOVA, E played the major role in preventing the increase in the bone resorption markers, whereas T had no significant effect. By contrast, serum osteocalcin, a bone formation marker, decreased in the absence of both hormones, and both E and T maintained osteocalcin levels. We conclude that in aging men, E is the dominant sex steroid regulating bone resorption, whereas both E and T are important in maintaining bone formation.

Unequal decrease in bone density of lumbar spine and ultradistal radius in Colles' and vertebral fracture syndromes.

We measured bone mineral density (BMD) at the lumbar spine (LS-BMD) and ultradistal radius (UDR-BMD) in 42 postmenopausal normal women and in 108 postmenopausal osteoporotic women (55 with vertebral fracture, 34 with Colles' fracture, and 19 with both fractures). By receiver operating characteristic analysis, LS-BMD was better than UDR-BMD (P less than 0.01) as an indicator of vertebral fracture; the converse was true for Colles' fracture (P less than 0.01). Although UDR-BMD and LS-BMD were lower in each of the three fracture groups than in controls (P less than 0.01), the pattern of bone loss differed (P less than 0.001, analysis of variance): with vertebral fracture, LS-BMD decreased relatively more than UDR-BMD; with Colles' fracture, UDR-BMD decreased relatively more than LS-BMD; and with both fractures, decreases in LS-BMD and UDR-BMD were similar. We conclude that both types of fracture are caused by excessive bone loss but the difference in bone loss at the two sites is a major factor in determining which will fracture.

Incidence and secular trend of multiple myeloma in Olmsted County, Minnesota: 1965-77.

The average annual age-adjusted incidence rate of multiple myeloma for Olmsted County, Minnesota, for 1965-77 was 2.7/10(5) person-years. The sex-specific rates for males and females were 3.5 and 2.2/10(5) person-years, respectively; the male-to-female incidence ratio was 1.6:1.0. These rates were similar to rates reported for white people from the Third National Cancer Survey and the New York and Connecticut tumor registries. This average incidence rate did not appear different from the rate for the 20-year period 1945-64 in Olmsted County. The incidence of multiple myeloma was not shown to have increased in the past 33 years, and the observed increase in mortality from this disease reported in other parts of the country indicated improved case ascertainment during recent years, a factor not likely to be important in Olmsted County.

Perturbation of the T-cell repertoire in patients with unstable angina.

BACKGROUND: Monocytes are constitutively activated in unstable angina (UA), resulting in the production of IL-6 and the upregulation of acute phase proteins. Underlying mechanisms are not understood. To explore whether the production of the potent monocyte activator IFN-gamma is altered in UA, we compared cytokine production by T lymphocytes in patients with UA (Braunwald's class IIIB) and with stable angina (SA). METHODS AND RESULTS: Peripheral blood lymphocytes were collected at the time of hospitalization and after 2 and 12 weeks. Cytokine-producing CD4(+) and CD8(+) T cells were quantified by 3-color flow cytometry after stimulation with phorbol myristate acetate and ionomycin. UA was associated with an increased number of CD4(+) and CD8(+) T cells producing IFN-gamma, whereas patients with SA had higher frequencies of IL-2(+) and IL-4(+) CD4(+) T cells. Expansion of the IFN-gamma( +) T-cell population in UA persisted for at least 3 months. Increased production of IFN-gamma in UA could be attributed to the expansion of an unusual subset of T cells, CD4(+)CD28(null) T cells. CONCLUSIONS: Patients with UA are characterized by a perturbation of the functional T-cell repertoire with a bias toward IFN-gamma production, suggesting that monocyte activation and acute phase responses are consequences of T-cell activation. IFN-gamma is produced by CD4(+)CD28(null) T cells, which are expanded in UA and distinctly low in SA and controls. The emergence of CD4(+)CD28(null) T cells may result from persistent antigenic stimulation.

Independent association of high blood pressure and aortic atherosclerosis: A population-based study.

BACKGROUND: Atherosclerosis of the thoracic aorta is associated with stroke. The association between hypertension, a major risk factor for stroke, and aortic atherosclerosis has not been determined in the general population. METHODS AND RESULTS: Transesophageal echocardiography was performed in 581 subjects, a random sample of the Olmsted County (Minnesota) population aged >/=45 years participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. Blood pressure was assessed by multiple office measurements and 24-hour ambulatory blood pressure monitoring. The association between blood pressure variables and aortic atherosclerosis was evaluated by multiple logistic regression, adjusting for other associated variables. Among subjects with atherosclerosis, blood pressure variables associated with complex aortic atherosclerosis (protruding plaques >/=4 mm thick, mobile debris, or ulceration) were determined. Age and smoking history were independently associated with aortic atherosclerosis of any degree (P:

Frequency of atrial septal aneurysms in patients with cerebral ischemic events.

BACKGROUND: Atrial septal aneurysm (ASA) is a putative risk factor for cardioembolism. However, the frequency of ASA in the general population has not been adequately determined. Therefore, the frequency in patients with cerebral ischemic events, compared with the frequency in the general population, is poorly defined. We sought to determine the frequency of ASA in the general population and to compare the frequency of ASA in patients with cerebral ischemic events with the frequency in the general population. METHODS AND RESULTS: The frequency of ASA in the population was determined in 363 subjects, a sample of the participants in the Stroke Prevention: Assessment of Risk in a Community study (control subjects), and was compared with the frequency in 355 age- and sex-matched patients undergoing transesophageal echocardiography in search of a cardiac source of embolism after a focal cerebral ischemic event. The proportion with ASA was 7.9% in patients versus 2.2% in control subjects (P=0.002; odds ratio of ASA, 3.65; 95% CI, 1.64 to 8.13, in patients versus control subjects). Patent foramen ovale (PFO) was detected with contrast injections in 56% of subjects with ASA. The presence of ASA predicted the presence of PFO (odds ratio of PFO, 4.57; 95% CI, 2.18 to 9.57, in subjects with versus those without ASA). In 86% of subjects with ASA and cerebral ischemia, transesophageal echocardiography did not detect an alternative source of cardioembolism other than an associated PFO. CONCLUSIONS: The prevalence of ASA based on this population-based study is 2.2%. The frequency of ASA is relatively higher in patients evaluated with transesophageal echocardiography after a cerebral ischemic event. ASA is frequently associated with PFO, suggesting paradoxical embolism as a mechanism of cardioembolism. In patients with cerebral ischemia and ASA, ASA (with or without PFO) commonly is the only potential cardioembolic source detected with transesophageal echocardiography.

Incidence of multiple myeloma in Olmsted County, Minnesota: 1978 through 1990, with a review of the trend since 1945.

PURPOSE: Incidence rates of multiple myeloma appear to have increased in recent decades, but it is difficult to compare the incidence rates over time because of changes in laboratory procedures, differences in diagnostic criteria, and variations in indexing of medical records. However, Olmsted County, Minnesota, provides a rare opportunity to minimize these limitations, because the medical care has been provided mainly by the Mayo Clinic. PATIENTS AND METHODS: Records of Olmsted County residents with a diagnosis of multiple myeloma from January 1, 1978 through December 31, 1990 were reviewed. Criteria for diagnosis and residency were the same as in previous Olmsted County studies. RESULTS: The incidence rate per 100,000 age-adjusted to the 1950 United States white population was 5.4 for males and 2.8 for females; the overall rate was 4.1. The rates were age-adjusted to the 1950 United States population for comparison with earlier data from this population. The rates increased with age for both sexes. There was no significant change in incidence rates from 1945 through 1990. A comparison of the median age for Olmsted County patients with the age of those referred to the Mayo Clinic from elsewhere indicated that the local patients were appreciably older (74 v. 62 years, respectively). Thirty-two of 55 patients (58%) with multiple myeloma from 1978 through 1990 had a monoclonal plasma-cell proliferative process before the diagnosis of multiple myeloma. CONCLUSION: The incidence rate of multiple myeloma in Olmsted County, Minnesota, has not changed significantly during the past 46 years. We believe that reports of increasing rates over time are mainly due to improved case ascertainment.

Epidemiology of persistent proteinuria in type II diabetes mellitus. Population-based study in Rochester, Minnesota.

Clinical risk factors for nephropathy were assessed in a population-based study of Rochester, Minnesota, residents with diabetes mellitus initially diagnosed between 1945 and 1969 (incidence cohort). The 1031 Rochester residents with non-insulin-dependent diabetes mellitus (NIDDM) were followed through their complete medical records in the community to 1 January 1982. The prevalence of persistent proteinuria was 8.2% at the diagnosis of NIDDM. Among those initially free of persistent proteinuria, the subsequent incidence was 15.3/1000 person-yr. Twenty years after the diagnosis of diabetes, the cumulative incidence of persistent proteinuria was 24.6%. A proportional hazards model identified the following risk factors for persistent proteinuria in NIDDM: elevated initial fasting blood glucose (P less than .01); older age at onset of diabetes (P less than .01); male gender (P = .05); and presence of macrovascular disease (P = .05), diabetic retinopathy (P = .05), or glycosuria (P = .07) at the diagnosis of diabetes. Separate analyses controlling for attained age indicated no association between duration of NIDDM and the incidence of persistent proteinuria. Stratified analysis of the two most significant risk factors (fasting blood glucose and age) indicated that hyperglycemia was a stronger risk factor for proteinuria in younger diabetic subjects, perhaps because of a competing risk of death in the elderly diabetic patient. In contrast to a recently described decreasing secular trend of proteinuria in Danish insulin-dependent diabetes mellitus patients, there was no decrease over the past 40 yr in proteinuria risk in this NIDDM incidence cohort.

Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment.

BACKGROUND: The management of unruptured intracranial aneurysms is controversial. Investigators from the International Study of Unruptured Intracranial Aneurysms aimed to assess the natural history of unruptured intracranial aneurysms and to measure the risk associated with their repair. METHODS: Centres in the USA, Canada, and Europe enrolled patients for prospective assessment of unruptured aneurysms. Investigators recorded the natural history in patients who did not have surgery, and assessed morbidity and mortality associated with repair of unruptured aneurysms by either open surgery or endovascular procedures. FINDINGS: 4060 patients were assessed-1692 did not have aneurysmal repair, 1917 had open surgery, and 451 had endovascular procedures. 5-year cumulative rupture rates for patients who did not have a history of subarachnoid haemorrhage with aneurysms located in internal carotid artery, anterior communicating or anterior cerebral artery, or middle cerebral artery were 0%, 2. 6%, 14 5%, and 40% for aneurysms less than 7 mm, 7-12 mm, 13-24 mm, and 25 mm or greater, respectively, compared with rates of 2 5%, 14 5%, 18 4%, and 50%, respectively, for the same size categories involving posterior circulation and posterior communicating artery aneurysms. These rates were often equalled or exceeded by the risks associated with surgical or endovascular repair of comparable lesions. Patients' age was a strong predictor of surgical outcome, and the size and location of an aneurysm predict both surgical and endovascular outcomes. INTERPRETATION: Many factors are involved in management of patients with unruptured intracranial aneurysms. Site, size, and group specific risks of the natural history should be compared with site, size, and age-specific risks of repair for each patient.

Influence of coronary heart disease on morbidity and mortality after carotid endarterectomy: a population-based study in Olmsted County, Minnesota (1970-1988)

To evaluate the prognostic importance of coronary artery disease among patients undergoing carotid endarterectomy, 177 residents of Olmsted County, Minnesota who underwent carotid endarterectomy during the period 1970 through 1988 were followed up to July 1, 1989. Patients were stratified as to the presence (n = 64) or absence (n = 93) of overt coronary artery disease or prior myocardial revascularization (n = 20) at the time of endarterectomy. At 30 days after carotid endarterectomy, there were no significant differences between patients with or without coronary artery disease in the occurrence of death, myocardial infarction or stroke. Kaplan-Meier estimate of 8-year relative survival after carotid endarterectomy (assessed as a percent of survival in age- carotid endarterectomy (assessed as a percent of survival in age- and gender-matched control subjects) was 89% in those without and 75% in those with overt coronary artery disease. Of the 59 total deaths, 29 (49%) had a cardiac cause and 4 (7%) were due to stroke (p less than 0.0001). The cumulative incidence of a cardiac event at 8 years after carotid endarterectomy was greater in those with than in those without overt coronary artery disease (61% vs. 25%, p less than 0.0001). In multivariable analysis, uncorrected coronary artery disease and diabetes were the only independent predictors of subsequent cardiac events, whereas age was the only independent predictor of death. These population-based data suggest that carotid endarterectomy can be safely undertaken in patients with stable coronary artery disease. In long-term follow-up of these patients, coronary rather than cerebral vascular disease is the most frequent cause of morbidity and mortality. Thus, these data lend strong support to the concept of early identification and management of coronary artery disease in patients undergoing carotid endarterectomy.

Influence of coronary heart disease on morbidity and mortality after lower extremity revascularization surgery: a population-based study in Olmsted County, Minnesota (1970-1987).

OBJECTIVES: The aim of this study was to evaluate the short- and long-term postoperative cardiac outcome of patients undergoing lower extremity revascularization surgery in a geographically defined patient group. BACKGROUND: Among patients with peripheral vascular disease, cardiac events have an important effect on long-term outcome after peripheral vascular surgery. However, long-term outcome is poorly documented. METHODS: We examined the entire community medical records of 173 residents of Olmsted County, Minnesota, who underwent peripheral artery bypass surgery between 1970 and 1987 and were followed up to January 1, 1991. Patients were allocated to subgroups of 60 patients with and 106 patients without overt coronary artery disease. RESULTS: There were no significant differences in perioperative death, myocardial infarction or stroke between subgroups at 30 days after operation. The 5- and 10-year Kaplan-Meier survival rate after operation was 77% and 51% in those without and 54% and 24% in those with overt coronary artery disease (p < 0.001), respectively. For both groups, survival was significantly poorer than that expected for an age- and gender-matched group. Patients undergoing aortoiliac surgery were more likely to be alive at 10 years than those undergoing femoropopliteal surgery (47% vs. 28%, p = 0.001). The 5-year cumulative incidence of cardiac events was greater in those with overt coronary artery disease (50% vs. 28%, p = 0.003). In multivariable analysis, age, coronary artery disease and diabetes were independent predictors of death. CONCLUSIONS: Coronary events are the most important cause of long-term morbidity and mortality after peripheral vascular surgery. Patients without overt coronary artery disease are at significant risk for long-term cardiac events.

Aortic valve sclerosis and aortic atherosclerosis: different manifestations of the same disease? Insights from a population-based study.

OBJECTIVES: The aim of this study was to examine the association between atherosclerosis risk factors, aortic atherosclerosis and aortic valve abnormalities in the general population. BACKGROUND: Clinical and experimental studies suggest that aortic valve sclerosis (AVS) is a manifestation of the atherosclerotic process. METHODS: Three hundred eighty-one subjects, a sample of the Olmsted County (Minnesota) population, were examined by transthoracic and transesophageal echocardiography. The presence of AVS (thickened valve leaflets), elevated transaortic flow velocities and aortic regurgitation (AR) was determined. The associations between atherosclerosis risk factors, aortic atherosclerosis (imaged by transesophageal echocardiography) and aortic valve abnormalities were examined. RESULTS: Age, male gender, body mass index (odds ratio [OR]: 1.07 per kg/m(2); 95% confidence interval [CI]: 1.02 to 1.12), antihypertensive treatment (OR: 1.93; CI: 1.12 to 3.32) and plasma homocysteine levels (OR: 1.89 per twofold increase; CI: 0.99 to 3.61) were independently associated with an increased risk of AVS. Age, body mass index and pulse pressure (OR: 1.21 per 10 mm Hg; CI: 1.00 to 1.46) were associated with elevated (upper quintile) transaortic velocities, whereas only age was independently associated with AR. Sinotubular junction sclerosis (p = 0.001) and atherosclerosis of the ascending aorta (p = 0.03) were independently associated with AVS and elevated transaortic velocities, respectively. CONCLUSIONS: Atherosclerosis risk factors and proximal aortic atherosclerosis are independently associated with aortic valve abnormalities in the general population. These observations suggest that AVS is an atherosclerosis-like process involving the aortic valve.

Dialysis support of patients with primary systemic amyloidosis. A study of 211 patients.

BACKGROUND: The study assessed dialysis support in patients with primary systemic amyloidosis without associated multiple myeloma in whom renal insufficiency developed. METHODS: The study group consisted of 211 patients with biopsy-proved primary systemic amyloidosis examined at the Mayo Clinic, Rochester, Minn. No patient was lost to follow-up. RESULTS: Thirty-seven (18%) of the patients received dialysis therapy. Of those presenting with renal amyloid, one third received dialysis. The median time from diagnosis to initiation of dialysis was 13.8 months. The median survival for patients from the start of dialysis was 8.2 months. There was no survival difference between hemodialysis (n = 27) and peritoneal dialysis (n = 10). The most important predictors of which patients would ultimately require dialysis were the 24-hour urinary protein loss and serum creatinine values at the time amyloidosis was diagnosed. None of the patients seen at diagnosis with a normal serum creatinine value and proteinuria of less than 2 g/d required dialysis during follow-up. Of the 37 patients who received dialysis, 31 died, and 21 of the 31 died as a result of extrarenal progression of their systemic amyloidosis. Fifteen of the 31 deaths were a result of cardiac amyloidosis. All long-term survivors had normal echocardiograms without evidence of amyloid. CONCLUSION: Eighteen percent of patients with primary amyloidosis undergo dialysis. The 24-hour urinary protein loss and creatinine values are helpful in predicting which patients eventually will require dialysis. The median survival for patients starting dialysis is less than 1 year. Patients whose two-dimensional echocardiograms are normal are most likely to derive long-term benefit from dialysis.

Risk of age-related fractures in patients with primary hyperparathyroidism.

BACKGROUND: Bone mass is reduced, but the influence of primary hyperparathyroidism (HPT) on fracture risk is controversial. We addressed this issue in a population-based retrospective cohort study. METHODS: Ninety residents of Rochester, Minn, were first diagnosed with HPT in 1965 through 1976 and an equal number of age- and sex-matched control subjects from the community were identified. Fractures were assessed through review of each subject's complete (inpatient and outpatient) medical records in the community. RESULTS: Prior to the date of diagnosis, Rochester residents with HPT were more likely to have a history of fractures than were matched control subjects from the same population (30% vs 18%). Subsequently, 36% of cases and 31% of control subjects experienced one or more new fractures during 1072 person-years of follow-up; survival free of a new fracture was almost the same in the two groups. Women had more fractures than men, and fracture rates increased with age. Fractures appeared to be somewhat more frequent in those with baseline serum calcium levels of 2.74 mmol/L or more, in those with comorbid conditions possibly due to HPT and in those who did not undergo parathyroidectomy, but these differences were not statistically significant. In a multivariate analysis, only age at diagnosis was an independent predictor of fracture risk, with a 36% increase in risk per 10-year increase in age. CONCLUSIONS: Overall fracture risk was increased prior to diagnosis of HPT but not afterward. Because the numbers involved were small, however, we cannot exclude an increased likelihood of fractures in certain subgroups of HPT patients.

Outcome of anesthesia and surgery in hypothyroid patients.

We retrospectively examined the outcome of anesthesia and surgery in 59 hypothyroid patients and in 59 paired euthyroid matched controls. Hypothyroid patients had more preoperative risk factors but did not differ as a group from controls with regard to duration of surgery or anesthesia, lowest temperature and BP recorded during surgery, need for vasopressors, time to extubation, fluid and electrolyte imbalances, incidence of arrhythmias, pulmonary and myocardial infarction, sepsis, need for postoperative respiratory assistance, bleeding complications, or time to hospital dismissal. Analysis of subsets of hypothyroidism (thyroxine level, less than 1.0, less than 3.0, and greater than or equal to 3.0 micrograms/dL) also failed to disclose any significant differences compared with matched controls. Among patients with mild or moderate hypothyroidism, we found no evidence to justify deferring needed surgery until the hypothyroidism has been corrected.

Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study.

BACKGROUND: The incidence of venous thromboembolism has not been well described, and there are no studies of long-term trends in the incidence of venous thromboembolism. OBJECTIVES: To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe trends in incidence. METHODS: We performed a retrospective review of the complete medical records from a population-based inception cohort of 2218 patients who resided within Olmsted County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990. RESULTS: The overall average age- and sex-adjusted annual incidence of venous thromboembolism was 117 per 100000 (deep vein thrombosis, 48 per 100000; pulmonary embolism, 69 per 100000), with higher age-adjusted rates among males than females (130 vs 110 per 100000, respectively). The incidence of venous thromboembolism rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the incidence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than 55 years, and increased for women older than 60 years. CONCLUSIONS: Venous thromboembolism is a major national health problem, especially among the elderly. While the incidence of pulmonary embolism has decreased over time, the incidence of deep vein thrombosis remains unchanged for men and is increasing for older women. These findings emphasize the need for more accurate identification of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis.

Deep venous thrombosis and pulmonary embolism. Risk of subsequent malignant neoplasms.

We conducted a noncurrent prospective study of all Olmsted County, Minnesota, residents who had had a lower-extremity venogram, pulmonary angiogram, or lung scan performed because of suspicion of deep venous thrombosis or pulmonary emboli. One hundred thirteen cancer-free patients were followed for 386 person-years from the date of procedure. Nine subsequent cancers were observed compared with 4.5 expected (relative risk, 2.0; 95% confidence interval, 0.9 to 3.8), using total cancer incidence rates for the Rochester, Minn, population. Five hundred seventeen cancer-free controls were followed for 2072 person-years. Twenty subsequent cancers were observed compared with 11.6 expected, yielding a relative risk of 1.7 (95% confidence interval, 1.1 to 2.7). When cases and controls were compared directly, no statistically significant difference in cancer-free survival was found.

The incidence of cholelithiasis and cholecystitis in Rochester, Minn, 1950 through 1969.

During the period 1950 through 1969, 2344 persons (755 men and 1589 women) in Rochester, Minn, met diagnostic and residency criteria for cholelithiasis. The age-adjusted average annual incidence rates per 100,000 population were 217 for men and 370 for women (adjusted rates were 255 and 276, respectively). Incidence rates increased with age in both sexes, but more rapidly so for men, so that by 70 years of age the rate for men was higher than that for women. For the decades covered in this study, no secular trend in incidence was detected for the two sexes combined or separately.