Calcium channel blockers, cancer incidence, and cancer mortality in a cohort of U.S. women: the nurses' health study

BACKGROUND: Some studies have suggested that the use of calcium channel blockers may increase the risk of cancer. A possible association of the use of calcium channel blockers with cancer incidence and cancer mortality was addressed using data from the Nurses' Health Study. METHODS: In this study, a total of 18,635 female nurses reported regularly taking at least 1 of 4 cardiovascular medications in 1988: diuretics, beta-blockers, calcium channel blockers, and/or angiotensin-converting enzyme (ACE) inhibitors. Cancer incidence and cancer deaths were ascertained until 1994. RESULTS: During 6 years of follow-up, 852 women were newly diagnosed with cancer and 335 women died of cancer. Women who reported the use of calcium channel blockers had no increased risk of newly diagnosed cancer compared with those taking other cardiovascular drugs (relative risk=1.02; 95% CI 0.83-1.26). The relative risk of dying from cancer associated with the self-reported use of calcium channel blockers was 1.25 (95% CI 0.91-1.72). Relative risks were adjusted for the following self-reported factors: age; weight; height; cholesterol level; systolic and diastolic blood pressure; smoking; alcohol intake; physical activity; menopausal status; postmenopausal hormone use; aspirin use; and history of diabetes, cancer, stroke, myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, angina, and hypertension. Regarding site specific cancer incidence and mortality, only lung cancer incidence was somewhat increased (RR=1.61; 95% CI 0.88-2.96). CONCLUSIONS: These data suggest no important increase in overall cancer incidence or cancer mortality related to the self-reported use of calcium channel blockers.     

The effect of N-acetylcysteine on total serum anti-oxidant potential and urinary albumin excretion in critically ill patients

PURPOSE: Calcium channel blockers have been reported to increase the risk of gastrointestinal bleeding. We tested this hypothesis, and also assessed whether beta blockers decrease this risk. SUBJECTS AND METHODS: A nested case-control design within a population-based cohort of all 34,074 new users of beta blockers, angiotensin-converting enzyme (ACE) inhibitors, or calcium channel blockers in Saskatchewan, from 1990 to 1993 and followed up to March 1995, was used. We identified all 311 subjects hospitalized because of gastrointestinal bleeding during this period, each of whom was matched to 10 randomly selected controls. RESULTS: The rate of hospitalization for gastrointestinal bleeding was 3.0 per 1,000 per year. The adjusted rate ratio of gastrointestinal bleeding for current use of calcium channel blockers was 1.1 (95% confidence interval [CI] 0.8 to 1.4) and 0.66 (95% CI 0.44 to 0.98) for beta blockers compared with no current use of anti-hypertensive drugs. The adjusted rate ratio for ACE inhibitor use was 1.0 (95% CI 0.7 to 1.3) while that for diuretic use was 1.4 (95% CI 1.0 to 2.0). CONCLUSIONS: The use of calcium channel blockers does not appear to increase the risk of gastrointestinal bleeding in the first five years of treatment, while beta blockers may prevent this adverse event. The unexpected elevated risk associated with the use of diuretics needs to be investigated further.     

Prospective study of calcium channel blocker use, cardiovascular disease, and total mortality among hypertensive women: the Nurses' Health Study

BACKGROUND: In several observational studies, patients prescribed calcium channel blockers had higher risks of cardiovascular diseases and mortality than those prescribed other antihypertensive medications. We explored these associations in the Nurses' Health Study. METHODS AND RESULTS: A total of 14 617 women who reported hypertension and regular use of diuretics, beta-blockers, calcium channel blockers, ACE inhibitors, or a combination in 1988 were included in the analyses. Cardiovascular events and deaths were ascertained through May 1, 1994. We documented 234 cases of myocardial infarction. Calcium channel blocker monodrug users had an age-adjusted relative risk (RR) of myocardial infarction of 2.36 (95% CI, 1.43 to 3.91) compared with those prescribed thiazide diuretics. Women prescribed calcium channel blockers had a higher prevalence of ischemic heart disease. After adjustment for these and other coronary risk factors, the RR was 1.64 (95% CI, 0.97 to 2.77). Comparing the use of any calcium channel blocker (monodrug and multidrug users) with that of any other antihypertensive agent, the adjusted RR was 1.42 (95% CI, 1.01 to 2.01). An association between calcium channel blocker use and myocardial infarction was apparent among women who had ever smoked cigarettes (covariate-adjusted RR, 1.81; 95% CI, 1.20 to 2.72) but not among never-smokers (RR, 0.94; 95% CI, 0.48 to 1.84). CONCLUSIONS: In analyses adjusted only for age, we found a significant elevation in RR of total myocardial infarction among women who used calcium channel blockers compared with those who did not. After adjustment for comorbidity and other covariates, the RR was reduced. Whether the remaining observed elevated risk is real, or a result of residual confounding by indication, or chance, or a combination of the above cannot be evaluated with certainty on the basis of these observational data.     

Overview of knowledge of health effects of smokeless tobacco. Increased risk of cardiovascular diseases and mortality because of snuff

Oral snuff, used by 20% of all Swedish males in 1996, causes blood nicotine levels similar to those in smokers. In a report by the National Board of Health and Welfare in 1997, it is concluded that scientific evidence of oral snuff as a cause of oral cancer is weak. Epidemiological studies of more than 100,000 construction workers showed hypertension (blood pressure > 160/90) to be more common among oral snuff users than among non-users. Twelve-year follow-up showed the relative risk of death due to cardiovascular disease to be 2-fold greater among snuff users, but 3-fold greater among smokers, as compared to never-users of tobacco (p < 0.001). The risk of death due to cancer was similar among snuff users and among never-users. In a clinical study of 151 healthy middle-aged men, 24-hour monitoring showed daytime heart rates and blood pressure to be significantly higher in snuff users > or = 45 years of age than in age-matched non-users (p < 0.05). The estimated 10-year future risk of cardiovascular events was 13.2% for smokers (p < 0.001) and 4.6% for oral snuff users (p = 0.3) as compared with 3.4% for never-users. As compared with non-users, oral snuff users manifested neither significant signs of accelerated atherosclerosis nor significantly reduced maximum physical capacity. Oral snuff usage causes physiological nicotine dependence, and results in the release of sympatho-adrenergic stimuli associated with an increased risk of cardiovascular stress, which might in turn exacerbate the risk of fatal cardiovascular events. However, oral snuff usage does not seem to be associated with the same risk of accelerated atherosclerosis as is smoking.     

Influence of risk factors and pharmacological treatment on mortality in patients with essential hypertension

BACKGROUND: The V JNC consensus stated that although new antihypertensive agents, such as angiotensin converting enzyme inhibitors and calcium channel blockers, are considered safer drugs, there is no firm evidence from large controlled trials that these drugs are associated with a lower cardiovascular mortality. AIM: To study the association between cardiovascular risk factors, blood pressure levels, pharmacological treatment and mortality in a group of hypertensive patients followed at an hypertension outpatient clinic. PATIENTS AND METHODS: Patients with essential hypertension were treated with different antihypertensive medications, according to physicians criteria, and controlled until death or loss from follow up. Causes of death were obtained from hospital records and death certificates. Survival was analyzed using life tables, comparisons between groups of patients were done using chi square or a Cox's proportional hazards model. RESULTS: Three hundred thirty-nine hypertensive patients aged 33 to 80 years old were followed for a mean period of 9.8 +/- 4.9 years. Eighty-six were treated with beta blockers, 64 with diuretics, 133 with calcium antagonists and 56 with ACE inhibitors. Blood pressure dropped similarly with all medications. During follow up, 79 patients died. Life table analysis showed that patients with a history of angina, diabetes or myocardial infarction had higher mortality rates. Similarly, patients treated with beta blockers and diuretics had higher mortality than patients treated with calcium antagonists or angiotensin converting enzyme inhibitors. The proportional hazards model showed that the effect of treatment modality persisted after correction for the other risk factors for mortality. CONCLUSIONS: In this series of hypertensive patients, those treated with beta blockers or diuretics had higher mortality rates than those receiving calcium channel antagonists or angiotensin converting enzyme inhibitors.     

Use of antihypertensive drugs and trends in blood pressure in the elderly

BACKGROUND: During the 1980s data became available from randomized trials concerning the clear benefits of treating hypertension in the elderly. In three large communities, we examined the impact of these findings on rates of treatment, use of specific antihypertensive drugs, and rates of elevated blood pressure as well as distributions of levels. METHODS: In 1981 the National Institute on Aging initiated population-based cohort studies in the residents of three communities who were 65 years and older. East Boston, Mass; Washington and Iowa counties, Iowa; and New Haven, Conn. Participation rates ranged from 80% to 85% across sites with 10,294 community-dwelling participants in the combined cohorts. Baseline evaluation included inhome blood pressure assessment and medication inventory. Repeated in-home evaluations occurred 3 and 6 years after baseline and follow-up rates ranged from 71% to 88%. RESULTS: Use of antihypertensive drugs increased over time in all three communities: the age- and sex-adjusted rates of use were between 14% and 32% higher in 1988 and 1989 relative to 1982 and 1983. Parallel declines in the use of thiazide diuretics occurred in all three populations along with large increases in the use of angiotensin-converting enzyme inhibitors and calcium channel blockers. In East Boston and New Haven mean systolic blood pressure decreased substantially over time and the prevalence of elevated systolic pressure (> or = 160 mmHg) decreased overall as well as by age and sex. In Iowa the mean levels of systolic blood pressure were lowest at baseline and increased slightly. CONCLUSIONS: The reported evidence about the benefits of treatment for hypertension in the elderly was followed by substantial increases in treatment rates. The use of drugs with proven efficacy declined while the use of newer agents with theoretical advantages, not yet tested in clinical trials of mortality, increased. In the United States, the ongoing therapeutic efforts to lower elevated blood pressure in elderly populations may be contributing to the continuing decline in cardiovascular and stroke mortality.     

Calcium channel blocker use and the risk of prostate cancer

A recent study suggested that the risk of all cancers, including prostate cancer, is increased by the use of calcium channel blockers. The objective of this study was to determine whether prostate cancer is associated with calcium channel blocker use. A case-control study was conducted in Massachusetts using cases diagnosed from December 1992 through February 1995. Cases were men identified by tumor registrars who were less than 70 years old with newly diagnosed prostate cancer. Controls were men with no history of prostate cancer or symptoms of undiagnosed prostate cancer, and were matched to the cases on precinct of residence and half-decade of age. A total of 1217 cases of prostate cancer and 1400 community controls are included in this analysis. Data were collected by telephone interview. Multiple logistic regression was used to estimate relative risks for calcium channel blockers use while controlling for confounding. The relative risk for prostate cancer for any use of calcium channel blockers relative to nonuse was 1.2 (95% confidence interval [CI], 0.9-1.5). There was no evidence of a trend according to duration of use. When the analysis was confined to symptomatic men, the relative risk estimate was 1.1 (0.8-1.4) overall and 1.2 (0.8-1.7) among those aged 65 to 69 years. Relative risk estimates for the use of other classes of antihypertensive drugs among symptomatic men were close to 1.0; the corresponding estimates among asymptomatic men were generally further from 1.0. These findings suggest that calcium channel blockers do not increase the risk of prostate cancer. The differences in the relative risk estimates between symptomatic and asymptomatic men are compatible with detection bias. Because of the widespread use of Prostate-Specific Antigen testing for early detection of prostate cancer, potential detection bias needs to be considered in future studies of prostate cancer.     

Risk of esophageal and gastric adenocarcinomas in relation to use of calcium channel blockers, asthma drugs, and other medications that promote gastroesophageal reflux

Incidence of adenocarcinomas of the esophagus and gastric cardia has risen dramatically over the past 2 decades in the U. S., for reasons that are not yet clear. A number of common medications (e.g., calcium channel blockers, tricyclic antidepressants, and certain asthma medications) promote gastroesophageal reflux by relaxing the lower esophageal sphincter (LES). Reflux is thought to increase cancer risk by promoting cellular proliferation, and by exposing the esophageal epithelium to potentially genotoxic gastric and intestinal contents. Recent studies have suggested that calcium channel blockers may also increase cancer risk by inhibiting apoptosis. Using personal interview data from a multicenter, population-based case-control study conducted between 1993 and 1995 in three areas of the U. S., we evaluated whether the use of LES-relaxing drugs was associated with increased risk of adenocarcinomas of the esophagus and gastric cardia. Cases of esophageal adenocarcinoma (n = 293) and gastric cardia adenocarcinoma (n = 261) were compared with general population controls (n = 695). Information on additional case groups of esophageal squamous cell carcinoma (n = 221) and noncardia gastric cancer (n = 368) were also available for comparison. Overall, 27.4% of controls had used one or more of these drugs for at least 6 months, compared with 30.2% of esophageal adenocarcinoma and 23.8% of gastric cardia adenocarcinoma cases. The adjusted odds ratios (ORs) for ever use were 1.0 [95% confidence interval (CI) = 0.7-1.5] and 0.8 (95% CI = 0.5-1.1), respectively. There was little evidence of increasing risk with increasing duration of use of all LES-relaxing drugs together. We found an increased risk of esophageal adenocarcinoma among persons reporting use of asthma drugs containing theophylline (OR = 2.5; 95% CI = 1.1-5.6) or beta agonists (OR = 1.7; 95% CI = 0.8-3.8). Risks were higher among long-term users (>5 years) of these drugs (OR = 3.1; 95% CI = 0.9-10.3 and OR = 2.3; 95% CI = 0.8-7.0, respectively). In contrast, there was no evidence that the use of calcium channel blockers or other specific groups of drugs increased the risk of any of the cancers studied. These results provide reassuring evidence that the increases in incidence of adenocarcinomas of the esophagus and gastric cardia are not likely to be related to the use of LES-relaxing drugs as a group, or calcium channel blockers in particular, but they do suggest that persons treated for long-standing asthma may be at increased risk of esophageal adenocarcinoma.     

Temporal patterns of antihypertensive medication use among older adults, 1989 through 1992. An effect of the major clinical trials on clinical practice?

OBJECTIVE: To describe the changing patterns of antihypertensive medication use in the years immediately before and after the publication of the results of three major clinical trials of the treatment of hypertension in older adults. DESIGN: In this cohort study, adults 65 years or older were examined annually on four occasions between June 1989 and May 1992, and the use of antihypertensive medications was assessed by inventory at each visit. The four visits defined the boundaries of three study periods. For each study period, participants receiving antihypertensive therapy were either continuous users (n = 1667, 1643, and 1605, respectively) or starters (n = 157, 142, 120) of hypertensive therapy. The large clinical trials that convincingly proved the efficacy and safety of low-dose diuretic therapy in older adults were published during the latter parts of period 2 and the early parts of period 3. RESULTS: Among starters, the proportion initiating therapy on diuretics increased from 35.9% in period 2 to 47.5% in period 3, significantly so among women (P = .04). The proportions initiating other drugs displayed no significant trends. Among continuous users, the use of diuretics, beta-blockers, and vasodilators generally decreased over the 3-year period, while the use of calcium channel blockers and angiotensin-converting enzyme inhibitors increased significantly in each of the three periods (P < .05). The decline of 2.7% in the prevalence of diuretic use in period 1 abated during period 2 (1.8% decline), and it slowed significantly (P = .03) to almost a complete halt during period 3 (0.2% decline). The rate of increase in the use of calcium channel blockers slowed significantly (P = .01) between period 1 (+6.7%) and period 3 (+2.8%). CONCLUSIONS: Although other factors such as cost may have been important, the temporal trends in antihypertensive drug therapy coincided in time with and may have reflected in part the influence of the major clinical trials on the patterns of clinical practice.     

Reversal of left ventricular hypertrophy in essential hypertension. A meta-analysis of randomized double-blind studies

OBJECTIVE: To determine the ability of various antihypertensive agents to reduce left ventricular hypertrophy, a strong, blood pressure-independent cardiovascular risk factor, in persons with essential hypertension. DATA SOURCES: MEDLINE, DIMDI, RINGDOC, ADES, EMBASE, and review articles through July 1995 (English-language and full articles only). STUDY SELECTION: Meta-analysis of all published articles including only double-blind, randomized, controlled clinical studies with parallel-group design. DATA EXTRACTION: Intensive literature search and data extraction according to a prefixed scheme performed independently by 2 investigators. Reduction of left ventricular mass index after antihypertensive therapy with placebos, diuretics, beta-blockers, calcium channel blockers, or angiotensin-converting enzyme (ACE) inhibitors was the principal parameter. DATA SYNTHESIS: Of 471 identified references describing the effects of antihypertensive drugs on left ventricular hypertrophy, only 39 clinical trials fulfilled the inclusion criteria of our study. We found that the decrease in left ventricular mass index was more marked the greater was the decline in blood pressure (systolic r=0.46, P<.001; diastolic r=0.21, P=.08) and the longer was the duration of therapy (r=0.38, P<.01). After adjustment for different durations of treatment (mean duration of treatment, 25 weeks), left ventricular mass decreased 13% with ACE inhibitors, 9% with calcium channel blockers, 6% with beta-blockers, and 7% with diuretics. There was a significant difference between drug classes (P<.01): ACE inhibitors reduced left ventricular mass more than beta-blockers (significant, P<.05) and diuretics (tendency, P=.08). Similar differences between drug classes were found with regard to effect on left ventricular wall thickness (P<.05). CONCLUSIONS: The database of articles published through July 1995 is small and incomplete, and most of the articles are of poor scientific quality. In this first meta-analysis including only double-blind, randomized, controlled clinical studies, decline in blood pressure, duration of drug treatment, and drug class determined the reductions in left ventricular mass index. The ACE inhibitors seemed to be more potent than beta-blockers and diuretics in the reduction of left ventricular mass index; calcium channel blockers were somewhat in the intermediate range. The ACE inhibitors and, to a lesser extent, calcium channel blockers emerged as first-line candidates to reduce the risk associated with left ventricular hypertrophy.     

Paediatric rheumatology: clinical practice review. Physiotherapy and occupational therapy for juvenile chronic arthritis: custom and practice in five centres in the UK, USA and Canada

Calcium channel blockers can block calcium signals that trigger cell differentiation and apoptosis, which are important mechanisms of cancer growth regulation. To ascertain whether calcium channel blocker use was associated with an increased risk of cancer, 750 hypertensive persons age > or = 71 years, with no history of cancer at baseline, were followed from 1988 through 1992. The patients were using either beta-blockers, angiotensin converting enzyme inhibitors or calcium channel blockers (verapamil, nifedipine, and diltiazem; mainly of the short-acting variety). Compared to beta-blockers (n = 424, 28 events), after adjusting for age, gender, race, smoking, body mass index, and number of hospital admissions not related with cancer, the relative risks of cancer (95% confidence interval) for angiotensin converting enzyme inhibitors (n = 124, 6 events) and calcium channel blockers (n = 202, 27 events) were 0.73 (0.30 to 1.78) and 2.02 (1.16 to 3.54), respectively. These findings indicate that calcium channel blocker therapy might increase the risk of cancer. New data are needed in patients using modern calcium channel blocker agents with more gradual absorption. This report should encourage further study of cancer outcomes in elderly patients who are vulnerable to cancer and who are receiving calcium channel blockers.     

Performance of a commercial polymerase chain reaction test for endocervical Chlamydia trachomatis infection in a university hospital population

The rate of survival and causes of mortality in a cohort of 2103 psychiatric patients registered on a psychiatric case register and followed up for 7 years are compared with those of a general population sample (n = 2382) randomly extracted from the municipal census in Valencia (Spain). Using multivariate analysis by Cox regression, patients suffering organic psychoses and those diagnosed with drug abuse or dependency exhibited a greater risk of death than the general population for the total causes of death; no interaction was found between sociodemographic variables and psychiatric pathology. In terms of the causes of death, and controlling for the effect of age and sex, organic psychoses involved a greater risk of death due to cardiovascular and respiratory causes, and a greater risk of non-natural deaths than the general population. Schizophrenia and related conditions, the abuse of alcohol/ other drugs, and neurosis/personality disorders all presented a higher risk of death from liver disease. The major affective disorders involved a greater risk of death due to suicide or accidents. The study concludes with a discussion of the possible explanations of these results.     

Use of digoxin, diuretics, beta blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers in older patients in an academic hospital-based geriatrics practice

OBJECTIVE: To investigate the prevalence of and indications for digoxin use and the prevalence of beta blocker and calcium channel blocker use in older patients with previous myocardial infarction or coronary artery disease (CAD), and the prevalence of use of diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers in older patients with hypertension in an academic hospital-based geriatrics practice. DESIGN: A retrospective analysis of charts from 528 unselected older patients, seen from June 1995 through July 1996 at an academic hospital-based geriatrics practice, was performed to investigate the prevalence of digoxin use and indications for digoxin use, the prevalence of beta blocker and calcium channel blocker use in older patients with previous myocardial infarction or coronary artery disease (CAD), and the prevalence of use of diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers in older patients with hypertension. SETTING: An academic hospital-based, primary care geriatrics practice staffed by fellows in a geriatrics training program and full-time faculty geriatricians. PATIENTS: A total of 416 women and 112 men, mean age 81 +/- 8 years (range 58 to 101), were included in the study. MEASUREMENTS AND MAIN RESULTS: Ninety-two of the 528 patients (17%) were taking digoxin. Recorded indications for digoxin were atrial fibrillation with or without congestive heart failure (CHF) in 39% of patients, CHF with sinus rhythm and abnormal left ventricular ejection fraction (LVEF) in 18% of patients, a clinical assessment of CHF with sinus rhythm and no recorded measurement of LVEF in 20% of patients, paroxysmal atrial fibrillation in 14% of patients, and coronary artery disease (CAD) in 9% of patients. Of 121 patients with previous myocardial infarction, 23 (19%) were prescribed beta blockers, and 54 (45%) were taking calcium channel blockers. Of 173 patients with CAD, 41 (24%) were treated with beta blockers, and 79 (46%) were taking calcium channel blockers. LVEF was not recorded in the charts of 90 of 121 patients (74%) with prior myocardial infarction and of 125 of 173 patients (72%) with CAD. Of 480 older patients with hypertension, 154 (37%) were treated with diuretics, 55 (13%) were treated with beta blockers, 160 (38%) were treated with ACE inhibitors, and 197 (47%) were treated with calcium channel blockers. CONCLUSIONS: In 528 older patients seen in an academic hospital-based geriatrics practice, the prevalence of digoxin use was 19%. Appropriate indications for digoxin were documented clearly in the charts of 53 of 92 patients (57%). Calcium channel blockers were used more often than beta blockers in patients with previous myocardial infarction or CAD. Calcium channel blockers were the most frequently used antihypertensive drugs.     

Sexual and drug use behaviors among women crack users: implications for prevention

The literature suggests that important and contributing factors in the rise of HIV and AIDS among women are crack use and the exchange of sex for drugs or money. However, not all women who use crack report they are exchanging sex for drugs or money. Thus, women are at differential risk for HIV and AIDS. The purpose of this study is to compare and describe women crack users (n = 292) who reported exchanging sex for drugs and money with women crack users who did not report exchanging sex. Results indicated that both women crack users who exchanged sex (n = 162) and women crack users who did not exchange sex (n = 130) were likely to be African American, to be about the same age, to have had incomes below +500 during the previous month, to have had similar education and martial backgrounds, to have had unprotected sexual intercourse as often, to have had similar drug use patterns, and to have initiated drug use at similar ages. However, women who exchanged sex had more sexual partners, had unprotected oral sex more often, used drugs before and during sex more often, and had a higher rate of sexually transmitted diseases than women who did not exchange sex. In addition, women who exchanged sex were also twice as likely to be homeless, four times more likely to have been in treatment, and twice as likely to have been arrested and charged/booked two or more times in their lifetime than women who did not exchange sex.     

Prospective study of exogenous hormones and risk of pulmonary embolism in women

BACKGROUND: Current use of oral contraceptives (OCs) is a well-recognised risk factor for venous thrombosis and consequent pulmonary embolism (PE). Little is known about residual effects of past OC use. Furthermore, few epidemiological studies have assessed the relation between postmenopausal use of hormones and thrombotic disease. METHODS: In this prospective study information was obtained through questionnaires sent every 2 years (1976-92) to 1125,93 women aged 30-55 in 1976. We excluded women with previously diagnosed cardiovascular disease or cancer in 1976 and at the beginning of each subsequent 2-year follow-up period. FINDINGS: From self-reports and medical records, we documented 123 cases of primary PE (no identified antecedent cancer, trauma, surgery, or immobilisation). Current users of postmenopausal hormones had an increased risk of primary PE (relative risk adjusted for multiple risk factors 2.1 [95% CI 1.2-3.8]). However, past use showed no relation to PE (1.3 [0.7-2.4]). In current users of OCs the risk of primary PE was about twice that in non-users (2.2 [0.8-5.9]), but this finding was based on only five cases who were current OC users. Users of OCs in the past had no increase in risk of PE (0.8 [0.5-1.2]). These relations were consistent irrespective of cigarette-smoking status. INTERPRETATION: Primary PE was uncommon in this cohort. The risk was increased by current though not past use of postmenopausal hormones or OCs.     

Infection with HIV and hepatitis C virus among injecting drug users in a prevention setting: retrospective cohort study

OBJECTIVES: To estimate the incidence of HIV and hepatitis C virus and risk factors for seroconversion among a cohort of injecting drug users. DESIGN: Retrospective cohort study. SETTING: Primary healthcare facility in central Sydney. SUBJECTS: Injecting drug users tested for HIV-1 antibody (n=1179) and antibodies to hepatitis C virus (n=1078) from February 1992 to October 1995. MAIN OUTCOME MEASURES: Incidence of HIV-1 and hepatitis C virus among seronegative subjects who injected drugs and underwent repeat testing. Demographic and behavioural risk factors for hepatitis seroconversion. RESULTS: Incidence of HIV-1 among 426 initially seronegative injecting drug users was 0.17/100 person years (two seroconversions) compared with an incidence of hepatitis C virus of 20.9/100 person years (31 seroconversions) among 152 injecting drug users initially negative for hepatitis C virus. Incidence of hepatitis C virus among injecting drug users aged less than 20 years was 75.6/100 person years. Independent risk factors for hepatitis C virus seroconversion were age less than 20 years and a history of imprisonment. CONCLUSIONS: In a setting where prevention measures have contributed to the maintenance of low prevalence and incidence of HIV-1, transmission of hepatitis C virus continues at extremely high levels, particularly among young injecting drug users.     

Calcium antagonists and mortality risk in men and women with hypertension in the Framingham Heart Study

BACKGROUND: Several recent studies have suggested that calcium antagonist drugs, which are widely used for the treatment of hypertension, are associated with increased risk of cardiovascular disease. These studies have cast doubts on the long-term safety of calcium antagonists. OBJECTIVE: To examine the association of calcium antagonist use with mortality in subjects with hypertension followed up in the Framingham Heart Study. SUBJECTS AND METHODS: We stratified 3539 subjects (mean+/-SD age, 64+/-13 years) from the Framingham Heart Study who had hypertension at routine clinic examinations, according to the use of calcium antagonists and presence of coronary heart disease at the baseline examination. At each follow-up examination (every 2-4 years), subjects were reclassified with regard to the use of calcium antagonists. The end point of the study was all-cause mortality. Hazard ratios and 95% confidence intervals associated with the use of calcium antagonists were obtained using Cox proportional hazards regression models. RESULTS: There were 970 deaths during follow-up. Hazard ratios for mortality associated with the use of calcium antagonists were 0.93 (95% confidence interval, 0.72-1.21; P=.59) for subjects with hypertension without coronary heart disease, and 0.92 (95% confidence interval, 0.69-1.24; P=.58) for those with coronary heart disease at baseline. All models were adjusted for age, sex, current smoking, systolic and diastolic blood pressure, use of beta-blockers, and use of other antihypertensive medications. CONCLUSIONS: In this cohort of 3539 subjects with hypertension there were no differences in mortality among subjects with hypertension using a calcium antagonist compared with those who were not. Results were similar among subjects with hypertension with and without coronary heart disease. The results of ongoing long-term, randomized clinical trials will provide more definitive data on the safety of calcium antagonists.     

Actual epidemiological problems of bloodborne diseases

The use of acetylsalicylic acid and other non-steroidal, anti-inflammatory drugs was studied prospectively in 207 patients admitted for suspected upper gastrointestinal bleeding. In addition to detailed drug history, plasma samples for drug analyses were obtained from the majority of the patients. 64 of the patients admitted recent intake of ulcerogenic drugs, and the plasma samples revealed another 11 users. Acetylsalicylic acid was the most prevalent substance, but all available non-steroidal, anti-inflammatory drugs were represented in the material. Gastroduodenal ulcers were found in 94 (44%) of the patients; two thirds of the users and one third of the non-users. Gastric ulcer was slightly more prevalent than duodenal ulcer in both groups. Six patients with drug-associated bleeding had previously had a verified drug-associated ulcer. Only 12 users and 16 non-users denied dyspeptic complaints before admission. The users were older, they generally had a lower Hgb on admission than non-users had, and a slightly higher transfusion requirement, but these factors did not result in significant differences as to clinical outcome. The drug analyses of plasma samples showed a discrepancy to the anamnestic data in 25% of the patients and may be a useful addition to drug history in these studies.