Relation between blood pressure and stroke mortality.

The relation between stroke mortality and blood pressure was investigated in 10,186 hypertensive patients followed up in the Department of Health Hypertension Care Computing Project for an average of 9 years. An untreated blood pressure measurement was available in 3,472 men and 3,405 women. The age-adjusted risk of stroke death increased by 1% for every 1 mm Hg increase in untreated systolic blood pressure. The relative hazard rate was 1.014 (95% confidence interval [CI], 1.007, 1.021) in men and 1.009 (1.003, 1.016) in women. The corresponding increases for 1 mm Hg for untreated diastolic blood pressure were almost 3% in men and again 1% in women (relative hazard rate 1.026 [95% CI, 1.014, 1.038] in men and 1.010 [1.000, 1.021] in women). Treated blood pressure measurements were available in 3,073 men and 3,148 women. Stroke mortality increased by 2% for a 1 mm Hg increase in treated systolic pressure and 3% for the corresponding increase in diastolic blood pressure. The relation between stroke mortality and blood pressure was similar over and under the age of 65, although the increase in mortality with pressure was greater for treated diastolic blood pressure in women under the age of 65 than over this age. There was no evidence for a J-shaped relation between stroke mortality and either systolic or diastolic pressure in men. In women there was a suggestion of such a relation, but since this relation was also observed for untreated pressures, any increase in risk at lower pressures is unlikely to be a result of treatment.

Treated blood pressure, rather than pretreatment, predicts survival in hypertensive patients. A report from the DHSS Hypertension Care Computing Project (DHCCP).

A group of hypertensive patients (n = 2855) with an untreated diastolic blood pressure greater than or equal to 90 mmHg were followed in the Department of Health and Social Security (DHSS) Hypertension Care Computing Project (DHCCP) for periods of up to 10 years. During this period 191 of these patients died. Survival was assessed in relation to pretreatment blood pressure levels and blood pressure achieved during treatment. The blood pressure during treatment was a useful predictor of mortality, but the pretreatment pressure was not. After adjusting for age, mortality was particularly related to the height of the systolic and diastolic blood pressure during the second and third years of treatment. In men, age-standardized 5-year mortality was greater than 10% in those with a first year treated systolic pressure greater than 150 mmHg or a diastolic pressure greater than 95 mmHg. In women, age standardized 5-year mortality was greater than 5% with the same levels of treated blood pressure. The longest survival occurred with the lowest bands of treated pressure, i.e. systolic pressure less than 140 and diastolic pressure less than 90 mmHg; the 5-year mortality being less than 7% in men and less than 3% in women. Treated systolic and diastolic pressures were useful in predicting death from ischaemic heart disease (IHD).

The survival of treated hypertensive patients and their causes of death: a report from the DHSS hypertensive care computing project (DHCCP).

A prospective study has been carried out to determine the causes of death and risk factors for survival in 4994 patients referred with a diagnosis of hypertension to hospital specialist clinics and 457 patients treated by their general practitioners for this condition. At the time of entering the prospective study, 69% of the patients were already being treated for hypertension. Four hundred and eleven patients have died, and their causes of death and death rates have been compared with the rates for the population of England and Wales. Ischaemic heart disease accounted for over one-third of the deaths and stroke for one-fifth. The death rates for these conditions were two to five times those expected for men and women aged 50-59 years and up to twice the rate expected for the age group 60-69 years. Survival in these selected patients was impaired by the following independent risk indicators: cigarette smoking, previous history of myocardial infarction or stroke, diagnosis of angina, impaired renal function and raised blood sugar. The following factors were not independent positive risk factors: smoking a pipe or cigars, obesity, a low plasma potassium and an elevated serum uric acid.

Mortality associated with captopril and enalapril: a report from the DHSS Hypertension Care Computing Project.

In 1986, the Committee on Safety of Medicines published a report suggesting that enalapril may have an adverse effect on renal function. The prescription event monitoring scheme subsequently published figures on adverse drug reactions and mortality for patients treated with enalapril. They concluded that enalapril did not have an adverse effect on renal function and survival. Similar data were not available for captopril, as the drug was marketed before prescription event monitoring had been developed. In the Department of Health and Social Security (DHSS) Hypertension Care Computing Project (DHCCP), 368 hypertensive patients treated with captopril and 371 treated with enalapril were followed for an average of 3.1 and 1.6 years, respectively. Thirty-two patients died; none had renal failure as an underlying cause of death. The death rate was similar in both drug groups, at 17.5 (enalapril) and 24.0 (captopril) per 1000 patient-years. The present report shows that, for patients treated for high blood pressure, the relative risk of mortality with captopril compared with enalapril was 1.37, an insignificant difference (95% confidence interval 0.63, 2.98).

Relation between treated blood pressure and death from ischaemic heart disease at different ages: a report from the Department of Health Hypertension Care Computing Project.

OBJECTIVE: To determine the relation between mortality from ischaemic heart disease (IHD) and treated blood pressure at different ages. DESIGN: Prospectively, 6216 patients were studied for a mean of 107 months. SETTING: Of the total patients, 95% were followed in five hospital-based hypertension clinics and the remainder in four group general practices. PATIENTS: Respectively, 2250 and 2126 hypertensive men and women aged < 60 years and 822 and 1018 aged > or = 60 years. MAIN OUTCOME MEASURES: Mortality (any mention on the death certificate) from IHD. RESULTS: Four hundred and sixty-seven patients died with IHD mentioned on the death certificate. The relation between both diastolic blood pressure (DBP) and systolic blood pressure (SBP) during the first 3-12 months of treatment and subsequent IHD mortality was examined. Under the age of 60 years the relative hazard rate (RHR) for death from IHD tended to increase with DBP in both men and women. Above the age of 60 years there was no important or significant relation between IHD mortality and treated DBP. For SBP there was no reduction in the positive relation between IHD mortality and blood pressure in the older age groups. The RHR for SBP ranged between 1.008 and 1.021 in men and women over and under the age of 60 years. CONCLUSIONS: The positive relation between DBP and IHD mortality decreased with increasing age and, in women aged > or = 60 years, even inverted, partly explaining the negative relation reported between DBP and total mortality in the very old.

Alcohol intake and cardiovascular mortality in hypertensive patients: report from the Department of Health Hypertension Care Computing Project.

OBJECTIVE: To determine the benefits and risks of drinking alcohol in treated hypertensives. DESIGN: A prospective study of 6,369 hypertensives (3,161 men) attending primarily hospital clinics in the UK. METHODS: Relative risks both for drinkers compared with non-drinkers and for level of alcohol consumption were calculated for mortality from ischaemic heart disease, stroke, non-circulatory and all causes. RESULTS: At presentation 76% of the men and 48% of the women reported recent alcohol consumption. Compared with drinkers, non-drinkers were older, less likely to smoke and had a higher untreated blood pressure. After adjustment for confounding factors, male drinkers had a reduced risk of stroke mortality and possibly of ischaemic heart disease mortality. Similar results were observed in women for stroke mortality but not for ischaemic heart disease mortality. The trend remained after adjustment for previous cardiovascular disease. In men the lowest risk of ischaemic heart disease mortality occurred at intakes of > 21 units per week and stroke mortality was lowest at 1-10 units per week. Men consuming > 21 units per week had a twofold higher non-circulatory mortality. Total mortality was lowest in men who drank 1-10 units per week. Similar effects of alcohol on cardiovascular mortality were observed in women. CONCLUSIONS: Alcohol intake may reduce stroke mortality in treated hypertensives. Ischaemic heart disease mortality in men may also be reduced, especially at higher intakes ( > 21 units per week). The beneficial effects were offset by increasing incidence of non-circulatory causes of death. Alcohol consumption of 1-10 units per week was associated with the lowest mortality in men.

An evaluation of automatic coding of surgical pathology reports.

The use of the Systematised Nomenclature of Pathology as the basis of an indexing system to histopathological data is outlined. Two computer programs which perform the task of producing codes from free English summaries are compared. It is concluded that a simple system has a great deal to offer the pathologist who is prepared to accept a set of constraints.

Calcium channel blockers, ACE inhibitors, and the risk of cancer in hypertensive patients: a report from the Department of Health Hypertension Care Computing Project (DHCCP)

OBJECTIVE: Recent studies have shown inconsistent results on the risk of cancer in hypertensive patients using calcium channel blockers (CCBs) and angiotensin-converting enzyme (ACE) inhibitors. We investigated a large number of patients from the Department of Health Hypertension Care Computing Project (DHCCP) observational database treated with these drugs for hypertension to see whether the use of CCBs for hypertension is associated with an increased risk of cancer mortality and the use of ACE inhibitors with a reduction. DESIGN: Matched case-control study and a longitudinal study of survival from 1 year after presentation. PATIENTS: A total of 11663 patients treated for hypertension from 1971 through 1987. They were recruited on presentation to one of the hospital hypertension clinics or general practices involved. MAIN OUTCOME MEASURES: Death with any mention of cancer on the death certificate in patients treated with an Index drug group; CCBs, ACE inhibitors, beta adrenergic blocking drugs (BBs), or receiving a diuretic. The treatment groups were mutually exclusive. RESULTS: A total of 391 cases of cancer were matched with 1050 controls. In this case-control study the adjusted relative risk estimate in comparison to diuretic treatment for CCBs was 0.79 (95% CI 0.37 to 1.69), and for CCBs plus a diuretic, 1.05 (0.65 to 1.69). Non-significant results were also observed for ACE inhibitors (1.48 (0.43 to 5.1), and 1.40 (0.56 to 3.50) with a diuretic), and also for the BB and methyldopa groups. In the longitudinal survival study, the adjusted relative risk estimate for CCBs was 1.1 (0.60 to 1.94) and 1.0 (0.53 to 1.86) for CCBs plus a diuretic, and for ACE inhibitors 1.33 (0.37 to 4.76) and 1.47 (0.67 to 3.23), respectively. CONCLUSIONS: In this population there was no increased cancer mortality with the use of CCBs and a relative risk greater than 1.7 to 2.0 was excluded with 95% confidence. The suggestion that ACE inhibitors reduce cancer mortality was not supported with best estimates of relative risk of 1.3 to 1.5 and exclusion of values less than 0.4 to 0.7.

Calcium channel blockers and cardiac mortality in the treatment of hypertension: a report from the Department of Health Hypertension Care Computing Project (DHCCP).

OBJECTIVE: A case control study has reported a 60% higher risk of myocardial infarction in hypertensives treated with a calcium channel blocker (CCB). We examined the Department of Health Hypertension Care Computing Project (DHCCP) data to see if we could confirm or refute this suggestion. DESIGN: Two case control studies, matched and unmatched, plus two longitudinal studies from 1 year of presentation, one for all subjects given a CCB for more than 1 year compared with those not given this drug, and the second comparing survival on the different drugs initially given between 3 and 12 months of follow-up. SUBJECTS: A total of 9328 subjects were included in the analyses and 2154 died. Of these, 6406 received one or more of the following index drugs: 26% a calcium channel blocker (CCB); 84% a diuretic; 29% alpha methyldopa; 12% a beta-blocker (BB); and 11% an angiotensin-converting enzyme (ACE) inhibitor. The CCBs were nifedipine, diltiazem or verapamil. RESULTS: In the case control studies a group given diuretics +/- other treatments (but not including one of the index drugs) provided a reference group with a relative risk (RR) of 1.0. In the matched case control study the adjusted RR for a CCB without a diuretic was 1.32 (95% CI 0.64-2.70) for IHD mortality and 1.05 (95% CI 0.60-1.84) for cardiovascular mortality. Similar results were observed for methyldopa, BBs and ACE inhibitors. The results in the unmatched case control analysis were also similar. The longitudinal study comparing all those treated for over 1 year with a CCB with all other treatments showed a RR for total mortality of 1.03 (95% CI 0.85-1.25). The longitudinal study of total mortality according to treatment initiated at 3-12 months found results of a similar magnitude for CCBs, methyldopa and BBs. CONCLUSIONS: The reference diuretic group had less severe cardiovascular disease than other groups. Treatment with a CCB, BB or methyldopa was associated with an excess mortality in comparison with this reference group. The excess was similar in the different drug groups.

The determinants of left ventricular hypertrophy defined by Sokolow-Lyon criteria in untreated hypertensive patients.

Left ventricular hypertrophy (LVH) measured by electrocardiography (ECG LVH) in hypertensive patients has been shown to be associated with an increased risk of cardiovascular sequelae. Analysis of the determinants predisposing to ECG LVH may be helpful in the prevention of LVH. The Department of Health and Social Security Hypertension Care Computer Project studied 2994 hypertensive patients in whom an electrocardiogram was recorded while not on treatment. LVH was determined as the voltage sum SV1+RV5 or RV6>or=35 mm using Sokolow-Lyon voltage criteria. The relations were determined between the presence of LVH or voltage sum and different variables. Untreated systolic (SBP) and diastolic (DBP) blood pressure and pulse pressure were positively related to the increasing ECG voltage, while body mass index (BMI) and serum cholesterol were inversely related. Blood glucose and age did not correlate significantly. Patients with the presence of ECG LVH were more often men, black people, smokers and users of alcohol. In multiple logistic regression analyses, SBP, DBP, male gender and black race were positively, whereas BMI was negatively related to the presence of LVH. The positive relation of smoking and negative relation of serum cholesterol concentration to the presence of ECG LVH were apparent in men but not in women. This study confirms the adverse association between ECG LVH and SBP and DBP, male gender, black race and decreased BMI. It also addresses the less well-known associations of blood glucose, cholesterol, smoking and alcohol consumption.

Beta adrenoceptor blockade is associated with increased survival in male but not female hypertensive patients: a report from the DHSS Hypertension Care Computing Project (DHCCP).

The DHCCP is a multicentre observational study of patients being treated for hypertension in the United Kingdom. The influence of the type of anti-hypertensive therapy on survival was examined in 2,697 patients followed from 1971 with 206 deaths up to November 1981. Patients were classified by three types of treatment after one year in the project: betablockers (1,387), methyldopa (452) and others (667), (70% on diuretics only). The data were analysed both for all patients and for a subset excluding patients with previous ischaemic heart disease by all cause and IHD age-adjusted rates and life table analysis. Men on beta blockers had lower rates for total mortality, when compared with men on methyldopa (64% of the methyldopa rate, P less than 0.05) and when compared with men on other treatments (76% of the other treatment rate, P less than 0.1). The results for IHD mortality were similar. This improved survival of men in the beta blocker group was also found in the subset with no prior history of IHD. The benefit of beta blockers was not apparent in women: the lowest rates were observed for women on methyldopa, but the confidence limits for the ratios of relative rates were wide. Adjustment for blood pressure and cigarette smoking using the Cox proportional hazards model did not substantially modify the ratios of the mortality rates for the treatment groups. A sub-group analysis showed the reduction in all cause and IHD mortality associated with beta blockers was mainly due to the effect in non-smoking men.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between a low treated blood pressure and IHD mortality: a report from the DHSS Hypertension Care Computing Project (DHCCP).

The suggestion that treating blood pressure to below a certain level may increase IHD mortality is controversial. We investigated the influence of treated blood pressure on mortality in the DHSS Hypertension Care Computer Project. Mortality was examined by quintiles of treated diastolic blood pressure (DBP) in 2,145 patients treated for a minimum period of one year and subsequently followed for an average of four years. One hundred and seventy five patients died; 71 from IHD. In men and women all cause mortality increased with level of treated DBP. In men IHD mortality showed a U-shaped distribution with an age-adjusted rate of 15.2 per 1,000 person years in the lowest fifth (DBP less than 86 mmHg) comparable to that of 15.6 per 1,000 in the upper (DBP greater than or equal to 103 mmHg). A similar pattern could not be established in women due to very few IHD deaths. IHD mortality was further examined separately for men by prior history of IHD. An increase in IHD deaths in the lowest fifth of treated blood pressure was found for men both with and without a history of IHD. No similar pattern of IHD mortality was obtained for untreated DBP or treated systolic pressure. However, we cannot exclude the possibility that the risk of low treated DBP is secondary to ischaemic heart disease.

The effects of anti-hypertensive drugs on sexual function in men and women: a report from the DHSS Hypertension Care Computing Project (DHCCP).

One thousand, two hundred and eighty-five men and 1,080 women being followed in the DHSS Hypertension Care Computing Project answered the questions on sexual activity included in a self-administered questionnaire. In men, both impotence and sexual inactivity were increased in patients receiving hydralazine. No gross excess of these complaints could be determined in patients receiving either beta-adrenoceptor blocking drugs or methyldopa, nor was failure of ejaculation increased with these drugs. The survey could not exclude any deterioration in sexual function occurring uniformly across all treatment groups. However, the rates of complaint were similar in men taking a diuretic alone, a beta-adrenoceptor blocking drug alone and those taking the combination of these two drug groups. In women with hypertension, frequency of sexual intercourse and the achievement of orgasm was not associated with the giving of hydralazine, beta-adrenoceptor blocking drugs or methyldopa.

A randomised study of a domiciliary antenatal care scheme: maternal psychological effects.

The Cardiff Integrated Antenatal Care Scheme (CIACS) places emphasis on home-centred care for selected women with a high-risk pregnancy. The Scheme is intended to make better use of midwifery and obstetric resources, and it provides a new type of care where close surveillance is required. A randomised controlled trial was undertaken in which anxiety levels were compared between two groups of women with an identified high-risk pregnancy. Sixty-five women were eligible for entry to the study. Five refused randomisation and 60 were randomised 2:1 either to care under the CIAC Scheme (domiciliary group n = 40) or to conventional hospital antenatal care (conventional group n = 17). Zung depression and STAI 'trait' levels conducted at weekly intervals were similar in both groups whilst 'state' levels were 34.05 (SD 9.24) in the domiciliary group and 41.05 (SD 9.93) in the conventional care group (P less than 0.01). It is suggested that the observed difference is due to the greater security provided by the home environment coupled with individual support from a midwife.

Visit frequency for essential hypertension: observed associations.

Data from the British Department of Health and Social Services Hypertension Care Computing Project were analyzed to study determinants of visit frequency in hypertension management. The 457 patients from five general practices made 7974 visits between 1971 and 1985 resulting in 7391 intervals on which evaluation could be based. The mean interval between visits was 113 days (SD = 110 days) with a median interval of 91 days. Visit interval was influenced by level of blood pressure and length of time in follow-up. For diastolic pressures less than 104 mmHg the mean visit interval was 4 months, contrasting with 2 months for diastolic pressures greater than 130 mmHg. Visit intervals became longer with increasing length of time in follow-up, independent of level of blood pressure. Shorter intervals reflected initial management and getting the blood pressure reduced; longer intervals may reflect patients' failure to keep scheduled appointments. Between practices, mean visit intervals ranged from 99 to 193 days (median 72 to 164 days). These differences were reduced after adjustment for length of time the patients had been in follow-up. Patient age, sex, body mass index, and the presence of angina pectoris were not associated with visit interval. The analyses illustrate how process and outcome may be linked in ambulatory care practice as a means of determining rational guidelines for optimal utilization of health services.

Importance of assessing cytogenetic and molecular risk factors in acute myeloid leukemia therapy.

Acute myeloid leukemia (AML) is a heterogeneous disease in clinical presentation, outcome and therapeutic response. Cytogenetic and molecular characteristics are important prognostic indicators allowing the identification of distinct subtypes of AML, prognostic stratification and risk-adapted treatment. We present our experience during 5 years, in which we treated 245 patients with AML, of which we could genetically characterize 48 cases (26 females, 22 males) with a median age of 52 years. Cytogenetic analysis was performed by GTG banding on cultures of marrow cells treated with colcemid. Molecular analysis used RT-PCR performed on ABI 9700 platform in order to identify the following fusion genes: E2A-PBX1, TEL-AML1, AML1-ETO, PML-RARα, MLL-AF4, CBFC-MYH11, BCR-ABL, SIL-TAL, and MLL-AF9as well as mutations in Flt3, NPM1, WT1 genes. Fourteen patients were older than 60 years. In 12 we performed cytogenetic analysis showing 5 cases with complex karyotype, 2 normal karyotypes, 1 case of del(21), del (9), 11q- and t(3;15) respectively as well as 2 unevaluable karyotypes. These anomalies were associated with a high incidence of secondary AMLs (10/14) and with a low remission (CR) rate (5/14). Out of the 35 patients younger than 60 years, 25 were evaluated by cytogenetics showing a high incidence of favorable cytogenetic changes: 6 anomalies of chromosome 16 (5 inv (16) and 1 t (16; 16)), 3 t (15; 17), 3 cases of t (8; 21) of which 2 with additional abnormalities, 7 normal karyotypes and 1 case of 7q-, -y,-3 and respectively -8 associated with +18. In 25 cases molecular analysis was performed showing alterations in 21 patients: 6 cases with AML/ETO, 3 PML/RAR, 7 Flt3 mutations (2 associated with NPM1 mutation) as well as 1 case of isolated mutation of NPM1 and respectively WT1. CR rate was of 28/35. All cases with t (15; 17) and PML/RAR as well all cases with t (8; 21) and/or AML/ETO achieved CR. Out of the 7 cases with Flt3 mutations only 4 achieved CR including the 2 cases with associated NPM1 mutations. In our experience, genetic characteristics correlate with other prognostic markers such as age and secondary leukemia; "favorable" genetic anomalies were associated with a high CR rate; association of t (8; 21) with additional abnormalities did not influence CR rate.

What factors influence functional ability in patients with rheumatoid arthritis. Do they alter over time?

OBJECTIVES: To describe the changes in functional ability (FA) taking place over 5 yr in patients with rheumatoid arthritis (RA) starting disease-modifying anti-rheumatic drug (DMARD) therapy, to investigate the factors having most influence upon FA and to compare these factors at baseline and after 5 yr of treatment. METHODS: Three hundred and sixty-six patients with active RA were studied as part of a 5-yr randomized controlled study of DMARD therapy. FA was assessed by Health Assessment Questionnaire (HAQ) score every 6 months. Multiple linear regression was used to identify factors affecting FA at baseline and at 5 yr. The independent variables used were age, sex, visual analogue scale (VAS) pain, Ritchie articular index, C-reactive protein (CRP), Larsen score and log-transformed morning stiffness (EMS). RESULTS: Mean HAQ score was 1.64 at baseline, improved by 21% at 1 yr and gradually returned towards baseline levels by 5 yr. At baseline only 34% of variance in HAQ score could be explained; the most significant explanatory variables were the Ritchie articular index and CRP. At 5 yr the variance explained was 60%. The Ritchie articular index remained the strongest factor followed by VAS pain, log(10) EMS and Larsen score. CONCLUSIONS: Improvement in function did occur after commencement of the first DMARD therapy but was not maintained to 5 yr. The most consistent factor affecting function was joint tenderness. Global pain and duration of EMS were of lesser importance. Disease activity measures such as the CRP exerted an influence in the earlier, more active stages of disease: radiographic damage assumed greater importance as the arthritis progressed.

Assessing birth weight-for-dates on a continuous scale.

Mathematical models have been fitted to the widely used standards of birth weight by gestational age that were published by Thomson, Billewicz and Hytten (1968). The models give a close fit to the data and allow an individual infant's weight to be scored on a continuous scale as a number of standard deviations from the expected weight.

Nomograms for precise determination of birth weight for dates.

We have derived a mathematical model (Altman and Coles, 1980) that matches closely the birth weight standards derived from the large Aberdeen survey (Thomson et al, 1968). From this, we have drawn nomograms that can be used to assess an infant's position in relation to these standards. The nomograms are easy to use and give adequate precision.