Low blood pressure and depression in older men: a population based study.

OBJECTIVE--To determine if an association exists between low blood pressure and depressive symptoms in older men living in the community. DESIGN--Cross sectional, population based study. SETTING--Town of Rancho Bernardo, California, United States. SUBJECTS--846 men aged 60-89 years. Comparisons between hypotensive, normotensive, and hypertensive groups were limited to 594 men not taking drugs for hypertension. MAIN OUTCOME MEASURES--Mean scores on Beck depression inventory and prevalence of scores > or = 13. RESULTS--Men with diastolic blood pressure < 75 mm Hg had significantly higher depression scores (mean scores 6.35 v 4.96; P < 0.001) and more categorical depression (7.6% v 1.8% with scores > or = 13; P < 0.01) than men with diastolic blood pressure levels between 75 and 85 mm Hg. Men with diastolic blood pressure levels > 85 mm Hg had higher depression scores than men with intermediate blood pressure levels (mean scores 5.85 v 4.96; P < 0.05). Men with diastolic hypotension scored significantly higher on both affective and somatic item subscales of the Beck depression inventory and on individual measures of fatigue, pessimism, sadness, loss of appetite, weight loss, and preoccupation with health. Low diastolic blood pressure was a significant predictor of both mean depression score and prevalence of categorical depression, independent of age and change in weight since the baseline visit. The presence of several chronic diseases was associated with depressed mood and higher blood pressure but not with low blood pressure. CONCLUSION--The association of relatively low diastolic blood pressure with higher depressive symptom scores and rates of categorical depression was independent of age or weight loss. Since fatigue is a prominent symptom of depression, any association of low blood pressure with fatigue could reflect depressive disorders or clinically important depression.     

Incidence of myocardial infarction in elderly men being treated with antihypertensive drugs: population based cohort study.

OBJECTIVE: To analyse the association between use of antihypertensive treatment, diastolic blood pressure, and long term incidence of ischaemic cardiac events in elderly men. DESIGN: Population based cohort study. Baseline examination in 1982-3 and follow up for up to 10 years. SETTING: Malmŏ, Sweden. SUBJECTS: 484 randomly selected men born in 1914 and living in Malmŏ during 1982. MAIN OUTCOME MEASURES: Observational comparisons of incidence rates and rate and hazard ratios of ischaemic cardiac events (myocardial infarction or death due to chronic ischaemic cardiac disease). RESULTS: The crude incidence rate of ischaemic cardiac events was higher in those subjects who were taking antihypertensive drugs than in those who were not (rate ratio 2.6 (95% confidence interval 1.7 to 3.9)). After adjustment for potential confounders (differences in baseline smoking habits, blood pressure, time since diagnosis of hypertension, ischaemic or other cardiovascular disease, hypercholesterolaemia, hypertriglyceridaemia, diabetes mellitus, obesity, and raised serum creatinine concentration) this rate was reduced but still raised (hazard ratio 1.9 (1.0 to 3.7)). In men with diastolic blood pressure > 90 mm Hg, antihypertensive treatment was associated with a twofold increase in the incidence of ischaemic cardiac events (rate ratio 2.0 (1.1 to 3.6)), which vanished after adjustment for potential confounders (hazard ratio 1.1 (0.5 to 2.6)). In those subjects with diastolic blood pressure < or = 90 mm Hg, antihypertensive treatment was associated with fourfold increase in incidence (rate ratio 3.9 (2.1 to 7.1)), which remained after adjustment for potential confounders (hazard ratio 3.8 (1.3 to 11.0)). CONCLUSION: Antihypertensive treatment may increase the risk of myocardial infarction in elderly men with treated diastolic blood pressures < or = 90 mm Hg.     

Waist circumference action levels in the identification of cardiovascular risk factors: prevalence study in a random sample.

OBJECTIVE--To determine the frequency of cardiovascular risk factors in people categorised by previously defined "action levels" of waist circumference. DESIGN--Prevalence study in a random population sample. SETTING--Netherlands. SUBJECTS--2183 men and 2698 women aged 20-59 years selected at random from the civil registry of Amsterdam and Maastricht. MAIN OUTCOME MEASURES--Waist circumference, waist to hip ratio, body mass index (weight (kg)/height (m2)), total plasma cholesterol concentration, high density lipoprotein cholesterol concentration, blood pressure, age, and lifestyle. RESULTS--A waist circumference exceeding 94 cm in men and 80 cm in women correctly identified subjects with body mass index of > or = 25 and waist to hip ratios > or = 0.95 in men and > or = 0.80 in women with a sensitivity and specificity of > or = 96%. Men and women with at least one cardiovascular risk factor (total cholesterol > or = 6.5 mmol/l, high density lipoprotein cholesterol < or = 0.9 mmol/l, systolic blood pressure > or = 160 mm Hg, diastolic blood pressure > or = 95 mm Hg) were identified with sensitivities of 57% and 67% and specificities of 72% and 62% respectively. Compared with those with waist measurements below action levels, age and lifestyle adjusted odds ratios for having at least one risk factor were 2.2 (95% confidence interval 1.8 to 2.8) in men with a waist measurement of 94-102 cm and 1.6 (1.3 to 2.1) in women with a waist measurement of 80-88 cm. In men and women with larger waist measurements these age and lifestyle adjusted odds ratios were 4.6 (3.5 to 6.0) and 2.6 (2.0 to 3.2) respectively. CONCLUSIONS--Larger waist circumference identifies people at increased cardiovascular risks.     

Case-control study of stroke and the quality of hypertension control in north west England.

OBJECTIVE: To examine the risk of stroke in relation to quality of hypertension control in routine general practice across an entire health district. DESIGN: Population based matched case-control study. SETTING: East Lancashire Health District with a participating population of 388,821 aged < or = 80. SUBJECTS: Cases were patients under 80 with their first stroke identified from a population based stroke register between 1 July 1994 and 30 June 1995. For each case two controls matched with the case for age and sex were selected from the same practice register. Hypertension was defined as systolic blood pressure > or = 160 mm Hg or diastolic blood pressure > or = 95 mm Hg, or both, on at least two occasions within any three month period or any history of treatment with antihypertensive drugs. MAIN OUTCOME MEASURES: Prevalence of hypertension and quality of control of hypertension assessed by using the mean blood pressure recorded before stroke) and odds ratios of stroke (derived from conditional logistic regression). RESULTS: Records of 267 cases and 534 controls were examined; 61% and 42% of these subjects respectively were hypertensive. Compared with non-hypertensive subjects hypertensive patients receiving treatment whose average pre-event systolic blood pressure was controlled to < 140 mm Hg had an adjusted odds ratio for stroke of 1.3 (95% confidence interval 0.6 to 2.7). Those fairly well controlled (140-149 mm Hg), moderately controlled (150-159 mm Hg), or poorly controlled (> or = 160 mm Hg) or untreated had progressively raised odds ratios of 1.6, 2.2, 3.2, and 3.5 respectively. Results for diastolic pressure were similar; both were independent of initial pressures before treatment. Around 21% of strokes were thus attributable to inadequate control with treatment, or 46 first events yearly per 100,000 population aged 40-79. CONCLUSIONS: Risk of stroke was clearly related to quality of control of blood pressure with treatment. In routine practice consistent control of blood pressure to below 150/90 mm Hg seems to be required for optimal stroke prevention.     

Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland.

OBJECTIVE: To examine the association between plasma vitamin C concentrations and the risk of acute myocardial infarction. DESIGN: Prospective population study. SETTING: Eastern Finland. SUBJECTS: 1605 randomly selected men aged 42, 48, 54, or 60 who did not have either symptomatic coronary heart disease or ischaemia on exercise testing at entry to the Kuopio ischaemic heart disease risk factor study in between 1984 and 1989. MAIN OUTCOME MEASURES: Number of acute myocardial infarctions; fasting plasma vitamin C concentrations at baseline. RESULTS: 70 of the men had a fatal or non-fatal myocardial infarction between March 1984 and December 1992.91 men had vitamin C deficiency (plasma ascorbate < 11.4 mumol/l, or 2.0 mg/l), of whom 12 (13.2%) had a myocardial infarction; 1514 men were not deficient in vitamin C, of whom 58 (3.8%) had a myocardial infarction. In a Cox proportional hazards model adjusted for age, year of examination, and season of the year examined (August to October v rest of the year) men who had vitamin C deficiency had a relative risk of acute myocardial infarction of 3.5 (95% confidence interval 1.8 to 6.7, P = 0.0002) compared with those who were not deficient. In another model adjusted additionally for the strongest risk factors for myocardial infarction and for dietary intakes of tea fibre, carotene, and saturated fats men with a plasma ascorbate concentration < 11.4 mumol/l had a relative risk of 2.5 (1.3 to 5.2, P = 0.0095) compared with men with higher plasma vitamin C concentrations. CONCLUSIONS: Vitamin C deficiency, as assessed by low plasma ascorbate concentration, is a risk factor for coronary heart disease.     

Blood pressure and five year survival in the very old

During 1977-8 we measured blood pressure in 561 old people (83% of those aged 85 or more living in Tampere) and analysed their five year survival according to their blood pressure group. The subjects were divided into six groups on the basis of their blood pressures (from <120 to >200 mm Hg systolic, from <70 to >110 diastolic). The greatest mortality was observed in those in the lowest systolic and lowest diastolic groups. Mortality was least in subjects with systolic pressures of 160 mm Hg or more and diastolic pressures of 90 mm Hg or more.The most essential finding in this series of the very old was an increased mortality in the lowest blood pressure groups.     

Blood pressure in prospective population based cohort of newborn and infant twins.

OBJECTIVE--To describe blood pressure in twins during infancy. DESIGN--Prospective study of cohort of twins. SETTING--Teaching hospital in Florida. SUBJECTS--166 viable twin pairs born between July 1976 and December 1989. MAIN OUTCOME MEASURES--Blood pressure and body weight at birth, at 14 days, and at 1, 3, 6, 9, and 12 months. RESULTS--Both systolic and diastolic pressure correlated with body weight throughout infancy (at birth r = 0.41, P < 0.001 and r = 0.42, P < 0.001 respectively; at 1 year r = 0.23, P < 0.001 and r = 0.26, P < 0.001 respectively). In infants weighing < 1500 g at birth mean blood pressure rose from about 45/25 mm Hg to 101/55 mm Hg from birth to the age of 1 year, while in infants weighing > 3000 g at birth it rose from 63/39 mm Hg to 100/61 mm Hg; corresponding mean body weights at 1 year were 7.86 kg and 9.88 kg. Differences in birth weight within pairs of monozygotic twins were negatively correlated with such differences in systolic blood pressure at 1 year (r = -0.37, P < 0.01). CONCLUSIONS--Blood pressure and body weights in twins showed strongly positive but generally declining correlations throughout infancy. Twins of lower birth weight showed a more rapid rate of rise in blood pressure during infancy. At 1 year the catch up in blood pressure exceeded that in body weight. Greater differences in birth weights between monozygotic twins were associated with smaller differences in systolic blood pressure at 1 year, suggesting that intrauterine environmental factors related to birth weight are important in determining blood pressure in infancy.     

Effectiveness of health checks conducted by nurses in primary care: final results of the OXCHECK study. Imperial Cancer Research Fund OXCHECK Study Group.

OBJECTIVE--To determine the effectiveness of health checks, performed by nurses in primary care, in reducing risk factors for cardiovascular disease and cancer. DESIGN--Randomised controlled trial. SETTING--Five urban general practices in Bedfordshire. SUBJECTS--2205 men and women who were randomly allocated a first health check in 1989-90 and a re-examination in 1992-3 (the intervention group); 1916 men and women who were randomly allocated an initial health check in 1992-3 (the control group). All subjects were aged 35-64 at recruitment in 1989. MAIN OUTCOME MEASURES--Serum total cholesterol concentration, blood pressure, body mass index, and smoking prevalence (with biochemical validation of cessation); self reported dietary, exercise, and alcohol habits. RESULTS--Mean serum total cholesterol was 3.1% lower in the intervention group than controls (difference 0.19 mmol/l (95% confidence interval 0.12 to 0.26)); in women it was 4.5% lower (P < 0.0001) and in men 1.6% (P < 0.05), a significant difference between the sexes (P < 0.01). Self reported saturated fat intake was also significantly lower in the intervention group. Systolic and diastolic blood pressures and body mass index were respectively 1.9%, 1.9%, and 1.4% lower in the intervention group (P < 0.005 in all cases). There was a 3.9% (2.4 to 5.3) difference in the percentage of subjects with a cholesterol concentration > or = 8 mmol/l, but no significant differences in the number with diastolic blood pressure > or = 100 mm Hg or body mass index > or = 30 kg/m2. There was no significant difference between the two groups in prevalence of smoking or excessive alcohol use. Annual rechecks were no more effective than a single recheck at three years, but health checks led to a significant increase in visits to the nurse according to patients'' degree of cardiovascular risk. CONCLUSIONS--The benefits of health checks were sustained over three years. The main effects were to promote dietary change and reduce cholesterol concentrations; small differences in blood pressure may have been attributable to accommodation to measurement. The benefits of systematic health promotion in primary care are real, but must be weighed against the costs in relation to other priorities.     

Screen detected high blood pressure under 40: a general practice population followed up for 21 years.

OBJECTIVE--To assess hypertension detected under 40 in a general practice population. DESIGN--Prospective case-control study. SETTING AND SUBJECTS--Former coal mining community in south Wales. Systematic case finding for hypertension and associated risk factors applied to a mean total population of 1945 from age 20 on a five year cycle through 21 years. Mean population aged 20-39, 227 men and 213 women. Case criteria: age < 40 and mean systolic pressure > or = 160 mm Hg or diastolic pressure > or = 100 mm Hg. Age and sex matched controls randomly sampled from the same population. MAIN OUTCOME MEASURES--Mean initial pressures and pressures at follow up in 1989 or preceding death, and all cardiovascular events. RESULTS--25 men and 16 women met criteria. Estimated five yearly inceptions were 26/1000 for men and 18/1000 for women. Male group mean initial blood pressure was 164/110 mm Hg for cases, falling to 148/89 mm Hg at follow up. Five male cases died at mean age 47.8, compared with two controls at 49.5. Female group mean initial pressure was 172/107 mm Hg for cases, falling to 145/86 mm Hg at follow up. One female case died aged 50, no controls. 10 male cases had non-fatal cardiovascular events at mean age 40.2, compared with two controls at mean age 50.5. Four female cases had non-fatal events at mean age 47.2, compared with one control aged 58. Male differences were statistically significant. CONCLUSIONS--Hypertension under 40 is dangerous, commoner in men than women, rarely secondary to classic causes, and may be controlled in general practice on a whole community basis.     

Clinical and angiographic predictors of stroke and death from carotid endarterectomy: systematic review.

OBJECTIVE: To identify risk factors for operative stroke and death from carotid endarterectomy. DESIGN: Systematic review of all studies published since 1980 which related risk of stroke and death to various preoperative clinical and angiographic characteristics, including unpublished data on 1729 patients from the European carotid surgery trial. MAIN OUTCOME MEASURE: Operative risk of stroke and death. RESULTS: Thirty six published studies fulfilled our criteria. The effect of 14 potential risk factors was examined. The odds of stroke and death were decreased in patients with ocular ischaemia alone (amaurosis fugax or retinal artery occlusion) compared with those with cerebral transient ischaemic attack or stroke (seven studies; odds ratio 0.49; 95% confidence interval 0.37 to 0.66; P < 0.00001). The odds were increased in women (seven studies; 1.44; 1.14 to 1.83; P < 0.005), subjects aged > or = 75 years (10 studies: 1.36; 1.09 to 1.71; P < 0.01), and with systolic blood pressure > 180 mm Hg (four studies; 1.82; 1.37 to 2.41; P < 0.0001), peripheral vascular disease (one study; 2.19; 1.40 to 3.60; P < 0.0005), occlusion of the contralateral internal carotid artery (14 studies; 1.91; 1.35 to 2.69; P < 0.0001), stenosis of the ipsilateral internal carotid siphon (five studies; 1.56; 1.03 to 2.36; P = 0.02), and stenosis of the ipsilateral external carotid artery (one study; 1.61; 1.05 to 2.47; P = 0.03). Operative risk was not significantly related to presentation with cerebral transient ischaemic attack versus stroke, diabetes, angina, recent myocardial infarction, current cigarette smoking, or plaque surface irregularity at angiography. Multiple regression analysis of data from the European carotid surgery trial identified cerebral versus ocular events at presentation, female sex, systolic hypertension, and peripheral vascular disease as independent risk factors. CONCLUSIONS: The risk of stroke and death from carotid endarterectomy is related to several clinical and angiographic characteristics. These observations may help clinicians to estimate operative risks for individual patients and will also facilitate more meaningful comparison of the operative risks of different surgeons or at different institutions by allowing some adjustment for differences in case mix.     

Effectiveness of programme for reducing cardiovascular risk for men in one general practice.

OBJECTIVES--To assess the effectiveness of a programme for reducing cardiovascular risk in men in terms of clinical measurements and perceptions of patients. DESIGN--Collection of paired data on men attending well person clinics over three to five years. Questionnaire to determine changes in risk related habits. SETTING--Well person clinics in rural general practice with five partners in mid-Wales. SUBJECTS--The first 687 men seen in the clinic: analysable data obtained on 520. Initial age range 28-60 years. MAIN OUTCOME MEASURES--Analysis of serum cholesterol concentration (mmol/l) and blood pressure (mm Hg). Changes in diet, exercise, smoking, and drinking. RESULTS--Mean (SD) cholesterol concentration for all subjects increased from 5.8 (1.0) to 6.0 (1.0), p < 0.001. Overall percentage of ideal weight and mean systolic blood pressure also increased. Mean diastolic blood pressure was unchanged at 84 mm Hg. Professed dietary change, age, and number of visits all had significant effects on final cholesterol concentration. Those seen more often showed a significant decrease in cholesterol concentrations (in those seen more than twice mean (SD) initial value 6.7 (0.9) mmol/l v final value 6.5 (1.0) mmol/l, p < 0.001). Those over 45 years at start of study showed a significant decrease in diastolic blood pressure (mean (SD) initial value 89 (9) mm Hg v final value 86 (7) mm Hg, p < 0.001). CONCLUSIONS--These clinics are not effective in achieving a reduction in mean cholesterol concentration or blood pressure, despite evidence that the message of reduction in risk had been successfully transmitted. Success was achieved in older patients and those in whom a definite problem was identified. Identification of high risk groups and clinical case finding with appropriate long term follow up may be more cost effective in reducing cardiovascular risk than non-specific screening of the whole population.     

Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38

Objective: To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes.Design: Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of <150/85 mm Hg (with the use of an angiotensin converting enzyme inhibitor captopril or a β blocker atenolol as main treatment) with less tight control aiming at a blood pressure of <180/105 mm Hg.Setting: 20 hospital based clinics in England, Scotland, and Northern Ireland.Subjects: 1148 hypertensive patients with type 2 diabetes (mean age 56, mean blood pressure at entry 160/94 mm Hg); 758 patients were allocated to tight control of blood pressure and 390 patients to less tight control with a median follow up of 8.4 years.Main outcome measures: Predefined clinical end points, fatal and non-fatal, related to diabetes, deaths related to diabetes, and all cause mortality. Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography.Results: Mean blood pressure during follow up was significantly reduced in the group assigned tight blood pressure control (144/82 mm Hg) compared with the group assigned to less tight control (154/87 mm Hg) (P<0.0001). Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24% in diabetes related end points (95% confidence interval 8% to 38%) (P=0.0046), 32% in deaths related to diabetes (6% to 51%) (P=0.019), 44% in strokes (11% to 65%) (P=0.013), and 37% in microvascular end points (11% to 56%) (P=0.0092), predominantly owing to a reduced risk of retinal photocoagulation. There was a non-significant reduction in all cause mortality. After nine years of follow up the group assigned to tight blood pressure control also had a 34% reduction in risk in the proportion of patients with deterioration of retinopathy by two steps (99% confidence interval 11% to 50%) (P=0.0004) and a 47% reduced risk (7% to 70%) (P=0.004) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study (ETDRS) chart. After nine years of follow up 29% of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures.Conclusion: Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinically important reduction in the risk of deaths related to diabetes, complications related to diabetes, progression of diabetic retinopathy, and deterioration in visual acuity.

Key messages

• This study showed that tight control of blood pressure based on captopril or atenolol as first agents and aiming for both a systolic blood pressure <150 mm Hg and diastolic pressure <85 mm Hg achieved a mean 144/82 mm Hg compared with 154/87 mm Hg in a control group
• 29% of patients in the tight control group required three or more hypotensive treatments
• Tight control of blood pressure reduced the risk of any non-fatal or fatal diabetic complications and of death related to diabetes; deterioration in visual acuity was also reduced
• Reducing blood pressure needs to have high priority in caring for patients with type 2 diabetes

     

Low blood pressure and dementia in elderly people: the Kungsholmen project.

OBJECTIVE--To examine the relation between blood pressure and dementia in elderly people. DESIGN--Cross sectional, population based study. SETTING: Kungsholmen district of Stockholm, Sweden. SUBJECTS-- 1642 subjects aged 75-101 years. MAIN OUTCOME MEASURES--Prevalence and adjusted odds ratio of dementia by blood pressure. RESULTS--People with systolic pressure < or = 140 mm Hg were more often diagnosed as demented than those with systolic pressure >140 mm Hg: odds ratios (95% confidence interval) adjusted for age, sex, and education were 2.98 (2.17 to 4.08) for all dementias, 2.91 (1.93 to 4.38) for Alzheimer''s disease, 2.00 (1.09 to 3.65) for vascular dementia, and 5.07 (2.65 to 9.70) for other dementias. Similar results were seen in subjects with diastolic pressure < or = 75 mm Hg compared with those with higher diastolic pressure. When severity and duration of dementia were taken into account, only moderate and severe dementia were found to be significantly related to relatively low blood pressure, and the association was stronger in subjects with longer disease duration. Use of hypotensive drugs and comorbidity with cardiovascular disease did not modify the results for all dementias, Alzheimer''s disease, and other dementias but slightly reduced the association between vascular dementia and diastolic blood pressure. CONCLUSIONS--Both systolic and diastolic blood pressure were inversely related to prevalence of dementia in elderly people. We think that relatively low blood pressure is probably a complication of the dementia process, particularly Alzheimer''s disease, although it is possible that low blood pressure may predispose a subpopulation to developing dementia.     

Effectiveness of health checks conducted by nurses in primary care: results of the OXCHECK study after one year. Imperial Cancer Research Fund OXCHECK Study Group.

OBJECTIVE--To assess the effectiveness of health checks by nurses in reducing risk factors for cardiovascular disease in patients from general practice. DESIGN--Randomised controlled trial. SETTING--Five urban general practices in Bedfordshire. SUBJECTS--2136 patients receiving an initial health check in 1989-91 and scheduled to be re-examined one year later in 1990-2 (intervention group); 3988 patients receiving an initial health check in 1990-2 (control group). All patients were aged 35-64 years at recruitment in 1989. MAIN OUTCOME MEASURES--Serum total cholesterol concentration, blood pressure, body mass index, confirmed smoking cessation. RESULTS--Mean serum total cholesterol was 2.3% lower in the intervention group than in the controls (difference 0.14 mmol/l (95% confidence interval 0.08 to 0.20)); the difference was greater in women (3.2%, P < 0.0001) than men (1.0%, P = 0.18). There was no significant difference in smoking prevalence, quit rates, or body mass index. Systolic and diastolic blood pressure were 2.5% and 2.4% lower respectively in the intervention group. The proportion of patients with diastolic blood pressure > or = 100 mm Hg was 2.6% (55/2131) in the intervention group and 3.4% (137/3987) in the controls (difference 0.9% (0.0 to 1.7)); the proportion with total cholesterol concentration > or = 8 mmol/l 4.8% (100/2068) and 7.6% (295/3905) (difference 2.7% (1.5 to 4.0)); and that with body mass index > or = 30 12.4% (264/2125) and 14.0% (559/3984) (difference 1.6% (-0.2 to 3.4)). CONCLUSIONS--General health checks by nurses are ineffective in helping smokers to stop smoking, but they help patients to modify their diet and total cholesterol concentration. The public health importance of this dietary change depends on whether it is sustained.     

Double blind randomised controlled trial of effect of metoprolol on myocardial ischaemia during endoscopic cholangiopancreatography.

OBJECTIVE--To evaluate the effect of metoprolol, a beta adrenergic blocking drug, on the occurrence of myocardial ischaemia during endoscopic cholangiopancreatography. DESIGN--Double blind, randomised, controlled trial. SETTING--University Hospital. SUBJECTS--38 (two groups of 19) patients scheduled for endoscopic cholangiopancreatography. INTERVENTIONS--Metoprolol 100 mg or placebo as premedication two hours before endoscopy. MAIN OUTCOME MEASURES--Heart rate, arterial oxygen saturation by continuous pulse oximetry, ST segment changes during endoscopic cholangiopancreatography (an ST segment deviation > 1 mV was defined as myocardial ischaemia), electrocardiogram monitored continuously with a Holter tape recorder. RESULTS--All patients had increased heart rate during endoscopy compared with rate before endoscopy, but heart rate during endoscopy was significantly lower in the metoprolol group compared with the placebo group (P = 0.0002). Twenty one patients (16 placebo, 5 metoprolol; P = 0.0008) developed tachycardia (heart rate > 100/min) during the procedure, and 11 patients (10 placebo, 1 metoprolol; P = 0.003) developed myocardial ischaemia. One patient in the placebo group had an acute inferolateral myocardial infarction. In the 10 other patients with signs of myocardial ischaemia during endoscopy the ST deviation disappeared when the endoscope was retracted. In all patients myocardial ischaemia was related to increases in heart rate, and 10 of the 11 patients had tachycardia coherent with myocardial ischaemia. CONCLUSIONS--Metoprolol prevented myocardial ischaemia during endoscopic cholangiopancreatography, probably through lowering the heart rate. Thus, tachycardia seems to be a key pathogenic factor in the development of myocardial ischaemia during endoscopy.     

Coronary flow reserve and the J curve relation between diastolic blood pressure and myocardial infarction.

The results of several large studies of hypertension and follow up studies on insured people have indicated that the lower the blood pressure the better for longevity. These studies excluded subjects with overt ischaemia. More recently long term studies of hypertension that included patients with more severe forms of hypertension and did not exclude those with overt ischaemia have shown a J shaped relation between diastolic blood pressure during treatment and myocardial infarction; the lowest point (the J point) was at a diastolic blood pressure (phase V) between 85 and 90 mm Hg. The J curve seems to be independent of treatment, pulse pressure, and the degree of fall in diastolic blood pressure and is unlikely to be caused by poor left ventricular function. The most probable explanation is that subjects who have severe stenosis of the coronary artery as well as hypertension have a poor coronary flow reserve, which makes the myocardium vulnerable to coronary perfusion pressures that are tolerated by patients without ischaemia, particularly at high heart rates. An optimal diastolic blood pressure (phase V) for such patients is about 85 mm Hg, though particular caution is appropriate when treating very old patients (84 and over) and patients aged 60-79 who have isolated systolic hypertension.     

Prolonged Subcutaneous Administration of Oxytocin Accelerates Angiotensin II-Induced Hypertension and Renal Damage in Male Rats

Oxytocin and its receptor are synthesised in the heart and blood vessels but effects of chronic activation of this peripheral oxytocinergic system on cardiovascular function are not known. In acute studies, systemic administration of low dose oxytocin exerted a protective, preconditioning effect in experimental models of myocardial ischemia and infarction. In this study, we investigated the effects of chronic administration of low dose oxytocin following angiotensin II-induced hypertension, cardiac hypertrophy and renal damage. Angiotensin II (40 μg/Kg/h) only, oxytocin only (20 or 100 ng/Kg/h), or angiotensin II combined with oxytocin (20 or 100 ng/Kg/h) were infused subcutaneously in adult male Sprague-Dawley rats for 28 days. At day 7, oxytocin or angiotensin-II only did not change hemodynamic parameters, but animals that received a combination of oxytocin and angiotensin-II had significantly elevated systolic, diastolic and mean arterial pressure compared to controls (P < 0.01). Hemodynamic changes were accompanied by significant left ventricular cardiac hypertrophy and renal damage at day 28 in animals treated with angiotensin II (P < 0.05) or both oxytocin and angiotensin II, compared to controls (P < 0.01). Prolonged oxytocin administration did not affect plasma concentrations of renin and atrial natriuretic peptide, but was associated with the activation of calcium-dependent protein phosphatase calcineurin, a canonical signalling mechanism in pressure overload-induced cardiovascular disease. These data demonstrate that oxytocin accelerated angiotensin-II induced hypertension and end-organ renal damage, suggesting caution should be exercised in the chronic use of oxytocin in individuals with hypertension.     

Obesity Is Associated with Lower Coronary Microvascular Density

Background

Obesity is associated with diastolic dysfunction, lower maximal myocardial blood flow, impaired myocardial metabolism and increased risk of heart failure. We examined the association between obesity, left ventricular filling pressure and myocardial structure.

Methods

We performed histological analysis of non-ischemic myocardium from 57 patients (46 men and 11 women) undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation or loop diuretic therapy.

Results

Non-obese (body mass index, BMI, ≤30 kg/m², n=33) and obese patients (BMI >30 kg/m², n=24) did not differ with respect to myocardial total, interstitial or perivascular fibrosis, arteriolar dimensions, or cardiomyocyte width. Obese patients had lower capillary length density (1145±239, mean±SD, vs. 1371±333 mm/mm³, P=0.007) and higher diffusion radius (16.9±1.5 vs. 15.6±2.0 μm, P=0.012), in comparison with non-obese patients. However, the diffusion radius/cardiomyocyte width ratio of obese patients (0.73±0.11 μm/μm) was not significantly different from that of non-obese patients (0.71±0.11 μm/μm), suggesting that differences in cardiomyocyte width explained in part the differences in capillary length density and diffusion radius between non-obese and obese patients. Increased BMI was associated with increased pulmonary capillary wedge pressure (PCWP, P<0.0001), and lower capillary length density was associated with both increased BMI (P=0.043) and increased PCWP (P=0.016).

Conclusions

Obesity and its accompanying increase in left ventricular filling pressure were associated with lower coronary microvascular density, which may contribute to the lower maximal myocardial blood flow, impaired myocardial metabolism, diastolic dysfunction and higher risk of heart failure in obese individuals.     

Intravenous diazoxide in treatment of hypertension associated with recent myocardial infarction

Twenty patients with blood pressure over 180/110 mm Hg one hour after admission to a coronary care unit with recent acute myocardial infarction were given intravenous diazoxide in a bolus of 300 mg. The average blood pressure before diazoxide was 194/122 mm Hg. Blood pressure fell considerably in all patients, though six patients required two injections. The average fall was 58 mm Hg systolic and 40 mm Hg diastolic. No patient became severely hypotensive. The heart rate increased by an average of 10 beats/min. In nine patients the electrocardiographic changes immediately after the administration of diazoxide suggested an increase in myocardial injury. Though none of the patients seemed to deteriorate clinically from the diazoxide the electrocardiographic changes suggested that the use of intravenous diazoxide to lower blood pressure in patients with acute myocardial infarction might possibly be deleterious.     

Antioxidant state and mortality from coronary heart disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50.

OBJECTIVE: To investigate possible risk factors and mechanisms behind the four times higher and diverging mortality from coronary heart disease in Lithuanian compared with Swedish middle aged men. DESIGN: Concomitant cross sectional comparison of randomly selected 50 year old men without serious acute or chronic disease. Methods and equipment were identical or highly standardised between the centres. SETTING: Linköping (Sweden) and Vilnius (Lithuania). SUBJECTS: 101 and 109 men aged 50 in Linköping and Vilnius respectively. MAIN OUTCOME MEASURES: Anthropometric data, blood pressure, smoking, plasma lipid and lipoprotein concentrations, susceptibility of low density lipoprotein to oxidation, and plasma concentrations of fat soluble antioxidant vitamins. RESULTS: Systolic blood pressure was higher (141 v 133 mm Hg, P < 0.01), smoking habits were similar, and plasma total cholesterol (5.10 v 5.49 mmol/l, P < 0.01) and low density lipoprotein cholesterol (3.30 v 3.68 mmol/l, P < 0.01) lower in men from Vilnius compared with those from Linköping. Triglyceride, high density lipoprotein cholesterol, and Lp(a) lipoprotein concentrations did not differ between the two groups. The resistance of low density lipoprotein to oxidation was lower in the men from Vilnius; lag phase was 67.6 v 79.5 minutes (P < 0.001). Also lower in the men from Vilnius were mean plasma concentrations of lipid soluble antioxidant vitamins (beta carotene 377 v 510 nmol/l, P < 0.01; lycopene 327 v 615 nmol/l, P < 0.001; and lipid adjusted gamma tocopherol 0.25 v 0.46 mumol/mmol, P < 0.001. alpha Tocopherol concentration did not differ). Regression analysis showed that the lag phase was still significantly shorter by 10 minutes in men from Vilnius when the influence of other known factors was taken into account. CONCLUSIONS: The high mortality from coronary heart disease in Lithuania is not caused by traditional risk factors alone. Mechanisms related to antioxidant state may be important.