Increased cardiovascular disease mortality rates in traumatic lower limb amputees.

We evaluated the 24-year mortality rates of male traumatic lower limb amputees (n = 201) of the Israeli army, wounded between 1948 and 1974 compared with a cohort sample representing the general population (n = 1,832). Mortality rates were significantly higher (21.9% vs 12.1%, p <0.001) in amputees than in controls. Cardiovascular disease (CVD) mortality was the main cause for this difference. The prevalence of selected risk factors for CVD was determined in 101 surviving amputees (aged 50 to 65 years) and a sample of the controls (n = 96) matched by age and ethnic origin. Amputees had higher plasma insulin levels (during fasting and in response to oral glucose loading) and increased blood coagulation activity. No differences were found in rates of current symptoms of ischemic heart disease or of cerebrovascular disease, obesity, hypertension, altered plasma lipoprotein profile, impaired physical activity, smoking, or nutritional habits. Traumatic lower limb amputees had increased mortality rates due to CVD. Surviving amputees had hyperinsulinemia, increased coagulability, and increased sympathetic and parasympathetic responses (described previously). These established CVD risk factors may explain the excess mortality due to CVD in traumatic amputees.

Comprehensive individualised nonpharmacological treatment programme for hypertension in physician-nurse clinics: two year follow-up.

A comprehensive programme of nonpharmacological control of hypertension (balanced nutrition, satisfactory weight, enhanced physical activity, relaxation technique, smoking cessation) by primary care physician-nurse (PN) teams who were instructed and routinely advised by a paramedical professional (PP) team (psychologist, nutritionist and physical activity instructor) was developed with the aim of increasing long-term compliance. To evaluate effectiveness, 52 mild and moderate hypertensives without target organ damage were randomly allocated to six weekly meetings of individual intensive instruction by PN teams alone, or direct group instructions by PP teams (24 and 28 patients, respectively). The respective results at 11 months and 24 months follow-up compared with baseline were: (1) 56.9% and 58.8% showed minimal satisfactory reduction of weight, (2) 49% and 58.8% showed minimal satisfactory increase in physical activity, (3) the reported increase in physical activity at 11 months follow-up was validated by significantly correlated improved performance in ergometry, (4) 75% and 40% of the patients performed relaxation vs. 2% at baseline and (5) 71% and 59% needed no medication or reduced dose to control BP, and these changes were significantly (P < 0.02) correlated with weight reduction and increased physical activity. As no differences were found between the two modes of treatment, we conclude that our programme can be successfully applied by the PN primary care teams to increase adherence to nonpharmacological measures in the control of hypertension.

Partial cost-benefit analysis of two different modes of nonpharmacological control of hypertension in the community.

In the Dan and Ashkelon areas of Israel, 28 male and 24 female mild to moderate hypertensives without target organ damage aged 35-65 years were randomly assigned to treatment programmes (based on nutritional management, exercise and stress management techniques) either on an individual basis administered by physician-nurse teams (PN) or on a group basis from a team of paramedical professionals (PP) consisting of a psychologist, nutritionist and physical activity instructor. At 11 and 24 months follow-up, there were similar significant improvements in both treatment modes for such risk factors as body mass index, caloric intake and physical activity levels. There was a significant decrease in drug use from $36.28 a month at baseline to $18.94 a month at 11 month follow-up (P = 0.01) and to an estimated $20.48 at 24 months. Mean BP remained unchanged, despite the reduction in drug use, indicating a reduction in the underlying BP. The net present value (NPV) of the reduction in drug utilisation totalled $740 per person over a five year time horizon and a 7.5% discount rate. The total extra costs of treatment, training, case-note writing, travelling and follow-up booster sessions, amounted to $95 per patient for the PN mode and $234 per patient for the PP mode, yielding benefit to cost ratios of 7.79/1 and 3.16/l, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Body mass index at age 18 years and during adult life and ovarian cancer risk.

During the years 1994-1999, a nationwide ovarian cancer case-control study was conducted in Israel. The present analysis addresses the question: Is epithelial ovarian cancer associated with body mass index at age 18 years and/or with weight changes in body mass index between adolescence and adult life? The study is based on 1,269 women with epithelial ovarian cancer and 2,111 matched controls. A significant decrease in risk of ovarian cancer was observed with parity, oral contraceptive use, and postmenopausal status. A significant increase in risk with family history of ovarian/breast cancer was also found. No significant association with age at menarche or infertility was found. For body mass index at age 18 years, the odds ratio of the highest versus lowest body mass index quartile was 1.42 (95% confidence interval: 1.08, 1.85) and after adjusting for confounders was 1.54 (95% confidence interval: 1.17, 2.02). However, no statistically significant risk associated with change in weight from age 18 years to adult life was found. The authors conclude that, in their population, body mass index at age 18 years is an independent risk factor for ovarian cancer.

Interrelationships among measures of autonomic activity and cardiovascular risk factors during orthostasis and the oral glucose tolerance test.

Overstimulation of sympathetic nervous system activity is related to atherosclerotic cardiovascular disease risk, but the role of parasympathetic activity in this association is not clear. This study evaluated sympathetic and parasympathetic function by spectral analysis of heart rate variability and plasma levels of norepinephrine (NE) epinephrine (EPI), dihydroxyphenylglycol (DHPG), dihydroxyphenylalanine (DOPA) and dihydroxyphenylacetic acid (DOPAC). It also examined the interrelationships among these parameters and established atherosclerotic cardiovascular disease risk factors in 53 men (mean age 59.5 years). During supine rest, low-frequency power correlated positively with high-frequency power (r = 0.58, p < 0.001), plasma NE correlated with plasma DHPG (r = 0.41, p < 0.001) and plasma DOPA with DOPAC (r = 0.47, p < 0.001) but neither low- nor high-frequency power was correlated with plasma levels of any catechol. Among risk factors, plasma NE correlated with fasting insulin and mean arterial blood pressure, and urine NE correlated with body mass index. Both low- and high-frequency power correlated positively with insulin levels. Orthostasis decreased high-frequency power and increased low-frequency power and plasma NE levels. During the oral glucose tolerance test, both high- and low-frequency power increased, plasma NE levels were unchanged, and plasma EPI levels decreased [88.5 +/- 18 (SEM) versus 52.5 +/- 12 pM, p = 0.001]. The results suggest that orthostasis decreases and the oral glucose tolerance test increases parasympathetic outflows, whereas both stimuli increase sympathetic outflows. Among all atherosclerotic cardiovascular disease risk factors, hyperinsulinaemia showed the strongest association with autonomic nervous system activity, especially parasympathetic activity. Estimates of sympathetic responses obtained from power spectral analysis of heart rate variability agree poorly with those from plasma levels of catechols, possibly because of a parasympathetic contribution to low-frequency power and independence of sympathoneural outflows to the arm and heart.

Insulin resistance and autonomic function in traumatic lower limb amputees.

This study examined plasma insulin response to oral glucose load and autonomic nervous system activity in male lower limb amputees (n = 52) aged 50-65 years, compared to matched controls (n = 53). The groups had similar body mass index, blood pressure and plasma lipid levels. The amputees had higher mean fasting plasma insulin levels (18.4 +/- 9.7 (SD) versus 13.7 +/- 5.1 mU/l, p = 0.005) and during an oral glucose tolerance test (OGTT) (1 h levels 88.1 +/- 45.3 versus 62.1 +/- 42.7, p = 0.016) with similar plasma glucose levels, indicating insulin resistance. At baseline with the subjects supine, there were no group differences in low- or high-frequency power of heart rate variability or in plasma levels of norepinephrine (NE) or epinephrine (EPI). In response to orthostasis, the groups had similarly increased plasma NE levels. During the OGTT, amputees had significantly larger increments in low-frequency power than did controls (2.2 +/- 1.3 versus 1.6 +/- 0.9 (beats/min)2 respectively, p < 0.01) and plasma NE levels increased significantly in amputees (1595 +/- 849 versus 1941 +/- 986 pM, p = 0.0008) but not in controls. At 1 h after glucose administration, plasma EPI levels were decreased significantly from baseline in both groups; at both 1 and 2 h after glucose administration, plasma EPI levels were higher in the amputees than controls. Amputees appear to have a combination of enhanced sympathoneural responsiveness and attenuated suppression of adrenomedullary secretion during glucose challenge. As catecholamines antagonize insulin effects, one possible explanation for insulin resistance in amputees is hyperglycaemia-induced sympathoneural activation and a failure of hyperglycaemia to decrease adrenomedullary secretion.