Michaela Modan

Effect of Weight Loss without Salt Restriction on the Reduction of Blood Pressure in Overweight Hypertensive Patients

Overweight patients with uncomplicated essential hypertension were followed up biweekly for six months: 24 not receiving antihypertensive-drug therapy (Group I) and 83 on regular but inadequate (despite drug manipulation) antihypertensive-drug therapy (Group II). All patients in Group I and 57 randomly selected patients from group II (IIa) participated in a weight-reduction program. The remaining 26 from Group II (IIb) did not receive a dietary program. Salt intake was in the normal range in all three groups. All patients on the dietary program lost at least 3 kg (mean, 10.5 kg), and all but two showed a meaningful reduction in blood pressure; 75 per cent of Group I and 61 per cent of Group IIa returned to normal blood pressure. The weight and blood-pressure reductions were highly significant (P less than 0.001), were present in both sexes and all ages, and were directly associated. In Group IIb, no significant change in blood pressure or weight occurred (P greater than 0.30).

Colchicine in the Prevention and Treatment of the Amyloidosis of Familial Mediterranean Fever

To determine whether colchicine prevents or ameliorates amyloidosis in patients with familial Mediterranean fever, we followed 1070 patients with the latter disease for 4 to 11 years after they were advised to take colchicine to prevent febrile attacks. Overall, at the end of the study, the prevalence of nephropathy was one third of that in a study conducted before colchicine was used to treat familial Mediterranean fever. Among 960 patients who initially had no evidence of amyloidosis, proteinuria appeared in 4 who adhered to the prophylactic schedule and in 16 of 54 who admitted non-compliance. Life-table analysis showed that the cumulative rate of proteinuria was 1.7 percent (90 percent confidence limits, 0.0 and 11.3 percent) after 11 years in the compliant patients and 48.9 percent (18.8 and 79.0 percent) after 9 years in the noncompliant patients (P less than 0.0001). A total of 110 patients had overt nephropathy when they started to take colchicine. Among 86 patients who had proteinuria but not the nephrotic syndrome, proteinuria resolved in 5 and stabilized in 68 (for more than eight years in 40). Renal function deteriorated in 13 of the patients with proteinuria and in all of the 24 patients with the nephrotic syndrome or uremia. We conclude that colchicine prevented amyloidosis in our high-risk population and that it can prevent additional deterioration of renal function in patients with amyloidosis who have proteinuria but not the nephrotic syndrome.

Elevated serum uric acid — a facet of hyperinsulinaemia

SummaryIn a representative sample of the adult Jewish population in Israel (n=1016) excluding known diabetic patients and individuals on antihypertensive medications, serum uric acid showed a positive association with plasma insulin response (sum of 1- and 2-hour post glucose load levels) in both males (r=0.316, p<0.001) and females (r=0.236, p<0.001). This association remained statistically significant in both sexes (p<0.001) after accounting by multiple regression analysis for age and major correlates of serum uric acid, i.e. body mass index, glucose response (sum of 1- and 2-hour post load levels), systolic blood pressure and total plasma triglycerides. The net portion of the variance of serum uric acid attributable to insulin response was 12% in males and 8% in females, the total variance accountable by all these variables being 17% and 19% respectively. We conclude that elevated serum uric acid is a feature of hyperinsulinaemia/insulin resistance.

After correcting for worse baseline characteristics, women treated with thrombolytic therapy for acute myocardial infarction have the same mortality and morbidity as men except for a higher incidence of hemorrhagic stroke. The Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Study.

BACKGROUND In the prethrombolytic era, women with myocardial infarction were reported to have a worse outcome than men. This analysis evaluates the association of sex with morbidity and mortality after thrombolytic therapy. METHODS AND RESULTS Data were analyzed from 8261 of the 8387 randomized patients with acute myocardial infarction who received thrombolytic therapy in the International Tissue Plasminogen Activator/Streptokinase Mortality Study (baseline data were missing for 126 patients) and were followed for 6 months. Women made up 23% (n = 1944) of the study population. Baseline characteristics were worse in women: they were 6 years older, were more likely to have a history of previous infarction (P < .01), antecedent angina (P < .01), hypertension (P < .0001), or diabetes (P < .0001); were in a higher Killip class on admission (P < .0002); and received thrombolytic therapy 18 minutes later than men (P < .0001). Fewer women were smokers (P < .0001). Women had a higher hospital (12.1% versus 7.2%, P < .0001) and 6-month mortality (16.6% versus 10.4%, P < .0001) and were more likely to develop cardiogenic shock (9.1% versus 6.3%, P < .0001), bleeding (7.2% versus 5.3%, P < .01), and hemorrhagic (1% versus 0.3%, P < .001) or total stroke (2.2% versus 1.1%, P < .0001) during hospitalization. Reinfarction rates and requirement for angioplasty or surgery did not differ. After correction for worse baseline characteristics, women had similar morbidity and mortality apart from a significantly higher incidence of hemorrhagic stroke, which remained significant even after accounting for weight and treatment allocation (odds ratio, 2.90; P < .01). CONCLUSIONS After thrombolytic therapy for acute myocardial infarction, women have similar morbidity and mortality to men but suffer from a higher incidence of hemorrhagic stroke.

Reduction of Mortality in General Medical In-patients by Low-Dose Heparin Prophylaxis

The effect of prophylactic low-dose heparin on mortality was tested in 1358 consecutive patients admitted to the medical wards of an acute care hospital. Eligibility for treatment or exclusion was ascertained on admission by predefined contraindications. Eligible patients with even-number hospital records were assigned to treatment (5000 U twice daily), those with odd-number records served as controls. Because determination of eligibility was open to bias, evaluation of treatment was based on comparison of the total even-number group (669 patients, of which 411 were treated with heparin), and the total odd-number group (689 patients, none treated with heparin). Mortality was significantly lower in the even-number group-7.8% (52 of 669 patients) versus 10.9% (75 of 689 patients) in the odd-number group; the difference increased consistently with length of hospitalization (p = 0.025). The estimated reduction in mortality attributable to heparin was 31.1%. We believe that low-dose heparin prophylaxis is appropriate in all immobilized medical patients who are not at risk of bleeding.

Significance of smoking in patients receiving thrombolytic therapy for acute myocardial infarction. Experience gleaned from the International Tissue Plasminogen Activator/Streptokinase Mortality Trial.

BackgroundDespite the fact that smoking is a well-established risk factor for the development of coronary artery disease, some investigators have noted that hospital mortality after acute myocardial infarction is lower in patients who smoke than in nonsmoking patients. To evaluate the association of smoking with mortality during hospitalization after thrombolytic therapy and 6 months afterward, we analyzed the results of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial. Methods and ResultsPatients were divided into three groups: nonsmokers (those who never smoked), ex-smokers, and active smokers. Multivariate and univariate comparisons were made with respect to baseline characteristics and clinical outcome. There were 2,366 nonsmokers, 2,244 ex-smokers, and 3,649 active smokers. The baseline characteristics of nonsmoking patients differed significantly from the ex-smokers and active smokers. The nonsmoking group included more women than the ex-smokers or active smokers (45% versus 10.6% and 17.6%, respectively), was older (67±10 years versus 64±10 years and 58±11 years), had a higher rate of diabetes mellitus (16.3% versus 11.1% and 7.5%), and had a worse Killip class at admission. Nonsmoking patients and ex-smokers experienced more in-hospital reinfarction than active smokers (4.7% and 5% versus 2.7%, p<0.0001, respectively). Nonsmokers experienced more in-hospital shock than the ex-smokers or active smokers (9.2% versus 6.4% and 5.8%, P<0.0001), stroke (1.9% versus 1.8% and 0.8%, p<0.0001), and bleeding (7.2% versus 6.5% and 4.4%, p<0.0001). They also experienced a higher in-hospital and 6-month mortality (12.8% and 17.6%) than ex-smokers (8.2% and 12.1%) or active smokers (5.4% and 7.8%) (p<0.0001). A multivariate analysis accounting for all baseline characteristics demonstrated a significant association between nonsmoking and increased hospital mortality, with an odds ratio of 1.42 (confidence limits, 1.15–1.72). Among active smokers, there was a nonsignificant trend for mortality rates to decrease with increasing numbers of cigarettes smoked per day. ConclusionsThis retrospective analysis indicates that smokers receiving thrombolytic therapy after acute myocardial infarction have significantly better hospital and 6-month outcome than nonsmokers or ex-smokers. However, smokers sustained their infarction at a significantly earlier age than nonsmokers, and strenuous efforts should continue to be made to decrease the incidence of new and continued smoking.

The improving outcome of triplet pregnancies.

During the period 1975 to 1988, 78 triplet pregnancies that reached a gestational age greater than or equal to 20 weeks were treated in our department--a prevalence of 1/849 deliveries. A total of 69 (88%) of the pregnancies occurred after treatment with ovulation-induction agents. The most common complication of pregnancy was premature contractions. Elective cervical cerclage neither prolonged gestation nor decreased fetal loss. The mean gestational age at delivery was 33.2 weeks + 3.8 weeks and 86% of the patients were delivered of premature infants. The perinatal and neonatal mortality rates were 93/1000 and 51/1000, respectively. Our results show a higher proportion of low Apgar scores and respiratory disorders in the third vaginally delivered infants. Follow-up of very low birth weight infants revealed four infants (10.5%) with severe neurologic handicaps. Results of this study suggest that cesarean section is the preferred mode of delivery in triplet pregnancies. Maternal, fetal, and neonatal risks of triplet gestations are relatively low and compare favorably with recent reports on twin pregnancies.

Effect of past and concurrent body mass index on prevalence of glucose intolerance and Type 2 (non-insulin-dependent) diabetes and on insulin response

SummaryA representative sample (n=2140) of the Israeli Jewish population aged 40–70 (excluding known diabetic patients), whose body mass index had been measured 10 years earlier, underwent an oral glucose tolerance test and redetermination of body mass index. Irrespective of weight changes, high concurrent and high past body mass index values (≥ 27) were associated with similarly increased rates of glucose intolerance as compared with body mass index values < 27 at both time-points (rate ratio 1.76, 90% confidence limits 1.56–1.99). Glucose intolerance here includes borderline and impaired tolerance as well as Type 2 diabetes. The rate of Type 2 diabetes increased only with increasing past body mass index, while concurrent body mass index had no effect [rate ratios: 2.36 (1.48–3.75) and 1.99 (1.48–2.68) respectively for the medium-(23–26.9) versus-low (<23) and high- (≥ 27) versus-medium past body-mass-index categories]. Weight reduction was associated with only slightly reduced rate of glucose intolerance and had no effect on the rate of diabetes. Mean sum insulin (summed 1 and 2 h levels, mU/l) increased significantly with increasing concurrent body mass index (123, 150 and 190 in the low, medium and high categories) with no effect of past body mass index. It also increased significantly (p < 0.001) in all concurrent body mass index categories from normal tolerance through borderline to impaired tolerance, and decreased significantly (p < 0.001) in diabetes relative to impaired tolerance, although it remained above normal. Means of sum insulin within each glucose tolerance level were similar in the two lower concurrent body mass index categories, with markedly higher (p < 0.001) levels in the high body mass index category. All these findings held after accounting for age, sex, ethnic group and use of antihypertensive medications. We conclude that body mass index ≥ 27 leads to early impairment in glucose tolerance. A prolonged period of obesity is apparently required for the development of Type 2 diabetes and its associated reduced insulin response. The reversibility of the deterioration of glucose tolerance seems to be limited.

Shoulo thrombolytic therapy be administered in the mobile intensive care unit in patients with evolving myocardial infarction? A pilot study

The growing recognition of the importance of early thrombolysis in evolving myocardial infarction was the basis for the present study, which evaluated the effectiveness, feasibility and safety of prehospital thrombolytic therapy. In a relatively small study, 118 patients were allocated to receive either prehospital treatment with recombinant tissue-type plasminogen activator (rt-PA) in the mobile intensive care unit (group A, 74 patients) or hospital treatment (group B, 44 patients). A total of 120 mg of rt-PA was infused over a period of 6 h. All patients were fully heparinized and underwent radionuclide left ventriculography and coronary angiography during hospitalization. Although group A was treated significantly earlier than group B after onset of symptoms (94 +/- 36 versus 137 +/- 45 min, respectively; p less than 0.001), no significant differences were observed between the groups in 1) extent of myocardial necrosis, 2) global left ventricular ejection fraction at discharge, 3) patency of infarct-related artery, 4) length of hospital stay, and 5) mortality at 60 days. However, a trend to a lower incidence of congestive heart failure at hospital discharge was observed in the prehospital-treated compared with the hospital-treated group (7% versus 16%, respectively; p = NS). No major complications occurred during transportation. It is concluded that myocardial infarction can be accurately diagnosed and thrombolytic therapy initiated relatively safely during the prehospital phase by the mobile intensive care team, thus instituting a beneficial clinical trend in favor of prehospital thrombolysis.

Significance of diabetes mellitus in patients with acute myocardial infraction receiving thrombolytic theraphy

Abstract Objectives. The purpose of this study was to evaluate the risks and benefits associated with thrombolytic theraphy in patients with diabetes presenting with acute myocardial infarction. Background. Diabetes mellitus is associated with adverse risk factors and a hypercoagulable state that may adversely affect the outcome of thrombolytic therapy. Methods. Data were analyzed from 8,055 of the 8,239 patients with acute myocardial infarction who received thrombolytic therapy in the International Tissue plasminogen Activator/Streptokinase Mortality trial (diabetes history was missing for 184 patients). Results. There were 883 patients with and 8,272 patients without diabetes. Among the diabetic patients, 160 were receiving insulin therapy. Baseline risk factors were significantly worse in diabetic patients, who were older and had a higher rate of previous infarction and antecedent angina and a higher Killip grade at admission. Bleeding and hemorrhagic and ischemic stroke rates were similar among diabetic and nondiabetic patients. Hospital and 6-month mortality rates were highest among diabetic patients receiving insulin therapy (16.9% and 23.1%, respectively), followed by diabetic patients not receiving insulin therapy (11.8% and 17.8%), and lowest in nondiabetic patients (7.5% and 10.7%, p 5-year duration was associated with a relative mortality risk of 1.38 (95% cofidence interval [CI] 0.88 to 2.15) and a > 10-year duration with a relative mortality risk of 1.99 (95% CI 1.40 to 2.81). The independent relative risk for incremental mortality from discharge to 6 months was 1.74 (95% CI 1.21 to 2.50). Mortality rate among diabetic was patients lowest in patients who received both streptokinase and heparin (9.8% vs. 16.1% in patients who received streptokinase but no heparin, p Conclusions. The relative mortality of diabetis versus nondiabetic patients was similar to that observed in previous studies of patients with myocardial infarction not receiving thrombolytic therapy, indicating that mortality in diabetic patients receiving thrombolytic therapy is reduced to the same extent as in nondiabetic patients. In addition, risk of bleeding and stroke was not increased, indicating that diabetic patients can safely receive thrombolytic therapy for the same indications as nondiabetic patients.