Natan Cohen

Warfarin for Stroke Prevention Still Underused in Atrial Fibrillation: Patterns of Omission

BACKGROUND AND PURPOSE The value of warfarin in preventing stroke in patients with chronic atrial fibrillation is well established. However, the prevalence of such treatment generally lags behind actual requirements. The aim of this study was to evaluate doctor- and/or patient-related demographic, clinical, and echocardiographic factors that influence decision for warfarin treatment. METHODS Between 1990 and 1998, 1027 patients were discharged with chronic or persistent atrial fibrillation. This population was composed of (1) patients with cardiac prosthetic valves (n=48), (2) those with increased bleeding risks (n=152), (3) physically or mentally handicapped patients (n=317), and (4) the remaining 510 patients, the main study group who were subjected to thorough statistical analysis for determining factors influencing warfarin use. RESULTS The respective rates of warfarin use on discharge in the 4 groups were 93.7%, 30.9%, 17.03%, and 59.4% (P=0.001); of the latter, an additional 28.7% were discharged on aspirin. In the main study group, warfarin treatment rates increased with each consecutive triennial period (29.7%, 53.6%, and 77.1%, respectively; P=0.001). Age >80 years, poor command of Hebrew, and being hospitalized in a given medical department emerged as independent variables negatively influencing warfarin use: P=0.0001, OR 0.30 (95% CI 0.17 to 0.55); P=0.02, OR 0.59 (95% CI 0.36 to 0.94); and P=0.0002, OR 0.26 (95% CI 0.12 to 0.52), respectively. In contrast, past history of stroke and availability of echocardiographic information, regardless of the findings, each increased warfarin use (P=0.03, OR 1.95 [95% CI 1.04 to 3.68], and P=0.0001, OR 3.52 [95% CI 2.16 to 5.72], respectively). CONCLUSIONS Old age, language difficulties, insufficient doctor alertness to warfarin benefit, and patient disability produced reluctance to treat. Warfarin use still lags behind requirements.

Effects of captopril and enalapril on zinc metabolism in hypertensive patients.

OBJECTIVE To investigate the effect of chronic captopril and enalapril treatment on zinc metabolism in hypertensive patients by assessing zinc levels in serum, urine and monocytes. METHODS Patients with newly diagnosed essential hypertension were randomly divided into two treatment groups: those treated with captopril only (n = 16) and those treated with enalapril only (n = 18). Ten healthy subjects served as controls. Prior to the start of treatment and again 6 months later, zinc was assessed in the serum, in urine collected over 24 hours, and in peripheral blood monocytes. RESULTS Significant enhancement of 24-hour urinary zinc excretion (micrograms/24 hour) after 6 months of treatment was observed only in the captopril-treated group (p < 0.01). However, intramonocytic zinc levels decreased significantly in both of the treated groups over the same period (p < 0.01 and P < 0.04 in the captopril- and enalapril-treated groups, respectively). CONCLUSION Treatment of hypertensive patients with captopril or enalapril may result in zinc deficiency.

Dietary Intake of Various Nutrients in Older Patients with Congestive Heart Failure

Background and Aims: Anorexia, nausea and premature satiety with eating, prevalent in congestive heart failure (CHF), have been held responsible for reduced dietary intake and deficiency of magnesium, potassium and probably other nutrients. Since solid data is not available, this study was undertaken with the following aims (1) to assess dietary intake in CHF, (2) to compare dietary intake in older CHF patients with a similar patient population free of CHF (control group), and (3) to evaluate these data in patients with moderate versus severe CHF. Methods and Results: Dietary intake of 57 consecutively hospitalized furosemide-treated CHF patients over the age of 60 was compared with that of 40 similar patients free of CHF. In addition, a statistical analysis was performed comparing the data of the 37 patients with moderate versus the 20 patients with severe CHF. Dietary content of various nutrients was assessed with the food frequency recall technique. Dietary intake was comparable in the two respective pairs of groups. However, the intake of magnesium, calcium, zinc, copper, manganese, energy, thiamin, riboflavin, and folate in all subgroups fell short of recommended levels for intake, while vitamins A, C and niacin contents exceeded those recommended. Intakes of potassium andproteins were within the recommended values. Conclusions: CHF per se, even severe CHF, is not responsible for a reduced dietary intake of various nutrients. A population-related dietary culture, old age or other chronic conditions, rather than CHF, might be mainly involved. The increased intake of vitamins A, C and niacin in our patients may be attributed to the high content of fruits and vegetables in the Mediterranean diet. Insufficient intake of the above-mentioned group of electrolytes and essential nutrients may contribute to the frequently observed negative balance of some of them. This is especially relevant in furosemide-treated CHF patients. Therefore, supplementation should be considered.

Zinc balance and medications commonly used in the management of heart failure

Heart failure (HF) is a prevalent syndrome resulting in a high mortality rate. HF may be associated with zinc deficiency through a reduction in dietary intake, decreased absorption due to gastrointestinal edema, impaired motility or intestinal zinc losses. Diseases concomitant with HF such as diabetes mellitus (DM) and hypertension may enhance zinc deficiency. Medications given for HF may affect zinc metabolism in different ways. It was shown that thiazides may cause zincuria and a decrease in tissue zinc concentration. There is conflicting evidence about furosemide, even though patients with chronic furosemide treatment showed low tissue zinc levels in autopsies. Treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) resulted in zincuria and zinc deficiency, but this outcome was not consistent in all studies. Beta-blockers did not alter plasma zinc concentration. Matrix metalloproteinases (MMPs) and ACE are zinc-containing enzymes, which play a role in the process of remodeling in HF. It was shown that ACE inhibitors may inhibit the activity of different MMPs. The exact interrelationship between HF, zinc-containing enzymes, zinc deficiency and the clinical manifestation of HF has to be investigated.

Hereditary angioneurotic edema with severe hypovolemic shock

Hereditary angioneurotic edema (HAE) is characterized by recurrent attacks of edema of the upper airways, face, and limbs, and/or abdominal pains sometimes mimicking surgical abdomen. Our patient, a 24-year-old woman, had undergone laparotomy on a previous attack, at which a large amount of serious peritoneal fluid and edema of the intestinal wall were found. This time she presented with severe abdominal pain and profound hypovolemic shock requiring replacement of great amounts of fluids in addition to fresh frozen plasma. There was no evidence of bleeding, and the patient recovered rapidly. Based on clinical and ultrasonographic grounds and findings on previous laparotomy, we concluded that the shock was produced by fluid sequestration in the peritoneal cavity and intestinal wall. We propose that patients with HAE who present with abdominal pain, hypotension, hemoconcentration, and leukocytosis form a distinct subgroup with a high risk of hypovolemic shock. This dangerous development should be anticipated in these patients.

Seating-Induced Postural Hypotension Is Common in Older Patients with Decompensated Heart Failure and May Be Prevented by Lower Limb Compression Bandaging

Background: Postural hypotension induced by transition from supine to sitting position and measures for its prevention in heart failure has not been investigated. Objective: Our purpose was to evaluate the prevalence of postural hypotension and associated clinical manifestations as well as the contribution of various risk factors for postural hypotension on transition from lying to sitting in older patients with decompensated heart failure, and to study the eventual preventive effect of leg bandaging. Methods: Seating-induced postural hypotension (≥20 mm Hg systolic and/or ≥10 mm Hg diastolic blood pressure fall) was assessed on the first study day in 108 patients aged ≥60 years, hospitalized for acutely decompensated heart failure. On the next day, in patients manifesting postural hypotension, compression bandages were applied along both legs before seating. Blood pressure, heart rate, O2 saturation, and the occurrence of dizziness or palpitations were recorded prior to and 1, 3 and 5 min following seating. Results: Postural hypotension occurred in 49.1% of patients. Dizziness and/or palpitations manifested in 25%. Diastolic (36.1%) versus systolic (23.1%) postural hypotension prevailed (p = 0.05). On univariate analysis, postural hypotension was associated with female sex (p = 0.03), more severe heart failure (p = 0.05), longer bedrest (p = 0.04), higher supine systolic (p = 0.01) or diastolic (p = 0.002) blood pressure, nonischemic heart failure (p = 0.002), and not using nitrates (p = 0.01). On multivariate analysis, longer bedrest (OR = 1.58, 95% CI = 1.13–2.2, p < 0.001), higher supine diastolic blood pressure (OR = 1.33, 95% CI = 1.1–1.61, p = 0.001), and nonischemic heart failure (OR = 3.48, 95% CI = 1.4–8.63, p = 0.009) were the most predictive of postural hypotension. Compression bandages prevented postural hypotension in 21 of 49 patients and decreased the degree of postural blood pressure fall (p < 0.001). Conclusion: Seating-induced postural hypotension is common among older inpatients with decompensated heart failure, especially with longer bedrest, higher supine diastolic blood pressure and non-ischemic etiology. Leg compression bandaging may be useful for the prevention of postural hypotension in these patients.

Increased concanavalin A-induced suppressor cell activity in humans with occupational lead exposure

E-rosette-forming cells (E-RFC), mitogen-induced blast transformation, OKT4+, OKT8+ cells, and their ratio were found to be normal in 10 subjects chronically exposed to lead with blood levels of 40-51 micrograms%. However, concanavalin A (Con A)-induced suppressor cell activity (SCA) in these subjects was significantly greater than in normal matched controls. The clinical relevance of this observation is not clear, but it may have some bearing on the various immunologic defects described in lead exposure.

Clinical characteristics and prognostic significance of serum albumin changes in an internal medicine ward

BACKGROUND The prognostic significance of hypoalbuminemia and the dynamic changes in serum albumin during hospitalization in internal medicine wards has not been sufficiently investigated. METHODS Demographic, clinical and laboratory data were collected from 276 patients admitted to our internal medicine ward for a variety of acute disorders. Following discharge, all-cause mortality was recorded. These data were compared between patient groups, according to levels of albumin: hypoalbuminemia or normoalbuminemia (serum albumin <34 g/l and ≥ 34 g/l, respectively), on admission and discharge. RESULTS Hypoalbuminemia on admission and on discharge was found in 46% and 54% of patients, respectively. Anemia, renal dysfunction, malignant disease, hypocholesterolemia, lymphopenia and albuminuria were more prevalent in patients with hypoalbuminemia, compared to those with normoalbuminemia (p ≤ 0.03). During a median follow-up period of 23 months, 107 of 276 patients died. Mortality was significantly higher (p<0.001) in patients with hypoalbuminemia than normoalbuminemia on admission (52.0% vs. 27.5%) and on discharge (53.7% vs. 21.2%), including those admitted with normoalbuminemia and discharged with hypoalbuminemia (43.6%). Survival rate was higher for patients admitted with hypoalbuminemia and discharged with normoalbuminemia than for those remaining with hypoalbuminemia (82.4% vs. 42.8%, p=0.004). The level of albumin on discharge (each 10 g/l decrement) was the most powerful predictor of shortened survival (relative risk 2.79, 95% confidence interval 2.04-3.70). CONCLUSIONS Hypoalbuminemia on admission, as well as persistence or development of hypoalbuminemia throughout hospitalization, was associated with poor prognosis. Treatment aimed at increasing low albumin or maintaining its normal level may improve survival.

First morning standing up may be risky in acutely ill older inpatients

Information about orthostatic hypotension (OH) among elderly patients hospitalized for acute conditions in short‐term facilities is scarce. Many older inpatients carry various predisposing factors for OH. However, its existence goes frequently unrecognized. In this context, first morning standing up following admission for an acute disease may be dangerous. The aim of this study was to investigate OH and associated manifestations in this situation. OH (⩾20 mmHg systolic and/or ⩾10 mmHg diastolic blood pressure fall), heart rate, arrhythmias and appearance of dizziness or palpitations were recorded in 121 sequential inpatients aged >65 years, prior to and 1, 3 and 5 min following first morning standing. OH occurred in 64.5% of patients, while dizziness and/or palpitations appeared in 76%. Severe adverse effects were registered in 11.5% of OH patients. Significantly associated with OH were: bed rest lasting 9–24 h (vs ⩽8 h, p<0.001), appearance of dizziness or palpitations (p<0.001 and p = 0.005, respectively), heart failure (p = 0.02) and renal dysfunction (p = 0.04). OH and/or associated symptoms are frequent in acutely ill older inpatients on first morning standing up following nocturnal bed rest. The ominous potential consequences call for alertness to this phenomenon and application of appropriate preventive measures.

Hydrochlorothiazide‐amiloride causes excessive urinary zinc excretion

Serum zinc levels and urinary zinc excretion were compared in 15 patients with essential hypertension taking chronically a combination of hydrochlorothiazide and amiloride as monotherapy, eight patients maintained with hydrochlorothiazide alone, and eight control subjects. Serum zinc values were statistically comparable in all three groups. However, urinary zinc excretion was abnormally elevated in the two patient groups. In the dosage used, amiloride did not have a zinc‐sparing effect.