The trusted source for
healthcare information and
Clinical Briefs in Primary Care
Alendronate for Osteoporosis
Source: Bone HG, et al. N Engl J Med. 2004;350:1189-1199.
The bisphosphonates alendronate (ALE) and risedronate are the most commonly used pharmacologic agents for the treatment and prevention of osteoporosis (OSPS). Bisphosphonates have been shown to reduce fracture rates and improve bone mass, but previous studies have been limited to windows of observation no longer than 5 years. Because patients may be receiving bisphosphonates for decades, longer-term studies are of great value.
The study population reported by Bone and colleagues included women (n = 247) from an original study group of 994 who were randomized to a placebo- controlled 3-year study of ALE. At the conclusion of that study, women were invited to extend treatment with ALE 5 or 10 mg/d for an additional 2-7 years. Some of the women who had been originally assigned to ALE ware given placebo, which also allowed determination of whether bone accrual effects would recede upon discontinuation of treatment.
Both ALE doses provided increases in bone density over 10 years, maximally in the lumbar spine (13.7% increase) and least in the femoral neck (5.4% increase). The nonvertebral fracture rate during the years 6-10 of the study was similar to that seen in the first 3 years, in which there were approximately 20% fewer fractures in the ALE group. Bone markers indicated that ALE benefits gradually diminished upon discontinuation. ALE is well tolerated and maintains efficacy with long-term administration.
Exercise Training in Patients with Chronic Heart Failure
Source: ExTraMATCH Collaborative. BMJ USA. 2004;4:109-112.
In the not too-distant past, clinicians were apprehensive about exercise for patients with chronic heart failure (CHF). Evolution of knowledge about optimizing treatment in CHF has recognized that exercise may indeed provide symptomatic benefits. The effect of exercise upon mortality has not been examined, or study populations have been too small to derive meaningful data. By meta-analysis, data from 9 studies (n = 801) provides a sturdier picture of the impact of exercise upon mortality.
In the studies used to comprise the meta-analysis group, exercise programs attained peak oxygen consumption intensity ranging from 50-80%, by means of cycling, walking, or other aerobic activities. All programs provided supervised activity, ranging from 30-60 minutes per day on multiple days per week. Followup was up to approximately 2 years. To ensure that effects were related to exercise, and not changes in pharmacotherapy, drug regimens were examined. No changes in ACE inhibitors, beta blockers, or antialdosterone agents occurred during exercise study periods.
Exercise provided a favorable 35% risk reduction in mortality and 28% reduction in the combined end point of death or hospitalization. The optimum intensity, duration, method, and frequency of exercise remain unknown, but clinicians should be encouraged that aerobic exercise may be life-prolonging in patients with CHF.
Cardiovascular Prognosis of "Masked Hypertension"
Source: Bobrie G, et al. JAMA. 2004;291:1342-1349.
There is consistent agreement that ambulatory blood pressure monitoring (ABPM) provides a better indicator of ultimate cardiovascular risk than office blood pressure (OBP). Because measurement of BP at home (HBP) often frees the patient from stressors which could lead to spuriously elevated BP (white coat HTN), we are sometimes aided by such measurements in directing treatment. Unfortunately, trial data based upon HBP measurement is sparse.
The Self Measurement of BP at Home in the Elderly study followed almost 5,000 participants for 3 years. Subjects had BP measured in the office after a 5-minute rest. At home, patients measured BP 3 times each morning and evening.
During followup, 205 deaths occurred (85 cardiovascular). HBP was predictive of cardiovascular events in men and women, for both systolic and diastolic BP. There was a small group of individuals (9% of total group) whose BP was elevated on HBP measurement, but not in the office. These individuals also reflected an increased cardiovascular risk. Bobrie and associates conclude that HBP measurement is a better prognostically than office BP. Indeed, they have identified a heretofore little-described population known as masked hypertension’, who have elevated blood pressures at home despite normal office BP.
Short-term Intensive Insulin Therapy in Newly Diagnosed DM2
Source: Ryan EA, et al. Diabetes Care. 2004;27:1028-1032.
The best initial treatment for the newly diagnosed type 2 diabetic (DM2) remains a matter of debate. Although there is consensus that DM2 is characterized by both insulin secretory and insulin responsivity defects, and that hyperglycemia may contribute to both (so-called glucotoxicity’), it is unclear whether intensive early treatment, with a goal of prompt eradication of glucotoxicity, results in any long-term benefits. Since insulin is capable of providing the most rapid, consistent, and substantial declines in glucose, it was a logical choice for studying this issue.
Newly diagnosed DM2 patients (n = 16) were instructed in appropriate use of short-acting insulin before each meal (5 u regular, starting dose), and intermediate acting insulin at bedtime (10-15 u NPH at HS, starting dose). Insulin doses were increased 2-5 u per dose on a daily basis until postprandial and fasting goals were achieved. Clinic visits occurred twice weekly during the first 2-3 weeks until goals were achieved. After 3 weeks insulin was discontinued, and patients were seen monthly (with phone contact every 2 weeks) for one year.
At 1 year, 7 of the subjects were able to maintain glucose control on diet alone, the remaining subjects requiring oral hypoglycemic agents (n = 8) or insulin (n = 1) to maintain control. The subjects who were characterized as requiring less insulin to achieve goals (0.37 u/kg/d vs 0.73 u/kg/d), and attaining a lower fasting glucose (5.9 vs 7.7 mmol/L) during the 3 week intensive insulin program were shown to be able to best sustain control with diet alone. These data support the concept that brisk resolution of glucose toxicity provides some potentially sustained restoration of beta-cell function and/or insulin responsivity.
Endothelial Dysfunction and Risk of Type 2 Diabetes Mellitus
Source: Meigs JB, et al. JAMA. 2004;291:1978-1986.
The primary cause of mortality in type 2 diabetes (DM2) is cardiovascular disease (CVD). Indeed, our most recent national guidelines have recognized that at the point of diagnosis, a person with DM2 has a similar or greater risk of subsequent coronary heart disease (CHD) end point as a person who has already suffered a myocardial infarction. The prominent CVD risk seen in DM2 has been variously, but somewhat unconvincingly ascribed to such risk factors as insulin resistance and hyperinsulinemia. In an effort to better elucidate the pathophysiologic underpinnings of DM2-related CVD, Meigs and colleagues studied plasma biomarkers of endothelial dysfunction in ostensibly healthy women at the time of enrollment into the Nurses Health Study (n = 32,826) in 1989-1990. Biomarkers measured included E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1.
By the year 2000, 737 women had developed DM2. Baseline biomarkers in these women, when compared to an equal number of controls, showed that E-selectin, ICAM-1, and VCAM-1 each were predictive of future DM2 development. Even after adjustment for BMI, family history, diet, alcohol, and activity level, the likelihood of developing DM2 was increased more than 5-fold in the highest baseline quintile of E-selectin, and approximately 4-fold for the top quintile of ICAM-1.
Endothelial dysfunction presages DM2, and helps explain the disproportionate burden of CVD in this population.
Treatment of Parkinson’s Disease with Pergolide and Relation to Restrictive Valvular Heart Disease
Source: Van Camp G, et al. Lancet. 2004;363:1179-1183.
Even medications that are generally considered safe and effective may cause adverse effects that are sufficiently uncommon that they escape adequate identification. Although valvular heart disease (VHD) has been described as potentially associated with pergolide treatment, initial estimates suggested a very low frequency (one in 20,000). To provide a better estimate of the VHD risk with pergolide treatment, 78 pergolide-treated Parkinson’s disease patients were compared with a population of Parkinsonian subjects who had not received an ergot-derived dopamine agonist. All subjects underwent transthoracic echocardiography. The echocardiographic measurement used to define restrictive VHD was tenting distance and area.’
Even when restricting analysis to only those with major suspicion of VHD on echocardiography, almost 20% of pergolide-treated patients manifest some degree of disease. Frequency of VHD correlated both with dose-intensity, and cumulative dose of pergolide.
This frequency of here-to-fore little-recognized valvulopathy associated with pergolide should stimulate clinicians to investigate for VHD in appropriately symptomatic individuals. Indeed, a case can be made for consideration of routine echocardiography in recipients of pergolide. The frequency of VHD detected in this study is similar to the valvulopathy rate seen amongst women who utilized appetite suppressants such as dexfenfluramine (Redux).