Review of Predictors of Maintenance of Normotension After Withdrawal of Antihypertensive Drugs

Source: Nelson M, et al. Am J Hypertension. 2001;14:98-105.

A substantial minority of pa-tients receiving antihypertensive medications remains normotensive upon cessation of treatment. Some of these individuals were treated prematurely, without adequately establishing a diagnosis of hypertension (HTN) with certainty. Others have eliminated the etiology for their elevated blood pressures (eg, obesity or alcohol) but continue on unnecessary medication. All the reasons for restoration of normotension in some hypertensive patients are unknown. Clinicians and their patients would benefit from knowing which predictors are associated with sustained normotension after medication withdrawal. To that end, the authors reviewed articles that examined withdrawal of antihypertensive medications in persons who subsequently remained normotensive for at least 12 months.

Approximately 42% of patients in whom medication was withdrawn remained normotensive for at least 12 months. Patients with lower pretreatment or on-treatment BP, those with good control on fewer agents or lower doses, and those who used weight reduction and salt restriction at the time of medication withdrawal predictably experienced greater likelihood of remaining normotensive upon cessation of antihypertensive therapy. Patients with mild-to-moderate hypertension, especially those with favorable predictors, should be periodically considered for a trial of treatment cessation.

Routine PSA Testing: What Do Men Believe?

Source: Zemencuk JK, et al. Am J Med. 2001;110:309-313.

The controversy about the merit (or lack of merit) in PSA screening for asymptomatic men remains unabated, despite an apparent increase in use of the testing by both clinician and patient initiation. The current study examined men’s knowledge about PSA testing, specifically in regards to perceived benefits of, recommendations for, and controversy around PSA testing.

A survey was administered to 442 adult men (³ age 50) at 2 sites in the United States and 1 in Canada, asking such questions as, "How much can regular PSA testing reduce a man’s chance of dying from prostate cancer" and "How beneficial do you believe regular PSA testing would be for you?"

Most men believed that regular PSA testing could significantly reduce the risk of dying from prostate cancer, though this belief was substantially more widespread in American than Canadian men (80% vs 63%). Even among men who had discussed PSA testing with their physician, there was no consistent awareness of any attendant controversy.

It has been suggested by some that the choice for PSA testing should be offered to the patient, after informed consent. Apparently, men are currently ill-informed about PSA testing, having a much more confident view of the potential value of PSA testing than has ever been demonstrated in a prospective, randomized, double-blind trial.

Aggressive vs. Conventional Lipid Lowering on Atherosclerosis Progression in Familial Hypercholesterolaemia (ASAP)

Source: Smilde TJ, et al. Lancet. 2001;357:577-581.

Cholesterol lowering by means of HGMCoA Reductase agents (statins) has proven favorable for reduction of cardiovascular end points. It is not clear whether the greatest reductions in cardiovascular end points are correlated with the greatest degree of lipid lowering. Rather, there may be some threshold effect, or pharmacologic aspects of different members of the statins class may have differential effects.

Using carotid intima media thickness (IMT) as a surrogate marker for vascular atherosclerosis, Smilde and associates compared (n = 325) atorvastatin 80 mg q.d. with simvastatin 40 mg q.d. administered over 2 years time.

Atorvastatin provided greater cholesterol reduction than simvastatin. Carotid IMT demonstrated reduction in the atorvastatin recipients, but progression in persons treated with simvastatin.

This trial demonstrates a more favorable impact of atorvastatin than simvastatin on degree of cholesterol lowering, triglyceride reduction, and carotid IMT. Whether these favorable effects associated with more aggressive cholesterol reduction will be reflected in comparable cardiovascular end point attenuation remains to be fully elucidated.

Prior Alcohol Consumption and Mortality Following Acute Myocardial Infarction

Source: Mukamal KJ, et al. JAMA. 2001;285:1965-1970.

Population studies have demonstrated a U-shaped distribution of the relationship between alcohol intake and coronary heart disease (CHD), in that persons with the most "moderate" alcohol consumption appear to enjoy lesser CHD than either nondrinkers or heavy drinkers. Whether the alcohol itself exerts a beneficial effect, or moderate alcohol consumption is associated with other lifestyle factors which enhance cardiovascular health remains unknown.

The current study, the first of its kind, examined the relationship of alcohol consumption to mortality in individuals suffering an acute myocardial infarction (AMI). Mukamal and colleagues interviewed men and women (n = 1935) within a few days of having an AMI about their alcohol consumption in the previous year, stratified by grams of ethanol per week into abstainers, light drinkers (< 7 drinks/week), and moderate drinkers (> 7 drinks/week).

Almost half of the patients reported no alcohol intake in the prior year. Higher alcohol intake correlated with higher educational attainment and higher income. AMI mortality was highest among abstainers, and lowest in moderate drinkers. Mukamal et al conclude that in this population, moderate alcohol intake in the year prior to AMI was associated with a more favorable survival outcome than abstention or light alcohol consumption.

A Re-evaluation of the Duration of Survival After the Onset of Dementia

Source: Wolfson C, et al. N Engl J Med. 2001;344:1111-1116.

Life expectancy among persons with dementia has been reported to be substantially reduced, ranging from 5-9 years on average. Such observations suffer from length bias—persons with rapidly progressive dementia and demise participate less often in studies—which would tend to underestimate the effect of dementia on mortality.

In order to gain a clearer picture of the effect dementia imparts on survival, Wolfson and colleagues used data from a randomly selected large Canadian population (n = 10,263) of persons older than age 65 who were screened for cognitive impairment. In addition to determining the presence of dementia, date of onset for cognitive impairment was noted. Subjects were followed for 5 years.

In the cognitively impaired subjects (n = 821), most had Alzheimer’s disease, but almost one-fourth had vascular dementia.

Unadjusted median survival for the group, which did not differ significantly between those with probable Alzheimer’s disease, possible Alzheimer’s disease, or vascular dementia, was 6.6 years. When adjusted for length bias, this median survival was reduced to 3.3 years. This survival is substantially less than in previously reported data, and Wolfson et al note that this places dementia in a category with other substantially mortal disorders like congestive heart failure.

Effectiveness of St. John’s Wort in Major Depression

Source: Shelton RC, et al. JAMA. 2001;285:1978-1986.

St. john’s wort (sjw) is a widely popular treatment for depression, both in the United States and Europe. Meta-analysis has concluded that SJW is superior to placebo, with approximately equal efficacy to traditional proprietary pharmacologic agents, and often fewer side effects. There has been some criticism of previous study flaws that may have undermined the certainty with which conclusions about SJW efficacy may be drawn. This prospective, randomized, double-blind, placebo-controlled (n = 200) investigation was designed to evaluate the comparative efficacy of 300 mg of SJW over an 8-week period. Study participants had suffered depression for an average of more than 2 years.

Because of the risk of suicide in depressed persons, and since this study contained a placebo arm, any demonstration of suicide risk was a reason for exclusion. Additionally, deterioration from baseline depression scores also resulted in exclusion from the trial.

Despite the use of multiple measurement tools for depression outcome (eg, Beck Depression Inventory, Clinical Global Impression, Hamilton Anxiety Scale), Shelton and colleagues were not able to demonstrate an antidepressant response significantly greater than placebo.