JNC 7—NEW HYPERTENSION GUIDELINES

The National Heart, Lung, and Blood Institute has issued “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure” (JNC 7), which provides a new guideline for hypertension prevention and management. Among the key messages in the JNC 7 report—published in the May 21 JAMA—is an increased emphasis on controlling systolic blood pressure as a risk factor of cardiovascular disease, including myocardial infarction, heart failure, stroke, and kidney disease, particularly in individuals older than 50. The JNC 7 report also stated that the risk of cardiovascular disease beginning at 115/75 mm Hg doubles with each increment of 20/10 mm Hg and that individuals who are normotensive at age 55 still have a 90% lifetime risk of developing hypertension. The previously “normal” blood pressures of 120/80 mm Hg should now “be considered as prehypertensive and require health-promoting lifestyle modifications to prevent cardiovascular disease,” the investigators added.

Additionally, the JNC 7 report proposed that thiazide-type diuretics should be used to treat most cases of uncomplicated hypertension, either as monotherapy or in combination with other drugs. Angiotensin-converting enzyme inhibitors and other drugs were recommended for the treatment of hypertension in “certain high-risk conditions,” and the investigators noted that “most patients with hypertension will require two or more antihypertensive medications to achieve goal blood pressure.” Finally, they acknowledged that physician empathy is important in reinforcing patient motivation, a critical factor in controlling hypertension, regardless of the effectiveness of a particular therapy.

In an accompanying editorial, Thomas E. Kottke, MD, MSPH, and colleagues emphasized the importance of the new guidelines and recommendations but remarked that the JNC 7 report also “documents the failure of the health care system to translate current knowledge into action.” Touching particularly upon the physician-patient relationship, they commented that “Hypertension awareness has not changed in the past decade, and treatment rates have increased by less than 10%. Control rates are stagnant at 34%.” Calling hypertension a manifestation of “lifestyle syndrome,” they warned that “by choosing not to act [ie, to use the tools described in the JNC 7 report to prevent hypertension] the consequences of the lifestyle syndrome epidemic will be dire…. Failing to take advantage of the knowledge that research has generated represents a wasted opportunity to improve and prolong the lives of individuals everywhere and to avert a looming chronic disease crisis,” they concluded.

Suggested Reading
Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-2572.
Kottke TE, Stroebel RJ, Hoffman RS. JNC 7—it’s more than high blood pressure. JAMA. 2003;289:2573-2575.

POSSIBLE BIOMARKERS FOR ALZHEIMER’S DISEASE?

Alzheimer’s disease is associated with a significant decrease in cerebrospinal fluid (CSF) ß-amyloid1-42 levels along with an increase in CSF tau levels, suggesting that both measures may be used as biological markers of Alzheimer’s disease pathophysiology, reported a study in the April 23/30 JAMA. Researchers sought to determine antemortem biomarkers by comparing CSF ß-amyloid1-42 and tau levels in Alzheimer’s disease patients and healthy controls.

One hundred thirty-one patients with Alzheimer’s disease (mean age, 68.1) and 72 control subjects (mean age, 59.4) were examined for the study. The participants with Alzheimer’s disease were mildly to moderately impaired, with mean Mini-Mental State Examination scores of 19.7; the controls were younger and more educated than the patients. The investigators evaluated the participants using medical screenings, neurocognitive profiling, MRI, lumbar puncture, and behavioral observation for one to two weeks. They also conducted a meta-analysis of studies comparing CSF ß-amyloid1-42 and tau levels in patients with Alzheimer’s disease and controls.

The researchers found that across all patients with Alzheimer’s disease and controls, “the CSF ß-amyloid1-42 and tau levels were significantly negatively correlated.” Mean CSF ß-amyloid1-42 levels were considerably lower in patients with Alzheimer’s disease compared with the controls, and CSF tau levels were higher in those with Alzheimer’s disease than in controls. Fourteen of 17 studies in the CSF ß-amyloid1-42 meta-analysis displayed similar data, as did all 34 studies in the CSF tau meta-analysis. However, despite the significant differences between the two groups in the current study, “the data showed considerable variance, resulting in significant overlap between groups.” The investigators feel that “it is evident that the diagnostic sensitivity and specificity of these individual CSF ß-amyloid1-42 and tau assays is simply not sufficient to warrant general clinical use of these biomarkers for individual use.”

Suggested Reading
Sunderland T, Linker G, Mirza N, et al. Decreased ß-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA. 2003;289:2094-2103.

RISK OF VASCULAR EVENTS STILL HIGH AFTER NON-RECENT TIA

The overall risk of major vascular events remains high for patients 10 to 15 years after a transient ischemic attack (TIA), according to a study in the May Journal of Neurology, Neurosurgery and Psychiatry. These patients would typically be considered low risk, as they had been stroke-free for months or years. The investigators sought to determine the risks of stroke, myocardial infarction, and vascular death in patients with a history of non-recent TIA.

Two hundred ninety patients were recruited from the Oxfordshire community stroke project and an Oxford cohort study of hospital-referred patients with TIA. The median age of the cohort was 69 and was predominantly male (62%). The participants were interviewed to ensure that they remained free of stroke and to record their baseline clinical characteristics; blood samples for biochemical and hematological tests were drawn.

During the 10-year follow-up, 20 subjects had a fatal stroke, and 53 had a fatal myocardial infarction or coronary heart disease. In addition, there were 25 non-fatal strokes and14 non-fatal myocardial infarctions.

Researchers found that while “the number of stroke deaths was only slightly greater than expected,” the number of deaths from myocardial infarction or coronary heart disease exceeded expectations. The 10-year risk for stroke was 18.8%, and the 10-year risk for myocardial infarction or coronary heart disease was 27.8%. In light of these results, researchers stressed that “it is important to continue vascular preventive strategies in the long term in patients with a previous TIA, even if they have been free of any major vascular events for several years.”

Suggested Reading
Clark TG, Murphy MFG, Rothwell PM. Long term risks of stroke, myocardial infarction, and vascular death in “low risk” patients with a non-recent transient ischaemic attack. J Neurol Neurosurg Psychiatry. 2003;74:577-580.

EARLY DEPRESSION IS A RISK FACTOR FOR ALZHEIMER’S DISEASE

Depression is significantly associated with the risk of developing Alzheimer’s disease—even when the depressive symptoms manifest themselves as early as 25 years before the onset of Alzheimer’s disease, according to researchers at Boston University School of Medicine.

The MIRAGE (Multi-Institutional Research in Alzheimer’s Genetic Epidemiology) study, a 10-year study of genetic and historical risk information, provided the cohort for Robert C. Green, MD, MPH, and colleagues to examine the association between symptoms of depression and Alzheimer’s disease in 4,046 subjects. A cross-sectional, family-based, case-control administration of standardized self- and proxy-questionnaires was used to collect information on depression and other risk factors for Alzheimer’s disease from 1,953 subjects (mean age, 70.3) with diagnoses of probable Alzheimer’s disease or autopsy confirmation of Alzheimer’s disease, and 2,093 nondemented family members (mean age, 70.1). The results were published in the May Archives of Neurology.

After adjusting for variables, Dr. Green and colleagues found a significant overall association between symptoms of depression and Alzheimer’s disease (odds ratio [OR], 2.13). Additionally, their data for a temporal association between the two diseases revealed that in families where the symptoms of depression first occurred within one year of the onset of Alzheimer’s disease, the association was higher (OR, 4.57), while in families where the depressive symptoms first occurred more than one year prior to the onset of Alzheimer’s disease, the association was lower (OR, 1.38). However, even when the depression first appeared more than 25 years in advance of Alzheimer’s disease, the association remained significant (OR, 1.71), they reported.

The researchers suggested that symptoms of depression developed within one year of the manifestation of Alzheimer’s disease likely represent “early symptoms of the as yet occult Alzheimer’s disease.” They declared their other findings more “difficult to interpret,” postulating that depression may be “toxic” to the brain and predisposing to a vulnerability to Alzheimer’s disease, and even that Alzheimer’s disease may begin “much earlier in life than conventionally thought, perhaps as early as young or midadulthood.” The answer remains unclear, they said, and they called for the continued delineation of genetic and non-genetic risk factors in order to build an accurate model of individuals at the highest risk for Alzheimer’s disease.

Suggested Reading
Green RC, Cupples LA, Kurz A, et al. Depression as a risk factor for Alzheimer’s disease. Arch Neurol. 2003;60:753-759.

IS THERE A LINK BETWEEN TOPIRAMATE DOSE AND ADVERSE EVENTS IN EPILEPSY PATIENTS?

Psychiatric adverse events associated with topiramate are related to the titration schedule of the drug, stated researchers in the May Epilepsia. Psychiatric adverse events were defined as a “psychiatric manifestation that occurred during topiramate therapy and were not related to other antiepileptic drug changes, physical illness, or personal events.” The investigators sought to classify the adverse effects and assess their severity relative to drug use.

Researchers examined 431 patients treated with topiramate. They documented demographic data, diagnostic and clinical characteristics, adverse events related to topiramate, and cognitive adverse events. Patients with psychiatric adverse events were compared with patients without events for all variables. Among patients who experienced adverse events, the investigators compared different psychiatric subgroups for seizure pattern and use of topiramate (including dosage and titration).

Psychiatric adverse effects occurred in 103 patients (23.9%). Forty-six patients developed an affective disorder and 16 a psychotic disorder; 24 patients demonstrated aggressive behavior, and 17 patients showed other behavioral abnormalities. Researchers determined that those who had adverse events also had, among other factors, a family psychiatric history, a diagnosis of symptomatic epilepsy, and a high starting dose and rapid titration schedule of topiramate. The investigators recommend a slow titration and a low starting dose of topiramate, especially for more vulnerable patients.

NR

Suggested Reading
Mula M, Trimble MR, Lhatoo SD, Sander JWAS. Topiramate and psychiatric adverse events in patients with epilepsy. Epilepsia. 2003;44:659-663.

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