STATINS REDUCE THE INCIDENCE OF VASCULAR EVENTS

Statin therapy can safely reduce the incidence of major coronary events, coronary revascularization procedures, and stroke by lowering LDL cholesterol, according to Colin Baigent, MD, and colleagues. “These findings reinforce the need to consider prolonged statin treatment with substantial LDL cholesterol reductions in all patients at high risk of any type of major vascular event,” they said. Their results were published in the October 8 Lancet.

The researchers conducted a prospective meta-analysis of data from 90,056 persons participating in 14 randomized trials of statins. They obtained weighted estimates of effects on different clinical outcomes—such as all-cause mortality, coronary heart disease (CHD) mortality, and non-CHD mortality—per 1.0-mmol/ L reduction in LDL cholesterol. Secondary outcomes included major coronary events, stroke, cancer, and vascular procedures.

During a mean period of 4.7 years, there were a total of 8,186 deaths; 4,655 were from vascular causes and 3,531 were from nonvascular causes. According to the researchers, 3,832 (8.5%) of 45,054 participants allocated statins and 4,354 (9.7%) of 45,002 participants in the control group died. “This difference represents a 12% proportional reduction in all-cause mortality per mmol/L LDL cholesterol reduction,” they said.

The results also indicated an overall proportional reduction of about 21% in the incidence of major vascular events per 1.0-mmol/L reduction in LDL cholesterol. This finding reflected similar proportional reductions in major coronary events, coronary revascularization procedures, and strokes. The researchers observed a 10% proportional reduction in major vascular events during the first year after initiating treatment, followed by highly significant reductions of approximately 25% during each subsequent year. “Taking all the years together,” said Dr. Baigent and his colleagues, “the overall reduction of about one fifth per mmol/L LDL cholesterol reduction translated into 48 fewer participants having major vascular events per 1,000 among those with pre-existing CHD at baseline, compared with 25 fewer per 1,000 among participants with no such history.”

The researchers noted that there was no evidence that use of statins increased the risk of cancer overall or at any particular site. Also, the five-year risk of rhabdomyolysis was small and not significant.

Dr. Baigent and his colleagues suggested that “assessment of baseline risk should be based on any type of occlusive vascular event (rather than on coronary events alone), since lowering LDL cholesterol with a statin lowers the risk not just of coronary events but also of revascularization procedures and of ischemic strokes. Secondly, treatment goals for statin treatment should aim chiefly to achieve substantial absolute reductions in LDL cholesterol (rather than to achieve particular target levels of LDL cholesterol), since the risk reductions are proportional to the absolute LDL cholesterol reductions.”

Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267-1278.

FISH CONSUMPTION MAY SLOW COGNITIVE DECLINE

Eating one or more fish meals per week may protect against cognitive decline in the elderly, according to Martha Clare Morris, ScD, and colleagues. The study was published in the online edition of Archives of Neurology and is scheduled to appear in the December print edition.

The investigators examined data from the ongoing Chicago Health and Aging Project. A total of 3,718 people 65 or older were included in the analyses. Diet was assessed using a modified Harvard Food Frequency Questionnaire, which asked about usual intake of 139 different foods in the past year and included four seafood categories—tuna fish sandwich, fish sticks/fish cakes/ fish sandwich, fresh fish as a main dish, and shrimp/lobster/crab. Cognition was measured using four tests: the East Boston tests of Immediate and Delayed Recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test.

Results indicated that 21.0% of participants ate two or more fish meals per week, 36.3% ate one fish meal per week, and 42.6% ate less than one fish meal per week. Those who consumed fish were more likely to be African-American, to have a cardiovascular-related health condition, and to drink less alcohol.

According to Ms. Morris and her colleagues, the mean cognitive score at baseline was 0.18 standardized units (SU), which declined by 0.04 SU per year. They reported that cognitive decline was slower among people who consumed fish at least once a week. Participants who consumed one fish meal per week and those who consumed two or more fish meals per week experienced annual rates of cognitive decline that were 10% and 13% slower, respectively, than those of participants who did not consume fish, said the researchers.

The association between fish consumption and cognitive decline “was not accounted for by cardiovascular-related conditions or fruit and vegetable consumption but was modified after adjustment for intakes of saturated, polyunsaturated, and trans fats,” said the researchers. They added that “there was little evidence that the omega-3 polyunsaturated fatty acids were associated with cognitive change.”

Morris MC, Evans DA, Tangney CC, et al. Fish consumption and cognitive decline with age in a large community study. Arch Neurol. 2005; E-pub ahead of print.

EFFECTIVENESS OF CAROTID ENDARTERECTOMY FOR STROKE PREVENTION

Prompted by the wealth of evidence that has emerged since their 1990 statement on carotid endarterectomy for stroke prevention, the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology has issued a revised clinical practice guideline that evaluates the strength of the available evidence behind key clinical questions regarding carotid endarterectomy. Their report was published in the September 27 Neurology.

The guideline authors analyzed data from studies conducted between 1990 and 2004 examining the efficacy of carotid endarterectomy, excluding case reports, review articles, technical studies, and single-surgeon case series. They found that among symptomatic patients with 70% to 99% stenosis, carotid endarterectomy reduced stroke risk (16% absolute risk reduction at five years) compared with medical therapy alone. A smaller benefit (4.6% absolute risk reduction at five years) was seen in symptomatic patients with 50% to 69% stenosis. Researchers recommended that when treating the latter set of patients, clinicians should consider additional clinical and angiographic variables. They also stated that carotid endarterectomy should not be considered for symptomatic patients with less than 50% stenosis. In such patients, medical management is preferred to carotid endarterectomy.

Among asymptomatic patients with 60% to 99% stenosis, a small benefit was seen if risk of perioperative complication was low (less than 3%); however, this benefit was smaller than the benefit seen in symptomatic patients.

According to the revised guideline, patients with hemispheric transient ischemic attack/stroke had greater benefit from carotid endarterectomy than did patients with retinal ischemic events. They also found that patients operated on within two weeks of their last transient ischemic attack or mild stroke benefited more from carotid endarterectomy. Lead author Seemant Chaturvedi, MD, and colleagues recommended that symptomatic and asymptomatic patients undergoing carotid endarterectomy “be given aspirin (81 or 325 mg/day) prior to surgery and for at least three months following surgery to reduce the combined end point of stroke, myocardial infarction, and death.”

The investigators said future research should address the following areas: the setting of urgent carotid endarterectomy in patients with progressing stroke, the appropriateness of carotid endarterectomy in community settings, the management of coexisting carotid and coronary artery disease, the timing of carotid endarterectomy in patients with recent stroke, how carotid endarterectomy compares with less invasive endovascular treatment with stenting, the role of cerebral hemodynamics in risk stratification for patients with carotid stenosis, and the effects of newer antiplatelet agents and angiotensin receptor blockers in patients with carotid stenosis.

Chaturvedi S, Bruno A, Feasby T, et al. Carotid endarterectomy—an evidence-based review: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2005;65:794-801.

FRONTOTEMPORAL DEMENTIA PROGRESSES MORE RAPIDLY THAN ALZHEIMER’S DISEASE

Frontotemporal lobar degeneration progresses more rapidly than Alzheimer’s disease, with the fastest progression seen in patients with the frontotemporal dementia clinical subtype, coexisting motor neuron disease, or tau-negative neuropathology, according to a study in the September 13 Neurology.

Erik D. Roberson, MD, of the Gladstone Institute of Neurological Disease at the University of California, San Francisco, and colleagues sought to characterize survival in frontotemporal lobar degeneration by comparisons with survival in Alzheimer’s disease and corticobasal degeneration/progressive supranuclear palsy. The researchers assessed a total of 619 patients: 177 with frontotemporal lobar degeneration, 395 with Alzheimer’s disease, and 47 with corticobasal degeneration/progressive supranuclear palsy.

They found that 80 patients with frontotemporal lobar degeneration, 80 patients with Alzheimer’s disease, and 14 patients with corticobasal degeneration/progressive supranuclear palsy had died. Those with Alzheimer’s disease were older than those in the other cohorts, and those with frontotemporal dementia had the youngest age at onset. Most conditions were more common in men, with the exception of progressive aphasia and Alzheimer’s disease. Mini-Mental State Examination scores at initial evaluation were 21.2 in the frontotemporal lobar degeneration group and 20.2 in the Alzheimer’s disease group.

Median survival in frontotemporal lobar degeneration was 11 years from onset of first symptom and 3.6 years from presentation to clinic, the investigators reported. Of the three frontotemporal lobar degeneration subtypes—progressive aphasia, semantic dementia, and frontotemporal dementia—frontotemporal dementia had the shortest survival time. Median survival was longer in patients with Alzheimer’s disease than in patients with frontotemporal lobar degeneration. Also, when comparing survival in frontotemporal lobar degeneration to that in corticobasal degeneration/progressive supranuclear palsy, they found that survival was similar (11.8 years from onset and 3.6 years from presentation to clinic).

Age at onset, gender, or education did not affect survival, reported the researchers. Among the neuropsychological measures examined, impaired letter fluency was associated with reduced survival. Frontotemporal lobar degeneration patients with amyotrophic lateral sclerosis (ALS) had significantly reduced survival, compared with those without ALS. The investigators observed that patients with tau-positive inclusions had the slowest progression.

“Understanding why frontotemporal dementia progresses more rapidly than Alzheimer’s disease may contribute to a better understanding of the underlying disease mechanisms and could highlight aspects of the disease that should receive high priority as treatment targets,” said Dr. Roberson and his colleagues.

The investigators suggested that future studies of frontotemporal dementia should focus on “elucidating the pathophysiology of tau-negative cases and understanding the link between frontotemporal dementia and ALS.”

Roberson ED, Hesse JH, Rose KD, et al. Frontotemporal dementia progresses to death faster than Alzheimer disease. Neurology. 2005;65:719-725.

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