July 21, 2011 — Vascular changes are "important" contributors to cognitive impairment and dementia and should be routinely addressed in clinical practice, according to a new scientific statement from the American Heart Association (AHA) and the American Stroke Association (ASA).
The 42-page statement, Vascular Contributions to Cognitive Impairment and Dementia, was published online July 21 in Stroke and will appear in the September print issue of the journal. The American Academy of Neurology and the Alzheimer's Association have endorsed the statement. The Alzheimer's Association participated in its development.
In comments to Medscape Medical News, Philip B. Gorelick, MD, MPH, cochair of the writing group for the statement and director of the Center for Stroke Research at the University of Illinois College of Medicine at Chicago, said vascular factors "have long been thought to be an important contributor to cognitive decline and dementia in later life."
Still, they have not received as much attention as Alzheimer's disease, "which has been on the center stage of scientific inquiry," he added.
Introducing 'Vascular Cognitive Impairment'
Dr. Gorelick and the writing group systematically reviewed published studies, guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, offer recommendations for care.
"Over time and with careful study, vascular factors have been found to play a role in both vascular and so-called neurodegenerative forms of cognitive impairment such as Alzheimer disease," Dr. Gorelick said.
On the basis of the evidence, the writing group formally introduces the construct of "vascular cognitive impairment" (VCI). This, they say, captures "the entire spectrum of cognitive disorders associated with all forms of cerebral vascular brain injury — solely stroke — ranging from mild cognitive impairment through fully developed dementia.
"The neuropathology of cognitive impairment in later life is often a mixture of Alzheimer disease and microvascular brain damage," the study authors note, "which may overlap and synergize to heighten the risk of cognitive impairment."
In this regard, magnetic resonance imaging (MRI) and other neuroimaging techniques "play an important role" in detecting and defining VCI, they advise.
What's Good for the Heart is Good for the Brain
It is now "accepted," the team writes, that many of the traditional risk markers for heart disease and stroke are also risk markers for VCI and Alzheimer's disease.
"Stroke and heart disease are linked by a number of cardiovascular risk factors, such as hypertension, hypercholesterolemia, diet, tobacco exposure, and other factors,” Dr. Gorelick explained. "These vascular factors and others may play a causal role in the development of cognitive impairment and dementia in later life."
Carotid intimal-medial thickness and arterial stiffness are "emerging as markers of arterial aging and may serve as risk markers for VCI," the writing group points out.
Detection and control of the traditional risk factors for stroke and cardiovascular disease may help guard against VCI. "We encourage clinicians to use screening tools to detect cognitive impairment in their older patients and continue to treat vascular risks according to nationally- and regionally-accepted guidelines," the study authors write.
"At the very least," Dr. Gorelick said, screening for and treatment of vascular risk factors, including hypertension, hyperglycemia, and hypercholesterolemia, may reduce the occurrence of stroke and heart disease. "There may be an added benefit of prevention and treatment of vascular risk factors — the prevention of cognitive impairment and dementia in later life," he added.
Specifically, in persons at risk for VCI, the writing group concludes that
- Smoking cessation is reasonable (Class IIa; Level of Evidence A);
- Moderation of alcohol intake, weight control, and physical activity may be reasonable (all Class IIb; Level of Evidence B); and
- Use of antioxidants and B vitamins is not useful, based on current evidence (Class III; Level of Evidence A).
For individuals with vascular dementia, they conclude that
- Donepezil can be useful for cognitive enhancement (Class IIa; Level of Evidence A);
- Galantamine can be beneficial for individuals with mixed Alzheimer disease/vascular dementia (Class IIa; Level of Evidence A); and
- The benefits of rivastigmine and memantine are not well established in vascular dementia (Class IIb; Level of Evidence A).
The study authors also note that a Mediterranean-type dietary pattern has been associated with less cognitive decline in several studies and may be reasonable (Class IIb; Level of Evidence B).
Vitamin supplementation is not proven to improve cognitive function, even if homocysteine levels have been positively influenced, and its usefulness is not well established (Class IIb; Level of Evidence B). The effectiveness of antiaggregant therapy for VCI is not well established (Class IIb; Level of Evidence B).
Reached for comment, Thomas Russ, MD, PhD, from the University of Edinburgh, Scotland, said, "This is a clear outline of the difficulties surrounding the rather complicated overlap and interaction between vascular changes and the neuropathological changes of Alzheimer disease both resulting in cognitive impairment and dementia.
"The recommendations for prevention are a useful restatement of the current state of knowledge and a helpful reminder that we need to intervene sufficiently early in a condition which develops over the course of years and decades — ie, middle age," added Dr. Russ, who was not involved in the writing group.
Dr. Gorelick has disclosed no relevant financial relationships. A complete list of disclosures for writing group members is available with the original article. Dr. Russ has disclosed no relevant financial relationships.
Stroke. Published online July 21, 2011.
Abstract
Inflammation is highly prevalent in patients with chronic kidney disease (CKD) and is consistently associated with cardiovascular morbidity and mortality. Clinical event rates increase with declining renal function and activation of the acute-phase response. Statins are potent anti-inflammatory drugs that reduce the incidence of cardiovascular events. Owing to the increased prevalence of inflammation in patients with CKD and the potent effect of statins in individuals with elevated levels of C-reactive protein, these drugs should be especially effective in patients with CKD. Whereas data indicate that pravastatin may prevent loss of kidney function to a greater extent in individuals with evidence of increased inflammation than in those who show no inflammation, two large, randomized statin trials in patients on hemodialysis found no benefit of statin therapy, neither in the whole study group nor after stratifying for inflammation. Irrespective of inflammation, guidelines recommend treatment of dyslipidemia in early stages of CKD, which is supported by results from recent meta-analyses, and the Study of Heart and Renal Protection (SHARP), a large, randomized, placebo-controlled trial.
Introduction
Atherosclerosis is thought to be an inflammatory disease.[1] C-reactive protein (CRP) is the most extensively studied marker of inflammation and has continuous associations with the risk of atherosclerotic diseases. Although it has been suggested that the associations between CRP and ischemic vascular disease depend considerably on conventional risk factors and other markers of inflammation,[2] the ability of CRP to predict vascular risk might still be useful in identifying individuals who are at high risk of vascular events and who might benefit from therapies to reduce this risk. To study this relationship, investigators of the Justification for the Use of Statin in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) randomly assigned 17,802 apparently healthy men and women with normal LDL-cholesterol levels, but with high-sensitivity CRP (hsCRP) levels of >19.1 nmol/l to double-blind treatment with rosuvastatin versus placebo.[3] After a median follow-up of 1.9 years, rosuvastatin effectively lowered the hazard of the primary end point (occurrence of a first cardiovascular event) by 44% as compared with placebo; furthermore, hsCRP and LDL-cholesterol concentrations were reduced by 37% and 50%, respectively. The investigators concluded that in individuals without hyperlipidemia but with elevated hsCRP concentrations, rosuvastatin significantly reduced the incidence of major cardiovascular events as compared with placebo (P <0.001).[3]
Inflammation is highly prevalent in patients with chronic kidney disease (CKD), with CRP levels of between 47.6 nmol/l and 76.2 nmol/l commonly reported.[4-10] Reduced kidney function is associated with a considerably increased risk of death and cardiovascular events,[11] resulting in mortality rates as high as 20% in the first year of renal replacement therapy.[12,13] In these patients, CRP levels have been shown to be a potent risk marker for cardiovascular events and mortality.[14] Identifying treatments that decrease inflammation in patients with CKD could, therefore, translate into improved outcomes. Following the results from JUPITER, the question arises as to whether statins would be effective for reducing cardiovascular events in patients with CKD with differing levels of CRP; that is, do patients with higher CRP levels benefit more from statin therapy than patients with lower CRP levels? Furthermore, statins have been proposed in the treatment of erythropoietin hyporesponsiveness and have also been shown to improve survival in sepsis events.[15,16] These effects were observed in patients presenting with 'normal' LDL-cholesterol levels, similar to those in participants in JUPITER, suggesting that statins have benefits other than their lipid-lowering effects.
In this Review we describe the extent of the inflammatory state in patients with CKD and uremia, outlining the causes of the acute-phase response and its impact on prognosis. We also discuss the effect of statins on surrogate and hard outcomes in patients with CKD who show evidence of inflammation. A short overview of the benefit of statin therapy in patients with CKD and an outlook towards the future is also provided.
Section 1 of 10 Next: Inflammation in Patients with CKD »
Summary and Comment
Acid-Suppressive Medication in Noncritical Patients
Bleeding risk was reduced slightly, but the absolute benefit was very small.
Acid-suppressive medication helps to prevent stress-related gastrointestinal (GI) bleeding in critically ill patients, but the practice has spread to noncritical patients despite no good evidence of benefit. Various studies have shown that up to 70% of all inpatients receive acid-suppressive medication. Boston investigators sought to supplement the results of smaller randomized trials with a retrospective cohort study of about 79,000 adults admitted for diagnoses other than GI bleeding; about 46,000 (59%) of them received acid-suppressive medications.
The rate of nosocomial GI bleeding (i.e., bleeding occurring more than 24 hours after admission) was 0.29%. In adjusted analyses that compared patients treated and not treated with acid-suppressive medication, the rate of GI bleeding was lower by roughly 37% in those taking medication.
Comment: These results, while retrospective and uncontrolled, further support the recommendation against use of acid-suppressive medication in noncritical patients. The benefits are very small with such use, and patients are exposed to a wide range of risks, including the development Clostridium difficile infections and hospital-acquired pneumonia.
— Thomas L. Schwenk, MD
Published in Journal Watch General Medicine June 30, 2011
50 years who took gastroprotective agents, patients with UGI events were identified. Adherence to gastroprotective therapy was determined using pharmacy data and compared between patients with and without UGI events.
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