Translating current knowledge into dementia prevention.

Considerable knowledge has been gained from epidemiologic studies and randomized clinical trials regarding risk factors for dementia, including Alzheimer disease (AD) and vascular dementia (VaD). Most identified risk factors for dementia are similar to vascular disease risk factors for heart disease and stroke. In 2010, the National Institutes of Health Conference concluded that there are no validated modifiable factors to reduce the incidence of AD or to change its course. This research perspective specifically concerning AD disregards the fact that in community-dwelling elderly, the most common forms of dementia involve the cerebral macrovasculature and microvasculature, manifesting as VaD and mixed dementia (the combination of VaD and AD) in autopsy-confirmed cases. Thus, prevention of dementia in clinical practice should be considered from this broader and more relevant view and not just a research perspective on "pure" AD. Practicing clinicians can reasonably state to patients that, although more definitive research is clearly needed, the management and treatment of vascular disease risk factors are likely beneficial not only to prevent heart disease and stroke, but also common forms of dementia in the community.

Ranolazine for chronic stable angina.

Ranolazine is a new and unique antianginal drug that has been approved for the treatment of chronic stable angina pectoris. The drug is administered as a sustained-release formulation. Although the drug's mechanism of action has not been fully elucidated, current thinking is that ranolazine, a selective inhibitor of late sodium influx, attenuates the abnormalities of ventricular repolarisation and contractility associated with ischaemia. Three randomised trials have shown efficacy for ranolazine in increasing exercise testing or reducing anginal episodes or use of glyceryl trinitrate. Side-effects include dizziness, constipation, nausea, and the potential for prolongation of the QT(c) interval. Ranolazine seems to be a safe addition to current traditional drugs for chronic stable angina, especially in aggressive multidrug regimens.

Nuts as part of a healthy cardiovascular diet.

The increasing trend of obesity has been associated with a greater prevalence of type 2 diabetes mellitus and may lead to more vascular disease. Nuts, a rich source of monounsaturated fatty acids and fiber, have been shown to decrease the risk of cardiovascular disease and the risk of developing type 2 diabetes mellitus. Numerous studies have demonstrated that nuts favorably affect serum lipids. They also exhibit a number of nonlipid benefits, including improved weight management, greater insulin sensitivity, and favorable endothelial effects, as well as having anti-inflammatory properties. Incorporating nuts into the diets of more people may lead to a variety of cardiovascular benefits.

Cardiovascular risk factors and dementia.

BACKGROUND: Dementias, such as Alzheimer's disease (AD) and vascular dementia, are disorders of aging populations and represent a significant economic burden. Evidence is accumulating to suggest that cardiovascular disease (CVD) risk factors may be instrumental in the development of dementia. OBJECTIVE: The goal of this review was to discuss the relationship between specific CVD risk factors and dementia and how current treatment strategies for dementia should focus on reducing CVD risks. METHODS: We conducted a review of the literature for the simultaneous presence of 2 major topics, cardiovascular risk factors and dementia (eg, AD). Special emphasis was placed on clinical outcome studies examining the effects of treatments of pharmacologically modifiable CVD risk factors on dementia and cognitive impairment. RESULTS: Lifestyle risk factors for CVD, such as obesity, lack of exercise, smoking, and certain psychosocial factors, have been associated with an increased risk of cognitive decline and dementia. Some evidence suggests that effectively managing these factors may prevent cognitive decline/dementia. Randomized, placebo-controlled trials of antihypertensive medications have found that such therapy may reduce the risk of cognitive decline, and limited data suggest a benefit for patients with AD. Some small open-label and randomized clinical trials of statins have observed positive effects on cognitive function; larger studies of statins in patients with AD are ongoing. Although more research is needed, current evidence indicates an association between CVD risk factors--such as hypertension, dyslipidemia, and diabetes mellitus--and cognitive decline/dementia. CONCLUSIONS: From a clinical perspective, these data further support the rationale for physicians to provide effective management of CVD risk factors and for patients to be compliant with such recommendations to possibly prevent cognitive decline/dementia.

Use of vascular ultrasound in clinical trials to evaluate new cardiovascular therapies.

Though progress has been made in the fight against cardiovascular disease (CVD), the increasing global prevalence of cardiovascular (CV) risk factors ensures that CVD rates remain high. In order to reduce CVD incidence, a huge effort has been made to uncover additional targets for therapy and novel methods of identifying patients at risk. A low level of high-density-lipoprotein (HDL) cholesterol is recognized as an important independent risk factor for occurrence of a CV event, and new therapies capable of producing effective, clinically relevant increases in this key lipoprotein particle are in development. These therapies will most likely be assessed in comparison with proven CV-risk-reducing therapies such as statin treatment, rather than against a placebo comparator. Inevitably, therefore, clinical end-point trials will increase in both complexity and longevity. Potential efficacy data on new therapies may be revealed sooner by trials using surrogate end points, biomarkers of disease progression known to correlate with clinical events. For novel CV therapies, ultrasound-measured changes in atherosclerosis, such as the change in atheroma burden or plaque volume measured by intravascular ultrasound (IVUS), or ultrasound-measured increase in carotid intima-media thickness (CIMT), may represent useful biomarkers. Both IVUS and CIMT are being widely deployed in trials of new and existing CV therapies to assess their impact on slowing the progression of atherosclerosis, and their use in this regard is the subject of this review.

Cardiovascular disease risk factors and cognitive impairment.

The role of cardiovascular disease risk factors in the occurrence and progression of cognitive impairment has been the subject of a significant number of publications but has not achieved widespread recognition among many physicians and educated laymen. It is apparent that the active treatment of certain of these cardiovascular disease risk factors is accompanied by a reduced risk for cognitive impairment. Patients with hypertension who are treated experience fewer cardiovascular disease events as well as less cognitive impairment than similar untreated patients. Patients who exercise may present with less cognitive impairment, and obesity may increase the risk for cognitive impairment. Lipid abnormalities and genetic markers are associated with an increased risk for cardiovascular disease and cognitive impairment. Autopsy studies have demonstrated a correlation between elevated levels of cholesterol and amyloid deposition in the brain. Research has demonstrated a relation between atherosclerotic obstruction lesions in the circle of Willis and dementia. Diabetes mellitus is associated with an increased risk for cardiovascular disease and cognitive impairment. A number of nonpharmacologic factors have a role in reducing the risk for cognitive impairment. Antioxidants, fatty acids, and micronutrients may have a role, and diets rich in fruits and vegetables and other dietary approaches may improve the outlook for patients considered at risk for cognitive impairment.

The clinical implications and management of concomitant hypertension and dyslipidemia.

Hypertension and dyslipidemia often coexist, increasing the risk of cardiovascular disease. Evidence suggesting that concomitant hypertension and dyslipidemia are compelling candidates for a unified approach to treating cardiovascular risk is reviewed in this article. The authors also discuss important new findings documenting the need for, and benefits of, a more integrated approach to treating this dangerous duo.

Relationship of C-reactive protein, metabolic syndrome and diabetes mellitus: potential role of statins.

Atherosclerosis and the metabolic derangements of insulin resistance, metabolic syndrome and diabetes mellitus are all associated with underlying inflammatory processes. C-reactive protein (CRP), a marker of inflammation, has been shown to be a strong independent predictor of vascular events. It adds to cardiovascular disease risk at all levels of low-density-lipoprotein cholesterol and Framingham risk scores, and elevated levels are also associated with increasing severity of the metabolic syndrome. The development of a simple, stable, noninvasive test to measure high-sensitivity CRP has provided a clinical tool that may have an important role in the identification and assessment of individuals likely to develop cardiovascular or metabolic disease. The role of CRP in predicting cardiovascular risk is less clear in African Americans, however, than in white populations. Statins and thiazolidinediones are being investigated for their potential role in the prevention and treatment of the inflammatory processes involved in the metabolic syndrome and cardiovascular disease. In the future, assessment of CRP levels may contribute importantly to clinical decision-making in reducing cardiovascular risk.

Statins. Evidence of effectiveness in older patients.

As the population ages, increasing numbers of older adults are becoming candidates for lipid-lowering therapy with HMG CoA reductase inhibitors (statins) and lifestyle modification. Available evidence shows that statins reduce cardiovascular events and invasive revascularization in older adults. Statins have not only been shown to be safe and effective for lowering LDL cholesterol, but appear to have ancillary pleiotropic effects that are beneficial in other conditions to which older adults are prone. Despite these benefits, older adults are currently undertreated for this highly treatable cardiovascular risk factor.

Cardiovascular risk beyond LDL-C levels. Other lipids are performers in cholesterol story.

High levels of low-density lipoprotein cholesterol (LDL-C) are an obvious culprit in coronary artery disease (CAD). However, the search for lipid factors that influence cardiovascular health does not end there. In this article, Dr Nash presents the various lipid factors involved, for better or worse, in CAD. He emphasizes that although studies have expanded the understanding of this disease, the knowledge needs to be put to use more consistently in clinical practice in order to provide optimal patient care.

Keeping an eye on cardiovascular risk. A practical, case-study approach to assessment in office practice.

Primary care physicians typically encounter patients who are not at obvious risk for CAD but who nonetheless need and can benefit from lipid-lowering therapy. Applying algorithms or scoring systems can be helpful in estimating an individual patient's risk, but the basic tools available in everyday clinical practice can be used to alert physicians to elevated CAD risk in their patients. Those patients whose LDL-C level is at or above 220 mg/dL (5.69 mmol/L) should routinely and deservedly get clinical attention, but they account for only 2.5% to 5% of the population. Those with an "average" LDL-C level number in the millions, and from this patient pool come the coronary events that fill clinics and hospitals. Aggressive treatment approaches are required to meet NCEP objectives, and every indication suggests that these goals are just the minimum. The third report of the NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) has broadened the indications for drug therapy, reclarifying diabetes and peripheral vascular or cardiovascular disease equivalents and using a global evaluation concept, which will identify 30 million Americans in need of drug treatment. The statins safely and effectively lower LDL-C levels, which is the basis for instituting drug therapy, according to NCEP guidelines. Using these drugs also raises HDL-C levels, which is somewhat protective, and decreases triglyceride levels. The efficacy of statin therapy in both primary and secondary prevention of CAD is now well established. If used more often when dietary therapy fails, which happens quite often, and in doses sufficient to work effectively, statins have the power to turn the corner on the prevention and treatment of atherosclerotic coronary disease in the United States.

Gluten sensitivity: new epidemic or new myth?

Fueled in part by recent bestselling books that warn of the evils of gluten in our diets, a significant proportion of our population is now either avoiding foods that contain gluten or eliminating gluten entirely from their diets, and these numbers continue to grow. The gluten-free trend-and the accompanying multibillion-dollar industry it has created-stems from the spreading belief that eating foods containing wheat or other gluten-laden grains may not only result in weight gain and obesity, but can also lead to a laundry list of ailments ranging from depression and anxiety to arthritis and autism. One popular book contends that current recommendations for a high-grain/low-fat diet underlie much of today's chronic health problems and that a low-carbohydrate, high-fat/cholesterol diet is ideal. Every major change in our diet carries with it the possibility of unforeseen risks. Concern about the impact of such popularized dietary recommendations on overall well-being-and on cardiovascular health in particular-warrants discussion in the medical community.

Gluten sensitivity: new epidemic or new myth? Every major change in our diet carries with it the possibility of unforeseen risks.

Fueled in part by recent best-selling books that warn of the evils of gluten in our diets, a significant proportion of our population is now either avoiding foods that contain gluten or eliminating gluten entirely from their diets, and these numbers continue to grow. The gluten-free trend-and the accompanying multibillion dollar industry it has created-stems from the spreading belief that eating foods containing wheat or other gluten-laden grains may not only result in weight gain and obesity but can also lead to a laundry list of ailments ranging from depression and anxiety to arthritis and autism. One popular book contends that current recommendations for a high-grain, low-fat diet underlie much of today's chronic health problems and that a low-carbohydrate, high-fat/cholesterol diet is ideal. Every major change in our diet carries with it the possibility of unforeseen risks. Concern about the impact of such popularized dietary recommendations on overall well-being-and on cardiovascular health in particular-warrants discussion in the medical community.

Cholesterol, lipoproteins, and cognitive impairment.

This article discussed the central role of the deposition of amyloid beta in the pathogenesis of Alzheimer disease. (AD), and the animal data which supports the role of cholesterol on its deposition. The effect of mid-life cholesterol is discussed, and the presence of cardiovascular disease risk factors in the patients with evidence for AD and vascular disease. The role of statin therapy is mentioned, although concrete evidence in controlled prospective trials has not been published in a large trial. The value of hygienic approaches including exercise, diet and behavioral changes is mentioned. Currently there are no safe and effective drugs which have been proven to reduce the incidence or the progression of AD, although research in this important area is ongoing.

Valsartan combination therapy in the management of hypertension - patient perspectives and clinical utility.

The morbidity and mortality benefits of lowering blood pressure (BP) in hypertensive patients are well established, with most individuals requiring multiple agents to achieve BP control. Considering the important role of the renin-angiotensin-aldosterone system (RAAS) in the pathophysiology of hypertension, a key component of combination therapy should include a RAAS inhibitor. Angiotensin receptor blockers (ARBs) lower BP, reduce cardiovascular risk, provide organ protection, and are among the best tolerated class of antihypertensive therapy. In this article, we discuss two ARB combinations (valsartan/hydrochlorothiazide [HCTZ] and amlodipine/valsartan), both of which are indicated for the treatment of hypertension in patients not adequately controlled on monotherapy and as initial therapy in patients likely to need multiple drugs to achieve BP goals. Randomized, double-blind studies that have assessed the antihypertensive efficacy and safety of these combinations in the first-line treatment of hypertensive patients are reviewed. Both valsartan/HCTZ and amlodipine/valsartan effectively lower BP and are well tolerated in a broad range of patients with hypertension, including difficult-to-treat populations such as those with severe BP elevations, prediabetes and diabetes, patients with the cardiometabolic syndrome, and individuals who are obese, elderly, or black. Also discussed herein are patient-focused perspectives related to the use of valsartan/HCTZ and amlodipine/valsartan, and the rationale for use of single-pill combinations as one approach to enhance patient compliance with antihypertensive therapy.

Achieving BP goals with valsartan and HCTZ alone and in combination: pooled analysis of two randomized, double-blind, placebo-controlled studies.

BACKGROUND: Most patients with hypertension will require combination therapy to achieve blood pressure (BP) goals, especially the elderly, obese, or those with stage 2 hypertension. OBJECTIVE: To assess BP response and time to achieve BP goals in a diverse population of hypertensive patients treated with hydrochlorothiazide, valsartan, or a combination. METHODS: For this secondary post-hoc analysis, data were pooled from two similar randomized, double-blind, 8-week trials that evaluated hydrochlorothiazide (12.5-25 mg) and valsartan (160 mg) monotherapies, their combination (160/12.5 mg), and placebo. Subgroups were defined by age, hypertension severity, and obesity. Adults with diastolic BP > or =95 and < or =115 mmHg were included. Goal rates were estimated from a logistic model with treatment, study, age group, race, and baseline body mass index as factors and baseline diastolic BP as a covariate. Kaplan-Meier estimates were used to calculate the time to achieve BP goals. MAIN OUTCOME MEASURES: Efficacy variables were reductions from baseline to study end in systolic BP and diastolic BP, rates of achieving BP goals (<140/90 mmHg), and time to achieve BP goals. Adverse events were also reported for the pooled trials. RESULTS: BP reductions at study end and goal achievement rates were greater with combination therapy (-20/15 mmHg and 72%, respectively) than with either monotherapy (valsartan 160 mg: -14/11 mmHg, 61%; hydrochlorothiazide 25 mg: -14/10 mmHg, 50%) for the overall population (N=1313) and in patient subgroups. Patients treated with initial combination therapy reached goal in 27-56% of the time needed for those treated with monotherapy. Combination therapy was well tolerated and was associated with a decreased incidence of hypokalemia compared with hydrochlorothiazide monotherapy. CONCLUSIONS: Compared with monotherapy, combination therapy resulted in greater reductions in BP and achievement of goal BP in a shorter period of time. Although interpretation of this study is subject to the limitations associated with any post-hoc analysis, the results suggest that initiating treatment with combination therapy may be considered for expedient and effective BP control.