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Patients with type 2 diabetes mellitus are at high risk for cardiovascular events and heart failure. The major serious complication of this disorder is large vessel atherosclerosis leading to myocardial infarction and stroke. Aggressive target setting for modifiable cardiovascular risk factors such as dyslipidemia, hypertension, and a procoagulant state, and judicious choice of efficacious therapies have been shown to produce significant reductions in cardiovascular events. The effectiveness of percutaneous coronary intervention (PCI) in diabetes is discussed, and the factors that may influence outcomes are explored. A major unresolved question is the potential role of tight glucose control for reducing macrovascular complications in patients with diabetes. With the increased attention being given to cardiovascular risk factor reduction, the opportunity exists to substantially decrease the largest causes of mortality in diabetic patients. This article reviews the current and emerging therapeutic strategies for these purposes from the cardiologists' point of view.
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PMID:[Type 2 diabetes mellitus and cardiovascular diseases: evaluation, treatment and prevention strategies]. 1650 21

von Willebrand factor (VWF), a glycoprotein involved in arterial thrombus formation, is released into the circulation by secretion from endothelial cells. Plasma VWF levels are determined by genetic factors including ABO blood groups and VWF mutations, and by non-genetic factors including aging, impaired nitric oxide production, inflammation, free radical production and diabetes. Plasma VWF levels have been proposed as a risk factor for cardiovascular events. Although they are only weakly associated with the risk of coronary heart disease (CHD) in the general population, they are a more promising CHD risk factor in high-risk populations with previous cardiovascular events, diabetes or old age. However, is it still unclear whether VWF levels directly determine the rate and severity of arterial thrombus formation or whether they merely reflect alteration in other endothelial functions. The future status of VWF levels as a cardiovascular risk factor depends on additional studies on the genetic determinants of both VWF levels and cardiovascular outcomes. Further studies on VWF levels as a predictor of the risk of stroke (rather than CHD) in elderly or other high-risk population are also promising. Such studies could lead to the clinical use of plasma VWF levels to refine the estimation of the cardiovascular risk and of the expected benefit of antithrombotic agents.
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PMID:von Willebrand factor, endothelial dysfunction, and cardiovascular disease. 1670 57

Approximately one-third of the adult population has hypertension. Large-scale clinical trials have convincingly demonstrated that the treatment of isolated systolic and systolic/diastolic hypertension reduces rates of total mortality, cardiovascular mortality, and stroke in older adults, yet control of systolic hypertension remains poor. This article reviews systolic blood pressure as a cardiovascular risk factor and discusses effective management of elevated systolic blood pressure. The role of combination therapy is emphasized, focusing on the combination of a calcium-channel blocker and an angiotensin-converting enzyme inhibitor. In addition to blood pressure-lowering efficacy, the combination of these two classes of metabolically neutral agents may offer benefit in terms of tolerability and cognitive function.
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PMID:Systolic hypertension. 1758 94

Hypertension is the most important cardiovascular risk factor for stroke. Blood pressure reduction by antihypertensive treatment is clearly efficacious in the prevention of stroke (both primary and secondary), although no clear differences have yet been observed between antihypertensive drug classes. However, a recent study reported the clear superiority of the angiotensin-receptor blocker eprosartan over the calcium channel blocker nitrendipine in cardiovascular protection of hypertensive patients with a previous stroke. Comparative studies using angiotensin-receptor blockers have also suggested the superiority of this class of drugs on primary stroke prevention. This effect may be linked to their beneficial actions on left ventricular hypertrophy, atrial enlargement, and supraventricular arrhythmias, endothelial dysfunction, inflammation, and remodelling, as well as a direct neuroprotective effect mediated through the stimulation of the angiotensin II type-2 receptor. In addition, a sympathoinhibition observed with the renin-angiotensin system blockers and particularly demonstrated with eprosartan, may help to explain the better cardiovascular and cerebrovascular protection in comparison with the calcium antagonist nitrendipine.
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PMID:Effects of eprosartan on target organ protection. 1731 72

The endocannabinoid system has been recently recognized as an important modulatory system in the function of brain, endocrine, and immune tissues. It appears to play a very important regulatory role in the secretion of hormones related to reproductive functions and response to stress. The important elements of this system are: endocannabinoid receptors (types CB1 and CB2), their endogenous ligands (N-arachidonoylethanolamide, 2-arachidonoyl glycerol), enzymes involved in their synthesis and degradation, as well as cannabinoid antagonists. In humans this system also controls energy homeostasis and mainly influences the function of the food intake centers of the central nervous system and gastrointestinal tract activity. The endocannabinoid system regulates not only the central and peripheral mechanisms of food intake, but also lipids synthesis and turnover in the liver and adipose tissue as well as glucose metabolism in muscle cells. Rimonabant, a new and selective central and peripheral cannabinoid-1 receptor (CB1) blocker, has been shown to reduce body weight and improve cardiovascular risk factor (metabolic syndrome) in obese patients by increasing HDL-cholesterol and adiponectin blood levels as well as decreasing LDL-cholesterol, leptin, and C-reactive protein (a proinflammatory marker) concentrations. It is therefore possible to speculate about a future clinical use of CB1 antagonists, as a means of improving gonadotrophin pulsatility and fertilization capacity as well as the prevention of cardiovasculary disease and type 2 diabetes mellitus. Drugs acting as agonists of CB1 receptors (Dronabinol, Dexanabinol) are currently proposed for evaluation as drugs to treat neurodegenerative disorders (Alzheimer's and Parkinson's diseases), epilepsy, anxiety, and stroke.
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PMID:[The role of the endocannabinoid system in the regulation of endocrine function and in the control of energy balance in humans]. 1736 78

(1) Elevated blood pressure is an independent and progressive cardiovascular risk factor. The risk starts to increase above a threshold of 115/75 mmHg. (2) The threshold values for blood pressure with practical implications for patients' health have been determined from clinical trial results. These are, for example, 160/95 mmHg in patients without diabetes and complications of hypertension, and 140/80 mmHg in patients with diabetes or a history of stroke. (3) A prospective cohort analysis confirmed the progressive nature of the relation between blood pressure and the risk of cardiovascular events: after about 12 years the incidence of cardiovascular events was 7% when blood pressure was less than 120/80 mmHg and 12% when it was between 130/85 and 140/90 mmHg. However, patients with these moderately elevated blood pressure values were also more likely to be diabetic. (4) The only trial involving patients with systolic pressure values between 130 and 139 mmHg, levels referred to by some as 'prehypertension', was not designed to determine either the clinical benefits or the adverse effects of treatment with candesartan. Two years after withdrawal of this antihypertensive drug, there was no statistically significant difference in the proportion of patients requiring antihypertensive treatment (threshold 160/100 mmHg). (5) In practice, 'prehypertension' is not a useful concept for patient management. The blood pressure thresholds above which the risk-benefit balance for some treatments becomes positive, in terms of morbidity or mortality, remain at 160/95 mmHg for patients without diabetes or complications and 140/80 mmHg for patients with diabetes or a history of stroke.
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PMID:Arterial 'prehypertension': a useful concept for drug companies, useless for patients. 1746 Aug 59

Nonadherence with prescribed drug regimens is a pervasive medical problem. Multiple variables affecting physicians and patients contribute to nonadherence, which negatively affects treatment outcomes. In patients with hypertension, medication nonadherence is a significant, often unrecognized, risk factor that contributes to poor blood pressure control, thereby contributing to the development of further vascular disorders such as heart failure, coronary heart disease, renal insufficiency, and stroke. Analysis of various patient populations shows that choice of drug, use of concomitant medications, tolerability of drug, and duration of drug treatment influence the prevalence of nonadherence. Intervention is required among patients and healthcare prescribers to increase awareness of the need for improved medication adherence. Within this process, it is important to identify indicators of nonadherence within patient populations. This review examines the prevalence of nonadherence as a risk factor in the management of chronic diseases, with a specific focus on antihypertensive medications. Factors leading to increased incidence of nonadherence and the strategies needed to improve adherence are discussed. Medication nonadherence, defined as a patient's passive failure to follow a prescribed drug regimen, remains a significant concern for healthcare professionals and patients. On average, one third to one half of patients do not comply with prescribed treatment regimens.[1-3] Nonadherence rates are relatively high across disease states, treatment regimens, and age groups, with the first several months of therapy characterized by the highest rate of discontinuation.[3] In fact, it has recently been reported that low adherence to beta-blockers or statins in patients who have survived a myocardial infarction results in an increased risk of death.[4] In addition to inadequate disease control, medication nonadherence results in a significant burden to healthcare utilization - the estimated yearly cost is $396 to $792 million.[1] Additionally, between one third and two thirds of all medication-related hospital admissions are attributed to nonadherence.[5,6]Cardiovascular disease, which accounts for approximately 1 million deaths in the United States each year, remains a significant health concern.[7] Risk factors for the development of cardiovascular disease are associated with defined risk-taking behaviors (eg, smoking), inherited traits (eg, family history), or laboratory abnormalities (eg, abnormal lipid panels).[7] A significant but often unrecognized cardiovascular risk factor universal to all patient populations is medication nonadherence; if a patient does not regularly take the medication prescribed to attenuate cardiovascular disease, no potential therapeutic gain can be achieved. Barriers to medication adherence are multifactorial and include complex medication regimens, convenience factors (eg, dosing frequency), behavioral factors, and treatment of asymptomatic conditions.[2] This review highlights the significance of nonadherence in the treatment of hypertension, a silent but life-threatening disorder that affects approximately 72 million adults in the United States.[7] Hypertension often develops in a cluster with insulin resistance, obesity, and hypercholesterolemia, which contributes to the risk imposed by nonadherence with antihypertensive medications. Numerous strategies to improve medication adherence are available, from enhancing patient education to providing medication adherence information to the healthcare team and will be discussed in this article.
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PMID:Medication nonadherence: an unrecognized cardiovascular risk factor. 1809 64

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's dementia (AD). It is characterized by loss of executive function with milder memory loss as compared with AD and is associated with cerebral brain infarction or hemorrhage. Treatment is predominantly focused on cardiovascular risk factor reduction, but anticholinesterase inhibitors and memantine may play a role. The data is most robust for donepezil.
Top Stroke Rehabil
PMID:Vascular dementia. 1825 70

It is well established that diabetes is associated with an increased risk of stroke. Once a stroke has occurred, patients with diabetes experience poorer outcomes (functional status, mortality). Convincing data now support aggressive glucose control and comprehensive cardiovascular risk factor management to prevent stroke in patients with diabetes. However, there remains a distinct paucity of information concerning secondary stroke prevention. Hyperglycemia in the acute stroke setting is a marker for poor outcomes, but it remains unclear whether intensive in-hospital lowering of blood glucose levels improves clinical outcomes. Targeting insulin resistance as a modifiable risk factor for stroke is a novel strategy currently under investigation.
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PMID:Diabetes mellitus, insulin resistance, hyperglycemia, and stroke. 1836 34

The natriuretic peptide system includes three known peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). They contribute to the regulation of cardiovascular homeostasis through diuretic, natriuretic, and vasodilatory properties. Among them, ANP has received particular attention because of its effects on blood pressure regulation and cardiac function. Although the potential for its therapeutic application in the treatment of hypertension and heart failure has been evaluated in several experimental and clinical investigations, no pharmacological approach directly targeted at modulation of ANP levels has ever reached the stage of being incorporated into clinical practice. Recently, ANP has also received attention as being a possible cardiovascular risk factor, particularly in the context of hypertension, stroke, obesity, and metabolic syndrome. Abnormalities in either peptide levels or peptide structure are thought to underlie its implied role in mediating cardiovascular diseases. Meanwhile, BNP has emerged as a relevant marker of left ventricular (LV) dysfunction and as a useful predictor of future outcome in patients with heart failure. This review deals with the major relevant findings related to the cardiovascular and metabolic effects of natriuretic peptides, to their potential therapeutic use, and to their role in mediating cardiovascular diseases.
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PMID:Natriuretic peptides: an update on bioactivity, potential therapeutic use, and implication in cardiovascular diseases. 1846 48


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