Showing papers in "Vascular Health and Risk Management in 2007"
Journal Article•
TL;DR: Control of hyperglycemia remains the best way to improve endothelial function and to prevent atherosclerosis and other cardiovascular complications of diabetes.
Abstract: Diabetes mellitus is associated with an increased risk of cardiovascular disease, even in the presence of intensive glycemic control. Substantial clinical and experimental evidence suggest that both diabetes and insulin resistance cause a combination of endothelial dysfunctions, which may diminish the anti-atherogenic role of the vascular endothelium. Both insulin resistance and endothelial dysfunction appear to precede the development of overt hyperglycemia in patients with type 2 diabetes. Therefore, in patients with diabetes or insulin resistance, endothelial dysfunction may be a critical early target for preventing atherosclerosis and cardiovascular disease. Microalbuminuria is now considered to be an atherosclerotic risk factor and predicts future cardiovascular disease risk in diabetic patients, in elderly patients, as well as in the general population. It has been implicated as an independent risk factor for cardiovascular disease and premature cardiovascular mortality for patients with type 1 and type 2 diabetes mellitus, as well as for patients with essential hypertension. A complete biochemical understanding of the mechanisms by which hyperglycemia causes vascular functional and structural changes associated with the diabetic milieu still eludes us. In recent years, the numerous biochemical and metabolic pathways postulated to have a causal role in the pathogenesis of diabetic vascular disease have been distilled into several unifying hypotheses. The role of chronic hyperglycemia in the development of diabetic microvascular complications and in neuropathy has been clearly established. However, the biochemical or cellular links between elevated blood glucose levels, and the vascular lesions remain incompletely understood. A number of trials have demonstrated that statins therapy as well as angiotensin converting enzyme inhibitors is associated with improvements in endothelial function in diabetes. Although antioxidants provide short-term improvement of endothelial function in humans, all studies of the effectiveness of preventive antioxidant therapy have been disappointing. Control of hyperglycemia thus remains the best way to improve endothelial function and to prevent atherosclerosis and other cardiovascular complications of diabetes. In the present review we provide the up to date details on this subject.
667 citations
TL;DR: Patients with critical rest limb ischemia or severe progressive claudication need to be treated with revascularization to minimize the chance of limb loss, reduce symptoms, and improve quality of life.
Abstract: Peripheral arterial disease (PAD) is part of a global vascular problem of diffuse atherosclerosis. PAD patients die mostly of cardiac and cerebrovascular-related events and much less frequently due to obstructive disease of the lower extremities. Aggressive risk factors modi. cation is needed to reduce cardiac mortality in PAD patients. These include smoking cessation, reduction of blood pressure to current guidelines, aggressive low density lipoprotein lowering, losing weight, controlling diabetes and the use of oral antiplatelet drugs such as aspirin or clopidogrel. In addition to quitting smoking and exercise, cilostazol and statins have been shown to reduce claudication in patients with PAD. Patients with critical rest limb ischemia or severe progressive claudication need to be treated with revascularization to minimize the chance of limb loss, reduce symptoms, and improve quality of life.
330 citations
Journal Article•
TL;DR: After reviewing a number of physical activity intervention studies performed in children, it appears as though 40 minutes of moderate to vigorous aerobic-based physical activity 3–5 days/week is required to improve vascular function and reduce blood pressure in obese children.
Abstract: Obesity is a growing problem in developed countries and is likely a major cause of the increased prevalence of high blood pressure in children. The aim of this review is to provide clinicians and clinical scientists with an overview of the current state of the literature describing the negative influence of obesity on blood pressure and it's determinants in children. In short, we discuss the array of vascular abnormalities seen in overweight children and adolescents, including endothelial dysfunction, arterial stiffening and insulin resistance. We also discuss the potential role of an increased activation of the sympathetic nervous system in the development of high blood pressure and vascular dysfunction associated with obesity. As there is little consensus regarding the methods to prevent or treat high blood pressure in children, we also provide a summary of the evidence supporting relationship between physical activity and blood pressure in children and adolescents. After reviewing a number of physical activity intervention studies performed in children, it appears as though 40 minutes of moderate to vigorous aerobic-based physical activity 3-5 days/week is required to improve vascular function and reduce blood pressure in obese children. Future studies should focus on describing the influence of physical activity on blood pressure control in overweight children.
196 citations
Journal Article•
TL;DR: The aim of this review is to define the main characteristics of the disease in order to simplify its detection and early treatment by all physicians by mean of practical guidelines.
Abstract: Familial combined hyperlidemia (FCH) is a common metabolic disorder characterized by: (a) increase in cholesterolemia and/or triglyceridemia in at least two members of the same family, (b) intra-individual and intrafamilial variability of the lipid phenotype, and (c) increased risk of premature coronary heart disease (CHD). FCH is very frequent and is one of the most common genetic hyperlipidemias in the general population (prevalence estimated: 0.5%-2.0%), being the most frequent in patients affected by CHD (10%) and among acute myocardial infarction survivors aged less than 60 (11.3%). This percentage increases to 40% when all the myocardial infarction survivors are considered without age limits. However, because of the peculiar variability of laboratory parameters, and because of the frequent overlapping with the features of metabolic syndrome, this serious disease is often not recognized and treated. The aim of this review is to defi ne the main characteristics of the disease in order to simplify
92 citations
Journal Article•
TL;DR: While ischemic preconditioning significantly reduces DNA fragmentation and apoptotic myocyte death associated with ischemia-reperfusion, the potential mechanisms underlying this effect have not been fully clarified.
Abstract: The phenomenon of ischemic preconditioning has been recognized as one of the most potent mechanisms to protect against myocardial ischemic injury. In experimental animals and humans, a brief period of ischemia has been shown to protect the heart from more prolonged episodes of ischemia, reducing infarct size, attenuating the incidence, and severity of reperfusion-induced arrhythmias, and preventing endothelial cell dysfunction. Although the exact mechanism of ischemic preconditioning remains obscure, several reports indicate that this phenomenon may be a form of receptor-mediated cardiac protection and that the underlying intracellular signal transduction pathways involve activation of a number of protein kinases, including protein kinase C, and mitochondrial K(ATP) channels. Apoptosis, a genetically programmed form of cell death, has been associated with cardiomyocyte cell loss in a variety of cardiac pathologies, including cardiac failure and those related to ischemia/reperfusion injury. While ischemic preconditioning significantly reduces DNA fragmentation and apoptotic myocyte death associated with ischemia-reperfusion, the potential mechanisms underlying this effect have not been fully clarified. A comprehensive understanding of these mechanisms and application to clinical scenarios will provide new directions in research and translate this information into new treatment approaches for reducing the extent of ischemia/reperfusion injury.
90 citations
Journal Article•
TL;DR: The objective of this review article is to present a concise overview of the management of AF, with reference to the recent evidence-based National Institute of Clinical Excellence (NICE) National Clinical Guidelines for themanagement of AF.
Abstract: Atrial fibrillation (AF) is a condition of genuine clinical concern. This arrhythmia increases patient morbidity and mortality, most notably due to stroke, thromboembolism and heart failure. Consequentially, there is a strong impetus to acquire a greater understanding of its natural history and course in order to provide crucial evidence-based treatment and resource allocation in the future. The objective of this review article is to present a concise overview of the management of AF, with reference to the recent evidence-based National Institute of Clinical Excellence (NICE) National Clinical Guidelines for the management of AF.
86 citations
TL;DR: According to the algorithm, hospitalized medical patients ≥40 years-old with decreased mobility, and ≥1 RFs should receive chemoprophylaxis with heparin, provided they don’t have contraindications, and an easy-to-use algorithm was created based on the results of the review.
Abstract: Hospital Universitario Professor Edgard Santos da Universidade Federal da Bahia, Rua AlbertoValenca, 148, Salvador, Bahia 41810-825
79 citations
Journal Article•
TL;DR: The results of in vivo and in vitro studies indicate that the statins have beneficial effects unrelated to cholesterol lowering, such as improving endothelial function, increasing myocardial perfusion, and enhancing the availability of nitric oxide.
Abstract: Statin-induced inhibition of HMG-CoA reductase reduces cholesterol production and prevents the formation of many non-steroidal isoprenoid compounds, such as farnesylpyrophosphate and geranylgeranylpyrophosphate, that act as lipid attachments for the post-translational modification of various proteins, including the G-proteins and transcription factors involved in a number of cell processes. However, the blockade of isoprenylation elicited by statin treatment also has biological effects on cell function that go beyond the decrease in cholesterol synthesis: these are the so-called “pleiotropic” effects that mainly relate to vascular function. Endothelial dysfunction is an independent predictor of cardiovascular events that correlates with inflammation markers/mediators and robust predictors of cardiovascular diseases such as increased high-sensitivity C-reactive protein levels. The results of in vivo and in vitro studies indicate that the statins have beneficial effects unrelated to cholesterol lowering, such as improving endothelial function, increasing myocardial perfusion, and enhancing the availability of nitric oxide. This review describes the pleiotropic effects of statins that may be involved in modulating/preventing endothelial dysfunction and inflammatory processes, as well as the cellular and molecular mechanisms through which they improve endothelial function.
78 citations
Journal Article•
TL;DR: The possibility of using apoAI and apoB levels to estimate the risk of development of cardiovascular diseases and to monitor intervention to treat these diseases is addressed.
Abstract: Apolipoprotein (apo) AI and apoB are the major apolipoproteins of high-density lipoprotein (HDL) and low-density lipoprotein (LDL), respectively. ApoB assembles the precursor of LDL, very-low-density lipoprotein (VLDL), in the liver. The assembly starts with the formation of a primordial particle, which is converted to VLDL2. The VLDL2 particle is then transferred to the Golgi apparatus and can either be secreted or converted to triglyceride-rich VLDL1. We have reviewed this assembly process, the process involved in the storage of triglycerides in cytosolic lipid droplets, and the relationship between these two processes. We also briefly discuss the formation ofHDL. ApoB mediates the interaction between LDL and the arterial wall. Two regions in apoB are involved in this binding. This interaction and its role in the development of atherosclerosis are reviewed. ApoB can be used to measure the number of LDL or VLDL particles present in plasma, as there is one molecule of apoB on each particle. By contrast, the amount of cholesterol and other lipids on each particle varies under different conditions. We address the possibility of using apoAl and apoB levels to estimate the risk of development of cardiovascular diseases and to monitor intervention to treat these diseases.
78 citations
Journal Article•
TL;DR: Modifying proteoglycan synthesis and structure may represent a prime target to prevent LDL binding and entrapment in the vessel wall and thus prevent the development and progression of atherosclerosis.
Abstract: Atherosclerosis is the underlying pathology of most cardiovascular disease and it represents the major cause of premature death in modern societies. Current therapies target risk factors being hypertension, hypercholesterolemia, hypertriglyceridemia and hyperglycemia when diabetes is present however the maximum efficacy of these strategies is often 30% or less. Areas of vascular biology that may lead to the development of a complementary vascular wall directed therapy are: inflammation, oxidation, endothelial dysfunction, diabetes-specific factors - hyperglycemia and advanced glycation endproducts and lipid retention by vascular matrix specifically proteoglycans. The major structural features of proteoglycans that determine low-density lipoprotein (LDL) binding are the length and sulfation pattern on the glycosammoglycan (GAG) chains. Emerging data discussed in this review indicates that these structural properties are subject to considerable regulation by vasoactive substances possibly using novel signaling pathways. For example, GAG elongation stimulated by platelet-derived growth factor is not blocked by the receptor tyrosine kinase antagonist, genistein suggesting that there may be a previously unknown signaling pathway involved in this response. Thus, modifying proteoglycan synthesis and structure may represent a prime target to prevent LDL binding and entrapment in the vessel wall and thus prevent the development and progression of atherosclerosis.
75 citations
TL;DR: The global interventional cardiology community now has a wealth of evidence in support of the use of sirolimus-eluting coronary stents resulting in dramatically improved patient outcomes after percutaneous intervention.
Abstract: The sirolimus-eluting coronary stent received CE Mark approval in Europe in April 2002. In the US, FDA approval followed in April 2003. Since the preliminary results from the First-in-Man feasibility study were presented, several randomized, controlled trials have documented the profound antiproliferative effects of sirolimus, a macrolide antibiotic and potent cytostatic inhibitor of smooth muscle cell proliferation. Subsequently, the body of clinical evidence was increased by the second wave of evidence from trials in more complex lesions (such as in-stent restenosis, small vessels, chronic total occlusions) and “high-risk” patients such as those with diabetes. More recently we have had the opportunity to compare the two commercially available drug-eluting stents following the presentation of data from six head-to-head trials. As a result of numerous single and multi-center, national and international studies in which the safety and efficacy of sirolimus-eluting coronary stents have been subjected to close scrutiny, the global interventional cardiology community now has a wealth of evidence in support of the use of this technology resulting in dramatically improved patient outcomes after percutaneous intervention.
Journal Article•
TL;DR: It is revealed that vascular health appears to have a strong effect on skeletal health, and vice versa, and the importance of addressing the risk benefit of preventative interventions in both conditions is highlighted.
Abstract: In this narrative review of the current literature, we examine the traditional risk factors and patient profiles leading to cardiovascular disease and osteoporosis. We discuss the interrelationships between risk factors and common pathophysiological mechanisms for cardiovascular disease and osteoporosis. We evaluate the increasing evidence that supports an association between these disabling conditions. We reveal that vascular health appears to have a strong effect on skeletal health, and vice versa. We highlight the importance of addressing the risk benefit of preventative interventions in both conditions. We discuss how both sexes are affected by these chronic conditions and the importance of considering the unique risk of the individual. We show that habitual physical activity is an effective primary and secondary preventative strategy for both cardiovascular disease and osteoporosis. We highlight how a holistic approach to the prevention and treatment of these chronic conditions is likely warranted.
Journal Article•
TL;DR: The three noninvasive modalities to study arterial stiffness reliably measures arterials stiffness however, they do not correlate with ultrasound measures of vascular function and structure in young and apparently healthy subjects.
Abstract: Background
Many noninvasive arterial assessment techniques have been developed, measuring different parameters of arterial stiffness and endothelial function. However, there is little data available comparing different devices within the same subject. Therefore, the purpose of this study was to examine the repeatability and interrelationships between 3 different techniques to measure arterial stiffness and to compare this with forearm-mediated dilation.
Journal Article•
TL;DR: Results from controlled clinical trials reveal that duloxetine administered at 60 mg qd or 60 mg bid is efficacious in treating diabetic neuropathic pain relative to placebo, providing support for the proposed role of serotonin and norepinephrine as key mediators of the descending pain inhibition pathways of the brain stem and spinal cord.
Abstract: Duloxetine is a balanced selective serotonin norepinephrine reuptake inhibitor (SNRI) which, in 2004, became the first agent to receive regulatory approval for the treatment of painful diabetic neuropathy in the US. This compound has no other significant receptor or channel activities other than the serotonin and norepinephrine reuptake inhibition mechanisms and works to diminish or control the symptoms of diabetic neuropathy. Duloxetine has no known neuroprotective or other effects which prevent the development of neuropathy in patients with diabetes. The purpose of this review article is to discuss the background of painful diabetic neuropathy, the pharmacology of duloxetine, and its safety and efficacy in clinical trials and long-term observations. The authors will also comment on its use in clinical practice. Results from controlled clinical trials reveal that duloxetine administered at 60 mg qd or 60 mg bid is efficacious in treating diabetic neuropathic pain relative to placebo. Positive treatment outcomes are also seen for other measures of pain and quality of life. A minor but statistically significant increase in blood glucose compared with placebo treated patients has been observed in controlled clinical trials. Otherwise, controlled and open-label clinical studies have demonstrated a high degree of safety and tolerability for the compound. These findings provide support for the proposed role of serotonin and norepinephrine as key mediators of the descending pain inhibition pathways of the brain stem and spinal cord.
Journal Article•
TL;DR: The demonstration of clinical efficacy, low incidence of acute hepatic toxicity, and low risk of drug–drug interactions support the role of ambrisentan for the treatment of PAH.
Abstract: Pulmonary arterial hypertension (PAH) is a rare fatal disease Current disease-specific therapeutic interventions in PAH target 1 of 3 established pathways in disease pathobiology: prostacyclin, nitric oxide, and endothelin-1 Endothelin receptor antagonists (ERAs) act on the endothelin pathway by blocking binding of endothelin-1 to its receptors (endothelin type-A [ET(A)] and/or type-B [ET(B)]) on the surface of endothelial and smooth muscle cells Ambrisentan is an oral, once-daily, ET(A)-selective ERA in development for the treatment of PAH In Phase 3 clinical trials in patients with PAH, ambrisentan (25-10 mg orally once-daily) improved exercise capacity, Borg dyspnea index, time to clinical worsening, WHO functional class, and quality of life compared with placebo Ambrisentan provided durable (at least 2 years) improvement in exercise capacity in a Phase 2 long-term extension study Ambrisentan was well tolerated with a lower incidence and severity of liver function test abnormalities compared with the ET(A)/ET(B) ERA, bosentan, and the ET(A)-selective ERA, sitaxsentan Ambrisentan does not induce or inhibit P450 enzymes; therefore, ambrisentan is unlikely to affect the pharmacokinetics of P450-metabolized drugs The demonstration of clinical efficacy, low incidence of acute hepatic toxicity, and low risk of drug-drug interactions support the role of ambrisentan for the treatment of PAH
Journal Article•
TL;DR: The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) Programme is expected to provide the ultimate evidence of whether improved endothelial function translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartAn, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade).
Abstract: Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin-angiotensin system (RAS), has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB) and/or angiotensin-converting enzyme (ACE) inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) Programme is expected to provide the ultimate evidence of whether improved endothelial function translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade). Completion of ONTARGET is expected in 2008.
Journal Article•
TL;DR: A review of peer review is presented in this paper, where the authors consider the problem of plagiarism in the peer review process and present a review of the existing laws to deal with it.
Abstract: Peer review is an essential component of the process that is universally applied prior to the acceptance of a manuscript, grant or other scholarly work. Most of us willingly accept the responsibilities that come with being a reviewer but how comfortable are we with the process? Peer review is open to abuse but how should it be policed and can it be improved? A bad peer review process can inadvertently ruin an individual’s career, but are there penalties for policing a reviewer who deliberately sabotages a manuscript or grant? Science has received an increasingly tainted name because of recent high profile cases of alleged scientific misconduct. Once considered the results of work stress or a temporary mental health problem, scientific misconduct is increasingly being reported and proved to be a repeat offence. How should scientific misconduct be handled—is it a criminal offence and subject to national or international law? Similarly plagiarism is an ever-increasing concern whether at the level of the student or a university president. Are the existing laws tough enough? These issues, with appropriate examples, are dealt with in this review.
Journal Article•
TL;DR: This review will address the currently available evidence on diabetic cardiomyopathy and the potential role of combination therapy with pioglitazone and metformin.
Abstract: The rising incidence of obesity and insulin resistance to epidemic proportions has closely paralleled the surge in the prevalence of diabetes and outpaced therapeutic advances in diabetes prevention and treatment Current evidence points to obesity induced oxidative stress and chronic inflammation as the common denominators in the evolution of insulin resistance and diabetes Of all the hypoglycemic agents in the pharmacological arsenal against diabetes, thiazolidinediones, in particular pioglitazone, as well as metformin appear to have additional effects in ameliorating oxidative stress and inflammation; rendering them attractive tools for prevention of insulin resistance and diabetes In addition to their hypoglycemic and lipid modifying properties, pioglitazone and metformin have been shown to exert anti-oxidative and anti-inflammatory effects in vascular beds, potentially slowing the accelerated atherosclerosis in diabetes, which is the major cause of morbidity and mortality in the affected population The combination of pioglitazone and metformin would thus appear to be an effective pharmacological intervention in prevention and treatment of diabetes Finally, this review will address the currently available evidence on diabetic cardiomyopathy and the potential role of combination therapy with pioglitazone and metformin
Journal Article•
TL;DR: The current evidence for the adverse cardiovascular risk in PCOS and the other factors that may be implicated are addressed and the therapeutic options for treatment will be discussed.
Abstract: It is estimated that 60%-7% of women of reproductive age have polycystic ovarian syndrome (PCOS). Women with this condition exhibit an adverse cardiovascular risk profile, characteristic of the cardiometabolic syndrome and given the high prevalence of PCOS in the female population, this condition may contribute towards the acceleration of cardiovascular disease among young women. This article summarizes the recent development and findings in the cardiometabolic abnormalities in patients with PCOS. Patients with PCOS have the clinical features of oligomenorrhoea, hirsutism and infertility; however, they also exhibit hyperinsulinemia, obesity, hypertension, dyslipidemia, and an increased pro-thrombotic state. They have an increased risk of type 2 diabetes and impaired glucose tolerance, and sleep apnea is also found more commonly in this population. However, despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease it is unclear if they have accelerated atherosclerosis. End point studies are currently lacking and the available evidence are conflicting. Adipose tissue has emerged as an important endocrine organ over the last decade and gained recognition in having an important role in the cardiometabolic syndrome. Adiponectin that is secreted exclusively by adipocytes has recently been recognized as an important marker of cardiometabolic syndrome, obesity, type 2 diabetes, and coronary artery disease. Other adipocytokines like leptin and resistin have also recently been recognized. This article will address the current evidence for the adverse cardiovascular risk in PCOS and the other factors that may be implicated. Finally the therapeutic options for treatment will be discussed.
Journal Article•
TL;DR: The aim is to summarize the current knowledge on the effect of two important classes of drugs, lipid-lowering drugs and anti-hypertensive drugs, on homocysteine metabolism.
Abstract: Elevated plasma concentrations of homocysteine, a sulfur-containing amino acid, are a risk factor for coronary, cerebral and peripheral artery disease. Next to other factors, drugs used for the prevention or treatment of cardiovascular disease may modulate plasma homocysteine levels. Thus, a drug induced homocysteine increase may counteract the desired cardioprotective effect. The aim is to summarize the current knowledge on the effect of two important classes of drugs, lipid-lowering drugs and anti-hypertensive drugs, on homocysteine metabolism. Among the lipid-lowering drugs, especially the fibric acid derivatives, which are used for treatment of hypertriglyceridemia and low HDL-cholesterol, are associated with an increase of homocysteine by 20%-50%. This increase can be reduced, but not totally avoided by the addition of folic acid, vitamin B12 and B6 to fibrates. HMG-CoA reductase inhibitors (statins) do not influence homocysteine concentrations substantially. The effects of nicotinic acid and n3-fatty acids on the homocysteine concentrations are less clear, more studies are necessary to clarify their influence on homocysteine. Antihypertensive drugs have also been studied with respect to homocysteine metabolism. A homocysteine increase has been shown after treatment with hydrochlorothiazide, a lowering was observed after treatment with beta-blockers, but no effect with ACE-inhibitors. The clinical significance of the homocysteine elevation by fibrates and thiazides is not clear. However, individual patients use these drugs for long time, indicating that even moderate increases may be important.
Journal Article•
TL;DR: The present results confirm the importance of persistence on treatment for the management of hypertension in clinical practice and confirm the trend toward a better BP control was observed in response to lercanidipine vs other CCBs.
Abstract: Persistence on treatment affects the efficacy of antihypertensive treatment. We prospectively investigated the persistence on therapy and the extent of blood pressure (BP) control in 347 hypertensive patients (age 59.4 +/- 6 years) randomly allocated to a first-line treatment with: angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers (CCBs), beta-blockers, angiotensin-II receptor blockers (ARBs), or diuretics and followed-up for 24-months. Persistence on treatment was higher in patients treated with ARBs (68.5%) and ACE inhibitors (64.5%) vs CCBs (51.6%; p < 0.05), beta-blockers (44.8%, p < 0.05), and diuretics (34.4%, p < 0.01). No ARB, ACE inhibitor, beta-blocker, or diuretic was associated with a higher persistence in therapy compared with the other molecules used in each therapeutic class. The rate of persistence was significantly higher in patients treated with lercanidipine vs others CCBs (59.3% vs 46.6%, p < 0.05). Systolic and diastolic BP was decreased more successfully in patients treated with ARBs (-11.2/-5.8 mmHg), ACE inhibitors (-10.5/-5.1 mmHg), and CCBs (-8.5/-4.6 mmHg) compared with beta-blockers (-4.0/-2.3 mmHg p < 0.05) and diuretics (-2.3/-2.1 mmHg, p < 0.05). No ARB, ACE inhibitor, beta-blocker, or diuretic was associated with a higher BP control compared with the other molecules used in each therapeutic class. A trend toward a better BP control was observed in response to lercanidipine vs other CCBs (p = 0.059). The present results confirm the importance of persistence on treatment for the management of hypertension in clinical practice.
TL;DR: It is demonstrated that patient compliance with once-daily betaxolol is significantly better than with twice daily metoprolol, and this treatment provides better quality of life.
Abstract: BACKGROUND A randomized, controlled trial was conducted in an outpatient setting to examine the effect of beta-blocker dosing frequency on patient compliance, clinical outcome, and health-related quality of life in patients with stable angina pectoris. METHODS One hundred and twelve beta-blockers-naive outpatients with stable angina pectoris were randomized to receive betaxolol, 20 mg once daily or metoprolol tartrate, 50 mg twice daily for 8 weeks. The principal outcome measure was overall compliance measured electronically, whereas secondary outcome measures were drug effectiveness and health-related quality of life. RESULTS The overall compliance was 86.5 +/- 21.3% in the betaxolol group versus 76.1 +/- 26.3% in the metoprolol group (p < 0.01), and the correct number of doses was taken on 84.4 +/- 21.6% and 64.0 +/- 31.7% of treatment days, respectively (p < 0.0001). The percentage of missed doses was 14.5 +/- 21.5% in the once-daily group and 24.8 +/- 26.4% in the twice-daily group (p < 0.01). The percentage of doses taken in the correct time window (58.6% vs 42.0%, p = 0.01), correct interdose intervals (77.4% v 53.1%, p < 0.0001), and therapeutic coverage (85.6% vs 73.7%, p < 0.001) were significantly higher in the once-daily group. Both studied drugs had similar antianginal effectiveness. Health-related quality of life improved in both groups, but this increase was more pronounced in the betaxolol arm in some dimensions. CONCLUSIONS The study demonstrates that patient compliance with once-daily betaxolol is significantly better than with twice daily metoprolol. Similarly, this treatment provides better quality of life. These results demonstrate possible therapeutic advantages of once-daily over twice-daily beta-blockers in the treatment of stable angina pectoris.
Journal Article•
TL;DR: For treatment of severe bleeding in GT patients with platelet antibodies and platelet refractoriness, rFVIIa at dose 90 μg/kg every 2 h for 3 or more doses could be considered, but more “optimal regimen” derived from a recent International Survey needs confirmation with larger studies.
Abstract: Glanzmann’s thrombasthenia (GT) is a congenital qualitative platelet disorders due to the deficiency or defect of platelet membrane GPIIb/IIIa (integrin αIIbβ3). The standard treatment for bleeding is platelet transfusion but repeated transfusion may result in the development of anti-platelet antibodies (to HLA and/or GPIIbIIIa) rendering future platelet transfusion ineffective. Alternative effective agent(s) are needed. There are increasing reports documenting efficacy of high dose rFVIIa in GT patients with adverse events uncommon. The efficacy is supported by evidence that high concentration FVIIa binds to activated platelet surface and improves thrombin generation to enhance deposition (adhesion) and aggregation of platelets lacking GPIIb/IIIa. While there are increasing clinical experiences, evidence-based clinical data are not available. There is a need for more clinical studies, particularly clinical trials, to further assess the efficacy, safety (particularly thrombotic events) and optimal regimen of rFVIIa in GT patients, either singly or in combination with other hemostatic agents such as platelet transfusion. In the absence of this data, for treatment of severe bleeding in GT patients with platelet antibodies and platelet refractoriness, rFVIIa at dose 90 μg/kg every 2 h for 3 or more doses could be considered. This more “optimal regimen” derived from a recent International Survey needs confirmation with larger studies. What the optimal regimen for surgical coverage is remains unresolved.
Journal Article•
TL;DR: In this context TZD appear the more innovative drugs and have been shown to play a key role in the management of hypertension, dyslipidemia, inflammation and endothelial disfunction in diabetic patients.
Abstract: Obtaining the suggested glycemic control is the most important achievement in order to prevent cardiovascular complications in patients with type 2 diabetes. Monotherapy often fails after a period of treatment, so that multiple drugs are needed to achieve effective glycemic control. A number of oral glucose lowering drugs is now available such as metformin, sulfonylureas, non-sulfonylureas secretagogues (metiglinides derivatives), alpha-glucosidases inhibitors, and the newest agent: thiazolidinediones (TZD). The possible associations of oral glucose lowering drugs for optimal treatment of type 2 diabetes are briefly reviewed. In particular, the effects of different classes of drugs on cardiovascular risk factors (and particular hypertension and dyslipidemia) and well recognized cardiovascular disease markers in type 2 diabetes are analyzed: in this context TZD appear the more innovative drugs and have been shown to play a key role in the management of hypertension, dyslipidemia, inflammation and endothelial disfunction in diabetic patients. The possible adverse effects derived from the association of different drug classes are also considered.
Journal Article•
TL;DR: The recent PROspective pioglitazone Clinical Trial In macroVascular Events (PROactive) study showed that piog litazone can reduce the risk of secondary macrovascular events in a high-risk patient population with type 2 diabetes and established macrov arteries.
Abstract: Patients with type 2 diabetes face an increased risk of macrovascular disease compared to those without. Significant reductions in the risk of major cardiovascular events can be achieved with appropriate drug therapy, although patients with type 2 diabetes remain at increased risk compared with non-diabetics. The thiazolidinedione, pioglitazone, is known to offer multiple, potentially antiatherogenic, effects that may have a beneficial impact on macrovascular outcomes, including long-term improvements in insulin resistance (associated with an increased rate of atherosclerosis) and improvement in the atherogenic lipid triad (low HDL-cholesterol, raised triglycerides, and a preponderance of small, dense LDL particles) that is observed in patients with type 2 diabetes. The recent PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) study showed that pioglitazone can reduce the risk of secondary macrovascular events in a high-risk patient population with type 2 diabetes and established macrovascular disease. Here, we summarize the key results from the PROactive study and place them in context with other recent outcome trials in type 2 diabetes.
Journal Article•
TL;DR: The evolving real-world experience and ongoing studies will provide further insight into ADVATE® pharmacokinetics, alternative prophylactic dosing regimens, methods for perioperative hemostatic management, and utility in immune tolerance induction.
Abstract: Removal of blood-based additives from recombinant clotting factor concentrates continues to be advocated by the hemophilia community due to the history of infectious disease transmission with previous blood-derived clotting factor concentrates. In 2003, octocog-alpha, antihemophilic factor (recombinant), plasma/albumin-free method (ADVATE) was introduced, providing the first third-generation recombinant factor VIII (rFVIII) concentrate. Completed clinical trials have demonstrated ADVATE to be safe and effective in adult and pediatric subjects utilizing both prophylactic and on-demand treatment regimens, and for perioperative hemostatic coverage. In the five completed studies involving more than 200 previously treated patients (PTPs), a single incidence of low-titer, non-persistent inhibitor was reported. Active post authorization safety surveillance (PASS) is being performed to expand the efficacy and safety profile of ADVATE in routine clinical practice. Laboratory studies have documented the storage and post-reconstitution stability of ADVATE, conferring the desired versatility for home treatment. The evolving real-world experience and ongoing studies will provide further insight into ADVATE pharmacokinetics, alternative prophylactic dosing regimens, methods for perioperative hemostatic management, and utility in immune tolerance induction. Experience with ADVATE, and its place in today's treatment paradigm, is the focus of this article.
Journal Article•
TL;DR: Acute coronary syndromes could represent a clinical condition for addressing the early benefits of statins therapy, ie, within 24 h of the event, independent of LDL-C lowering, suggesting that the anti-inflammatory and the pleiotropic properties of statin may have clinical importance.
Abstract: The clinical benefits of statins are strongly related to their low density lipoprotein-cholesterol (LDL-C) lowering properties. However, because mevalonic acid (MVA), the product of 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase reaction, is the precursor not only of cholesterol but also of nonsteroidal isoprenoid compounds, the inhibition of HMG-CoA reductase may result in pleiotropic effects, independent of their hypocholesterolemic properties. The discrimination between the pleiotropic from LDL-C lowering effects may potentially be more evident during the early phase of treatment since plasma MVA levels drop up to 70% within 1–2 hours while a reduction of LDL-C, detectable after 24 hours, became significant after 6–7 days. Therefore, the deprivation of circulating MVA-derived isoprenoids in the early phase of treatment could be the main mechanism responsible for the atheroprotective effect of statins. This early window of protection in the absence of LDL-C lowering suggests that the anti-inflammatory and the pleiotropic properties of statins may have clinical importance. Therefore, acute coronary syndromes could represent a clinical condition for addressing the early benefits of statins therapy, ie, within 24 h of the event, independent of LDL-C lowering.
Journal Article•
TL;DR: Therapeutic intervention aimed to reduce vascular inflammation in hypertensive patients has been proposed and recent lines of evidence suggest that lifestyle modification and pharmacological approaches may reduce blood pressure and inflammation in patients with hypertension.
Abstract: Inflammatory processes are increasingly recognized as important participants in the pathophysiology of hypertension and cardiovascular disease. Angiotensin II may be to a large degree responsible for triggering vascular inflammation by inducing oxidative stress, resulting in up-regulation of inflammatory mediators. Inflammatory markers such as C-reactive protein are increased in the blood of patients with hypertension and predict the development of cardiovascular disease. Moreover, C-reactive protein may be a pro-inflammatory molecule under certain circumstances. C-reactive protein and high blood pressure in combination have additional predictive value for cardiovascular outcomes, as they contribute as independent determinants of cardiovascular risk. Therapeutic intervention aimed to reduce vascular inflammation in hypertensive patients has been proposed. Recent lines of evidence suggest that lifestyle modification and pharmacological approaches may reduce blood pressure and inflammation in patients with hypertension. Antagonism of the renin-angiotensin system with the selective angiotensin receptor blockers may improve cardiovascular outcome beyond blood pressure control, by reducing vascular inflammation and remodeling.
Journal Article•
TL;DR: The biochemical and molecular mechanisms involving the RAS in coronary atherosclerosis as well as the effects of RAS inhibition in clinical studies involving coronary Atherosclerosis are discussed.
Abstract: Activation of the renin–angiotensin system (RAS) is significant in the pathogenesis of cardiovascular disease and specifically coronary atherosclerosis. There is strong evidence that the RAS has effects on the mechanisms of action of atherosclerosis, including fibrinolytic balance, endothelial function, and plaque stability. Pharmacological inhibition of the renin angiotensin system includes angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and renin inhibitors. These agents have clinical benefits in reducing morbidity and mortality in the management of hypertension. In addition, ACE inhibitors and ARBs have shown to be effective in the management of congestive heart failure and acute myocardial infarction. This review article discusses the biochemical and molecular mechanisms involving the RAS in coronary atherosclerosis as well as the effects of RAS inhibition in clinical studies involving coronary atherosclerosis.
Journal Article•
TL;DR: The development of high-titer inhibitors to FVIII and less often to other coagulation factors are the most serious complication of hemophilia therapy and makes treatment of bleeds very challenging.
Abstract: The development of high-titer inhibitors to FVIII and less often to other coagulation factors are the most serious complication of hemophilia therapy and makes treatment of bleeds very challenging At present, bypassing agents, such as factor eight inhibitor bypass activity (FEIBA) and activated recombinant factor VII (rFVIIa) are the only coagulation factor concentrates available for the treatment of bleeds in inhibitor patients Both products are effective and safe, and their efficacy has been found to be comparable (approximately 80%) in a recent prospective study A significant number of patients report a better effect of one or the other of the products, and in a minority of the patients none of the products are particularly effective The hemostatic efficacy of bypassing agents is not considered equal to that of coagulation factor replacement in patients without inhibitors by most physicians An improvement in hemostatic efficacy may be achieved by optimizing the dosing of by passing agents However, the lack of standardized and validated laboratory assays reflecting the hemostatic efficacy of the bypassing agents is an obstacle to this achievement