Prevention Of Cardiovascular Disease In Patients Research Articles

Pharmacotherapeutic Options for the Prevention of Cardiovascular Disease in Patients with Type 2 Diabetes

Type 2 diabetes is well recognized as an independent risk factor for cardiovascular disease (CVD). In turn, CVD is the leading cause of morbidity and mortality in patients with type 2 diabetes. The impact of glycemic control in reducing microvascular complications is now well accepted. Although improving glycemic control is also beneficial for the prevention of macrovascular diseases, adequate treatment of hypertension and hyperlipidemia is also essential. In fact, studies have repeatedly demonstrated the safety and efficacy of antihypertensive and antihyperlipidemic therapies for the prevention of CVD in patients with type 2 diabetes. This article reviews the impact of commonly used antidiabetic, antihyperlipidemic, antihypertensive and antiplatelet agents on reducing CVD risk in patients with type 2 diabetes.

Guilty by Association: Platelet Reactivity and Inflammation in Psoriatic Arthritis

Patients with rheumatoid arthritis (RA) die prematurely from cardiovascular disease (CVD)1. The risk of adverse cardiovascular events and subsequent mortality in patients with RA is comparable to that associated with type 2 diabetes mellitus2. There is an emerging body of evidence that patients with other forms of inflammatory arthritis (IA), in particular psoriatic arthritis (PsA), are at a similarly elevated risk of CVD3. Platelets play a key role in the complex chain of events leading to the thrombotic occlusion of a coronary artery4. Antiplatelet therapy with aspirin and/or a variety of other agents is effective at reducing the mortality associated with incident CVD5 and is recommended for the primary prevention of same in patients at high risk of atherothrombotic events4. Despite the greatly increased risk of heart disease and strokes, there are currently no antiplatelet guidelines for the primary prevention of CVD in patients with IA3, and platelet function remains largely uninvestigated in this patient population. It is within this context that the recent work of Di Minno and colleagues, reported in this issue … Address correspondence to Dr. MacMullan; E-mail: pmacmullan{at}hotmail.com

Relationship of glycemia control to lipid and blood pressure lowering and atherosclerosis: the SANDS experience

Objectives Cardiovascular disease prevention for patients with type 2 diabetes is accomplished through hypertension and dyslipidemia management. Although studies have established strategies for lowering low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP), none have examined whether glycemia influences ability to achieve lipid and BP targets. This post hoc analysis from the Stop Atherosclerosis in Native Diabetics Study examines the role of baseline glycemia in achieving standard and aggressive targets and outcomes after 36 months. Methods Diabetic individuals aged >40 years with no cardiovascular events ( n=499) were randomized to aggressive versus standard targets for LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C) and systolic BP (SBP). Management algorithms were used for both groups. Carotid ultrasound and echocardiography were performed at baseline and after 36 months. Results No differences were observed in baseline hemoglobin A1c between treatment groups nor any significant change in A1c after 36 months in either group. Baseline A1c, however, was significantly and negatively related to achieving LDL-C ( P=.007), non-HDL-C ( P=.03) and SBP targets ( P=.007) and to changes in LDL-C ( P=.007), non-HDL-C ( P=.03) and SBP ( P=.001) in both groups. Baseline A1c failed to predict progression of carotid intima medial thickness (CIMT) ( P=.42) or left ventricular mass index (LVMI) ( P=.10), nor was it related to the effects of lipid and BP lowering on CIMT and LVMI over 36 months. Conclusions In diabetic adults with no cardiovascular disease events, A1c was negatively associated with ability to achieve LDL-C, non-HDL-C and SBP goals but was not independently related to treatment-associated changes in CIMT or LVMI over 36 months.

Diabetes and Hypertension: A Comprehensive Report on Management and the Prevention of Cardiovascular and Renal Complications

Diabetes and Hypertension: A Comprehensive Report on Management and the Prevention of Cardiovascular and Renal Complications

Telmisartan

Telmisartan (Micardis®, Pritor®), a well established angiotensin type 1 receptor antagonist, is indicated in the EU for the reduction of cardiovascular morbidity in patients with manifest atherothrombotic cardiovascular disease (CVD) or type 2 diabetes mellitus with documented target organ damage, as well as for the treatment of hypertension. In the pivotal ONTARGET trial, which enrolled ACE inhibitor-tolerant patients at high vascular risk, telmisartan 80 mg once daily added to existing, proven therapy was noninferior to ramipril 10 mg once daily (the gold standard cardioprotective ACE inhibitor) in terms of CVD prevention. Moreover, telmisartan was better tolerated than ramipril, as reflected in, for example, lower incidences of permanent treatment discontinuations due to cough and angioedema. The placebo-controlled TRANSCEND and PRoFESS studies provided supporting evidence for the (time-dependent) effectiveness of telmisartan in preventing cardiovascular events, although the drug appeared to have neither a beneficial nor a harmful impact on cardiovascular mortality. The TRANSCEND trial also demonstrated that telmisartan was well tolerated in ACE inhibitor-intolerant patients at high vascular risk. On the basis of these findings, telmisartan can be considered an effective treatment option for CVD prevention in patients at high vascular risk. Consideration may be given to prescribing the drug as an alternative to ramipril in patients who are able to tolerate ACE inhibitors and, potentially, instead of ramipril in patients who are unable to tolerate ACE inhibitors.

The Role of Renin-Angiotensin Agents in Altering the Natural History of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease (CVD) morbidity and mortality worldwide. Renin-angiotensin system (RAS) blockers have been indispensable in diminishing the macrovascular and microvascular complications of diabetes. In addition, cumulative evidence from retrospective studies pointed toward a beneficial effect of RAS agents in preventing the development and progression of T2DM. This disease-modifying potential of RAS blockers has been substantiated by recent prospective trials. Contemporary concepts regarding the natural history of T2DM and the pathophysiologic processes involved have increased our understanding of the mechanisms underlying the therapeutic potential of these agents in diabetes management. In addition to their established roles in the primary prevention of CVD in patients with diabetes, RAS blockers might be considered a suitable therapeutic choice for preventing the development of frank diabetes in high-risk patients.

Smooth Muscle Cell Pathophysiology and Advanced Glycation End Products (AGEs)

Accelerated atherosclerosis is the leading cause of coronary heart disease and stroke, which could account for high mortality rates in patients with diabetes. Although several hyperglycemia-elicited metabolic and hemodynamic derangements have been implicated in the pathogenesis of cardiovascular disease (CVD) in diabetes, the process of formation and accumulation of advanced glycation end products (AGEs) and their mode of action are most compatible with the phenomenon 'metabolic memory' and 'legacy effect', that is, vascular stresses during the diabetic exposure have persisted after glucose normalization. Further, there is a growing body of evidence that a receptor for AGEs (RAGE) is involved in signal transduction of AGEs in a variety of cells. In this paper, we review the role of the AGE-RAGE system in accelerated atherosclerosis, especially focusing on smooth muscle cell pathophysiology, and also discuss the possibility that the AGE/RAGE axis could be a potential therapeutic target for prevention of CVD in patients with diabetes.

Effect of Lovastatin on Primary Prevention of Cardiovascular Events in Mild CKD and Kidney Function Loss: A Post Hoc Analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study

Chronic kidney disease (CKD) is associated with an increased risk of incident cardiovascular disease (CVD); however, the role of statins for the primary prevention of acute cardiovascular events in patients with CKD and the effect of statins on kidney function loss in persons without prevalent CVD have not been studied. Post hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study. Multicenter, randomized, double-blind, placebo-controlled trial of 5,608 men and 997 women without CVD randomly assigned to treatment with lovastatin or placebo. Placebo or lovastatin, 20 mg/d. First major acute cardiovascular event in participants with mild CKD and kidney function loss in persons with or without CKD. Estimated glomerular filtration rate was calculated using the 4-variable Modification of Diet in Renal Disease Study equation. At baseline, mean estimated glomerular filtration rate in participants with CKD (n = 304) was 53.0 +/- 6.0 mL/min/1.73 m(2). After an average follow-up of 5.3 +/- 0.8 years, the incidence of a fatal and nonfatal CVD event was lower in participants with CKD receiving lovastatin than in those receiving placebo (adjusted relative risk [RR], 0.31; 95% CI, 0.13-0.72; P = 0.01). Tests for interaction suggested that the benefit of lovastatin was independent of the presence of CKD. Lovastatin did not reduce the annualized mean decrease in estimated glomerular filtration rate (-1.3 +/- 0.07 vs -1.4 +/- 0.07 mL/min/1.73 m(2)/y, respectively; P = 0.1) or the frequency of a > or = 25% decrease in kidney function (adjusted RR, 1.10; 95% CI, 0.96-1.28; P = 0.2) or incident CKD (adjusted RR, 1.04; 95% CI, 0.86-1.27; P = 0.6). Unable to determine the cause and duration of kidney disease, and information regarding proteinuria was not available. Lovastatin is effective for the primary prevention of CVD in patients with CKD, but is not effective in decreasing kidney function loss in persons with no CVD.

Strategies to enhance cardiovascular disease prevention in patients with diabetes

To describe current strategies to enhance cardiovascular disease (CVD) prevention in patients with abnormal glucose regulation. Early detection of glucose abnormalities and a multifactorial approach to all modifiable risk factors are effective strategies to reduce the burden of CVD in patients with diabetes mellitus. Available evidence suggests that an overly aggressive approach to lowering of glucose may contribute to complications; different hypoglycaemic agents may vary in the likelihood with which their use may give rise to complications. Thus, a decrease of glucose levels below that recommended in available guidelines is not recommended. Given its increasing prevalence and its substantial concomitant risk for CVD, diabetes mellitus can no longer be perceived as an endocrine disorder only bearing high risk of microvascular complications. Further research involving prospective clinical trials will be necessary to clarify the benefits of early detection and treatment of diabetes in preventing the subsequent development or exacerbation of CVD.

Hypertension and Diabetes: Emphasis on the Renin-Angiotensin System in Atherosclerosis

Cardiovascular diseases (CVDs) are the major causes of morbidity and mortality in persons with diabetes, and many factors, including hypertension, contribute to this high prevalence of macrovascular complications. Hypertension is approximately twice as frequent in subjects with diabetes compared with non-diabetic patients. Furthermore, up to 75Y% of CVD in diabetes may be attributable to hypertension, leading to recommendations for more aggressive treatment (i.e. reducing blood pressure to < 130/80 mmHg) in persons with coexistent diabetes and hypertension. Macroangiopathy in diabetes is manifested by accelerated atherosclerosis which affects heart, brain and peripheral arteries. The pathogenesis of this accelerated atherosclerosis is multifactorial and includes a very complex interaction. Several data suggest a key role for renin-angiotensin system (RAS) activation in the pathophysiology of macrovascular complications in diabetic hypertensive subjects. Consequently, RAS blockade exerts potent antiatherosclerotic effects, which are mediated by their antihypertensive, anti-inflammatory, antiproliferative, and oxidative stress lowering properties. Inhibitors of the system, ie, angiotensin converting enzyme inhibitors and angiotensin receptor blockers, are now first line treatment to prevent CVD in patients with diabetes and hypertension. In addition, recent clinical trials have suggested that RAS blockade may protect against the development of de-novo diabetes in at-risk patients. Finally, the recent identification of new components of the RAS should provide fertile territory to not only examine new targets linked to the RAS but potentially to design more rational treatments for the prevention of CVD in patients with diabetes and hypertension. Keywords: Diabetes, hypertension, renin-angiotensin system, atherosclerosis, ACE-inhibition, AT1 receptor blockade

Physical activity in cardiovascular disease prevention in patients with HIV/AIDS

The introduction of highly active antiretroviral therapy (HAART) has both extended life expectancy and reduced morbidity in people living with HIV/AIDS (PLWHA). These changes have resulted in the emergence of cardiovascular disease (CVD) and associated risk factors as a threat to the health of PLWHA. The major components of CVD risk associated with HIV infection include HIV, HAART, nonmodifiable factors such as genetics or environment, and modifiable risk factors such as inactivity and poor diet. Physical activity has been shown to be beneficial in reducing the risk of CVD through its effect on numerous modifiable risk factors, including functional aerobic impairment, dyslipidemia and insulin resistance, obesity, and atherosclerotic inflammation. A growing body of evidence indicates that exercise has similar benefits for these modifiable CVD risk factors that are exacerbated in PLWHA.

The JUPITER study: statins for the primary prevention of cardiovascular events in patients with inflammatory rheumatic diseases?

Patients with inflammatory rheumatic diseases have an increased risk of cardiovascular disease, raising questions of whether primary prevention strategies that are more aggressive than cardiac risk factor modification alone should be implemented. Recent trials demonstrating the efficacy of statins in reducing rates of cardiovascular events in healthy persons with elevated levels of C-reactive protein broaden the potential protective mechanisms of statins, but do not directly translate to primary cardiovascular disease prevention in patients with inflammatory rheumatic diseases.

Diabetes Mellitus and Mortality after Acute Coronary Syndrome as a First or Recurrent Cardiovascular Event

BackgroundDiabetes Mellitus (DM) is associated with adverse cardiovascular prognosis. However, the risk associated with DM may vary between individuals according to their overall cardiovascular risk burden. Therefore, we aimed to determine whether DM is associated with poor outcome in patients presenting with Acute Coronary Syndrome (ACS) according to the index episode being a first or recurrent cardiovascular event.Methods and FindingsWe conducted a retrospective analysis of a prospective cohort study involving 2499 consecutively admitted patients with confirmed ACS in 11 UK hospitals during 2003. Usual care was provided for all participants. Demographic factors, co-morbidity and treatment (during admission and at discharge) factors were recorded. The primary outcome was all cause mortality (median 2 year follow up), compared for cohorts with and without DM according to their prior cardiovascular disease (CVD) disease status. Adjusted analyses were performed with Cox proportional hazards regression analysis. Within the entire cohort, DM was associated with an unadjusted 45% increase in mortality. However, in patients free of a history of CVD, mortality of those with and without DM was similar (18.8% and 19.7% respectively; p = 0.74). In the group with CVD, mortality of patients with DM was significantly higher than those without DM (46.7% and 33.2% respectively; p<0.001). The age and sex adjusted interaction between DM and CVD in predicting mortality was highly significant (p = 0.002) and persisted after accounting for comorbidities and treatment factors (p = 0.006). Of patients free of CVD, DM was associated with smaller elevation of Troponin I (p<0.001). However in patients with pre-existing CVD Troponin I was similar (p = 0.992).ConclusionsDM is only associated with worse outcome after ACS in patients with a pre-existing history of CVD. Differences in the severity of myocyte necrosis may account for this. Further investigation is required, though our findings suggest that aggressive primary prevention of CVD in patients with DM may have beneficially modified their first presentation with (and mortality after) ACS.

Role of Asymmetric Dimethylarginine (ADMA) in Diabetic Vascular Complications

Nitric oxide (NO) is a well-recognized anti-atherogenic factor; it inhibits the inflammatory-proliferative processes in atherosclerosis. Indeed, endothelial dysfunction due to reduced synthesis and/or bioavailability of NO is thought to be an early step in the course of atherosclerotic cardiovascular disease (CVD). NO is synthesized from L-arginine via the action of NO synthase (NOS), which is known to be blocked by endogenous L-arginine analogues such as asymmetric dimethylarginine (ADMA), a naturally occurring amino acid found in plasma and various types of tissues. Recently, it has been demonstrated that plasma levels of ADMA are elevated in patients with diabetes. These findings suggest that the elevated ADMA in diabetes could contribute to acceleration atherosclerosis in this population. Further, since ADMA is mainly metabolized by dimethylarginine dimethylaminohydrolase (DDAH), it is conceivable that the inhibition of ADMA via up-regulation of DDAH may be a novel therapeutic target for the prevention of CVD in patients with diabetes. In this paper, we review the pathophysiological role of ADMA and DDAH system for accelerated atherosclerosis in diabetes and the therapeutic utility of ADMA suppression in CVD in diabetes.

Non-traditional risk factors predict coronary calcification in chronic kidney disease in a population-based cohort

The increased burden of cardiovascular disease in chronic kidney disease cannot be explained by traditional risk factors alone. Here, we evaluated the impact of non-traditional factors on the association of chronic kidney disease with coronary artery calcification using logistic regression among 2672 Dallas Heart Study patients of whom 220 had chronic kidney disease. The prevalence of coronary calcification significantly increased across all chronic kidney disease stages and this remained independently associated with coronary calcification after adjusting for traditional factors. The calcium x phosphorus product, homocysteine, and osteoprotegerin each diminished the magnitude of association between kidney disease and coronary calcification. After adjustment for these, the association between kidney disease and coronary calcification was no longer significant with the effects most prominent in the stages 3-5 subgroup. Our study has identified three non-traditional independent predictors of coronary calcification that diminished the association between chronic kidney disease and coronary calcification. These factors may represent novel mechanistic links warranting further investigation.

Prevention of Cardiovascular Disease in Persons with Type 2 Diabetes Mellitus: Current Knowledge and Rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial

Patients with type 2 diabetes mellitus die of cardiovascular disease (CVD) at rates 2-4 times higher than patients without diabetes but with similar demographic characteristics. The prevalence of diabetes is increasing in the United States and, thus, the prevention of CVD in patients with diabetes poses an urgent public health challenge. The objective of this report is to review the current knowledge base for the prevention of CVD in patients with diabetes, with particular emphasis on the control of glycemia, lipids, and blood pressure. Epidemiologic analyses suggest that each 1% increase in glycosylated hemoglobin increases the risk for CVD by approximately 18%; however, evidence from the randomized trials that have examined whether glucose lowering reduces this risk is conflicting. Randomized trials have shown that lowering low-density lipoprotein cholesterol reduces CVD event rates by 17%-43% in patients with diabetes. Limited data support a role for lowering triglycerides and increasing high-density lipoprotein cholesterol in the prevention of CVD. Evidence from clinical trials shows that reducing systolic blood pressure to <140 mm Hg results in 30%-60% reductions in CVD events; however, epidemiologic evidence suggests that lowering to optimal systolic blood pressure levels (<120 mm Hg) may be additionally beneficial. Important questions regarding prevention of CVD in patients with diabetes remain unresolved, including the benefits of near-normal glycemic control, comprehensive therapy for diabetes-related dyslipidemia, and optimal blood pressure control. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial will test hypotheses to address these unanswered questions.

Aspirina em baixa dosagem em pacientes com diabete melito: riscos e benefícios em relação às complicações macro e microvasculares

Aspirin is recommended as cardiovascular disease prevention in patients with diabetes mellitus. Due to the increased risk of bleeding and because of the hypothesis that there could be a worsening of microvascular complications related to aspirin, there has been observed an important underutilization of the drug. However, it is now known that aspirin is not associated with a deleterious effect on diabetic retinopathy and there is evidence indicating that it also does not affect renal function with usual doses (150 mg/d). On the other hand, higher doses may prove necessary, since recent data suggest that diabetic patients present the so called "aspirin resistance". The mechanisms of this resistance are not yet fully understood, being probably related to an abnormal intrinsic platelet activity. The employment of alternative antiplatelet strategies or the administration of higher aspirin doses (150-300 mg/d) should be better evaluated regarding effective cardiovascular disease prevention in diabetes as well as the possible effects on microvascular complications.

Cardiovascular disease prevention in patients with type 2 diabetes: the role of oral anti-diabetic agents

Multiple risk factor intervention is essential in order to prevent cardiovascular (CV) disease in patients with diabetes. Therefore, to reduce atherothrombotic events, an ideal oral anti-diabetic agent should be able to modulate most, and preferably all, cardiovascular risk factors associated with diabetes. Of the currently available agents, the insulin sensitisers (metformin, thiazolidinediones) seem to have most promise in cardiovascular protection. Metformin has a positive effect on several CV risk factors; outcome studies have shown that this agent reduces cardiac events in overweight subjects with diabetes. In a similar manner, thiazolidinediones (rosiglitazone, pioglitazone) have a wide spectrum of activity, favourably modulating most risk factors, with evidence to suggest a reduction in CV events with this class of drugs. Agents in the sulphonylurea group have beneficial, though inconsistent, effects on some risk factors but outcome studies have failed to show a cardioprotective role for these agents. New classes of drugs to manage type 2 diabetes are currently at various stages of development and their role in prevention of cardiovascular disease awaits evaluation. At present, first-line management of insulin-resistant type 2 diabetes should utilise metformin, with the addition of thiazolidinediones and sulphonylureas to achieve optimal glycaemic control.

Pharmacological Strategies to Reduce Cardiovascular Risk in Type 2 Diabetes Mellitus

Morbidity and mortality in patients with type 2 diabetes mellitus is largely dominated by the occurrence of cardiovascular disease (CVD). Treatment of known risk factors of CVD has proven to be beneficial in terms of reduction in risk of major CVD events in the general population. Recent trials have provided information on the treatment of hyperglycaemia, hypertension, dyslipidaemia and platelet aggregation in the patient with type 2 diabetes. Strict glycaemic control is not associated with a significant reduction in CVD risk, although new hypoglycaemic agents may offer additional benefits. In contrast, it has been demonstrated that treatment of hypertension and dyslipidaemia significantly reduce cardiovascular risk. Meticulous control of blood pressure to a level < or =130/80 mm Hg, preferably using renin-angiotensin system-modulating agents, is of proven value. Use of HMG-CoA reductase inhibitors (statins) as low-density lipoprotein (LDL)-cholesterol-lowering therapy, initiated at a level of > or =2.60 mmol/L is firmly established. Recent trials lend support to lowering the target level for LDL-cholesterol-lowering therapy to < or =1.81 mmol/L. Mainly based on risk analogy, international guidelines advocate the use of aspirin (acetylsalicylic acid) in the primary prevention of CVD in patients with type 2 diabetes. However, there is no support from large trials that the estimated 25% risk reduction in primary prevention in a high-risk population is the same in the subgroup with diabetes. An intensified approach in order to identify and treat cardiovascular risk factors in patients with type 2 diabetes, stratified to individual patients, is necessary to reduce the excess cardiovascular burden of these patients.

Challenges in preventing cardiovascular complications in type 2 diabetes in primary care

Background: Prevalence of type 2 diabetes mellitus (DM2) continues to increase worldwide. The associated cardiovascular morbidity and mortality are high.Objectives: To study daily practice in preventing cardiovascular disease (CVD) in an unselected primary care patient population with DM2, and to study factors influencing the care delivered.Methods: Cross-sectional univariate and multivariate analyses of baseline data from a primary care population-based sample of patients with DM2, participating in a shared care project in the Netherlands.Results: Of 1269 patients invited, 1149 (91%) participated. Hypertension was present in 78% of patients, 63% of whom were treated, 41% successfully. Lipid profile abnormalities were present in 51% of patients, 22% of whom were treated, 54% successfully. The treatment rates for lipid profile abnormalities were positively correlated with younger age and the registration of the lipid profile by the GP. For hypertension the treatment rates were higher for patients who were female, of an advanced age, in the presence of CVD, and/or whose blood pressure had been registered by the GP.Conclusion: A gap exists between recommended care and the care patients actually receive in the prevention of CVD in patients with DM2 in the primary care setting. Diagnosed CVD and the accurate registration of cardiovascular risk factors by GPs are associated with higher treatment rates. Improvement strategies could be directed at primary prevention of CVD and improving the registration of cardiovascular risk factors.