Therapeutic Advances in Cardiovascular Disease recent issues

Review: Prevention of coronary heart disease in women

Rohit Seth Loomba, , Arora, R. — 2008-09-22

Objective Coronary heart disease (CHD) mortality is higher in women than in men and misdiagnosis of CHD in women is one of the reasons for this, with differences in the presentation of CHD between men and women being a cause for the misdiagnosis. This review discusses the need for evidence-based guidelines to diagnose and treat CHD in women.

Methods Reviews, randomized controlled trials, and other studies pertinent to the topic were obtained using electronic search strategies, such as MEDLINE and Cochran Library, as well as manual selection. Sources selected were limited to those that discussed CHD, with specific emphasis placed on sources that focused on CHD in women. Selected studies were then assessed for quality of data and relevance via analysis of the study's methodology, results, and data. Results of selected studies were then stratified using a rating system devised to determine the quality of results using the scientific evidence provided for them. The references of the selected studies were then used to obtain and analyze additional studies in the same manner.

Results Control of lifestyle factors such as smoking, physical activity, diet, and weight are all necessary in women to control CHD, as is the maintenance of healthy lipid levels and blood pressure. Angiotensin-converting enzyme inhibitors and antiplatelets can help aid lifestyle changes in CHD management for women while hormone therapy and vitamin E have no proven benefits in CHD management.

Conclusions New gender- and evidence-based guidelines for the prevention of CHD in women need to be developed and adopted by physicians so that prevention, diagnosis, and treatment of CHD is made more effective.

Review: Hypercholesterolemia-associated endothelial progenitor cell dysfunction

Pirro, M., Bagaglia, F., Paoletti, L., Razzi, R., Mannarino, M. R. — 2008-09-22

Hypercholesterolemia has been associated with increased cardiovascular risk by contributing to mechanical endothelial injury and dysfunction. There is evidence that chronic exposure to increased plasma cholesterol levels might also impair the repair of lipoprotein-mediated endothelial injury, possibly by reducing the availability and function of circulating endothelial progenitors. This review summarizes current knowledge about the mechanisms of lipoprotein-mediated endothelial injury and endothelial progenitor cell assisted vascular repair; the influence of hypercholesterolemia on endothelial progenitor cell dysfunction will be also addressed.

Review: Cardiogenic potential of endothelial progenitor cells

Murasawa, S., Asahara, T. — 2008-09-22

Transplantation of endothelial progenitor cells (EPCs) are one of the promising strategies to recover the capillary flow in ischaemic diseases such as ischaemic heart disease and peripheral artery disease (PAD) in the leg. However, our previous and another group's works suggested the scarcity of the number of EPCs in peripheral blood might cause insufficient effect for the ischaemic diseases. There are several strategies to overcome this issue, such as (1) in vivo EPC expansion; (2) ex vivo EPC expansion; (3) local (not systemic) EPC injection; and (4) modification of EPC by gene transfer. Recent publications from our own and other groups have reported the possibility of cardiogenic potential of EPCs. We would like to focus on the strategies of EPC transplantation and cardiomyogenesis of EPCs in this review.

Review: Systemic and uteroplacental renin--angiotensin system in normal and pre-eclamptic pregnancies

Anton, L., Brosnihan, K. B. — 2008-09-22

Pregnancy is characterized by an increase in many of the different components of the circulating renin—angiotensin system (RAS). However, the physiological mechanisms of stimulated RAS activity during pregnancy are unknown. Even less understood is how this system may be altered in pre-eclampsia, a hypertensive disorder of pregnancy. Additional studies have shown the presence of a local tissue specific RAS in the uteroplacental unit of normal and pre-eclamptic pregnancies. Differences in normal pregnant and pre-eclamptic RAS component regulation may provide insight into the mechanisms responsible for the clinical pathological features of pre-eclampsia. Specifically, this review summarizes the key findings in the circulating and uteroplacental RAS in normal and pre-eclamptic pregnancies.

Review: Genetics of diabetic nephropathy

Maeda, S. — 2008-09-22

Genetic susceptibility has been proposed as an important factor for the development and progression of diabetic nephropathy, and research efforts have been invested worldwide to identify the susceptibility gene for diabetic nephropathy. Although, several candidate genes were shown to be associated with the disease, the results were not always consistent; most of the genes conferring susceptibility to diabetic nephropathy remain to be identified. Recent development of the single nucleotide polymorphism (SNP) typing technology and collation of information on linkage disequilibrium in the human genome have facilitated genome-wide association studies (GWASs) for investigating novel disease-susceptibility genes across the entire human genome. GWASs are considered a powerful and promising approach and are expected to be useful for identifying convincing susceptibility genes for several common diseases; however, to date, these studies have not been able to completely cover the entire human genome.

Review: New techniques for assessment of vascular function

Smith, R. D., Levy, P. J. — 2008-09-22

The noninvasive measurement of hemodynamic variables associated with hypertension and cardiovascular disease processes needs to be recognized as a viable adjunct to clinical practice. This review traces the history of the inception and development of noninvasive measurement of hemodynamic variable. It then identifies well established, useful, and available devices, and then notes clinical studies verifying the clinical relevance of these measurements. Given the need to intervene earlier in the course of cardiovascular disease processes, tools are needed to assist the medical team to evaluate, prognosticate, and guide their patient's therapy correctly. It is the goal of this review to heighten the awareness and enhance and encourage the implementation of these devices in our armamentarium for the betterment of our patient's health.

Review: Recurrent stroke: where do we stand with the secondary prevention of noncardioembolic ischaemic strokes?

Talelli, P., Greenwood, R. J. — 2008-09-22

Strokes recur in 6—20% of the patients, most commonly within the first year; after a TIA or minor stroke; most recurrences will occur within the first 90 days. Our ability to identify patients at high risk is poor and most recurrent strokes cannot be explained by traditional risk factors. In 30—45% of the cases the second stroke will be of a different subtype. Moreover, patients are faced with other risks, like cardiac events and cognitive decline. With the population aging, the need for timely and effective secondary prevention strategies is more pressing than ever. This paper summarizes recent advances in pharmacological secondary prevention after a non-cardioembolic ischaemic stroke, and highlights critical questions still in need of answers.

ACE-inhibitor, AT1-receptor-antagonist, or both? A clinical pharmacologist`s perspective after publication of the results of ONTARGET

Schindler, C. — 2008-08-18

Clinical Pharmacology is commonly accepted to be a bridging discipline between basic science observations and clinical practice. Today, it should be a major task of the clinical pharmacologist in academia to provide support in the interpretation of preclinical and clinical study data, to develop evidence-based treatment guidelines and to serve as drug expert supporting all disciplines of clinical medicine with specific pharmacological and therapeutic knowledge. The results of the ONTARGET-trial confront both researchers and clinicians with the unexpected truth that AT₁-receptor-blockade with an angiotensin-receptor-blocker (ARB) does not seem to have superior therapeutic benefit compared with an ACE-inhibitor (ACE-I) at reducing fatal and nonfatal cardiovascular events. The combination of the two drugs was associated with more adverse events without an increase in benefit. Therefore, the crucial question `ACE-I, ARB, or both?' requires a new and critical appraisal depending on the medical indication for which these renin-angiotensin-system (RAS)-inhibitors are used: In a population of high-risk patients suffering from cardiovascular disease or diabetes mellitus, the evidence to favor an ARB over an ACE-I is still limited after ONTARGET and because of the higher costs for ARBs one can rather support the old therapeutic advice that ARBs are equally effective as ACE-Is and therefore therapeutic alternatives for patients with ACE-I intolerance. With respect to a very moderate additive BP-lowering effect of dual therapy with an ACE-I and an ARB seen in metaanalysis which was not even clearly attributable to dual RAS-inhibition and the increased adverse event rate in the combination treatment group of ONTARGET, this regimen seems not to be recommendable for the treatment of hypertension. Dual-RAS-blockade using an ACE-I-ARB-combination is an effective therapy to treat proteinuria and might be of therapeutic benefit especially in diabetic patients without concomitant diseases. There may be a therapeutic rationale to prefer ARBs over ACE-Is in well-selected patients with congestive heart failure (CHF) because a considerable amount of angiotensin II (Ang II) is produced independent of angiotensin-conversion-enzyme (ACE) in the failing heart and is therapeutically unaffected by ACE-I treatment. The results of the Val-HeFt and the CHARM-added-study revealed additive effects of an ARB on heart failure related morbidity and mortality when added to existing therapy with an ACE-I suggesting a role for ACE-I-ARB-combination treatment in well selected heart failure patients. Independent of the medical indication for its use, the concept of dual RAS-blockade with an ARB-ACE-I-combination should clinically be used with caution and a close monitoring of potassium levels and kidney function. Although the results of ONTARGET revealed equity of ramipril and telmisartan at reducing fatal and nonfatal cardiovascular events, we should not forget that pharmacologically not all ARBs are the same and the question if the study results of ONTARGET with telmisartan are transferable to the complete class of ARBs still merits further investigation.

Review: Preeclampsia and future cardiovascular risk: formal risk factor or failed stress test?

Craici, I., Wagner, S., Garovic, V. D. — 2008-08-18

It is estimated that 10% of pregnancies are affected by hypertension worldwide. Approximately one-half of all hypertensive pregnancy disorders are due to preeclampsia, a pregnancy-specific disorder, its distinctive feature being either sudden onset, or worsening of pre-existing proteinuria. It has become increasingly recognized that women with a history of preeclampsia are at increased risk for future cardiovascular disease (CVD), but the mechanisms of this increase in risk are unclear. One possible explanation is that these two conditions share several common metabolic abnormalities as risk factors, including obesity, insulin resistance, and lipid abnormalities that may lead to preeclampsia and CVD at different times of a woman's life. Recent studies have revealed that, similar to CVD, several mediators of endothelial cell dysfunction are up-regulated in preeclampsia. Free radical derived oxidative stress, various inflammatory markers, including neutrophil response, C-reactive protein, and leukocyte adhesion, may contribute to endothelial dysfunction in both preeclampsia and coronary atherosclerosis. Alternatively, preeclampsia itself may induce metabolic and vascular changes that may increase the overall future risk for CVD in affected women. Therefore, at present, it remains unclear whether preeclampsia is a formal risk factor for CVD, or identifies women at increased risk for CVD later in life. Pending large-scale studies aiming to examine the causality of this association, women with a history of preeclampsia should be counseled regarding their increased risks for hypertension and other cardiovascular sequelae later in life, followed closely and treated aggressively for modifiable CVD risk factors.

Review: The role of the L-arginine-nitric oxide pathway in preeclampsia

Lopez-Jaramillo, P., Arenas, W. D., Garcia, R. G., Rincon, M. Y., Lopez, M. — 2008-08-18

Preeclampsia (PE) is a major cause of maternal and perinatal mortality, especially in developing countries. Its etiology involves multiple factors, but no specific cause has been identified. Evidence suggests that clinical manifestations are caused by endothelial dysfunction. Nitric oxide (NO), which is synthesized from L-arginine in endothelial cells by the endothelial nitric oxide synthase (eNOS), provides a tonic dilator tone and regulates the adhesion of white blood cells and platelet aggregation. Alterations in the L-arginine-NO pathway have been associated with the development of PE. Various studies, reporting decreased, elevated or unchanged levels of nitrite (NO₂) and nitrate (NO₃), two end products of NO metabolism, have been published. Our group contributed to those contradictory reports describing cases of PE with both elevated and decreased levels of NO₂ and NO₃. Apparently, diminished levels of NO could be related to deficiencies in the ingestion of dietary calcium associated to low levels of plasma ionic calcium, which is crucial to the eNOS' activity. Also, low levels of NO could be associated with the presence of eNOS polymorphisms or the presence of increased levels of ADMA, the endogenous inhibitor of NO. High levels of NO associated to low levels of cGMP suggest a decreased bioactivity of NO, which is probably related to an increased degradation of NO caused by a high production of superoxide in states of infection and inflammation. The present article analyses and reviews the reported paradoxical roles of the L-arginine-NO pathway in PE and gives a possible explanation for these results.

Review: Does lowering cholesterol have an impact on the progression of aortic stenosis?

Greve, A. M., Wachtell, K. — 2008-08-18

Several studies suggest that atherosclerotic disease is not a focal disease restricted to culprit lesions in the intima of the arterial wall, but seems to act as a general disease affecting the entire cardiovascular system. Evolving research has lately focused on the atherosclerotic component in calcific aortic stenosis (AS) as it seems that the valve is affected in a pattern similar to that of the vasculature. The hope is therefore, that we someday in the management of patients with calcific AS can apply some of the same treatment strategies as in atherosclerotic vascular disease. This article reviews the pathophysiological mechanisms of calcific AS, reviews current clinical trials of statin use in aortic stenosis and reports on on-going trials, evaluating whether cholesterol lowering therapy can slow disease progression in different populations. Finally, we review if computerized tomography, biomarkers, and clinical characteristics such as left ventricular ejection fraction, can be useful in stratifying patients to potential benefit of statin therapy.

Review: Stroke prevention: modifying risk factors

Romero, J. R., Morris, J., Pikula, A. — 2008-08-18

Risk factor modification remains as the principal aspect of care for stroke prevention. Understanding of risk factors has advanced and several options are now available to treat modifiable risk factors. However, effective treatment remains a challenging task in clinical practice. Prevention begins with awareness of risk factors by patients and clinicians. Risk factor assessment along with overall stroke risk estimation should be part of evaluation of patients with stroke, and used with careful clinical judgment. In this review, we discuss the impact of modifiable traditional vascular risk factors on ischemic stroke, interventions for stroke prevention, and evidence for early treatment of risk factors where available, as well as areas of research progress. Emphasis should be put on the education of patients, the community, and medical personnel. Future research in the field of genetic determinants of vascular risk factors and stroke will increase our understanding of the underlying mechanisms of cerebrovascular disease and likely result in development of new therapies and individualized programs for stroke prevention.

Review: Prehypertension: should we be treating with pharmacologic therapy?

Egan, B. M., Nesbitt, S. D., Julius, S. — 2008-08-18

Prehypertension, defined by Seventh Joint National Committee (JNC 7) as a blood pressure (BP) 120—139/80—89 mm Hg, was controversial. Approximately 31—37% of US adults are prehypertensive, and ~12—14% have BP of 130—139/85—89 mm Hg or `Stage 2' prehypertension, is associated with ~3-fold greater likelihood of developing hypertension and roughly twice the cardiovascular events than BP <120/80 mm Hg. Lifestyle change is the only intervention recommended for most prehypertensives. When fully implemented, lifestyle changes lower BP and prevent cardiovascular events, but evidence for community-wide effectiveness is limited. The Trial of Preventing Hypertension (TROPHY) documented that angiotensin receptor blockade safely lowers BP and prevents and/or delays hypertension in Stage 2 prehypertensives. Prehypertensives with diabetes or nephropathy are at high risk and should receive antihypertensive treatment according to JNC 7. Epidemiological data suggest that the number needed to treat to prevent a cardiovascular event in these at-risk Stage 2 prehypertensives is similar to Stage 1 hypertensives when both groups have one or more concomitant risk factors. Clinical trials are urgently needed to address this question. In the absence of clinical trials data, we believe it is prudent for the concerned clinician to consider initiating antihypertensive pharmacotherapy in selected Stage 2 prehypertensive patients at significant absolute risk for progression to hypertension and cardiovascular events.

Original Research: Local TAT-p27Kip1 Fusion protein inhibits cell proliferation in rat Carotid arteries

2008-06-18

Introduction: p27^Kip1 is a cyclin kinase inhibitor that induces cell cycle arrest. In this study, the efficacy of fusion protein TAT- p27^Kip1 to inhibit cell proliferation in rat perivascular injured carotid arteries was tested.

Methods: The cDNA of p27^Kip1 and GFP (green fluorescein protein) fused to the TAT epitope, which allows cell penetration, yielded TAT-p27 ^Kip1 and TAT-GFP fusion proteins. In vitro biological activity on cell proliferation was evaluated by [³H] thymidine DNA incorporation in rabbit aortic endothelial cells (REC). An in vivo model used a silicone collar filled with saline positioned around the carotid vessel for 14 days to produce an increased adventitia cross-sectional area.

Results: TAT-p27^Kip1 inhibited REC proliferation in vitro using either 100, 200, and 500 nM compared to control (88.2 ± 4.4, 81.3 ± 7, 71.9 ± 4.2 vs. 100 ± 6.7%, N = 3, respectively, p < 0.05). This response was stable for purified proteins stored at -20•C for at least 23 days. In vivo , TAT-p27^Kip1 solution reduced adventitia cross-sectional area in a dose-dependent manner compared to TAT-GFP (area in mm² — TAT-p27^Kip1: 200 nM, 0.160 ± 0.018; 500 nM, 0.050 ± 0.005 vs. TAT-GFP: 500 nM, 0.595 ± 0.066 vs. the contralateral: 0.047 ± 0.005, N = 7, p < 0.01).

Conclusion: Taken together, these results provide evidence that TAT-p27^Kip1 can inhibit vascular cells proliferation. It is the first successful demonstration that the cell permeable TAT-p27^Kip1 has potential as a vascular anti-proliferative agent.

Review: Avoiding restenosis: is there a role for glucocorticoids in the drug-eluting stent era?

2008-06-18

Restenosis is an important limitation of percutaneous coronary interventions (PCI). In-stent restenosis is mainly due to neointimal hyperplasia, a proliferative process modulated by inflammatory mechanisms. Numerous technical and pharmacological means have been tested to reduce restenosis rates, with frequently disappointing clinical results. Drug-eluting stents (DES) have demonstrated a high efficacy in reducing restenosis, but there are some associated problems that limit its generalized utilization. Glucocorticoids (GC), as potent anti-inflammatory agents, may exert beneficial effects on neointimal proliferation. Clinical studies with oral and intracoronary GC therapy have demonstrated reduction in restenosis rates in selected patients. Although further investigations are warranted, GC might have a potential role for restenosis prevention in selected cases.

Review: Hypertension, a health economics perspective

Alcocer, L., Cueto, L. — 2008-06-18

The economic aspects of hypertension are critical to modern medicine. The medical, economic, and human costs of untreated and inadequately controlled hypertension are enormous. Hypertension is distributed unequally and with iniquity in different countries and regions of the world. Treatment of hypertension requires an investment over many years to prolong disease-free quality years of life. The high prevalence and high cost of the disease impacts on the microeconomics and macroeconomics of countries and regions. The criteria used for inclusion in clinical guidelines for hypertension impact on the cost and cost/utility of diagnosis or treatment.

Review: Statins and stroke

2008-06-18

Statins play an important role in brain ischemia. These drugs reduce cholesterol levels, which have been related to a reduction in vascular event risk, but they also have other functions besides cholesterol metabolism, called pleiotropic effects. Statins play an important role during the acute phase of ischemia, and might have neuroprotective effects, as they act in several mechanisms during the acute phase of stroke, such as in nitric oxide (NO) and glutamate metabolism, inflammation, platelet aggregation, immune responses and apoptosis. They also have other functions that can be related, with better long-term outcome, to neurorepair mechanisms. Statins promote angiogenesis, endogenous cell proliferation, neurogenesis and new synapse formation.

Review: The therapeutic role of RAS blockade in chronic heart failure

Werner, C. M., Bohm, M. — 2008-06-18

Cardiovascular disease represents a continuum that starts with risk factors such as hypertension and progresses to atherosclerosis, end-organ damage, and ultimately to chronic heart failure (CHF) and premature death. Renin-angiotensin system (RAS) blockade with angiotensin converting enzyme (ACE) inhibitors and/or angiotensin II type 1 receptor blockers (ARBs) has turned out to be beneficial at all stages of this continuum. Several mechanisms govern the progression of structural myocardial damage to end-stage CHF. Chronic neuroendocrine activation fosters left ventricular remodeling and dilatation and leads to clinical symptoms of CHF via forward/backward failure. RAS inhibition is a cornerstone of neuroendocrine blockade in CHF patients, and combined RAS blockade is especially effective in patients presenting with repetitive cardiac decompensations. This review focuses on the therapeutic role of inhibitors of different RAS components in chronic heart failure caused by systolic left ventricular dysfunction.

Review: PPARs as new therapeutic targets for the treatment of cerebral ischemia/reperfusion injury

Collino, M., Patel, N. S.A., Thiemermann, C. — 2008-06-18

Stroke is a leading cause of death and long-term disability in industrialized countries. Despite advances in understanding its pathophysiology, little progress has been made in the treatment of stroke. The currently available therapies have proven to be highly unsatisfactory (except thrombolysis) and attempts are being made to identify and characterize signaling proteins which could be exploited to design novel therapeutic modalities. The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that control lipid and glucose metabolism. PPARs regulate gene expression by binding with the retinoid X receptor (RXR) as a heterodimeric partner to specific DNA sequences, termed PPAR response elements. In addition, PPARs may modulate gene transcription also by directly interfering with other transcription factor pathways in a DNA-binding independent manner. To date, three different PPAR isoforms, designated , β/, and , have been identified. Recently, they have been found to play an important role for the pathogenesis of various disorders of the central nervous system and accumulating data suggest that PPARs may serve as potential targets for treating ischemic stroke. Activation of all PPAR isoforms, but especially of PPAR, was shown to prevent post-ischemic inflammation and neuronal damage in several in vitro and in vivo models, negatively regulating the expression of genes induced by ischemia/ reperfusion (I/R). This paper reviews the evidence and recent developments relating to the potential therapeutic effects of PPAR-agonists in the treatment of cerebral I/R injury.

Review: Endothelial progenitor cells: markers of vascular reparative capacity

Povsic, T. J., Goldschmidt-Clermont, P. J. — 2008-06-18

Assessment of the propensity for vascular events has been based on measurement of risk factors predisposing one to vascular injury. These assessments are based on the strong associations between risk factors such as hypertension, cholesterol levels, smoking, and diabetes which were first described almost a half century ago. The more recent discovery of the relationship between ongoing inflammation and clinical outcomes has led to a variety of blood-based assays which may impart additional knowledge about an individual's propensity for future cardiovascular events. Vascular health is now better represented as a balance between ongoing injury and resultant vascular repair, mediated at least in part by circulating endothelial progenitor cells. To date, one's risk for vascular events has focused exclusively on assessing propensity for vascular damage, either by assessing conventional risk factors which were initially identified over half a century ago, or more recently by assessing markers of inflammation and other circulating factors which area related to subsequent clinical events. Circulating endothelial progenitor cells play important roles in accelerating endothelialization at areas of vascular damage, and EPC enumeration is a viable strategy for assessing reparative capacity. To date, EPC numbers have been correlated with the numbers of cardiovascular risk factors, extent of coronary disease, and future cardiovascular events. Given that EPC enumeration and functional characterization represent the only assessment of the reparative side of the balance between damage and renovation, this technique may offer independent and different assessment of propensity to cardiovascular injury, greatly improving risk stratification of patients.

Review: Atrial fibrillation and renin-angiotensin system

Serra, J. L., Bendersky, M. — 2008-06-18

Atrial Fibrillation (AF) is one of the most frequent arrhythmias, especially in elderly patients. Cardiac overload increases the incidence of AF. Clinical presentation of atrial fibrillation can occur as nonsustained paroxysms, persistent episodes and in chronic-permanent form. The physio-pathological mechanisms are:

• Circuit of multiple and anarchic re-entries

• Atrial fibrillatory conduction

• Re-entry circuit with fibrillatory conduction.

Remodeling (electrical or structural) facilitates the appearance and persistence of AF: Neurovegetative changes and cytosolic Ca overload facilitate AF. Interstitial atrial fibrosis, in which Renin-Angiotensin System (RAS) hyperactivity is a main aspect of remodeling. There is clinical evidence that supports the antiatrial fibrillatory actions of RAS blockade. Potential mechanisms are: (a) direct modulation of ionic channels, (b) hemodynamic improvement, (c) reduction of atrial stretching, (d) antifibrotic effects. There is less clinical evidence with antialdosterone drugs, but theoretically these might also be useful.

Editorial: Of gender, statins, and coronary artery interventions

Ferrario, C. M. — 2008-03-28

Editorial: On the selective inhibitors of Cyclooxygenase-2: Do we have a last word?

Ferrario, C. M. — 2008-03-28

Original Research: Capillary rarefaction in treated and untreated hypertensive subjects

Cheng, C., Daskalakis, C., Falkner, B. — 2008-03-28

This study aimed to determine if capillary rarefaction is detectable and associated with endothelial dysfunction in persons with mild systolic blood pressure (SBP) elevation. Capillary density and endothelial function were quantified for 150 nondiabetic participants, grouped by blood pressure (BP) as normotensive, untreated high BP, and treated high BP. Structural capillary rarefaction measures were not different between the three groups. Functional capillary rarefaction measures were significantly lower in both high BP groups compared to normotensives, and correlated inversely with endothelial function. The study findings indicate that the hypertensive vascular pathologic process is already underway at modest levels of blood pressure elevation.

Review: Endothelial dysfunction: A potential tool in gender related cardiovascular disease

Patel, P. D., Arora, R. R. — 2008-03-28

The overwhelming importance of distinctive cardiovascular disease profile in women has stimulated enormous efforts to disclose its cause. In this review, we discuss vascular endothelium as a potential phenotypic marker for the genetic difference. As it is a potentially modifiable factor for cardiovascular disease, every effort should be made to detect it, either directly or indirectly, at the earliest in females who are at risk, so that the future cardiovascular events might be prevented.

Review: Percutaneous coronary interventions and statins therapy

Nusca, A., Melfi, R., Di Sciascio, G. — 2008-03-28

Statins exert a number of beneficial effects on endothelial function and atherosclerotic plaque, modulating oxidative stress and inflammation, with subsequent, well documented, primary and secondary prevention of coronary artery disease. Periprocedural myocardial infarction and contrast induced nephropathy, after percutaneous coronary intervention (PCI), are associated with a worse outcome on long term follow-up. In the ARMYDA study, pretreatment with statins before elective PCI reduces periprocedural myocardial infarction in patients with stable angina. Moreover, the ARMYDA ACS was the first randomized, prospective trial that demonstrated that an acute loading with a high dose of atorvastatin prevents myocardial damage in patients with unstable syndromes undergoing early (<48 hours) coronary angiography and consequent angioplasty. Statins could also have beneficial effects by reducing expression of adhesion molecules in endothelial cells (ICAM-1 and E-Selectin) as demonstrated in the ARMYDA-CAMS study. Furthermore, patients receiving statins at the time of procedure show a significantly reduced incidence of contrast-induced nephropathy. All this evidence may strongly influence the clinical practice of an interventional cardiologist.

Review: Gender differences following percutaneous coronary intervention

Holmvang, L., Mickley, H. — 2008-03-28

PCI is effective for reducing symptoms in patients with stable angina pectoris but does not improve prognosis. In earlier trials PCI has been associated with more procedure related complications in women than men, but this difference between genders has been less pronounced in more recent studies. In acute coronary syndromes there is no evidence of gender differences regarding the benefit of primary PCI for ST-segment elevation myocardial infarction. However, several trials of unstable angina and non-ST-segment elevation myocardial infarction indicate that women do not have the similar benefit of a routine, early, invasive treatment strategy compared with men.

Review: Endurance exercise and resistance training in cardiovascular disease

Meka, N., Katragadda, S., Cherian, B., Arora, R. R. — 2008-03-28

Contrary to the age old taboo of exercise in cardiac patients, resistance training has been gaining importance recently as a safe, healthy fitness option in prevention of cardiovascular diseases, the leading killer disease in the population above 45 years in the United States. Endurance or aerobic exercise helps improve overall stamina and the ability of the heart to pump oxygenated blood in those with and without prior cardiovascular disease. In addition to modifying cardiovascular risks, resistance training has profound beneficial effects on improving muscle strength and endurance, preventing osteoporosis and improving quality of life both in the healthy and cardiovascular patients including women and heart failure patients. So resistance training should be regarded as a complementary fitness program rather that a substitute to endurance training. This review discusses the physiological phenomenon and benefits of exercise training programs on cardiovascular disease patients focusing on endurance exercise and resistance training.