Search

Inflammation as a cardiovascular risk factor has attracted increasing attention . The current standard of care for decreasing the occurrence of cardiovascular events includes controlling risk factors such as hypertension and maximizing the lowering of low-density lipoprotein cholesterol (LDL-C). However, a recent study demonstrated decreased cardiovascular risk with the anti-inflammatory agent canakinumab and created more interest in decreasing cardiovascular risk by decreasing inflammation. Canakinumab is not yet approved and will undoubtedly be very expensive, so interest in an established medication such as colchicine, which is inexpensive to produce, is appropriate if evidence-based benefit is adequately confirmed. Colchicine has existing indications for gout and familial Mediterranean fever and for decreasing the incidence of postpericardiotomy syndrome. If an evidence-based benefit in decreasing cardiovascular risk can be demonstrated for colchicine, it will be of significant importance. Meta-analyses and observational studies have provided evidence to suggest that colchicine decreases cardiovascular risk because of its anti-inflammatory effects. However, randomized controlled trials (RCTs) are needed, and the recently published COLCOT (Colchicine Cardiovascular Outcomes Trial) showed definite benefit on cardiovascular outcomes in adults who had experienced a myocardial infarction within the previous 30 days. Sufficient evidence now supports the use of colchicine for secondary prevention in patients at the highest cardiovascular risk who continue to have cardiovascular events despite good blood pressure control and maximum LDL-C reduction. Nevertheless, more RCTs will be necessary before widespread general use of colchicine in cardiovascular disease prevention can be recommended. The current acquisition cost issues with colchicine also need to be resolved.

Purpose of Review: The purpose of this review is to investigate and discuss two aspects of coronary artery disease (CAD)-genetic risk and therapeutic lifestyle change (TLC)-both of which have key importance for patients and their care but which actually receive inadequate attention., Recent Findings: Genetic risk has generally been relegated to a broad association with the presence of one or more inherited cardiovascular (CV) risk factors such as hypercholesterolemia, family history of atherosclerosis, hypertension, and diabetes mellitus. However, the future of genetic risk is an understanding of specific genes, a genetic risk score, specific genetic loci known as selective nucleotide polymorphisms (SNPs), specific alleles, and microribonucleic acids (miRNAs). Healthy lifestyle is fashionably referred to as TLC and encompasses physical fitness, exercise, behavioral modification, diet, and stress reduction. In the past decade, aggressive treatment of cholesterol with statins has received the major emphasis for CV risk reduction. Genetics, of course, can only be modified by factors that influence epigenetics, and TLC could have an effect on genetics by this mechanism. On the other hand, each individual component of TLC has been shown to contribute to a reduction of CV risk. Although aggressive pharmaceutical approaches are now in vogue, whatever TLC can contribute, depending on the degree of individual patient adherence, should never be forgotten.

The history of digitalis is rich and interesting, with the first use usually attributed to William Withering and his study on the foxglove published in 1785. However, some knowledge of plants with digitalis-like effects used for congestive heart failure (CHF) was in evidence as early as Roman times. The active components of the foxglove (Digitalis purpurea and Digitalis lanata) are classified as cardiac glycosides or cardiotonic steroids and include the well-known digitalis leaf, digitoxin, and digoxin; ouabain is a rapid-acting glycoside usually obtained from Strophanthus gratus. These drugs are potent inhibitors of cellular membrane sodium-potassium adenosine triphosphatase (Na + /K + -ATPase). For most of the twentieth century, digitalis and its derivatives, especially digoxin, were the available standard of care for CHF. However, as the century closed, many doubts, especially regarding safety, were raised about their use as other treatments for CHF, such as decreasing the preload of the left ventricle, were developed. Careful attention is needed to maintain the serum digoxin level at ≤ 1.0 ng/ml because of the very narrow therapeutic window of the medication. Evidence for benefit exists for CHF with reduced ejection fraction (EF), also referred to as heart failure with reduced EF (HFrEF), especially when considering the combination of mortality, morbidity, and decreased hospitalizations. However, the major support for using digoxin is in atrial fibrillation (AF) with a rapid ventricular response when a rate control approach is planned. The strongest support of all for digoxin is for its use in rate control in AF in the presence of a marginal blood pressure, since all other rate control medications contribute to additional hypotension. In summary, these days, digoxin appears to be of most use in HFrEF and in AF with rapid ventricular response for rate control, especially when associated with hypotension. The valuable history of the foxglove continues; it has been modified but not relegated to the garden or the medical history book, as some would advocate.

Purpose of Review: Coronary artery event includes acute coronary syndrome (ACS), percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery. Following such an event, risk of noncardiac surgery is increased. Of major concern is what can make this surgery safer?, Recent Findings: High functional capacity improves cardiovascular (CV) risk; at least 4.0 metabolic equivalents (METs) on stress test are favorable. Risk scores can suggest need for further evaluation. Coronary angiography prior to surgery usually is not indicated since revascularization shows disappointing CV risk reduction results. Due to high association of peripheral arterial disease (PAD) with coronary artery disease (CAD), low ankle-brachial index (ABI) indicates increased CV risk. New perioperative beta blockade has shown disappointing benefit, but if ongoing should be continued. De novo perioperative beta blockade is for the highest CV risk patient undergoing noncardiac vascular surgery. Good evidence supports CV risk reduction from new or existing statin in the perioperative period, especially for the diabetic. Diabetics should also be on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) secondarily, during the perioperative period to decrease 30-day perioperative mortality. Optimal timing of elective noncardiac surgery following a coronary artery event appears to be 180 days with CV risk decreased by a statin and an ACEI or an ARB.

Idiopathic Edema (IE), is a syndrome involving real or perceived weight gain secondary to the pathological retention of fluid. This syndrome of generalized edema is almost solely reported in women. The diagnosis of IE is one of exclusion and requires a careful history, physical exam, and clinical suspicion. The aim of this article is to provide a comprehensive review of the available literature in order to attempt to define IE, identify the possible causes, review the proposed pathophysiology, and discuss potential treatment options., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Carotid artery atherosclerosis (CAA) represents a significant form of atherosclerosis with stroke as a major consequence. Whether it is a unique form of atherosclerosis is not established. However, this is not of major clinical relevance as no specific preventive measures over and above the established ones for cardiovascular risk are well established. Major risk factors for CAA are elevated low-density lipoprotein cholesterol (LDL-C), diabetes mellitus, tobacco use, hypertension, and increased inflammation. Identification of CAA prior to a clinical event centers on imaging studies. Studies with magnetic resonance imaging result in the best definition of CAA plaque morphology. Medical measures that result in prevention are especially centered on statins (marked reduction of the LDL-C) and hypertension control. Nonprocedural therapeutic measures to avoid and delay complications involve antiplatelet medications. Benefits from other measures such as increasing high-density lipoprotein cholesterol and increased exercise appear desirable but require more clinical evidence. In conclusion, there are enough evidence-based medicine results to demand intensive medical preventive measures and not just relegate the patient with asymptomatic or symptomatic CAA to decision-making only involving the surgeon and interventionalist.

There are multiple guidelines for managing patients with high-risk cardiovascular disease, and unfortunately for the practicing clinician, these guidelines are quite variable. Some are fairly specific whereas others are not, resulting in a great deal of confusion regarding whether management of low-density lipoprotein cholesterol (LDL-C) should be tailored only, targeted only, or managed by a combination of both. In the management of cardiovascular disease, favorable cardiovascular outcomes can be obtained by simply lowering the LDL-C in the absence of any other medications. The advent of statins, the most potent LDL-C-lowering medication yet when developed, provided benefits augmented by the presence of multiple pleiotropic effects. Tailoring and/or targeting the decrease in LDL-C is also an issue of concern. Then, in 2016, the new proprotein convertase sutilisin-like/kexin type 9 (PCSK9) inhibitors appeared, providing a solution to patients with high-risk cardiovascular disease with statin intolerance and those who did not attain a desired LDL-C level while on a high-dose statin. These new PCSK9 inhibitors necessitate a determination of how low the LDL-C can and should go, most likely safely down to a beneficial level of 25 mg/dL for the highest-risk patient. These issues are documented and discussed with an attempt to help the reader make an informed risk management decision.

The history of proprotein convertase subtilisin/kexin type 9 (PCSK9) in medical science is fascinating and the evolution of knowledge of its function has resulted in new medications of major importance for the cardiovascular (CV) patient. PCSK9 functions as a negative control or feedback for the cell surface receptors for low-density lipoprotein including its component of cholesterol (LDL-C). The initial and key findings were that different abnormalities of PCSK9 can result in an increase or a decrease of LDL-C because of more or less suppression of cell surface receptors. These observations gave hints and awoke interest that it might be possible to prepare monoclonal antibodies to PCSK9 and decrease its activity, after which there should be more active LDL-C cell receptors. The rest is a fascinating story that currently has resulted in two PCSK9 inhibitors, alirocumab and evolocumab, which, on average, decrease LDL-C approximately 50%. Nevertheless, if there are no contraindications, statins remain the standard of prevention for the high-risk CV patient and this includes both secondary and primary prevention. The new inhibitors are for the patient that does not attain the desired target for LDL-C reduction while taking a maximum statin dose or who does not tolerate any statin dose whatsoever. Atherosclerosis can be considered a metabolic disease and the clinician needs to realize this and think more and more of CV prevention. These inhibitors can contribute to both the stabilization and regression of atherosclerotic plaques and thereby avoid or delay major adverse cardiac events. (United States)., (Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.)

Statins remain the mainstay of medical cardiovascular risk reduction because of their effectiveness in decreasing low-density lipoprotein cholesterol (LDL-C) as well as some other potentially beneficial effects. The latest US 2013 lipid guidelines essentially recommend only the prescription of a high-dose statin for the high-risk patient. However, both quite old and quite new outcomes evidence, such as reported for ezetimibe, emphasize that LDL-C lowering is, in and of itself, quite important for cardiovascular risk reduction. It appears that the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent a major new contribution to this effort, especially for patients with severe familial hypercholesterolemia, proven clinical cardiovascular disease, statin intolerance, or failure to attain an acceptably low LDL-C goal despite maximum available medical management. Very recent clinical trials have proven overwhelmingly the effectiveness and safety of PCSK9 inhibitors for lowering LDL-C. Both alirocumab and evolocumab have now been approved by the US FDA and there are some initial favorable outcomes data. This review is intended to summarize available evidence and emphasize the possible clinical role of these inhibitors following the approval of alirocumab and evolocumab. Understanding the negative receptor feedback of PCSK9 and the mechanism and beneficial effect of PCSK9 inhibitors for cardiovascular risk reduction is essential for the up-to-date practitioner of cardiovascular medicine. There is every reasonable hope for significant cardiovascular benefit from these new additions to our medical cardiovascular armamentarium.

Coenzyme Q-10 (CoQ10) is a widely used alternative medication or dietary supplement and one of its roles is as an antioxidant. It naturally functions as a coenzyme and component of oxidative phosphorylation in mitochondria. Decreased levels have been demonstrated in diseased myocardium and in Parkinson disease. Farnesyl pyrophosphate is a critical intermediate for CoQ10 synthesis and blockage of this step may be important in statin myopathy. Deficiency of CoQ10 also has been associated with encephalomyopathy, severe infantile multisystemic disease, cerebellar ataxia, nephrotic syndrome, and isolated myopathy. Although supplementation with CoQ10 has been reported to be beneficial in treating hypertension, congestive heart failure, statin myopathy, and problems associated with chemotherapy for cancer treatement, this use of CoQ10 as a supplement has not been confirmed in randomized controlled clinical trials. Nevertheless, it appears to be a safe supplementary medication where usage in selected clinical situations may not be inappropriate. This review is an attempt to actualize the available information on CoQ10 and define its potential benefit and appropriate usage.

Key thioredoxin (Trx) system components are nicotinamide adenine dinucleotide phosphate (NADPH), Trx reductase (TrxR), and Trx. TrxR catalyzes disulfide reduction in Trx with NADPH as cofactor. Because Trx is an antioxidant, oxidative stress results in an increase in Trx, which has a reduced disulfide component. If Trx is suppressed, oxidative stress in higher. In contrast a decrease in oxidative stress is associated with low Trx levels. Trx is involved in inflammation, apoptosis, embryogenesis, and cardiovascular disease (CVD). This review focuses on the Trx system in CVD. Abnormal Trx binding occurs in mouse familial combined hyperlipidemia; however, this has not been confirmed in humans. Congestive heart failure is a manifestation of many CVDs, which may be improved by attenuating oxidative stress through the suppression of Trx and decreased reactive oxygen species. Angiotensin II is associated with hypertension and other CVDs, and its receptor blockade results in decreased oxidative stress with reduced Trx levels. Inflammation is a major causative factor of CVDs, and myocarditis as an example, is associated with increased Trx levels. Vascular endothelial dysfunction has an association with CVD. This dysfunction is alleviated by hormone replacement therapy, which involves decreased oxidative stress and Trx levels. Diabetes mellitus has a major association with CVDs; increase in Trx levels may reflect insulin resistance. Identification of Trx system abnormalities may lead to innovative approaches to treat multiple CVDs and other pathologies.

General thinking has previously centered on managing carotid artery stenosis (CAS) by carotid endarterectomy and subsequently, stenting for higher risk patients. However for CAS and other forms of vascular disease, especially when asymptomatic, there is new emphasis on defining underlying mechanisms. Knowledge of these mechanisms can lead to medical treatments that result in possible atherosclerotic plaque stabilization, and even plaque regression, including in the patient with CAS. For now, the key medication class for a medical approach are the statins. Their use is supported by good cardiovascular clinical trial evidence including some directed carotid artery studies, especially with a demonstrated decrease in carotid intima-media thickness. Procedural controversy still exists but the current era in medicine offers significant support for medical management of asymptomatic CAS while techniques to recognize the vulnerable plaque evolve. If CAS converts to a symptomatic status, early referral for endarterectomy or stenting is indicated.

Purpose of Review: Cardiovascular disease considerations are associated with the menopause. Despite a misconception that women have a minimal risk for coronary heart disease (CHD), it is the major cause of female deaths. This review highlights issues of hormone replacement therapy (HRT) and CHD in women., Recent Findings: A woman under age 60, who suffers a myocardial infarction (MI), has a 2-year post-MI mortality of 28.9%; it is 19.6% in men. CHD and MI in women are subtle. In addition, female mortality from CHD increases after the menopause. The increased inflammatory risk factor status of women plays a role in development of atherosclerosis, before and after the menopause. Until after the menopause, women overall have a lower CHD mortality rate. Menopause is associated with unique symptoms, especially vasomotor ones; preexisting cardiovascular disease further exacerbates problems associated with the menopause. Use of HRT after the menopause is a major issue. Early menopause at age 39 years or younger and late menopause at age 56 years or older increase cardiovascular risk. HRT should not be prescribed for cardiovascular risk prevention, but when less than 10 years from menopause at a normal age, women can be reassured that cardiovascular risk from HRT is very low., Summary: Prescription of HRT should never be made only for cardiovascular risk reduction. However, when symptom-related and other indications are present, HRT is appropriate and well tolerated in the early years after menopause with onset at a normal age.

The prevalence of hypertension around the world has increased significantly with projections for an increasing major global burden of hypertension. Medication-resistant hypertension can be perplexing and frustrating. The existence of these difficult patients results in the need for additional approaches to treatment including surgery, percutaneous interventions, and device management. The sophistication of these techniques has progressed markedly and initial procedures such as classical sympathectomy and renal artery bypass are almost never performed. Newer techniques of angioplasty with stenting, renal artery denervation, and baroreflex activation therapy via electrical stimulation of the carotid baroreceptors are now in use with increasing evidence for significant benefit.

There are significant differences in coronary heart disease (CHD) in women whenever a comparison is made to men and these carry over to revascularization procedures including percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery. The coronary arteries of women are smaller, which presents additional challenges for PCI and CABG procedures. Unique atypical symptomatology in response to acute coronary syndrome (ACS) in women can confound diagnosis, women notoriously delay seeking medical help for ACS, and physicians and other caregivers have had a tendency to minimize the significance of these symptoms, contributing further to a delay in necessary care. There also appears to be an increased association of inflammation and CHD in women. The younger the female patient with CHD, the higher the mortality and that mortality clearly exceeds that of comparable male patients. For cardiovascular (CV) risk prevention in women, statins have had controversy associated with their use but overall, the proof of beneficial outcomes results from statins is also valid in women. An increased rate of adverse outcomes has been reported in women after PCI and CABG surgery. These worse clinical outcomes have persisted in contemporary years but lessened due to advancement in invasive techniques. Nevertheless, PCI that could improve clinical outcomes in women who have high-risk ACS is, unfortunately, performed on a less frequent basis and, in addition, there are greater delays involving women as compared to men. With increased clinical comorbidity associated with complex CHD in women, a lower anatomical SYNTAX score (from: SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery [SYNTAX] trial) appears necessary in order for women to achieve a similar long-term mortality benefit from CABG surgery as compared to PCI.

With a history that began in 800 A.D., coffee is the most popular drink known and as a result, the issues regarding its physiologic effects deserve attention. Maintaining alertness is a wellknown benefit and in addition, the cardiovascular (CV) effects of the active compounds, which include polyphenols and caffeine, must be considered. Genetics are relevant and where slow caffeine metabolism is inherent, the risk of nonfatal myocardial (MI) has been shown to be increased. Overall risk for coronary heart disease (CHD) is not supported and unless there is excessive intake, congestive heart failure (CHF) is not adversely affected; in moderation, there may be some benefit for CHF. There is no apparent increased risk of sudden cardiac death (SCD). Overall, there also appears to be a beneficial inverse association with all-cause mortality, although this is not absolute for extra heavy intake. Benefit in reducing stroke also has supportive evidence. Hypertension is not increased by coffee. Boiled and unfiltered coffee appears to increase plasma cholesterol and triglycerides but for the overall metabolic syndrome, there appears to be benefit. There is also some evidence that paper-filtered coffee results in an increase in some markers of inflammation. Association of coffee with arrhythmias has been a major concern though in moderation it is not a significant overall problem. Therefore, only if a patient were to associate major arrhythmic symptoms with coffee would cessation have to be advised. Where coffee clearly shines from a CV standpoint is in the established decrease in onset of type 2 diabetes mellitus (DM). Any benefit or harm has always been attributed to caffeine as the apparent major component. However, coffee contains a myriad of compounds, including polyphenols. These other substances may be most relevant for potential benefit or harm and some of these may be partially removed or altered by coffee preparation methods such as paper filtration. Multiple studies support this by what appears to be no CV advantage or disadvantage for decaffeinated coffee. The bottom line on coffee, for those who enjoy the brew, is that it is a wonderful beverage with rare associated CV disadvantage and with much to recommend it from an overall CV standpoint.

With a history that began in 800 A.D., coffee is the most popular drink known and as a result, the issues regarding its physiologic effects deserve attention. Maintaining alertness is a well-known benefit and in addition, the cardiovascular (CV) effects of the active compounds, which include polyphenols and caffeine, must be considered. Genetics are relevant and where slow caffeine metabolism is inherent, the risk of nonfatal myocardial (MI) has been shown to be increased. Overall risk for coronary heart disease (CHD) is not supported and unless there is excessive intake, congestive heart failure (CHF) is not adversely affected; in moderation, there may be some benefit for CHF. There is no apparent increased risk of sudden cardiac death (SCD). Overall, there also appears to be a beneficial inverse association with all-cause mortality, although this is not absolute for extra heavy intake. Benefit in reducing stroke also has supportive evidence. Hypertension is not increased by coffee. Boiled and unfiltered coffee appears to increase plasma cholesterol and triglycerides but for the overall metabolic syndrome, there appears to be benefit. There is also some evidence that paper-filtered coffee results in an increase in some markers of inflammation. Association of coffee with arrhythmias has been a major concern though in moderation it is not a significant overall problem. Therefore, only if a patient were to associate major arrhythmic symptoms with coffee would cessation have to be advised. Where coffee clearly shines from a CV standpoint is in the established decrease in onset of type 2 diabetes mellitus (DM). Any benefit or harm has always been attributed to caffeine as the apparent major component. However, coffee contains a myriad of compounds, including polyphenols. These other substances may be most relevant for potential benefit or harm and some of these may be partially removed or altered by coffee preparation methods such as paper filtration. Multiple studies support this by what appears to be no CV advantage or disadvantage for decaffeinated coffee. The bottom line on coffee, for those who enjoy the brew, is that it is a wonderful beverage with rare associated CV disadvantage and with much to recommend it from an overall CV standpoint.

Altitude physiology began with Paul Bert in 1878. Chronic mountain sickness (CMS) was defined by Carlos Monge in the 1940s in the Peruvian Andes as consisting of excess polycythemia. Hurtado et al performed studies in the Peruvian Andes in the 1950s to 1960s which defined acclimatization in healthy altitude natives, including polycythemia, moderate pulmonary hypertension, and low systemic blood pressure (BP). Electrocardiographic changes of right ventricular hypertrophy (RVH) were noted. Acclimatization of newcomers to altitude involves hyperventilation stimulated by hypoxia and is usually benign. Acute mountain sickness (AMS) in travelers to altitude is characterized by hypoxia-induced anorexia, dyspnea, headache, insomnia, and nausea. The extremes of AMS are high-altitude cerebral edema and high-altitude pulmonary edema. The susceptible high-altitude resident can lose their tolerance to altitude and develop CMS, also referred to as Monge disease. The CMS includes extreme polycythemia, severe RVH, excess pulmonary hypertension, low systemic BP, arterial oxygen desaturation, and hypoventilation., (© The Author(s) 2013.)

Purpose of Review: The relationship of altitude and cold to cardiovascular risk is complex. Cold is hard to separate from altitude. This review highlights the latest information on cardiovascular disease associated with high altitude and cold; both represent unique clinical situations., Recent Findings: Evolution and genetics are relevant to high altitude, with much new information available. Specific physiology explains some congenital heart disease at altitude. New reports of hematological changes associated with altitude and cold help clarify thrombosis, which is relevant to reports of very late in-stent thrombosis at altitude. Multiple cardiovascular risk factors are affected by altitude and cold, and an increased incidence of myocardial infarction occurs. There is new research on acute mountain sickness associated with inflammation with relevance for clinical study of pulmonary edema. Socioeconomics plays a part in altitude and cold effects on cardiovascular disease. In addition to acute disease, high altitude involves chronic mountain sickness with new knowledge of associated cardiovascular endothelial abnormalities., Summary: High altitude and cold involve acute disease, chronic disease, and public health issues. Continued research is essential to enable the best clinical management in this era of rapid worldwide travel.

Lifestyle modification is primary in cardiovascular (CV) disease prevention. A major contribution is the Mediterranean diet (MedDiet), defined by two of seven components. Italian investigators determined a significant decrease in peripheral arterial disease of 56 % for a high score. Multiple specific CV risk factors are also favorably modified by the MedDiet. This includes beneficial effect on inflammation, vascular endothelium, and insulin resistance. There is also evidence that coronary heart disease, diabetes mellitus, and metabolic syndrome are decreased. Benefit appears to extend to new migrants in France. The economics of dietary adherence are favorable with decreased total lifetime health costs. Although mixed nuts appear to be a major factor in the MedDiet, special emphasis goes to extra virgin olive oil. Benefit also extends to other noncommunicable diseases with a decrease in cancer, Parkinson's disease, and Alzheimer's disease. Further quantitation of benefit and understanding of mechanisms involved in dietary benefit is essential.

The clinical importance of lowering of total cholesterol and low-density lipoprotein cholesterol (LDL-C) to decrease cardiovascular (CV) risk has been verified over many years starting with significant support in 1984 of the then previous lipid hypothesis. Significant support of this hypothesis began that year with publication of the Lipid Research Clinic study. Since then, multiple other studies including outcomes studies have established the value of LDL-C reduction in decreasing CV risk. In addition, multiple other factors such as inflammation, endothelial dysfunction, nitric oxide, antioxidant properties, and plaque stabilization appear important for modifying CV risk and possible favorable alterations by medications such as statins must be considered. Nevertheless, reduction of LDL-C has well-established value and is being accepted by clinicians as a major guideline for CV disease prevention. However, there are still problems with adherence by many clinicians to CV risk modification. Therefore, abandoning LDL-C reduction as a target, as has been advocated by some, appears premature and contraindicated. A strategy of LDL-C reduction in no way interferes with increased understanding of the complexities of atherosclerosis and new approaches to CV disease prevention as they become supported by outcomes studies.

There is occurring a progressive increase in peripheral arterial disease (PAD) in the United States and around the World. This is undoubtedly associated with deterioration in health status and an increase in cardiovascular risk factors. There are multiple old and new antithrombotic and anticoagulation medications that have been used for the treatment of PAD. Several are considered in this review. The purpose of antithrombotics in surgery is the prevention of thrombosis of surgical bypass grafts in order to help maintain their patency. Multiple different medication approaches can be made in association with surgery. Just as in the case of peripheral vascular surgery, thrombosis also plagues the long-term maintenance of patency following peripheral vascular interventions (PVIs). Platelets play a key role in the initiation and propagation of thrombus formation following these PVIs and the use of antithrombotic medication helps reduce the likelihood of intravascular thrombus formation and adverse ischemic events during and after the procedure. Currently used antithrombotic agents after percutaneous peripheral revascularization include aspirin, clopidogrel, cilostazol and warfarin. Available medications remain in a state of flux and new oral direct thrombin and Factor Xa inhibitors may also find a place as clinical evidence-based medicine accumulates.

Despite issues about the value of statins, benefit for high cardiovascular (CV) risk outweighs problems. However, the practitioner must be aware of concerns, be prepared to respond, and justify statin usage. Symptoms of statin-related myopathy are of more concern than stated by pharmaceutical companies. Occurrence of myopathy symptoms, estimated to be up to 10.4%, can decrease statin adherence of high CV risk patients. Dosage modification, or use of pitavastatin, may help the problematic patient. There are concerns that there may be little benefit of statins for primary prevention in women. However, evidence appears to support statin use in women at high CV risk, both in primary and secondary prevention. Abandoning low-density lipoprotein cholesterol (LDL-C) as a valid target is unwarranted; there is much evidence to support "lower is better." The practitioner must be aware of the complicated processes causing atherosclerosis and when to incorporate new approaches to disease management. Tailoring therapy for CV risk, when indicated, may contribute further to LDL-C reduction. Liver inflammation can occur with statins but is of minimal concern; frequently, statins alleviate the problem. Unless liver transaminases are over three times normal, a statin should be prescribed, if indicated. The net effect of statins on cognition appears to be zero-no harm, no benefit. Despite reports of improved cognition, statins should not be prescribed for this. With diabetes mellitus (DM), statins can increase incidence, but the CV benefit far outweighs any risk. Therefore, statins should be prescribed in DM to reduce CV risk. Statins are a major medical contribution when used appropriately.