Managing Cardiovascular Risk Factors without Medications: What is the Evidence?

In this era of potent medications and interventional cardiovascular (CV) procedures, the importance of beginning with and including Therapeutic Lifestyle Changes (TLC) is frequently forgotten. A major goal of this review article is to show and emphasize that modification of CV risk with nonmedication approaches makes an essential contribution to CV risk reduction. Available information on TLC and modifiable CV risk factors was reviewed and assessed. Modifiable major CV risk factors include diabetes mellitus, hypertension, hyperlipidemia, tobacco abuse, obesity, stress, and a sedentary lifestyle. Age as a major CV risk factor is, of course, not susceptible to modification. A contribution to the control of CV risk factors can occur without the start of medications and there is proof of benefit for beginning with a non-pharmacological approach. TLC can benefit all of the major modifiable CV risk factors and there is good evidence for the additional benefit of supervised and group TLC. TLC includes physical activity, diet, and smoking cessation. Evidence for the benefits of TLC in reducing CV disease events is well established. However, medications must be added in those patients with higher CV risk to obtain maximum cholesterol reduction (lower is better for the low-density lipoprotein cholesterol) and good blood pressure control. The benefit of TLC is frequently forgotten in this era of potent medications and invasive procedures. The benefits of diet and physical activity are emphasized with supporting data. Many motivated patients can prolong their lives significantly by dedication to TLC. Therapeutic Lifestyle Change (TLC) especially encompasses increased physical activity, a healthy diet, and smoking cessation. There is extensive proof for the benefit of TLC in contributing to cardiovascular (CV) disease prevention. CV diseases have strong metabolic and inflammatory components, both of which can be improved by TLC.

Inflammation May be the Future of Cardiovascular Risk Reduction: Does Colchicine have a Current Indication?

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.

Securing the Future for a Major Academic Cardiovascular Program: Hardwiring a Referral Network and Preparing for a Transition to Value-Based Reimbursement.

The University of Kentucky College of Medicine and Albert B. Chandler Hospital opened over 50 years ago to serve Kentucky. After initial growth and expansion, both were struggling clinically, academically, and financially in the early 2000s. Difficulties were apparent in cardiovascular (CV) services, which captured only 11% of the regional patients hospitalized for cardiac disease. Over the next 15 years, CV services dynamically transformed to become the leading provider with a large network of regional partners, garnering 42% of market share. This article describes strategic plans and initiatives leading to clinical and academic growth. Future value-based initiatives are also described.

Hypertriglyceridemia: An Infrequent, Difficult-to-predict, Severe Metabolic and Vascular Problem Associated with Estrogen Administration.

Supplementary estrogen plays important roles for female patients as convenient birth control, relief of postmenopausal symptoms, and in the management of other selected problems. However, as is the case for essentially all medications, there are side effects. Short of a major pulmonary embolus, the most severe side effect of estrogen would appear to be sporadic, rare, and severe hypertriglyceridemia associated with acute pancreatitis. The occurrence of this fortunately rare problem usually happens in the presence of some preexisting and usually mild increase in triglycerides (TG). A case of chronic and severe recurrent acute pancreatitis is described in the introduction and the management was complete estrogen avoidance. Started close to menopause and continued for a relatively short period, estrogens may have some cardiovascular (CV) benefit but the general recommendation is not to prescribe them for CV disease prevention. Estrogens may contribute to decreased diabetes mellitus (DM) risk and control. Administration of estrogens by the transdermal route may decrease some problems such as venous thromboembolism (VTE) and elevation of TG. Administration of estrogen in the right situation brings significant benefit to the female patient but skillful, careful, and knowledgeable use is essential.

The Superior Mesenteric Artery: From Syndrome in the Young to Vascular Atherosclerosis in the Old.

This review is directed at increasing awareness of two diverse rare upper gastrointestinal problems that occur at opposite ends of the age spectrum and are difficult to diagnose and treat. The Superior Mesenteric Artery Syndrome (SMAS) likely involves a young patient, especially female, and is especially associated with rapid weight loss, resulting in relative strangulation of the duodenum by a narrowing of the angle between the Superior Mesenteric Artery (SMA) and the aorta. On the other hand, atherosclerosis of the SMA is associated most likely with postprandial upper intestinal ischemia and abdominal pain occurs in the elderly at high risk for cardiovascular (CV) disease. Medical management of the SMAS in the young involves good alimentation and weight gain to overall increase the intestinal fat pad. Medical management of SMA atherosclerotic ischemia in the elderly is directed at marked lipid lowering with atherosclerotic plaque stabilization or even regression. If needed, surgery for SMAS can be attempted laparoscopically with duodenojejunoscopy which is the most popular procedure but there are also more conservative possibilities that avoid division of the duodenum. In addition, sometimes direct vision is needed to successfully operate on SMAS. If surgery is needed for SMA atherosclerotic ischemia, it is usually attempted endoscopically with angioplasty and stent placement. Most important, in the case of these two rare clinical entities, is that the clinician have a suspicion of their presence when indicated so that the young or old patient can be spared unnecessary suffering and return to good health in a timely fashion.

Genetic Risk, Adherence to a Healthy Lifestyle, and Ischemic Heart Disease.

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.

Non-Traditional Cardiovascular Risk Markers in the Era of Established Major Risk Factors and Multiple Guidelines.

The non-traditional cardiovascular (CV) risk factors that appear to be of most clinical interest include: apolipoprotein A (ApoA), apolipoprotein B (ApoB), high-sensitivity C-Reactive protein (hsCRP), homocysteine, interleukin 1 (IL1), lipoprotein (a) [Lp(a)], the density of low-density lipoprotein (LDL) particles, the LDL particle number, tissue/tumor necrosis factor-α (TNF-α) and uric acid. These non-traditional risk factors may be of value in adding further confirmation and attention to suspected significant CV risk. They can also provide a better understanding of current concepts of atherogenesis (e.g. various potential mechanisms associated with inflammation) as an etiology and in guiding current plus future therapies. In the mid-20th century, atherosclerosis and CV disease were considered mechanistic occurrences with essentially no attention to possible metabolic and molecular etiologies. Therefore, the only treatments then centered around mainly surgical procedures to try to improve blood flow, first with peripheral arterial disease (PAD) and later coronary artery disease (CAD). Now, failure to treat CV risk factors, especially where there is good evidence-based medicine, as in the case of statins for high CV risk patients, is considered medical negligence. Nevertheless, many problems remain to be solved regarding atherosclerosis prevention and treatment.

Idiopathic "Cyclic" Edema: A Frustrating and Poorly Understood Clinical Problem.

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.

Clinical Use of Digitalis: A State of the Art Review.

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.

Outcomes, Access, and Cost Issues Involving PCSK9 Inhibitors to Lower LDL-Cholesterol.

The clinical importance and benefit of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors appears well established for the high-risk cardiovascular (CV) patient. This applies especially to the statin-intolerant patient or the patient who does not attain an appropriate low-density lipoprotein cholesterol (LDL-C) target. Therefore, the barriers to appropriate clinical use of the PCSK9 inhibitors involve cost and not the documented CV benefit or LDL-C lowering. Multiple roadblocks affect many high-risk CV patients in arranging approval of a PCSK9 inhibitor. Overcoming these roadblocks may require legal pressures, some increased regulation, and facilitation by competitive forces.

Management Strategies for Noncardiac Surgery Following a Coronary Artery Event.

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.

Medical Management and Risk Reduction of the Cardiovascular Effects of Underwater Diving.

Undersea diving is a sport and commercial industry. Knowledge of potential problems began with Caisson disease or "the bends", first identified with compressed air in the construction of tunnels under rivers in the 19th century. Subsequently, there was the commercially used old-fashioned diving helmet attached to a suit, with compressed air pumped down from the surface. Breathhold diving, with no supplementary source of air or other breathing mixture, is also a sport as well as a commercial fishing tool in some parts of the world. There has been an evolution to self-contained underwater breathing apparatus (SCUBA) diving with major involvement as a recreational sport but also of major commercial importance. Knowledge of the physiology and cardiovascular plus other medical problems associated with the various forms of diving have evolved extensively. The major medical catastrophes of SCUBA diving are air embolism and decompression sickness (DCS). Understanding of the essential referral to a hyperbaric recompression chamber for these problems is critical, as well as immediate measures until that recompression is achieved. These include the administration of 100% oxygen and rehydration with intravenous normal saline. Undersea diving continues to expand, especially as a sport, and a basic understanding of the associated preventive and emergency medicine will decrease complications and save lives.