CARDIOLOGY UPDATE:

ldl reduction and hdl management 2012

CHOLESTEROL is a wax-like steroid molecule that plays a critical role in metabolism. It is a major component of cellular membranes, where its concentration varies depending on the function of the particular cell. For example, the membrane of liver cells contains fairly large fractions of cholesterol (~30%). The cholesterol in cell membranes serves two primary functions. First, it modulates the fluidity of membranes, allowing them to maintain their function over a wide range of temperatures. Second, it prevents leakage of ions (molecules used by the cell to interact with its environment) by acting as a cellular insulator. This effect is critical for the proper function of neuronal cells, because the cholesterol-rich myelin sheath insulates neurons and allows them to transmit electrical impulses rapidly over distances. Cholesterol has other important roles in human metabolism. Cholesterol serves as a precursor to the steroid hormones, which include the sex hormones (androgens and estrogens), mineral-corticoids, which control the balance of water and minerals in the kidney), and glucocorticoids, which control protein and carbohydrate metabolism, immune suppression, and inflammation. Cholesterol is also the precursor to vitamin D. Finally, cholesterol provides the framework for the synthesis of bile acids, which emulsify dietary fats for absorption. TRIGLYCERIDES are storage lipids that have a critical role in metabolism and energy production. They are molecular complexes of glycerol (glycerin) and three fatty acids. While glucose is the preferred energy source for most cells, it is a bulky molecule that contains little energy for the amount of space it occupies. Glucose is primarily stored in the liver and muscles as glycogen. Fatty acids, on the other hand, when packaged as triglycerides, are denser sources of energy than carbohydrates, which make them superior for long-term energy storage (the average human can only store enough glucose in the liver for about 12 hours worth of energy without food, but can store enough fat to power the body for significantly longer).

Lipoproteins: Blood Lipid Transporters

Lipids (cholesterol and fatty acids) are unable to move independently through the blood stream, and so must be transported throughout the body as lipid particles. The lipid particles that transport cholesterol in circulation are called lipoproteins. Contained within these lipoproteins are one or more proteins, called apolipoproteins, which act as molecular signals to facilitate the movement of lipid-filled lipoproteins throughout the body. Lipoproteins can also carry fat-soluble antioxidants, like CoQ10, vitamin E, and carotenoids, which protect the transported lipids from oxidative damage. This is why vitamin E and CoQ10 have performed so well in cardiovascular studies because they prevent the oxidative modification of LDL particles, which in turn protects the blood vessel lining from damage. Four main classes of lipoproteins exist, and each has a different, important function:

Chylomicrons (CMs) are produced in the small intestines and deliver energy-rich dietary fats to muscles (for energy) or fat cells (for storage). They also deliver dietary cholesterol from the intestines to the liver. Very low density lipoproteins (VLDLs) take triglycerides, phospholipids, and cholesterol, from the liver and transport them to fat cells. Low density lipoproteins (LDLs) carry cholesterol from the liver to cells that require it. In aging people, LDL often transports cholesterol to the linings of their arteries where it may not be needed. High density lipoproteins (HDLs) transport excess cholesterol (from cells, or other lipoproteins like CMs or VLDLs) back to the liver, where it can be re-processed and/ or excreted from the body as bile salts. HDL removes excess cholesterol from the arterial wall.

Amongst its myriad of functions, the liver has a central role in the distribution of cellular fuel throughout the body. Following a meal, and after its own requirements for glucose have been satisfied, the liver converts excess glucose and fatty acids into triglycerides for storage, and packages them into VLDL particles for transit to fat cells. VLDLs travel from the liver to fat cells, where they transfer triglycerides/fatty acids to the cell for storage. VLDLs carry between 10 and 15% of the total cholesterol normally found in the blood. As VLDLs release their triglycerides to fat cells, their cholesterol content becomes proportionally higher (which also causes the VLDL particle to become smaller and denser). The loss of triglycerides causes the VLDL to transition to a low-density lipoprotein (LDL). The LDL particle, which averages about 45% cholesterol, is the primary particle for the transport of cholesterol from the liver to other cells of the body; about 60-70% of serum cholesterol is carried by LDL.

During the VLDL to LDL transition, an apolipoprotein buried just below the surface of the VLDL called ApoB-100, becomes exposed. ApoB-100 identifies the lipoprotein as an LDL particle to other cells. Cells which require cholesterol recognize ApoB-100 and capture the LDL, so that the cholesterol it contains can be brought into the cell. Each LDL particle expresses exactly one ApoB100 molecule, so measurement of Apo-B100 levels serves as a much more accurate indicator of LDL number than LDL-C (LDL cholesterol) level. Because of the correlation between elevated blood levels of cholesterol carried in LDL and the risk of heart disease, LDL is commonly referred to as the bad cholesterol. LDL is, however, more than just cholesterol, and its contribution to disease risk involves more than just the cholesterol it carries. All LDL particles are not created equal. In fact, LDL subfractions are divided into several classes based on size (diameter) and density, and are generally represented from largest to smallest in numerical order beginning with 1. The lower numbered classes are larger and more buoyant (less dense); size gradually decreases and density increases as the numbers progress. Smaller, denser LDLs are significantly more atherogenic for two reasons; they are much more susceptible to oxidation,5,6,7 and they pass from the blood stream into the blood vessel wall much more efficiently than large buoyant LDL particles.8 A more comprehensive lipid test, such as The Verticle Auto Profile (VAP) Test or NMR (nuclear magnetic resonance), allows for assessment of the size and density of LDL particles, a feature that dramatically increases the prognostic value and sets these advanced tests apart from conventional lipid tests. If an individual is found to have a greater number of small dense LDLs they are said to express LDL pattern B and are at greater risk for heart disease than an individual with more large buoyant LDL particles, which is referred to as pattern A. HDLs are small, dense lipoprotein particles that are assembled in the liver, and carry about 20-30% of the total serum cholesterol.9 Cholesterol carried in the HDL particle is called good cholesterol, in reference to the protective effect HDL particles can have on cardiovascular disease risk. HDL particles can pick up cholesterol from other tissues and transport it back to the liver for reprocessing and/or disposal as bile salts. HDL can also transport cholesterol to the testes, ovaries and adrenals to serve as precursors to steroid hormones. HDLs are identified by their apolipoproteins ApoA-I and ApoA-II, which allow the particles to interact with cell surface receptors and other enzymes. The movement of cholesterol from tissues to the liver for clearance, mediated by HDLs, is called reverse cholesterol transport. If the reverse cholesterol transport process is not functioning efficiently, lipids can build up in tissues such as the arterial wall. Thus, reverse cholesterol transport is critical for avoiding atherosclerosis. Interestingly, a link between the male hormone testosterone and reverse cholesterol transport has been discovered 3

testosterone enhances reverse cholesterol transport.10 Though it is known that testosterone decreases levels of HDL, it also improves HDL function. This effect is mediated by a protein in the liver called scavenger receptor B1 that acts to stimulate cholesterol uptake for processing and disposal. Testosterone beneficially increases scavenger receptor B1.Testosterone also increases the activity of an enzyme called hepatic lipase, another facilitator of reverse cholesterol transport. Aging men experience a decline in testosterone levels, as well as a simultaneous increase in heart disease risk, which suggests that these phenomena may be related. Indeed, studies have shown that men with even slightly lower testosterone levels were over three times as likely to exhibit signs of early coronary artery disease.In order to maintain optimal reverse cholesterol transport efficiency, aging men should strive to maintain a free testosterone in the youthful range of 20 25 pg/ml. The initial association between cholesterol and cardiovascular disease was born out of the detection of lipid and cholesterol deposits in atherosclerotic lesions during the progression of atherosclerosis. Subsequently, studies have elucidated a role of LDLs in cardiovascular disease development, particularly the role of oxidized LDL (ox-LDL; LDL particles that contain oxidized fatty acids) in infiltrating and damaging arterial walls, and leading to development of lesions and arterial plaques. Upon exposure of the fatty acid components of LDL particles to free radicals, they become oxidized and structural and functional changes occur to the entire LDL particle. The oxidized LDL (ox-LDL) particle can damage the delicate endothelial lining of the inside of blood vessels.Once the ox-LDL particle has disrupted the integrity of the endothelial barrier additional LDL particles flood into the arterial wall (intima). Upon recognition of the presence of the ox-LDL within the intima, immune cells (macrophages) respond by engulfing it in an effort to remove it. But, the immune cells have then become too enlarged (by engulfing multiple ox-LDL particles) to escape back through the endothelial layer and become trapped within the intima, where they continually release cytokines, causing oxidative and inflammatory reactions to occur, resulting in the oxidation of additional native LDL particles and recruitment of more immune cells. This accumulative cycle results in the formation of atherosclerotic plaque deposits, which cause the arterial wall to protrude and disrupt blood flow, a process referred to as stenosis. The recognition that ox-LDL is an initiator of endothelial damage allows for a clearer understanding of LDLs role in the grand scheme of heart disease. Though an elevated number of native LDL particles does not directly endanger endothelial cells, it does mean that there are more LDL particles available to become oxidized (or otherwise modified), which then become more likely to damage endothelial cells. 4

Lowering serum cholesterol to an optimal range (total cholesterol 160 180; LDL-C 50-99) is one of the most frequently used strategies for reducing heart disease risk in persons without CHD.This approach, however, only addresses a portion of the risk. The actual predictive power of high LDL cholesterol for cardiovascular risk is likely much more complex, and has been the subject of several investigations Reduction of total- and LDL-cholesterol (and/or triglycerides) by conventional medical therapies usually involves inhibiting cellular cholesterol production in the body, or preventing the absorption/reabsorption of cholesterol from the gut. By reducing the availability of cholesterol to cells, they are forced to pull cholesterol from the blood (which is contained in LDL particles). This has the net effect of lowering LDL-C. Therapies which increase the breakdown of fatty acids in the liver or lower the amount of VLDL in the blood (like fibrate drugs or high-dose niacin) also result in lower serum cholesterol levels. Often, complementary strategies (such as statin to lower cholesterol production plus a bile acid sequesterant to lower cholesterol absorption) are combined to meet cholesterol-lowering goals. Reduction of cellular cholesterol production is the most frequent strategy for reducing cardiovascular disease risk, with HMG-CoA reductase inhibitors (statins) being the most commonly prescribed cholesterol-lowering treatments. Statins inhibit the activity of the enzyme HMG-CoA reductase, a key regulatory step in cholesterol synthesis. Since cholesterol levels in cells are tightly controlled (cholesterol is critical to many cellular functions), the shutdown of cellular cholesterol synthesis causes the cell to respond by increasing the activity of the LDL receptor on the cell surface, which has the net effect of pulling LDL particles out of the bloodstream and into the cell. Statins may also reduce CHD risk by other mechanisms, such as by reducing inflammation. Statins may induce serious side effects in some individuals; most common being muscle pain or weakness (myopathy). The prevalence of myopathy is fairly low in clinical trials (1.5-3.0%), but can be as high as 33% in community based studies and may rise dramatically in statin users who are active (up to 75% in statin-treated athletes.)Occasionally, statins may cause an elevation of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). These enzymes can be monitored by doing a routine chemistry panel blood test. Additionally, by inhibiting HMG-CoA reductase (an enzyme not only required for the production of cholesterol, but other metabolites as well), statins may also reduce levels of the critically important antioxidant molecule CoQ10. Lowering cholesterol absorption from the intestines reduces LDL-C in a different fashion; by preventing uptake of intestinal cholesterol, cells respond by making more LDL receptor, which pulls LDL particles out of the blood 5

stream. Ezetimibe and bile acid sequestrants (colesevelam, cholestyramine, cholestopol) are two classes of prescription treatment that work in this fashion. Ezetimibe acts on the cells lining the intestines (enterocytes) to reduce their ability to take up cholesterol from the intestines. While ezetimibe does reduce LDL levels, the results of several major trials failed to show the benefit of ezetimibe as part of a combination therapy for reducing risk of cardiovascular disease, and it may actually increase the risk of atherosclerosis if prescribed to patients already on statins for reasons that are not clear. Bile acid sequestrants bind to bile acids in the intestine, which reduces their ability to emulsify fats and cholesterol. This has the net effect of preventing intestinal cholesterol absorption. Bile acid sequestrants may also increase HDL production in the liver, which is usually inhibited by the reabsorption of bile acids. The National Cholesterol Education Program's (NCEP's) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults creates updated clinical guidelines for testing and management of cholesterol. NCEP periodically updates existing recommendations based on new research. updates were added based on several clinical trials of statin therapy. The fact is, elevated low-density lipoprotein (LDL), the bad cholesterol, is a major cause of heart disease. LDL causes the build-up of fatty deposits within your arteries, reducing or blocking the flow of blood and oxygen your heart needs. This can lead to chest pain and heart attack. (Atherosclerosis, the medical term for "hardening of the arteries," is not limited to heart arteries, though. It also occurs in arteries elsewhere in your body, causing problems such as stroke, kidney failure and poor circulation.). In addition, studies show that lowering LDL cholesterol reduces risk for coronary heart disease. For this reason, ATPIII continues to focus goals of initiating treatment based on LDL. It is extremely important for everyone -- men and women of every age, with or without known heart disease to have a low LDL cholesterol level. The optimal guideline level of LDL cholesterol is less than 100 mg/dl. Research from the Cleveland Clinic (REVERSAL study) compared two cholesterol lowering drugs (pravastatin and atorvastatin) and found that lower levels of LDL, as low as 60 mg/dl had better outcomes. A second study called PROVE-IT also found that the lower the LDL cholesterol the better - the PROVE-IT study results stated - "These findings indicate that patients who have recently had an acute coronary syndrome benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels." TNT, Treating to New Targets also found that "internsive Atorvastatin therapy to acheive LDL cholesterol concentrations well below recommended target levels provides an incremental clinical benefit in pateints with stable coronary artery disease." These studies have impacted LDL goals and have provided now options as to when to initiate drug therapy as seen in the new updates.

Additional research has shown that statins, drugs used to treat high LDL cholesterol appear to also protect the heart in other ways. These drugs also reduce the progression of plaque buildup in the coronary arteries by reducing C-reactive protein, a measure of inflammation in the arteries. Therefore, it seems the lower the LDL cholesterol the better, and how you get there may be important as well.

IMPORTANCE OF CARDIAC REHABILITATION

Cardiac rehabilitation also called cardiac rehab is a customized program of exercise and education. Cardiac rehabilitation is designed to help you recover from a heart attack, other forms of heart disease or surgery to treat heart disease. Cardiac rehabilitation is often divided into phases that involve monitored exercise, nutritional counseling, emotional support, and support and education about lifestyle changes to reduce your risks of heart problems. The goals of cardiac rehabilitation are to help you regain strength, to prevent your condition from worsening and to reduce your risk of future heart problems. Cardiac rehabilitation programs increase your chances of survival. Both the American Heart Association and American College of Cardiology recommend cardiac rehabilitation programs. Cardiac rehabilitation is an option for people of all ages and with many forms of heart disease. In particular, you may benefit from cardiac rehabilitation if your medical history includes:

Heart attack Coronary artery disease Heart failure Peripheral arterial disease Chest pain (angina) Cardiomyopathy Certain congenital heart diseases Coronary artery bypass surgery Angioplasty and stents Heart transplant Heart valve replacements

Cardiac rehabilitation programmes are intended to enhance the effect of acute treatment actions and to prevent risk factors, thus leading to an improvement in the patient's well being and recovery. Accordingly, all cardiac rehabilitation activities do not take place at the same time, which is the reason

why the nurse's role changes in character over time. The aim of this paper is, therefore, to highlight the role of the nurse in cardiac rehabilitation programmes. The nurse's multiple roles in cardiac rehabilitation have a 'spider in the web-like' character and, depending on the phase of the patient's recovery, he/she acts as a container, a counsellor, a coach and an educator. To implement a successful cardiac rehabilitation, the nurse needs to have improved evaluation tools in clinical practice as well as to be self-critical and serve as a good role model. Finally, the cardiac rehabilitation nurse has to have a four-fold comprehensive perspective of the cardiac rehabilitation concept; an impact perspective, a timing perspective, a lifespan perspective, and a personal perspective.

Summary: After attending the cardiology update, I have realized the importance of nursing care and management to help the patient throughout the disease stage. Starting with the assessment of the patients risk and predisposing factors; diagnosing the presence of the disease by helping perform various procedures; providing care during the treatment, and ensuring the patients timely recovery by supervising and creating his rehabilitation program. The advancement in the treatment of cardiac patients leads to a lower mortality and disability rate, with higher rehabilitation and recovery. Alongside with the evolution of statin drugs that help maintain adequate level of hdl, lower ldl, and improve the vascular function, Thus reducing the risk or remissions of heart attack. Coordinating with the physician for the patients management, both therapeutic and pharmacologic is significant. However, explaining the situation to the patient himself will ensure better understanding, dexterity and compliance. Since rehabilitation for cardiac patients is a long and varied treatment, doing so will help the patient feel empowered and in control of the situation.

Richard c. bautista, r.n