Allopurinol and Cardiovascular Diseases: Systematic Review and Meta-Analysis - Dissertation Example

? Allopurinol and Cardiovascular Diseases: Systematic Review and Meta-Analysis By of 2342 Words Risk Factors and Treatment of Blood Pressure High blood pressure is perhaps the most common of all cardiovascular diseases. There are several risk factors associated with the condition. The risk factors of high blood pressure include age, race, family history, obesity, inactivity, tobacco use, excess sodium in diet, little potassium, excessive consumption of alcohol among others (Rizos, 2012). With regards to age, the risk of contracting high blood pressure is directly proportional to one’s age. High blood pressure is also reported to be more prevalent among black communities amongst which the condition is observed to develop at an earlier age compared to white communities. This trend is similar to the case of other diseases such as heart attack and stroke (Mozaffarian et al., 2012). High blood pressure also tends to run in families. With respect to being overweight, the more one weighs, the more blood is needed and supplied to supply oxygen and nutrients to body tissues. Similarly, as the amount of blood circulated in blood vessels increases, the pressure on the artery walls also increases. The other risk factor is physical inactivity, which implies that inactive people tend to have higher heart rates than physically active people (Mozaffarian et al., 2012). Tobacco use is the other risk factor since tobacco raises blood pressure temporarily. Worse still, tobacco chemicals have the effects of damaging the lining of artery walls increasing the likelihood of narrowing one’s arteries. Excessive salt (sodium) in diet also causes the body to retain excess fluid, thus increasing blood pressure. On the contrary, little potassium in one’s diet also increases the chances of contracting high blood pressure. It should be noted that Potassium assist in balancing the level of sodium in body cells. The other risk factors of high blood pressure are lack of vitamin D in the diet, high levels of stress, which may lead to a temporary but dramatic increase in blood pressure. Chronic conditions such as cholesterol, diabetes, kidney disease and sleep apnea and pregnancy may increase or contribute to high blood pressure. There are several treatment approaches or therapies through which blood pressure may be treated. Among the medications recommended and applied on high blood pressure are Thiazide diuretics, Beta blockers, Angiotensin-converting enzyme (ACE) inhibitors, Angiotensin II receptor blockers (ARBs), calcium channel blockers and central-acting agents among others. First, Thiazide diuretics, also known as water pills, act on the kidneys, helping the body to reduce or eliminate sodium and water. In the process, these actions lead to a reduced blood volume. On the other hand, Beta blockers lower the workload on the heart by opening the blood vessels. Consequently, they make the heart to beat slower using less force. Angiotensin-converting enzyme (ACE) inhibitors work by relaxing the blood vessels and by blocking the formation of a natural chemical, which would narrows blood vessels. On the other hand, Alpha blockers reduce nerve impulses to blood vessels and lower the effects of natural chemicals, which narrow blood vessels. Central-acting agents prevent the brain from signaling the CNS, increasing the heart rate and narrow blood vessels. The other treatment is Vasodilators, which work directly on the muscles on the walls of the arteries. This action prevents the artery muscles from tightening and arteries from narrowing. What Serum Uric Acid Is Prior to exploring the ways of lowering the levels of uric acid, it is necessary to understand what it actually is, its source, causes of high levels of uric acid and how to leads to gout. Uric acid is a derivative of the chemical breakdown of purines, found in cells and food (Perry & Smith, 2012). Purines are used for energy synthesis in the body as well as protein. In the process of providing these vital biochemical substances, uric acid is produced from purine metabolism in the bloodstream (Perry & Smith, 2012). The main use of uric acid is based on its being antioxidant and protects the internal linings of blood vessels. A high level of uric acid in the blood is referred to as hyperuricaemia and it could lead to the formation of uric acid crystals or urates (Perry & Smith, 2012). These urate crystals may settle on one’s joints, tendons and other tissues. The body’s defense systems will thus recognise these needle-like objects as intruding into the body. The symptoms of this condition, referred to as gout include redness, swelling, heat, inflammation, stiffness and rather great pain. The interconnections between uric acid and cardiovascular events and diseases have been studied for quite sometime, mainly in the last half a century to sixty years. The predictive connections and value of uric acid compounds and derivatives such as serum uric acid (SUA) and mild or adverse cardiovascular events in obese and overweight patients are not well established. However, such relationships are potentially significant for dealing with the problem of obesity and its relation with hyperuricaemia (Toncev & Samardzic, 2012). Among the cardiovascular events with which uric acid (in form of serum uric acid) is interconnected are nonfatal stroke, nonfatal myocardial infarction, resuscitated cardiac arrest or cardiovascular death and all-cause mortality (Heinig & Johnson, 2011). In a study conducted by Skak-Nielsen H, Torp-Pedersen C, Finer N, Caterson I. D., and Van Gaal L. on the subject of uric acid as a risk factor for cardiovascular disease and mortality in overweight/obese individuals, obese or overweight respondents were evaluated in a post-hoc analysis of the Sibutramine Cardiovascular Outcomes (SCOUT) trial. In this study, the Cox model was applied in assessing the role of serum uric acid as a risk factor for cardiovascular events and diseases. Of the study’s 9742 participants, 83.6% were found to have diabetes whereas 75.1% had cardiovascular diseases (Skak-Nielsen et al., 2013). In the 4.2 years follow-up time, 1043 of the participants had the primary outcomes of resuscitated cardiac arrest, stroke, cardiovascular death and myocardial infarction while 816 of the participants died during the 4.2 years follow-up period. From the study’s findings, the researchers concluded that serum uric acid was not quite an independent predictor of cardiovascular events or diseases in the high-risk obese or overweight people. Nonetheless, the results revealed that serum uric acid was an independent predictor of all-cause mortality in women. Relationship between Serum Uric and Cardiovascular Events Quite many scholars assume that uric acid could be a causative agent for renal disease and hypertension. In fact, according this class of researchers, arterial tension in gout is partly caused by uric acid and other toxic substances, which have the ability to increases the tonus of renal arterioles. The causative effects of uric acid on hypertension and cardiovascular disease were never explored in great details or depth mainly due to the fact that substances that could lower the levels of uric acid in the body were not present by then (Rizos, 2012). Thus, there were no studies to indicate the causal role of uric acid on cardiovascular disease. This scenario would prevail until 1950s and 1960s during which the association between uric acid and cardiovascular disease was rediscovered. Since this period, quite many studies and literatures have explored the relationship between serum uric acid levels and various types of cardiovascular conditions such as metabolic syndrome, hypertension, coronary artery disease, cerebrovascular disease, vascular dementia and preeclampsia and kidney disease (Pacher & Nivorozhkin, 2006). This relationship occurs with frank hyperuricaemia of more than 6 mg per deciliter [360 ?mol per liter in women, more than 7 mg per deciliter [420 ?mol per liter] in men) and the normal to high range (>5.2 to 5.5 mg per deciliter [310 to 330 ?mol per liter]) of uric acid levels (Pratviel, 2011). Nonetheless, controversies still surround the importance of this association between uric acid and cardiovascular disease. Specially, that uric acid is a risk factor for cardiovascular disease has been largely debated with some clinicians and professional association recommending patient assessment on other classic techniques rather than uric acid (Nakagawa et al., 2012). It is thus recommended that with the evidences so far gathered, it would really help to carry out some clinical trials to find out if reduced uric acid levels would have clinical benefits on the prevention and treatment of cardiovascular diseases. Since cardiovascular disease is often associated with high levels of uric acid, it is often unclear whether uric acid causes cardiovascular disease or a consequence of it (Mozaffarian et al., 2012). For instance, the levels of uric acid are always high in people with increased risks to contract cardiovascular diseases. These groups include blacks, hypertensive people, postmenopausal women, people with metabolic syndrome and those with renal disease (Highlander & Shaw, 2010). In addition, the apparent increase in the risks of cardiovascular disease observed with westernisation of native people and immigration to Western countries and rural-urban migration of communities has also been established to correlate with increased uric acid levels. The most common type of analysis used by epidemiologists to research the role and effects of uric acid on cardiovascular disease and events are multivariate analyses. In these studies, the objective is often to assess the interdependence between an elevated uric acid level and cardiovascular and its risk factors (Perry & Smith, 2012). Some of the past studies on the same subject have suggested that uric acid could be dependent on other established risk factors of cardiovascular disease such as hypertension. As a result, some professionals and expert groups opine that studies, which indicate that uric acid is an independent risk factor of cardiovascular disease do not effectively control the other established risk factors (Reikvam, 2011). What is more, this category of experts feels that if uric acid were an independent risk factor of cardiovascular disease, the mechanism by which it causes the disease should have been well established. An elevated uric acid level in cardiovascular patients has also been explained by its antioxidant role, which should be beneficial to cardiovascular disease patients. It has also been posited that high levels of uric acid could be due to reduced glomerular filtration rate, hyperinsulinemia, renal vasoconstriction, diuretic use, alcohol use, tissue ischemia and oxidative stress (Sparrow & Friedman, 2011). How to Lower Uric Acid Levels Several practices and techniques are currently being used to lower the levels or uric acid, which is associated with quite many cardiovascular diseases and other disorders. In other words, many people are moving away from the costly drug-based treatments for diseases such as gout and cardiovascular events that are associated with uric acid. The first technique for lowering uric acid level is use of water (George et al., 2012). Experts advise that people should drink between 2 and 3 liters of water daily. It is also advisable to consume small amounts of water throughout the day to keep the kidney fresh and to flush out uric acid from the body. Baking Soda is the other compound by which uric acid crystals may be dissolved and its levels reduced. It is worth noting that baking soda increases the solubility of uric acid. Noting that baking soda is high in sodium, one should opt for a salt-free diet as he/she takes this approach to lowering the levels of uric acid (George et al., 2012). Given that cherries have anthocyanins, which are anti-inflammatory, it is quite recommended to deal with gout attacks. Research has also shown that cherries have the effect of lowering uric acid serum levels. People are also advised to adopt a low purine diet since uric acid is a byproduct of purine metabolism (George et al., 2012). Gout patients should thus avoid diets that are rich in purines as this would reduce the levels of uric acid. However, high purine foods should be entirely avoided. These foods to be avoided include fatty red meats, offal, poultry and some seafood, alcohol or beer, which particularly triggers gout. How to Lower Uric Acid Using Allopurinol Allopurinol is to an orally-administered drug that is chiefly used to treat hyperuricaemia, a condition associated with excess uric acid in blood plasma. The drug is also used on other conditions or complications associated with excess uric acid in blood plasma such as chronic gout. Allopurinol acts by inhibiting the enzyme Xanthine Oxidase, which causes successive oxidation of hypoxanthine, which results in the secretion of uric acid, a product of human purine metabolism (Day t al., 2011). Allopurinol therapy is also used and recommended for ischemic reperfusion injury, kidney stones with a uric acid component, poor kidney function and protozoan infections not to mention renal disease, heart failure and Angina (Curhan & Mitch, 2012). Allopurinol has also been found to decrease the C-reactive protein besides slowing down the development of renal disease in patients with chronic kidney disease. The other areas in which Allopurinol is used are epilepsy, where it is used an add-on drug that inhibits glutamine release from excitatory neurons. Besides of its effects of lowering blood pressure and mild hypertension, allopurinol also affects metabolism (George et al., 2012). The drug has several side effects, which include its being a dosing complex, making some patients hypersensitive to it (Ansari et al., 2011). Its use should thus be thoroughly monitored. The drug also has rare but potentially fatal adverse effects on the skin. Included among its most dreaded and adverse effects is hypersensitivity syndrome, which is characterised by fever, skin rash, eosinophilia, hepatitis, worsened renal function and allopurinol hypersensitivity syndrome (Taylor & Mackenzie, 2012). The mechanism of action of Allopurinol entails its ability to slow down the processes by which uric acid is produced in the body (Rincon & Arroyo, 2010). In other terms, if the levels of uric acid is measured and found to have dropped after using allopurinol, it implies that the drug has been quite effective in interrupting the processes by which uric acid is produced in the body (Taylor et al., 2012). A high level of uric acid on the other hand is associated with conditions such as gout, kidney stones and other myriad health problems. Among the causes of elevated levels of uric acid are over-eating specific kinds of foods, taking certain classes of medicines and undergoing cancer treatment (Stamp, 2012). Several studies have been conducted to establish the relationship between uric acid on one hand blood pressure, left ventricular (LV) mass, Angina, brain blood flow and MI on the other. Allopurinol Studies Several studies have been conducted on allopurinol and its uses and effects. For instance, Daniel Feig, Richard J. Johnson and Beth Soletsky studied the effects of allopurinol on blood pressure, hence hypertension and published their findings in 2013. Specifically, the randomized-trial study was about the effect of Allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension between 2004 and 2007. The core objective of the study was to establish if reducing uric acid levels has the effect of lowering blood pressure (BP) in hyperuricemic adolescents just diagnosed as hypertensive (Feig et al., 2008). The study was a randomized, double-blind, placebo-controlled and crossover trial involving thirty adolescent participants aged between 11 and 17 years. Importantly, the participants were newly diagnosed as hypertensive and never treated for stage 1 essential hypertension and serum uric acid levels. That is, those with stage 2 hypertension, renal, cardiovascular, gastrointestinal tract, hepatic or endocrine disease were excluded form the treatment to which the participants were placed. The treatment was a randomized 200 mg of allopurinol, twice daily for 4 weeks, placebo, twice daily for 4 weeks, with a 2-week washout period between treatments (Feig et al., 2008). Changes in casual and ambulatory blood pressure were then measured. From the study’s findings, it was concluded that the treatment with allopurinol resulted in lowered blood pressure, making it a new and potential therapeutic approach to dealing with hypertension (Feig et al., 2008). Nonetheless, it is not an entirely developed therapeutic strategy and has its potential adverse effects. In addition, there is need for confirmation of these results using larger clinical trials. Researchers Struthers, A. D., Kao, M. P., Houton, J. G., Nadir M. A., and Gandy, S. J. also carried out a study on the effects of Allopurinol on left ventricular (LV) mass. In a randomised, double-blind, placebo-controlled, parallel-group study of patients of chronic kidney disease and left ventricular hypertrophy, 67 participants were subjected to allopurinol at 300 mg/d or placebo for nine months (Struthers et al., 2011). The left ventricular mass index (LVMI) was then measured with cardiac magnetic resonance imaging (MRI), the endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery, and the central arterial stiffness evaluated by pulse-wave analysis in the 53 patients that completed the study. It was established that Allopurinol considerably lowered the LVH (P=0.036) and improved both the endothelial function (P=0.009) and the central augmentation index (P=0.015) (Struthers et al., 2011). The study thus showed that Allopurinol regresses left ventricular mass besides improving endothelial functions in CKD patients. Dr. Aswan Noman of the University of Dundee, Scotland also studied Allopurinol use on Angina in a six-week long study in June 2010. The study sought to explore the anti-ischemic properties of the drug and its use in treating Angina. The study showed that allopurinol enabled angina sufferers to exercise for 25% longer before they complained of chest pain or had ST depression on ECG, compared with placebo. According to a senior researcher in the group, Allopurinol prolonged the distance that angina patients can walk before getting chest pain or showing any signs of oxygen deprivation. Thus, the drug was declared at least as effective as any other anti-angina drugs. References Ansari, A. R., Patel, N., and Sanderson, J. (2011) Low Dose Azathioprine or 6-Mercaptopurine in Combination with Allopurinol Can Bypass Many Adverse Drug Reactions in Patients with Inflammatory Bowel Disease. Aliment Pharmacological Therapy, 31(6): 640. Ceconi, C, Boraso A, Cargnoni A, Ferrari R. 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