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AusPharm CE Lifestyle factors… Published 15/12/2011 Lifestyle factors and impact on medicines: You are what you eat! Learning objectives: • Provide practical evidence-based information on the impact of foods on medications and health outcomes • Advise patients on diets proven to reduce cardiovascular morbidity and mortality • Assess dietary modifications for prevention of gout • Counsel patients on calcium and vitamin D supplements for optimal bone mass and in conjunction with anti-osteoporotic medicines • Counsel patients with or without hypertension on the benefits of dietary salt reduction The 2010 Competency Standards addressed by this activity include (but may not be limited to): 4.2.2, 6.1.2, 6.2.1, 6.2.2, 7.1.1, 7.1.2, 7.1.3, 7.1.4. Introduction Lifestyle interventions are an important adjunct or precursor to pharmacotherapy. Debate continues on the value of vitamin and mineral supplements, with several commonly used dietary vitamin and mineral supplements shown this year to be associated with increased total mortality risk.1 The National Preventative Health Taskforce has focused on the three key areas to tackle the burden of chronic disease obesity, tobacco and alcohol.2 One third of all cancers are caused by 4 common lifestyle factors — tobacco, diet, alcohol, and obesity.3 Lifestyle interventions reduce cardiovascular risk and risk of diabetes mellitus, and improve quality of life.4Dietary modifications for cardiovascular risk reduction, includingplant-based diets, have been shown to improve lipidstatus, obesity, hypertension, systemic inflammation, insulin sensitivity, thrombosis, and cardiovascular event risk.5On a global scale, the 52nation INTERHEART study found that diets high in fruits and vegetables were associated with substantially lower riskfor acute myocardial infarction compared with the Western diethigh in meat, eggs, and fried foods.6 Whilst there are many myths around the preventive benefits of food and specific diets, pharmacists have a responsibility to understand and advise patients on evidence-based interventionsfordiet and medications. This may be drug-food and alcohol interactions, or dietary prevention and management of chronic diseases. Some highlights of evidence published this year include: • People who eat baked or grilled fish once a week are up to five times less likely to develop cognitive decline;7 • Higher sodium-potassiumratio is associated with significantly increased risk of cardiovascular diseaseand all-cause mortality;8 AusPharm CE Lifestyle factors… Published 15/12/2011 • Dietary fiber may reduce the risk of deathfrom cardiovascular, infectious, and respiratory diseases;9 and • Nut consumption improves blood lipid levelsin a dose-related manner, particularly among subjects with higherLDL-C or with lower body mass index (BMI);10 and • Lifestyle modifications can prevent type 2diabetes among overweight people with impaired fasting glucoselevels.11 In addition, there has been further evidence against the use of many drugs for primary prevention. For example, analysis of the JUPITER (Justificationfor the Use of Statins in Primary Prevention) study does notsupport the use of statins for primary prevention.12 Lifestyle modification Lifestyle modification is the first step in the management of many chronic diseases such as diabetes mellitus, heart failure, hypertension, coronary heart disease and dyslipidaemia. Lifestyle changes and, especially dietary interventions are cost-effective means for the prevention of cardiovascular disease.13 In 2003 the concept of the Polypill was first proposed containing six pharmacological components (statin, ACE inhibitor, beta-blocker, thiazide diuretic, folic acid aspirin) that by modifying different risk factors ofcardiovascular disease multiplicatively might reducethe levels of cardiovascular disease in the populationby more than 80%.14 The 2004 Christmas edition of the BMJ then suggested a more natural, safer, and probably tastierstrategy than the Polypill.15 The evidence based recipe included wine, fish, dark chocolate, fruits,vegetables, garlic, and almonds.Combining the ingredients of the Polymeal would reduce cardiovascular disease events by 76%. Ingredient % reduction in risk of CVD Wine (150mL/day) 32% Fish (114g four times/week) 14% Dark chocolate (100g/day) 21% Fruit and vegetables (400g/day) 21% Garlic (2.7g/day) 25% Almonds (68g/day) 12.5% Combined effect 76% Table 1 - Cardiovascular disease risk benefits of Polymeal Mediterranean diet The Mediterranean diet emphasizes fruits, vegetables, legumes, and complex carbohydrates; and includes a moderate consumption of fish, olive oil, and red wine; and minimises simple carbohydrates. Data AusPharm CE Lifestyle factors… Published 15/12/2011 showing that Mediterranean diet is healthy first originated from the Seven Countries Study, published 25 years ago.16 Adherence to this diet has been linked to lower chances of dying from a heart attack, stroke or other vascular events.17 In a recent meta-analysis of 530,000 participants from 50 studies, greater adherence to the Mediterranean diet was associated with a lower risk for metabolic syndrome.18Adherence to the Mediterranean diet has an additional protective effect on the development of an acute coronary syndrome (ACS) or ischemic stroke.19 Gout and diet The ageing population, increasing obesity and lifestyle changes are likely to make gout more common in the general population. The peak age of onset in males is 40 to 60 years, whereas it is somewhat later in females. The prevalence increases with age and is higher among men than among women, with a ratio of 3 or 4 to 1 overall. However, this sex disparity decreases at older ages, at least in part because of declining levels of oestrogen, which has uricosuric effectsin women. Optimal management of gout is important as hyperuricaemia is associated with increased CV risk. The increased availability of purines from any of either exogenous, dietaryorendogenous sources, or tissues leads to excess urate (hyperuricaemia), either by overproduction or under excretion.Obesity associated with increased production and reduced excretion of urate.20 Restriction of exogenous purine intake through dietary modifications or the use of xanthine oxidase inhibitors (e.g. allopurinol) to block uric acid synthesis from endogenous purine metabolism can reduce the amount of urate that contributes to the total-body urate pool. Purine-rich foods include: • meat (beef, pork, or lamb; processed meat, including sausage, salami, andbologna; bacon; hot dogs; hamburgers; poultry,including chicken and turkey; chicken liver; andbeef liver); • seafood (tuna; dark fish; other fish; and prawns, lobster, or scallops); and • purine-rich vegetables(peas, beans, lentils, spinach, mushrooms, oatmeal,and cauliflower) Moderate intake of purine-rich vegetables or protein is not associatedwith an increased risk of gout.21 Drinking 4 or more cups of coffee a day reduces the risk of gout for men and women.22,23 Epidemiological data suggests that a diet rich in low fat dairy productsdecreases serum urate concentration; whereas diets containing meat, fish, alcohol (particularly beer and spirits) increase serum urate concentration.20,21 For example, one additional portion of low fat dairy product can reduce the risk of the first attack of gout by 21% and one additional serve of alcohol per day increases the risk by nearly 50%.20 No controlled trials of the effect of lifestyle change onthe incidence of recurrent gout have been carried out. Adherence to traditional low purine diets is poor andthey are not usually recommended. Patients with gout who are obese (body mass index > 28), or who haveone or more alcoholic drinks per day, should be advised to lose weight or decrease their alcohol consumption, or both to prevent recurrent gout.20 Data from the Health Professionals Study, a large ongoing longitudinal study involving 51,529 men aged 40 to AusPharm CE Lifestyle factors… Published 15/12/2011 75 years in 1986, however, suggest that thefollowing relatively simple changes may have animpact on incidence of recurrent gout: • Lose weight • Eat one less portion of meat or fish a day • Drink wine instead of beer • Drink a glass of skimmed milk a day Salt One of the most widely debated topics in 2011 was whether a reduction in dietary salt impacts on cardiovascular mortality and all-cause mortality. In aCochrane reviewthe relative risks for all-cause mortality and cardiovascular mortality for both normotensives and hypertensives were only mildly to moderately reduced, and not to a statistically significant degree.24 In patients with heart failure, salt restriction actually significantly increased all-cause deaths.24 A comment in The Lancet suggested that the “Cochrane reviewand the accompanying press release reflect poorly on the reputation of The Cochrane Library and the authors.25 Whilst currently available data from RCTs is not sufficient to demonstrate statistical significance for reductions in mortality or CV morbidity, the Cochrane review should not be interpreted as ruling out a clinically significant benefit on long term outcomes and should not deter people from following public health dietary advice regarding salt intake. In Australia, the estimated average consumption of salt is 10 grams per day for men and 7 grams per day for women.26 Reducing average salt intake by 3 grams per day would be expected to lead to a 22% reduction in deaths from strokes and a 16% reduction in deaths from coronary heart disease.26 Raised blood pressure (BP) is one of themost common and preventable riskfactors for cardiovascular disease. Many trials have shown that a diet rich in fruits, vegetables, low-fat dairy products, small amounts of red meat and sugar-containing beverages, decreased amounts of total and saturated fat and cholesterol lowers blood pressure (BP). The DASH diet has been shown to lower BP at high, intermediate and low levels of sodium intake.27 A reduction in sodium intake to less than 100mmol/day (2.3g Na or 5.8gNaCl) in addition to the DASH diet lowers systolic blood pressure (SBP) by 7.1 mmHg in patients without hypertension and 11.5 mmHg in patients with hypertension.27 The combined effects on BP of low sodium intake and DASH diet are greater than the effects of either alone.27 Australian data has shown reducing sodium intake by 100 mmol/day is associated with 2.3 mm Hg reduction in SBP.28 Urinary potassium, reflectingdietary intake, has been shown to have anindependent inverse association with BP, meaning that lower potassium intakes increases risk for elevated BP and hypertension. High urinary sodium-to-potassium ratio increases CV risk and mortality, independent of effects on BP.28 Current best available evidence suggests that salt reduction is beneficial in people with or without hypertension and may be associated with reduction in cardiovascular disease, stroke and all-cause mortality.However, no randomised controlled trials have studied the effect of reducing salt intake of populations on cardiovascular disease. The health benefits of a Mediterranean-style diet may be compromised by its high salt content.29 AusPharm CE Lifestyle factors… Published 15/12/2011 Significant reductions of salt intake from diet are difficult unless processed food salt is reduced or people have diet high in fruit and vegetables and little processed food. Bone health The evidence for adequate calcium and vitamin D by diet, sun exposure or supplements continued to grow in 2011. Adequate calcium and vitamin D intake, and exercise are important for reaching and maintaining optimal peak bone mass. Average dietary intake of calcium in Australia is below recommended levels and there is strong evidence of vitamin D insufficiency and deficiency, especially in residential care and high risk persons.30 Calcium supplements are only needed when dietary intake is insufficient and usually only in low doses due to concerns for increased risk of myocardial infarction.31,32 Key messages for healthy nutrition for bone health include:33 • An adequate calcium intake (1000mg dietary intake of calcium a day is recommended for all adults and 1300mgis recommended for women aged over 50 years and men aged over 70 years), should be ensured at all stages of life; • Dairy foods, calcium-set tofu, some green vegetables, nuts, and small canned fish with soft bones provide the most readilyavailable sources of dietary calcium; • An adequate supply of vitamin D is required, through sufficient exposure to the sun, through diet, or through supplements; • Adequate protein intake is necessary. Protein malnutrition is an important risk factor for hip fracture, and can also contribute to poor recovery in patients who have had a fracture; • Excessive alcohol consumption should be avoided; • Being underweight is a strong risk factor for osteoporosis (body mass index < 18.5 kg/m2); • If on a weight-reducing diet, ensure adequate intakes of calcium and vitamin D, and avoid 'fad' diets in which whole food groups are severely restricted or eliminated; • Include plenty of fruits and vegetables in the diet, as these are beneficial for both bone and overall health; • Magnesium is involved in calcium homeostasis, and in the formation of hydroxyapatite (bone mineral). However, there are no studies to date which demonstratethat magnesium supplementation is useful either inpreventing bone loss or reducing fracture risk; • Concerns have been raised that consumption of carbonatedsoft drinks, notably cola drinks, may adversely affectbone health. Although a few observational studies haveshown an association between high carbonated beverageconsumption and either decreased BMD or increasedfracture rates in teenagers, there is no convincing evidencethat these drinks adversely affect bone health; and • In addition to a nutritious diet, other complementary lifestyle practices such as taking regular exercise and avoiding smoking help to maintain bone density. AusPharm CE Lifestyle factors… Published 15/12/2011 Conclusions Lifestyle modification is first-line therapy for many chronic conditions and should be considered in conjunction with pharmacotherapy. Pharmacists should provide support and information to consumers in conjunction with prescription and over-the-counter medicines. Debbie Rigby 12 December 2011 MCQs 1. Which combinations of foods have been shown to reduce cardiovascular disease? a. Low fat dairy foods, beer, garlic b. Purine-rich vegetables, garlic, almonds c. Wine, dark chocolate, almonds d. Coffee, fish, red meat e. Fish, red wine, eggs 2. Which of the following lifestyle modifications are most likely to reduce the risk of recurrent gout? a. Drinking beer instead of wine or spirits b. Reduction in body weight and alcohol consumption c. Decrease in low fat dairy products d. Decrease in purine-rich vegetables e. Reducing coffee intake 3. Which of the following statements regarding gout is correct? a. The incidence of gout in women decreases after menopause b. Obesity is associated with increased production and increased excretion of uric acid c. Xanthineoxidase inhibitors block uric acid synthesis from exogenous purine intake d. Hypouricaemiais associated with increased cardiovascular risk e. Gout is more common in middle-aged males than pre-menopausal women 4. Which of the following statements regarding dietary salt is not supported by current evidence? a. Lower sodium excretion is associated with a higher risk for cardiovascular disease mortality b. Reducing sodium intake is associated with a reduction in systolic blood pressure AusPharm CE Lifestyle factors… Published 15/12/2011 c. Higher potassium intake increases risk for elevated BP and hypertension d. Combined effects on BP of low sodium intake and DASH diet are greater than the effects of either alone e. Epidemiological studies suggest lower salt intake results in a reduction in stroke and heart attacks 5. Which of the following best describes the calcium and vitamin D daily requirements for a 75-yearold postmenopausal woman consuming a non-vegan diet and receiving inadequate daily sunlight? a. 1300 mg of calcium and 800 IU of vitamin D b. 1000mg of calcium and 400IU of vitamin D c. 600mg of calcium and 200IU of vitamin D d. 1200mg of calcium and 400IU of vitamin D e. 2000mg of calcium and 200IU of vitamin D 1 Mursu J, Robien K, HarnackLJ, Park K, Jacobs Jr DR.Dietary Supplements and Mortality Rate in Older Women: The Iowa Women's Health Study.Arch Intern Med 2011;171(18):1625-1633. 2 National Preventative Health Taskforce.Australia: the healthiest country by 2020 A discussion paper. Available at: http://www.preventativehealth.org.au/ 3 Parkin M, Boyd L, Darby SC, Mesher D, Sasieni P, Walker LC, et al.The Fraction of Cancer Attributable to Lifestyle and Environmental Factors in the UK in 2010.Br J Cancer 2011;105(Suppl 2):Si-S81. 4 Eriksson MK,Hagberg L,Lindholm L, Malmgren-Olsson E,Österlind J,Eliasson M. Quality of Life and Cost-effectiveness of a 3-Year Trial of Lifestyle Intervention in Primary Health Care. Arch Intern Med 2010;170:1470-1479. 5 ZarragaIGE, Schwarz ER. Impact of dietary patterns and interventions on cardiovascular health.Circulation 2006;114(9):961-973. 6 Iqbal R, Anand S, Ounpuu S, Islam S, Zhang X, Rangarajan S,et al, INTERHEART Study Investigators. Dietary patterns and the risk of acute myocardial infarction in 52 countries: results of the INTERHEART study. Circulation 2008;118(19):1929-1937. 7 Radiological Society of North America (RSNA) 97th Scientific Assembly and Annual Meeting: Abstract SST11-04. Presented November 29, 2011. 8 Yang Q, Liu T, KuklinaEV, FlandersWD, Hong Y, Gillespie C, et al. Sodium and Potassium Intake and Mortality Among US AdultsProspective Data From the Third National Health and Nutrition Examination Survey.Arch Intern Med 2011;171(13):1183-1191. 9 Park Y, Subar AF, Hollenbeck A, Schatzkin A.Dietary Fiber Intake and Mortality in the NIH-AARP Diet and Health Study. Arch Intern Med 2011;171(12):1061-1068. 10 Sabaté J, Oda K, Emilio Ros E. Nut Consumption and Blood Lipid Levels:A Pooled Analysis of 25 Intervention Trials. Arch Intern Med 2010;170(9):821-827. 11 Saito T, Watanabe M, Nishida J, Izumi T, Omura M, Takagi T, et al. Lifestyle Modification and Prevention of Type 2 Diabetes in Overweight Japanese With Impaired Fasting Glucose Levels:A Randomized Controlled Trial. Arch Intern Med 2011;171(15):1352-1360. 12 de Lorgeril M, Salen P, Abramson J, Dodin S, Hamazaki T, Kostucki W, et al. Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER controversy: a critical reappraisal. Arch Intern Med 2010;170(12):1032-1036. 13 WHO. World Health Organization, Cardiovascular diseases (CVDs), Fact Sheet No. 317. Available at: http://www.who.int/mediacentre/factsheets/fs317/en/index.html [accessed 11 December 2011]. 14 Wald NJ, Law MR. A strategy to reduce cardiovascular disease by morethan 80%. BMJ2003;326:1419-23. 15 Franco OH, Bonneux L, de Laet C, Peeters A, SteyerbergEW,Mackenbach JP. The Polymeal: a more natural, safer, and probably tastier(than the Polypill) strategy to reduce cardiovasculardisease by more than 75%. BMJ2004;329:1147–50. 16 Keys A, Menotti A, KarvonenMJ, Aravanis C, Blackburn H, Buzina R, et al.The diet and 15-year death rate in the seven countries study.Am J Epidemiol 1986;124:903–915. AusPharm CE 17 Lifestyle factors… Published 15/12/2011 Gardener H,Wright CB, Gu Y, Demmer RT, Boden-Albala B, ElkindMSV, et al. Mediterranean-style diet and risk of ischemic stroke, myocardial infarction, and vascular death: the Northern Manhattan Study. Am J ClinNutr2011; 94(6): 1458-1464. 18 Kastorini CM, Milionis HJ, Esposito K, Giugliano D, GoudevenosJA, Panagiotakos DB. The effect of Mediterranean diet on metabolic syndrome and its components a meta-analysis of 50 studies and 534,906 individuals. J Am CollCardiol 2011;57:1299–1313. 19 Kastorini CM, MilionisHJ, Ioannidi A, Kalantzi K, Nikolaou V, VemmosKN, et al. Adherence to the Mediterranean Diet in Relation to Acute Coronary Syndrome or Stroke Nonfatal Events. Am Heart J2011;162(4):717-724. 20 Underwood M. Diagnosis and management of gout.BMJ2006;332;1315-1319. 21 Choi HK, Atkinson K, KarlsonEW, Willett W, Curhan G. Purine-richfoods, dairy and protein intake, and the risk of gout in men. N Engl J Med2004;350:1093-103. 22 Choi HK, Curhan G.Coffee consumption and risk of incident gout in women: the Nurses' Health Study.Am J Clin Nutr 2010;92:922-7. 23 HK Choi,Willett W, Curhan G.. Coffee consumption and risk of incident gout in men.Arthritis & Rheumatism 2007;56:2049-2055. 24 Taylor RS, Ashton KE, Moxham T, Hooper L, Ebrahim S. Reduced dietary salt for the prevention of cardiovascular disease: a meta-analysis of randomized controlled trials (Cochrane Review). Am J Hypertens 2011;8:843-853. 25 He FJ, MacGregor GA. Salt reduction lowers cardiovascular risk: meta-analysis of outcome trials. Lancet 2011;378:380-382. 26 Australian Division of World Action on Salt & Health. Available at: www.awash.org.au 27 Sacks FM, Svetkey LP, VollmerWM, AppelLJ, Bray GA, Harsha D, et al. Effects on Blood Pressure of Reduced Dietary Sodium and the Dietary Approaches to Stop Hypertension (DASH) Diet. N Engl J Med 2001; 344:3-10. 28 Huggins CE, O’Reilly S, Brinkman M, Hodge A, Giles GG, English Dr, et al. Relationship of urinary sodium and sodium-to-potassium ratio toblood pressure in older adults in Australia. Med J Aust2011; 195: 128–132. 29 Magriplis E,Farajian P,Pounis GD,Risvas G,Panagiotakos DB, Zampelas A. High sodium intake of children through ‘hidden’ food sources and its association with the Mediterranean diet: the GRECO study. J Hypertens 29(6):10691076. 30 Osteoporosis Australia. Calcium, vitamin D and osteoporosis - a guide for GPs. Sydney: Osteoporosis Australia, 2008. 31 BollandMJ, Avenell A, Baron JA, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ2010;341:c3691. 32 BollandMJ, Grey A, Avenell A, et al. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis. BMJ2011;342:d2040. 33 Invest in your bonesBone Appétit - The role of food and nutrition in buildingand maintaining strong bones. International Osteoporosis Foundation; 2006. Available at http://www.iofbonehealth.org/publications/boneappetit.html