MEDICAL PRACTICE CME
2016 Consensus statement on prevention of atherosclerotic cardiovascular disease in the Hong Kong population
Bernard MY Cheung, MB BChir (Cantab), PhD (Cantab)1; CH Cheng, MB, BS2; CP Lau, MB, BS, MD3; Chris KY Wong, MB, ChB (Glasg)4; Ronald CW Ma, MB BChir (Cantab)5; Daniel WS Chu, MB, BS (NSW)2; Duncan HK Ho, MB, BS4; Kathy LF Lee, MB, BS2; HF Tse, MD, PhD1; Alexander SP Wong, MB, BS2; Bryan PY Yan, MB, BS5; Victor WT Yan, MB, BS2
1 Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong
2 Private practice, Hong Kong
3 Institute of Cardiovascular Science and Medicine, The University of Hong Kong, Pokfulam, Hong Kong
4 Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong
5 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Corresponding author: Prof Bernard MY Cheung (email@example.com)
Introduction: In Hong Kong, the prevalence of atherosclerotic cardiovascular disease has increased markedly over the past few decades, and further increases are expected. In 2008, the Hong Kong Cardiovascular Task Force released a consensus statement on preventing cardiovascular disease in the Hong Kong population. The present article provides an update on these recommendations.
Participants: A multidisciplinary group of clinicians comprising the Hong Kong Cardiovascular Task Force—10 cardiologists, an endocrinologist, and a family physician—met in September 2014 and June 2015 in Hong Kong.
Evidence: Guidelines from the American College of Cardiology/American Heart Association, the European Society of Hypertension/European Society of Cardiology, and the Eighth Joint National Committee for the Management of High Blood Pressure were reviewed.
Consensus Process: Group members reviewed the 2008 Consensus Statement and relevant international guidelines. At the meetings, each topical recommendation of the 2008 Statement was assessed against the pooled recommendations on that topic from the international guidelines. A final recommendation on each topic was generated by consensus after discussion.
Conclusions: It is recommended that a formal risk scoring system should be used for risk assessment of all adults aged 40 years or older who have at least one cardiovascular risk factor. Individuals can be classified as having a low, moderate, or high risk of developing atherosclerotic cardiovascular disease, and appropriate interventions selected accordingly. Recommended lifestyle modifications include adopting a healthy eating pattern; maintaining a low body mass index; quitting smoking; and undertaking regular, moderate-intensity physical activity. Pharmacological interventions should be selected as appropriate after lifestyle modification.
Atherosclerotic cardiovascular disease (ASCVD), which includes coronary heart disease (CHD), peripheral vascular disease and stroke, is currently one of the most common causes of morbidity and mortality worldwide.1 Unfortunately the prevalence of ASCVD is expected to increase further over the next few decades due to a number of factors including an ageing population and increasing industrialisation. The latter is associated with increased exposure to known ASCVD risk factors such as smoking, low levels of physical activity, and poor dietary habits such as reduced consumption of fruit and vegetables and increased fat and salt intake.2
In Hong Kong, the prevalence of ASCVD risk factors has increased markedly over the past few decades. For example, the 2005-2008 Hong Kong Cardiovascular Risk Factor Prevalence Study-3 (CRISPS-3) reported an 8.6% increase in the prevalence of abdominal obesity (waist circumference ≥90 cm in men and ≥80 cm in women) and a 21.5% increase in the prevalence of hypertension among a cohort of 1803 subjects recruited from CRISPS-1, the first such survey conducted between 1995 and 1996.3 Of the 551 participants of the Hong Kong Cardiovascular Task Force Risk Management Programme, 65.4% had hypertension, 63.7% dyslipidaemia, and 33.3% diabetes at baseline (BMY Cheung, unpublished data).
Global efforts are underway to promote ASCVD prevention and reduce the risk of major ASCVD events. These efforts have yielded benefits—between 1990 and 2013, a substantial reduction in cardiovascular mortality was seen in central Europe (5.2%) and western Europe (12.8%), attributed primarily to birth cohorts’ decreased exposure to tobacco smoking, improvements in diet, improved treatment of cardiometabolic risk factors, and improved treatment of CVD.4
A multidisciplinary group of clinicians comprising the Hong Kong Cardiovascular Task Force—10 cardiologists, an endocrinologist, and a family physician—met in September 2014 and June 2015 in Hong Kong with the aim of updating the first Consensus Statement on Preventing Cardiovascular Disease in the Hong Kong Population published in 2008.5 Prior to the consensus meetings, group members reviewed the 2008 Consensus Statement and relevant guidelines from the American College of Cardiology/American Heart Association, the European Society of Hypertension/European Society of Cardiology, and the Eighth Joint National Committee for the Management of High Blood Pressure, among others.5 6 7 8 9 At the meetings, each topical recommendation of the 2008 Statement was assessed against the pooled recommendations on that topic from the international guidelines reviewed. A final recommendation on each topic was generated by consensus after discussion.
The recommendations included in this consensus statement constitute the consensus opinion of the members of the Hong Kong Cardiovascular Task Force regarding the most appropriate interventions for the Hong Kong population.
Total cardiovascular risk
Total ASCVD risk is based on the complex interactions of a number of different risk factors that together have a multiplicative effect. That is, the risk of ASCVD is amplified to a greater extent by the interaction of multiple risk factors than would be expected due to the cumulative effect of each risk factor alone.7 9 The present standard of practice for the primary prevention of ASCVD is to determine a patient’s total ASCVD risk using a formal risk scoring algorithm.1 7 9
Who to assess?
In Hong Kong, it is recommended that ASCVD prevention efforts should be focused on adults aged 40 years or older who have at least one ASCVD risk factor.1 9 The total ASCVD risk should be formally calculated for such individuals, and they should receive ASCVD prevention advice and/or treatment according to their determined level of risk (high, moderate, or low).1 9 High-risk patients will benefit most from treatment and include:
- patients with overt ASCVD (CHD, previous myocardial infarction, previous stroke, or peripheral vascular disease) or those who are symptomatic (eg have experience with angina)
- patients with diabetes mellitus
- patients with one major ASCVD risk factor (eg moderate-to-severe hypertension, severely elevated lipid levels)9
These patients automatically meet the threshold for intensive risk factor treatment and need not undergo formal risk scoring.1 9
How to assess?
It is important to note that the current recommendations do not espouse a preference for any particular method of risk projection, but recommend that formal ASCVD risk scoring should be performed for all potentially at-risk patients.
A patient’s 10-year (total) risk for ASCVD may be calculated using a variety of methods. The most recently published algorithm uses the American Pooled Cohort Risk Assessment Equations that are sex- and race-specific estimates for African-American and White men and women aged 40 to 79 years. They utilise age, total and high-density lipoprotein (HDL) cholesterol, systolic blood pressure (BP), diabetes, and current smoking status to calculate the total ASCVD risk.1 The European Systematic Coronary Risk Evaluation (SCORE) system is another well-validated system that uses sex, age, systolic BP, total cholesterol, and current smoking status to predict the risk of fatal cardiovascular events.7 Another risk assessment system, QRISK2, includes the risk factor of ‘self-assigned ethnicity’ (including Chinese) in the computation10 11; however, the model was validated for Chinese immigrants to the United Kingdom and, thus, its applicability to the local Chinese population is unknown.
The calculated risk score is used to stratify patients into low-, moderate-, and high-risk categories (Fig). When interpreting these scores, the clinician should bear in mind that they were developed and validated for western populations. In addition, it must be remembered that any calculated ASCVD score is simply an indicator of total cardiovascular risk.9 Although it can guide patient treatment, it cannot be a substitute for individualised patient evaluation and management. The clinician is advised to take all factors into account and to treat the patient individually rather than treat the risk score.
There is robust scientific evidence that the development of ASCVD in at-risk patients may be slowed and/or prevented by lifestyle modification, reduction of metabolic risk factors, and pharmacological treatment.7 9 10 11 12 13 14 15 16 17 18 19 Listed below are the major modifiable risk factors for ASCVD. The treatment goal is stated for each risk factor, along with general recommendations on how this goal may be achieved. Existing hypertension,7 8 dyslipidaemia,1 6 and diabetes20 21 22 treatment guidelines incorporate the latest evidence on how to treat these conditions and to what appropriate targets. The clinician is referred to these guidelines for further guidance.
Treatment goal: an overall healthy eating pattern
All patients at increased risk of ASCVD should be given advice and specific recommendations for eating a healthy diet. Advice should include9:
- matching energy intake with energy needs;
- eating a variety of fruits, vegetables, grains, low- or non-fat dairy products, legumes, fish, poultry, and lean meats;
- reducing saturated and trans fats to <10% of total daily caloric intake, through replacement with polyunsaturated fats (vegetables, nuts, seeds, and seafood);
- reducing cholesterol intake;
- reducing salt intake; and
- limiting alcohol intake to no more than two drinks per day for men and one drink per day for women.
Treatment goal: a minimum of 30 minutes of moderate-intensity physical activity at least 5 times a week, or a minimum of 15 minutes of vigorous-intensity physical activity at least 5 times a week9
- ‘Moderate intensity’ is defined as exercising at 64% to 76% of maximum heart rate (ie 220 minus age); activities include brisk walking, slow cycling, vacuuming, gardening, golf, tennis (doubles), ballroom dancing, and water aerobics.9 ‘Vigorous intensity’ is defined as exercising at 77% to 93% of maximum heart rate; activities include race walking, jogging or running, bicycling, heavy gardening, swimming laps, and tennis (singles).9
- The practice of the popular Chinese soft martial art tai chi may also be beneficial for individuals at risk of ASCVD. A systematic review has shown that tai chi has physiological and psychosocial benefits, and it also appears to be safe and effective in promoting flexibility, balance control, and cardiovascular fitness in older patients with chronic conditions.23
- All patients should consult their doctor prior to initiating graded exercise programmes.
Treatment goal: maintenance of normal body mass index and waist circumference
- Normal body mass index is 18.5-22.9 kg/m2 for Asians,24 and normal waist circumference is <90 cm (35.4 inches) for men and <80 cm (31.5 inches) for women.25
- Patients who are overweight or obese should strive to achieve normal body weight by restricting caloric intake and increasing physical activity.
- Drug therapy or surgical interventions may be a helpful adjunct for the treatment of severe obesity in some patients.
Treatment goal: complete smoking cessation
- Assess the patient’s tobacco use and strongly urge the patient to stop smoking.
- Determine the patient’s degree of nicotine addiction and his/her readiness to quit smoking. For patients identified as willing to quit, a plan should be developed that may involve pharmacotherapy, counselling, cessation support mechanisms (eg follow-up calls and visits), and referral to specialised programmes, if available.20 26
Risk factor reduction goal: blood pressure of <140/90 mm Hg for the general population aged <60 years, including patients with previous stroke or transient ischaemic attack; patients with coronary heart disease; and patients with chronic kidney disease. For patients with diabetes, a target blood pressure of <140/85 mm Hg is recommended. For the general population aged ≥60 years, a target blood pressure of <150/90 mm Hg is recommended7 8 9
- Patients with a systolic BP of ≥130 mm Hg or diastolic BP of ≥80 mm Hg should be given advice and specific recommendations on reducing lifestyle risk factors.
- Patients who do not meet their primary goals as defined above should be given drug therapy tailored to their circumstances.
- The choice of first-line therapy is the prerogative of the attending physician. Suitable antihypertensive drugs include calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs), either alone or in combination (Tables 1 and 2).7 9 Diuretics (chlorthalidone and indapamide) and β-blockers may also be used, but their long-term use is associated with increased risk of new-onset diabetes30 31; of note, there is no evidence that hydrochlorothiazide—one of the most commonly prescribed antihypertensives—in its usual dose of 12.5 to 25 mg daily reduces myocardial infarction, stroke, or death.32
- When target BP cannot be achieved with monotherapy or with a two-drug combination, doses can be increased; if target BP cannot be achieved by a two-drug combination at full doses, switching to another two-drug combination, or adding a third drug, may be considered.7 8 9 In patients with uncontrolled BP despite treatment with maximally tolerated doses of three antihypertensive medications, addition of the aldosterone antagonist spironolactone has achieved larger reductions in systolic BP than addition of the β-blocker bisoprolol, the alpha-adrenergic blocker doxazosin, or placebo.33
Risk factor reduction goal: low-density lipoprotein cholesterol level of <3 mmol/L. For patients with overt atherosclerotic cardiovascular disease, the target level should be <1.8 mmol/L9
- Low-density lipoprotein cholesterol (LDL-C) reduction decreases cardiovascular events.9
- Recommended target LDL-C level for patients stratified by ASCVD risk is as follows:
- Very high ASCVD risk: LDL-C <1.8 mmol/L, or a ≥50% reduction if the baseline is between 1.8 and 3.5 mmol/L (Table 3)
- High ASCVD risk: LDL-C <2.6 mmol/L, or a ≥50% reduction if the baseline is between 2.6 and 5.1 mmol/L
- Low-to-moderate ASCVD risk: LDL-C <3.0 mmol/L9
- Patients at low and moderate risk should be given advice and specific recommendations on lowering LDL-C through dietary adjustments, increased physical activity, and weight reduction. If the target is not met after 6 months, they should be given a lipid-lowering agent (Tables 4 and 5).35
- Patients at high risk should immediately be started on lipid-lowering therapy with a high-intensity statin (Tables 4 and 5).35 Importantly, however, pharmacokinetic studies have shown that Chinese patients achieve a higher plasma concentration of statin compared with Caucasians, and this may be associated with an increased risk of adverse effects.36 Consequently, the maximum approved doses of the statins available in Asia are around half the maximum approved doses in the United States.37 The clinician should, therefore, exercise caution when prescribing high-intensity statin therapy.
- Inhibitors of proprotein convertase subtilisin/kexin type 9 have recently been approved for use in the United Kingdom and the United States as an adjunct to diet and maximally tolerated statin therapy for the treatment of individuals with primary hypercholesterolaemia or mixed dyslipidaemia, or those with clinical ASCVD who require additional lowering of LDL-C.38 39 Clinical trials have demonstrated decreases in LDL-C by up to 60% in subjects receiving these agents38; definitive evidence of reduced cardiovascular event rates associated with their use may be provided by ongoing trials.
- All diabetic patients are considered high risk for the development of ASCVD9 21 and should receive appropriate management upon diagnosis. This includes guidance on diet modification and increased physical activity in conjunction with pharmacotherapy.20 21 22 Early initiation of medication is recommended to avoid any delay in treatment. Insulin is administered if treatment goals are not achieved with oral therapy.20 21 22 Treatment goal for glycaemia should be tailored according to the patient profile in order to avoid hypoglycaemia in those with co-morbidities or in elderly patients.22 40
- In diabetic patients, treat other ASCVD risk factors more aggressively,22 including hypertension. Nevertheless, present evidence suggests that a BP target of <140/85 mm Hg is appropriate in patients with diabetes, with a lower BP (systolic BP of <130 mm Hg) as an option in patients with hypertension and nephropathy. It should be noted that lower BP may be associated with increased risk of adverse events, especially in older patients or those with a long duration of diabetes, and the risk and benefit of intensive BP lowering needs to be considered individually according to the patient profile.22
The gap between evidence and practice
Although clear, evidence-based guidelines and recommendations for ASCVD prevention have been available for a number of years and are regularly updated, there is evidence that they are not routinely implemented in clinical practice.9 41 42 For example, Yusuf et al43 reported worldwide poor use of medications for the secondary prevention of ASCVD. Their study included 153 996 adults aged 35 to 70 years from rural and urban communities in high-, upper-middle–, lower-middle–, and low-income countries, 5650 of whom had had a self-reported CHD event and 2292 a stroke. Few individuals with ASCVD took antiplatelet drugs (25.3%), β-blockers (17.4%), ACE inhibitors or ARBs (19.5%), or statins (14.6%). As expected, drug use was higher in high-income countries, with 11.2% of patients in these countries not receiving any drugs compared with 45.1% of patients in upper-middle–income countries, 69.3% in lower-middle–income countries, and 80.2% in low-income countries. Notably, despite the relative accessibility of drugs for secondary prevention of ASCVD in high- and upper-middle–income countries, many patients remained untreated.
Of the patients who do receive treatment for ASCVD risk factors, only a few attain their treatment goals. Findings from the Hong Kong Cardiovascular Task Force Risk Management Programme indicate that 84% of enrolled hypertensive patients were treated with one or two antihypertensive drugs, most commonly ARBs (63.5%) and calcium channel blockers (47.2%; BMY Cheung, unpublished data). Similarly 64% of the diabetic patients were treated with metformin (68.8%) and/or gliptins (36%), while 78.1% of patients with dyslipidaemia were treated with a statin. Notably, however, treatment goals for hypertension (<130/80 mm Hg for diabetic patients, <140/90 mm Hg for non-diabetics) and diabetes (glycated haemoglobin <7%) were met by just over 50% of hypertensive patients and approximately 60% of diabetics.
Ensuring physician compliance with evidence-based guidelines and improving clinician understanding of factors affecting patient compliance with treatment may be the key to decreasing ASCVD risk in the Hong Kong population.
Differences between the 2008 and 2016 consensus statements
The present update of the 2008 Consensus Statement introduces the use of the new American Pooled Cohort Risk Assessment Equations that have superseded the Framingham Risk Evaluation; ASCVD risk can be assessed using either these equations or the European SCORE system to stratify patients into low-, moderate-, or high-risk categories to aid targeting of therapies as well as the establishment of suitable treatment goals. The risk factor reduction goals for hypertension and dyslipidaemia have been updated to reflect the most current recommendations from the Eighth Joint National Committee, the European guidelines on the management of arterial hypertension, and the European guidelines on cardiovascular disease prevention in clinical practice. The HDL-C target included in the 2008 Consensus Statement has been omitted from the current update as increased HDL-C has not been proven to reduce ASCVD risk.
The development of ASCVD in at-risk patients may be slowed and/or prevented by lifestyle modification, reduction of metabolic risk factors, and pharmacological treatment. The clinician plays a central role in ASCVD prevention—identifying at-risk patients, calculating the total ASVCD risk score, encouraging lifestyle changes, and providing targeted interventions to achieve specific treatment goals. Nonetheless, it is vital that the clinician is not overly focused on the treatment of isolated ASCVD risk factors but should instead adopt a ‘whole-person’ approach to diagnosis and therapy. Many patients present with multiple risk factors and, therefore, individualised, nuanced patient evaluation and management is essential to achieve optimum outcomes. Finally, none of these interventions will result in ASVCD prevention without the cooperation of the patient. Clinicians are encouraged to build strong partnerships with their patients, with the aim of establishing individual ownership of their treatment plans and, thus, improved treatment compliance.
The authors would like to acknowledge Ms Lianne Cowie and Dr Jose Miguel (Awi) Curameng of MIMS (Hong Kong) Limited for providing editorial and writing support, which was funded by Pfizer Corporation Hong Kong Limited. The meetings during which these consensus points were formulated and discussed were supported by an unrestricted educational grant from Pfizer Corporation Hong Kong Limited.
Source of support: Editorial and writing services, and the meetings during which these consensus points were formulated and discussed, were supported by an unrestricted educational grant from Pfizer Corporation Hong Kong Limited.
1. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):S49-73. CrossRef
2. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases. Part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation 2001;104:2746-53. CrossRef
3. Cheung MY, Ong KL, Tso WK, Lam TH, Lam SL. Increasing prevalence of hypertension in Hong Kong Cardiovascular Risk Factor Prevalence Study: role of general and central obesity. Proceedings of the 16th Medical Research Conference; 2011 Jan 22; Department of Medicine, The University of Hong Kong, Hong Kong. Hong Kong Med J 2011;17(Suppl 1):16S.
4. Roth GA, Huffman MD, Moran AE, et al. Global and regional patterns in cardiovascular mortality from 1990 to 2013. Circulation 2015;132:1667-78. CrossRef
5. Cheung MY, Chow CC, Chu DW, et al. The Hong Kong Cardiovascular Task Force. Towards cardiovascular disease protection. Consensus statement on preventing cardiovascular disease in the Hong Kong population. Med Prog 2008;35:473-9.
6. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63(25 Pt B):2889-934. CrossRef
7. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013;34:2159-219. CrossRef
8. James PA, Oparil S, Carter BL, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507-20. CrossRef
9. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;37:2315-81. CrossRef
10. Collins GS, Altman DG. Predicting the 10 year risk of cardiovascular disease in the United Kingdom: independent and external validation of an updated version of QRISK2. BMJ 2012;344:e4181. CrossRef
11. QRISK2. Available from: https://www.qrisk.org/2016/. Accessed 9 Jan 2017.
12. Scandinavian Simvastatin Survival Group. Randomized trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-9.
13. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-7. CrossRef
14. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53. CrossRef
15. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med 2000;342:381-9. CrossRef
16. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86. CrossRef
17. US Department of Health and Human Services. The health benefits of smoking cessation. Washington DC: US Department of Health and Human Services; 1990.
18. Taylor R, Brown A, Ebrahim S, et al. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Med 2004;116:682-92. CrossRef
19. Prevention of cardiovascular disease. Guidelines for assessment and management of cardiovascular risk. Geneva, World Health Organization; 2007.
20. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care 2014;37(Suppl 1):S14-80. CrossRef
21. The Hong Kong reference framework for diabetes care for adults in primary care settings. Available from: http://www.pco.gov.hk/english/resource/files/RF_DM_full.pdf. Accessed 1 Dec 2014.
22. Rydén L, Grant PJ, Anker SD, et al. ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 2013;34:3035-87. CrossRef
23. Wang C, Collet JP, Lau J. The effect of Tai Chi on health outcomes in patients with chronic conditions: a systematic review. Arch Intern Med 2004;164:493-501. CrossRef
24. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157-63. CrossRef
25. International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. Available from: http://www.idf.org/webdata/docs/MetSyndrome_FINAL.pdf. Accessed 10 Jul 2015.
26. West R, McNeill A, Raw M. Smoking cessation guidelines for health professionals: an update. Health Education Authority. Thorax 2000;55:987-99. CrossRef
27. National Institute for Health and Clinical Excellence. Hypertension in adults: diagnosis and management. NICE guideline (CG127). August 2011. Available from: https://www.nice.org.uk/guidance/cg127. Accessed 10 Jul 2015.
28. National Institute for Health and Clinical Excellence. Type 2 diabetes: The management of type 2 diabetes. NICE guideline (CG87). May 2009. Accessed 10 Jul 2015.
29. National Institute for Health and Care Excellence. Chronic kidney disease in adults: assessment and management. NICE guideline (CG182). July 2014. Accessed 10 Jul 2015.
30. Shen L, Shah BR, Reyes EM, et al. Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study. BMJ 2013;347:f6745. CrossRef
31. Bangalore S, Parkar S, Grossman E, Messerli FH. A meta-analysis of 94,492 patients with hypertension treated with beta blockers to determine the risk of new-onset diabetes mellitus. Am J Cardiol 2007;100:1254-62. CrossRef
32. Messerli FH, Bangalore S. Half a century of hydrochlorothiazide: facts, fads, fiction, and follies. Am J Med 2011;124:896-9. CrossRef
33. Williams B, MacDonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015;386:2059-68. CrossRef
34. National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification. NICE guideline (CG181). July 2014. Accessed 10 Jul 2015.
35. Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-78. CrossRef
36. Tomlinson B, Hu M, Zhang Y, Liu ZM, Chan P. Response to the letter “No evidence to support high-intensity statin in Chinese patients with coronary heart disease”. Int J Cardiol 2016;209:192-3. CrossRef
37. Liao JK. Safety and efficacy of statins in Asians. Am J Cardiol 2007;99:410-4. CrossRef
38. Everett BM, Smith RJ, Hiatt WR. Reducing LDL with PCSK9 inhibitors—the clinical benefit of lipid drugs. N Engl J Med 2015;373:1588-91. CrossRef
39. Mayor S. NICE recommends PCSK9 inhibitors for patients not responding to statins. BMJ 2016;353:i2609. CrossRef
40. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015;38:140-9. CrossRef
41. Ma J, Sehgal NL, Ayanian JZ, Stafford RS. National trends in statin use by coronary heart disease risk category. PLoS Med 2005;2:e123. CrossRef
42. Pearson TA. The prevention of cardiovascular disease: have we really made progress? Health Aff (Millwood) 2007;26:49-60. CrossRef
43. Yusuf S, Islam S, Chow CK, et al. Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE Study): a prospective epidemiological survey. Lancet 2011;378:1231-43. CrossRef