Bài giảng Tăng huyết áp - Khuyến cáo và ứng dụng lâm sàng

PGS TS Châu Ngọc Hoa Bộ môn Nội- ĐHYD Tp HCM TĂNG HUYẾT ÁP Khuyến cáo và ứng dụng lâm sàng Hypertension is the leading risk factor for CVD globally About 17% of global mortality can be attributed to HT World Health Organisation. Global atlas on cardiovascular disease prevention and control. 2011 Availableat: 5A Worldwide Prevalence of Hypertension in males (A) & females (B) ≥ 25 years B Lancet. 2019 Jul 18. pii: S0140-6736(19)30955-9 Lancet. 2019 Jul 18. pii: S0140-6736(19)31145-6 6 • 192,441 participants with hypertension • 29.9% received HTN treatment • 10.3% achieved HTN control In the best performing countries, treatment coverage reached up to 80% and control rates just less < 70%. But in some countries control was as low as < 30% What The World Needs to Do To reach the SDG 3.4 target of a 1/3 reduction of the risk of death among people ages 30 Target percent reduction to achieve SDG 3.4 50% 30% 27% overall 50% hypertension control 25% 100% 20% -69 Intervention Tobacco control* Sodium reduction* Prevention, detection, and treatment of cervical*, liver, colon, and other cancers Treatment of hypertension* Reduction of indoor air pollution Artificial trans fat elimination Reduction of harmful alcohol use* TOTAL CVD *WHO “Best Buy” for NCD prevention Note: some lives saved may be counted twice Estimated potential reduction in risk of death from selected NCDs ages 30-69 15.0% 5.5% 5.0% 4.8% 3.3% 1.9% 0.9% 36.4% 27.2% Adapted from Resolve to Save Lives 1 out of 5 adults are living with hypertension Low income countries are mainly affected In 40 years, the number of adults with hypertension has nearly doubled 70% of hypertensive patients are older than 65 years old 1. 2. SAND abstract N°169 from the BEACH program: Hypertension, comorbidity and blood pressure control. Sydney: FMRC University of Sydney.2011 ISSN1444-9072 c2011 3.Wozniak G et al.Hypertension Control Cascade: AFramework to Improve Hypertension. J Clin Hypertens. 2015:18(3):1-8 c 2015 Prevalence of hypertension Hypertension “There are few stories in the history of medicine that are filled with more errors or misconceptions than the story of hypertension and its treatment.” Prof Marvin Moser (1925-2015) Yale University School of Medicine Nonpharmacological Interventions Whelton PK, et al. J Am Coll Cardiol. 2017. SURPRISING TRENDS FROM THE FRONT LINES • 90% of cardiologists had no or minimal nutrition education during fellowship training • Only 8% had a “solid nutrition education” that they considered “adequate” Devries S, Agatston A, Aggarwal M, Aspry KE, Esselstyn CB, Kris-Etherton P, Miller M, O'Keefe JH,Ros E, Rzeszut AK, White BA, Williams KA, Freeman AM. A Deficiency of Nutrition Education and Practice in Cardiology. Am JMed. 2017 May 24. CVD Prevention Guidelines Get Your 30 • Adults should aim for 150 minutes per week of accumulated moderate- intensity physical activity or 75 minutes per week of vigorous-intensity physical activity. • Aim for 30 minutes day to keep it simple! • Get rid of the sedentary behavior • If unable to hit targets, do your best! The guidelines are favorable towardsANY activity, though targets should be striven for! ASCVD Risk Estimation to Guide the Management of Hypertension: The Time Has Come Ty J. Gluckman, MD, FACC, FAHA Medical Director, Center for Cardiovascular Analytics, Research and Data Science (CARDS) Providence Heart Institute Providence St. Joseph Health Portland, Oregon 2017ACC/AHA Hypertension Guideline Management of BP inAdults Yes Elevated BP SBP 120-129 AND DBP <80 Stage 2 HTN SBP > 140 OR DBP > 90 ASCVD or 10-year risk >10% Add BP- lowering therapy Stage 1 HTN SBP 130-139 OR DBP 80-89 Nonpharmacologictherapy NoBP-lowering therapy not needed Normal BP SBP <120 AND DBP <80 Promote optimal lifestyle habits Whelton P, et al. JACC 2018;71(19):e127-248. 2018 ESC/ESH Guidelines for the management of arterial hypertension European Heart Journal (2018) doi:10.1093/eurheartj/ehy339 Journal of Hypertension (2018) doi:10.1097/HJH.0000000000001940 www.escardio.org/guidelines 8 Aged 18 - 65yrs BP Threshold ≥140/90mmHg I A Aged 65 - 80yrs BP Threshold ≥140/90mmHg I A Aged > 80yrs BP Threshold SBP ≥160mmHg I A Very High CV Risk Treatment may be considered when BP ≥130/85mmHg II B What’s new in 2018? Office Blood Pressure Thresholds for Drug Treatment of Hypertension* *Lifestyle Interventions recommended for all when BP is high-normal (BP ≥130/85mmHg) Table 5. 10-year CV risk categories (SCORE system) 9 Very high-risk www.escardio.org/guidelines People with any of the following: Documented CVD, either clinical or unequivocal on imaging. • Clinical CVD includes; acute myocardial infarction, acute coronary syndrome, coronary or other arterial revascularization, stroke, TIA, aortic aneurysm, PAD. • Unequivocal documented CVD on imaging includes: significant plaque (i.e. ≥ 50% stenosis) on angiography or ultrasound. It does not include increase in carotid intima-media thickness. Diabetes mellitus with target organ damage, e.g. proteinuria or a with a major risk factor such as grade 3 hypertension or hypercholesterolaemia. Severe CKD (eGFR < 30 mL/min/1.73 m2). A calculated 10-year SCORE of ≥ 10%. 2018 ESC/ESH Guidelines for the management of arterial hypertension European Heart Journal (2018) doi:10.1093/eurheartj/ehy339 10 High-risk www.escardio.org/guidelines Table 5. 10-year CV risk categories (SCORE system) People with any of the following: Marked elevation of a single risk factor, particularly cholesterol > 8 mmol/L (> 310 mg/dL) e.g. familial hypercholesterolaemia, grade 3 hypertension (BP ≥ 180/110 mmHg). Most other people with diabetes mellitus (except some young people with type 1 diabetes mellitus and without major risk factors, that may be moderate risk). Hypertensive LVH. Moderate CKD eGFR 30–59 mL/min/1.73 m2). A calculated 10-year SCORE of 5–10%. 2018 ESC/ESH Guidelines for the management of arterial hypertension European Heart Journal (2018) doi:10.1093/eurheartj/ehy339 Study Group Coron Revasc Ang Pect UA MI CHD Death Stroke Stroke Death Card Fail TIA Framingham CHD X X X X ATPIII X X Framingham Global X X X X X PRO-CAM X X X QRISK X X X X X X X X Reynolds Men X X X X X Reynolds Women X X X X X EURO-SCORE X X Pooled Cohort X X X X Risk Score Revas c A P U A M I CHD Death Stroke Stroke Death Card Fail TIA Total CHD Events, including Revascularization Total CHD Events Hard CHD Events Hard ASCVD Events Hard ASCVD Events, includingCardiacFailure Ways to Assess Cardiovascular Risk Cardiovascular End Points Goff DC et al. J Am Coll Cardiol 2014;63:2935-2959 Edward D. Freis, MD We are not treating numbers, we are treating patients! • Blood pressure targets should be applied in the appropriate clinical context and on a patient by-patient basis. • In clinical practice, one size does not always fit all, as special cases exist. • Treating numbers rather than patients may result in unbalanced patient care. The optimal approach to blood pressure management relies on a comprehensive risk factor assessment and shared decision-making with the patient before setting specific blood pressure targets. Changing paradigm in hypertension management Universal ideal drugs Universal BP target Special indications in selected group for target and drug classes Precision target BP and combination therapy – a preferred approach for selected subgroup Stroke is the most devastating complication for older hypertensive patients 24 Age-specific incidence rates of stroke and acute myocardial infarction (MI) in women1 Age-specific incidence rates of stroke and acute myocardial infarction (MI) in men1 1. Gentil A et al. J Neurol Neurosurg Psychiatry. 2009;80:1006-1010.) Changes in overall disease burden in China: Stroke becomes the first cause of death ➢ Researchers from the Chinese Center for Disease Control and Prevention, the University of Washington Health Index and Evaluation Institute, and other institutions have conducted a comprehensive assessment of the disease burden in China (1990-2010). ➢ Studies have shown that, unlike the world's 235 death causes, ischemic disease is the first cause of death in China. China's top three fatal diseases in 2010 Stroke （1700000） COPD （934000） CHD （948700） Gonghuan Yang, et al. Lancet 2013; 381: 1987–2015. COPD=chronic obstructive pulmonary disease. H is to ry o f st ro ke an d co m o rb id it y ra te The statistical results were obtained from a total of 21,902 stroke patients from 132 hospitals across the country (including all 31 provincial administrative units including Hong Kong) from CNSR (China National Stroke Registry) 2007.9-2008.8. Among them, 63. 2% were hypertensive. Wang Y, et al. Int J Stroke. 2011 Aug;6(4):355-61. 27 Past stroke history Combined diabetes Hypertension Hyperlipidemia Coronary heart disease Atrial fibrillation Stroke patients with high rates of hypertension (China National Stroke Registry) Incidence of Stroke in the Asian Pacific Region (2002) 127.6 Atlas of Heart Disease and Stroke. MacKay J & Mensah G. 2004. Geneva. WHO Figures (not adjusted for age). 105.9 97.3 72.6 68.4 65.5 57.0 56.3 43.2 42.4 41.0 39.9 31.0 0 20 40 100 120 140 China South Korea Japan Vietnam Laos Myanmar Indonesia USA Cambodia Malaysia Thailand Singapore Philippines 60 80 Incidence per 100,000 Đột quị: tỉ lệ tử vong rất cao tại Việt Nam 32% Valery L. Feigin, Bo Norrving, George A. Mensah; Global Burden of Stroke; Circ Res. 2017;120:439-448n 2016: STROKE IS IN TOP 3 REASON OF MORTALITY IN VIETNAM - 80 mils VND if have surgery - 10 mils VND internal treatment for inpatients - 3 – 5 kinds of drugs for outpatients - 90% pts have after- effect Be paralysed, Diminish capacity, Depression - 1/3 will have recurrent stroke in 5 years. 200.000 cases/year 100.000 died Impact of Specific BP-lowering Treatments versus alternative class on Major Cardiovascular Outcomes & Mortality Justifies the focus of treatment on ACE-I or ARB, CCB or Diuretic Ettehad D, et al. Lancet 2016; 387: 957-967 ESH/ESC guidelines suggest a CCB or a diuretic may be particularly useful for elderly patients1 Khuyến cáo Cho bệnh nhân lớn tuổi 1. Mancia G et al. Eur Heart J. 2013;34:2159-2219. THA Người Cao Tuổi Khuyến Cáo Loại Mức Chứng Cứ Ngưỡng HA ở người ≥ 65 tuổi cần điều trị thuốc hạ áp là ≥ 140/90mmHg, THA > 80 tuổi ngưỡng HA cần điều trị ≥160/90 mmHg I B Đích hạ HA ở người THA ≥ 65 tuổi chung đối với HATT là trong ranh giới 130- <140mmHg và HATTr là 70-80mmHg I C Theo dõi sát các tác dụng phụ của thuốc điều trị I C Đích nầy khuyến cáo cho bệnh nhân ở bất kỳ mức nguy cơ nào và có bệnh tim mạch hay không I C Điều trị thuốc có thể cho ở bệnh nhân cao tuổi có hội chứng lão hóa nếu dung nạp IIb B Đối với người cao tuổi ≥65 tuổi có THA với bệnh đồng mắc và có hạn chế về tuổi thọ, cần thẩm định lâm sàng kỷ, điều kiện sống, để ưu tiên chăm sóc và đánh giá toàn diện giữa nguy cơ và lợi ích để quyết định xem xét điều trị tích cực hạ áp và chọn lựa thuốc thích hợp IIa C Các nhóm thuốc hạ HA được khuyến cáo và có thể dùng ở người cao tuổi, lợi tiểu và chẹn kênh canci có thể ưu tiên cho THA tâm thu đơn độc I A ESC/ESH 2018 BP Lowering Drugs in the Prevention of CVD RR estimates of CHD events and stroke in 46 drug comparison trials comparing each of the five classes of BP lowering drug with any other class of drug Law MR et al. BMJ 2009;338:b1665 Tiền THA THA + Tổn thương cơ quan đích THA + Bệnh lí trên lâm sàng B. Williams. Lancet 2006 Số thuốc • Co mạch • tăng kháng lực ngoại vi • tái cấu trúc mạch máu • hoạt hóa hệ RAAS & SNS Trẻ hơn Già hơn • Giảm GFR • Giữ muối • Tăng cung lượng tim •Cứng động mạch – THA tâm thu Renin huyết tương C: chẹn canxi D: lợi tiểu (loại thiazide-like) SỰ TIẾN TRIỂN CỦA TĂNG HUYẾT ÁP A: ức chế hệ RAAS B: chẹn beta 30 20 10 R e d u c ti o n ( % ) 0 40 Syst-EUR Reduction of Stroke in Elderly JAMA 1991, Lancet 1997, NEJM 2008 SHEP -36% -42% -30% HYVET Enshu Hospital, Hamamatsu, JapanPowles J. et al. BMJ Open 2013; 3: e003733 Amount of salt intake by country for ages 20+, average of both sexes, in 2010. Sodium (mg/day) Salt equivalent (g/day) US Sodium Intake From Antman EM et al. Circulation 2014;129:e660-e679 • US Average 3400 mg/d • Target <1500 mg/d Salt intake reduced by 1.4 g/day in the UK between 2000 and 2011 9.5 g/day 8.1 g/day at least 9,000 deaths averted have the ascetism of a religious zealot (Pickering 1948) To stay on a low salt diet is feasible, if you either get whipped periodically (Kempner 1997) are an inmate In Federal Prison (Jones et al. 2018) High prevalence and low control rates High sodium and low potassium intakes High night-time BP and low dipping Wang JG and Li Y. Curr Hypertens Rep 2012; 14:410-415. Characteristics of hypertension in Asians Diuretics have remained the cornerstone of antihypertensive treatment since at least the first Joint National Committee (JNC) report in 1977 [412] and the first WHO report in 1978 [413], and still, in 2003, they were classified as the only first-choice drug by which to start treatment, in both the JNC-7 [264] and the WHO/International Society of Hypertension Guidelines [55,264]. It has also been argued that diuretics such as chlorthalidone or indapamide should be used in preference to conventional thiazide diuretics, such as hydrochlorothiazide [271]. D: If diuretic treatment is to be initiated or changed, offer a Thiazide-like Diuretics like Chlortalidone (12.5-25 mg once daily) or Indapamide (1.5 modified-release or 2.5 once daily) in preference to a conventional thiazide diuretic such as Bendroflumethiazide or Hydrocholorothiazide. Lợi tiểu: bằng chứng với Indapamide 1. Beckett NS, Peters R, Fletcher AE, et al. N Engl J Med. 2008;358:1887-1898. 2. PROGRESS Collaborative Group. Lancet. 2001;358:1033-1041. 3. Patel A, Group AC, MacMahon S, et al. Lancet. 2007;370:829-840. Relative Risk of Treatment Discontinuation according to the Drug Initially Prescribed within Any Given Class 0 1 155 10 Risk of discontinuation 448/ 1629 354/ 1325 79/ 375 729/ 4116 805/ 4915 426/ 2842 121/ 604 230/ 1736 119/ 993 2007/17302 7019/73492 2975/32611 1076/15444 5145/81530 Captopril Moexipril Spirapril Fosinopril Quinapril Benazepril Trandolapril Delapril Cilazapril Lisinopril Enalapril Perindopril Zofenopril Ramipril Drug Discontinuers 0 1 15 1325/13063 226/ 2945 902/12579 1412/19712 943/14007 1446/21789 2584/44212 5 10 Risk of discontinuation Losartan Eprosartan Telmisartan Irbesartan Candesartan Valsartan Olmesartan Drug Discontinuers 0 1 15 269/ 523 1774/ 4460 45/ 29 1651/ 5838 2504/12266 562/ 3474 757/ 5052 3942/29695 25/ 198 13/ 106 445/ 4196 1534/15859 63/12348 5 10 Risk of discontinuation Nicardipine Diltiazem Nisoldipine Verapamil Nifedipine Felodipine Lacidipine Amlodipine Nitrendipine Isradipine Manidipine Lercanidipine Barnidipine Drug Discontinuers 0 1 15 2713/6002 859/1912 2799/9142 569/2375 572/3266 42/ 243 83/ 494 691/4800 5 10 Risk of discontinuation Torasemide Spironolactone Furosemide Canrenone K- canrenoate Hydrochlorothiazide Chlorthalidone Indapamide Drug Discontinuers 774/1794 57/ 222 2099/9698 177/1326 9/ 91 0 1 155 10 Risk of discontinuation Clonidine Terazosin Doxazosin Moxonidine Methyldopa Drug Discontinuers 0 1 15 5/ 126 386/ 2202 1940/ 7707 1026/ 4125 3808/17017 1823/ 8190 15/ 87 31/ 209 4687/34518 3/ 24 2918/27221 5/ 79 3/ 66 5 10 Risk of discontinuation Pindolol Propranolol Carvedilol Sotalol Bisoprolol Metoprolol Timolol Acebutolol Atenolol Labetalol Nebivolol Betaxolol Celiprolol Drug Discontinuers ACE Inhibitors ARB’S CCB’s Diuretics Antisympathetic Agents Beta Blockers Mancia G et al, J Hypertens 2010 Relative potency Oral bioavailability T1/2 Ineffective GFR<30-40 HCTZ 1 ~70% ~2.5h Yes Chlorthalidone 2* ~65% ~47h Yes Indapamide 20 ~93% ~14h No Metolazone 10 ~65% ? No *Twice as potent in lowering BPon mg-per-mg basis as HCTZ. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e . 2011 Pharmacotherapy:APathophysiologicApproach, 9e. 2014 Thiazide (-Like) Diuretics Rea F, et al. Eur Heart J, 2018 Early Cardiovascular Protection by initial two-drug single pill combination versus monotherapy in hypertension N = 37,078 monotherapy N = 7,456 SPC 2,212 CV events at 1 year The effect of starting treatment with a SPC versus Monotherapy on 1 year risk of CV outcomes High dimensional propensity score matched in 2212 patients with events at 1 year Healthcare utilization Database | Lombardi, Italy Risk ratios for stroke comparing treatment with combination CCB/thiazide-like diuretic vs other combinations Phối hợp chẹn calci/lợi tiểu thiazide giảm đột quỵ hiệu quả hơn vs các phối hợp khác CCB, calcium channel blocker; CI, confidence interval, Diu, diuretic; RR, risk ratio. 1. Rimoldi SF et al. J Clin Hypertens. 2015;17:193-199. Evidence-based combination therapy RAS blockade CCBDiuretic Demography Age Sex Race Factors that can contribute to BP reduction outcome Comorbidities and overall risk of death Life expectancy Concomitant drugs Additional factors BP variability Adherence Side effects Outcome ACEI Diuretic Betablocker CCB Which Drug(s)? ARB Right Drug for Right Person The objective of antihypertensive therapy should be to not only the blood pressure but to prevent the lethal and disabling cardiovascular sequelae.” lower