What Can We Learn from the Observational Studies and Clinical Trials of Prehypertension? Yuqing Zhang, M.D., FESC Department of Cardiology, Fu Wai Hospital. CAMS & PUMC, Beijing, China
At ARIC visit 4 the average age was 62.6 (SD 5.6) years, Hypertension. 2016;67:1150-1156. 2
Model 1: adjustment for age at visit 4; Model 3: adjustment for age at visit 4, sex, race, study center, obesity, diabetes mellitus, smoking status, hypertension medication use, and SBP at visit 4. Hypertension. 2016;67:1150-1156. 3
Results of this study strongly underscore the importance of maintaining BP below the guideline recommended levels throughout the life course. Our results also support clinical efforts aimed at preventing any increase in systolic BP, independent of its absolute value. Hypertension. 2016;67:1150-1156.
BP trajectories and associated CVD risks Circulation. 2017;136:1262 1264.
Number of risk factors clustering in prehypertension subjects Li G, et al. BMJ Open 2017;7:e015340. doi:10.1136/bmjopen-2016-015340
Prevalence of major cardiovascular disease risk factors in prehypertensive subjects Li G, et al. BMJ Open 2017;7:e015340. doi:10.1136/bmjopen-2016-015340
Elasticity and morphologic features comparison for ascending aorta Jia CF et al. Am J Hypert. 2017, 30; 61-66
Prehypertension and Left Ventricular Diastolic Dysfunction in Middle-Aged Koreans Korean Circ J 2016;46(4):536-541
Meta-analysis of the CVD risk in prehypertension Coronary events Huang et al. BMC Medicine 2013, 11:177
Meta-analysis of the CVD risk in prehypertension Stroke Huang et al. BMC Medicine 2013, 11:177
Effects of blood-pressure-lowering treatment on outcome incidence.12. Effects in individuals with high-normal and normal blood pressure Costas Thomopoulos, Gianfranco Paratib, Alberto Zanchetti. J Hypertens. 2017, 35:2150 2160
Effects of blood-pressure-lowering treatment on fatal and nonfatal outcomes Costas Thomopoulos, Gianfranco Parati, Alberto Zanchetti. J Hypertens. 2017, 35:2150 2160
Effects of blood-pressure-lowering treatment on fatal and nonfatal outcomes Risk ratios are standardized to a SBP/DBP difference of 10/5mmHg. Costas Thomopoulos, Gianfranco Parati, Alberto Zanchetti. J Hypertens. 2017, 35:2150 2160
Low moderate and high very high cardiovascular risk Costas Thomopoulos, Gianfranco Parati, Alberto Zanchetti. J Hypertens. 2017, 35:2150 2160
Outcomes in patients with different baseline risk? Risk ratios are standardized to a SBP/DBP difference of 10/5mmHg. Costas Thomopoulos, Gianfranco Parati, Alberto Zanchetti. J Hypertens. 2017, 35:2150 2160
High Normal BP (prehypertension): From low risk to high risk: 2013 ESH/ESC Guidelines
Low moderate cardiovascular risk? What is the primary endpoint of these studies? Costas Thomopoulos, Gianfranco Parati, Alberto Zanchetti. J Hypertens. 2017, 35:2150 2160
HOPE 3 - HT Intermediate Risk : Elevated waist:hip ratio Low HDL-cholesterol Smoking Dysglycemia Family history of premature coronary disease Mild renal dysfunction Subjects (n = 12,705): Men > 55y, Women >65 y. SBP < 160 mm Hg Intervention: Candesartan 16 mg/d + hydrochlorothiazide 12.5 mg/d vs. Placebo.
HOPE 3 blood pressure intervention 12,705 patients with Intermediate Risk, but no CV Disease. Mean Baseline BP 131.8/81.9 mm Hg 6.0 mm Hg. Lonn EM et al. N Engl J Med 2016. DOI: 10.1056/NEJMoa1600175
HOPE 3 blood pressure intervention Major Outcomes Lonn EM et al. N Engl J Med 2016. DOI: 10.1056/NEJMoa1600175
FEVER:Fatal and non-fatal stroke stratified by total risk On-treatment SBP/DBP (mmhg) Patient groups No. Felodipine Placebo HR HR 95% CI P CV riskvery high 4833 139.1/82.8 143.1/84.8 0.806 0.1004 CV risk-high 4878 137.1/82.4 141.3/84.7 0.656 0.0055 0.4 0.6 0.8 1.0 1.5 2.0 Felodipine better Placebo better YQ Zhang, et al. Eur Heart J (2011) first published online February 22, 2011
BP Treatment Threshold and the Use of CVD Risk Estimation to Guide Drug Treatment of Hypertension COR I I LOE SBP: A DBP: C-EO C-LD Recommendations for BP Treatment Threshold and Use of Risk Estimation* to Guide Drug Treatment of Hypertension Use of BP-lowering medications is recommended for secondary prevention of recurrent CVD events in patients with clinical CVD and an average SBP of 130 mm Hg or higher or an average DBP of 80 mm Hg or higher, and for primary prevention in adults with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk of 10% or higher and an average SBP 130 mm Hg or higher or an average DBP 80 mm Hg or higher. Use of BP-lowering medication is recommended for primary prevention of CVD in adults with no history of CVD and with an estimated 10-year ASCVD risk <10% and an SBP of 140 mm Hg or higher or a DBP of 90 mm Hg or higher. *ACC/AHA Pooled Cohort Equations (http://tools.acc.org/ascvd- Risk-Estimator/) to estimate 10-year risk of atherosclerotic CVD.
Management of high normal blood pressure It is true that two studies have shown that a few years administration of antihypertensive agents to individuals with high normal BP can delay transition to hypertension, but how far the benefit of this early intervention lasts and whether it can also delay events and be costeffective remains to be proven. 2013 ESH/ESC Guidelines
CHINOM-Chinese High Normal Blood Pressure Study To investigate the effects of antihypertensive treatment (telmesartan, indapamide, reserpine compound) or no treatment (placebo) on combined cardiovascular events in subjects with high-normal blood pressure (130-139/85-89mmHg) and additional cardiovascular risk factors.
CHINOM-Inclusion criteria Age: 50-79yrs(F), 45-79yrs (M) BP: 130 SBP<140 and DBP<90, 85 DBP< 90 and SBP<140 With one or more additional risk factors of CVD Informed consent obtained
Cardiovascular risk factors 1.Waist Circumference (WC): 85cm (Male), 80cm (female) or overweight(bmi >24kg/m2) 2. TC 5.70mmol/L, TG 1.70mmol/L or HDL-C< 1.03mmol/L 3. Glucose Level: 6.1 Fasting Glucose<7.0mmol/L and/or 7.8 OGTT 2hPG<11.1mmol/L 4. Current smoker 6. Proteinurea or microalbuminruia 7. Family history of early onset of cardiovascular diseases 8. Family history of hypertension or diabetes 9. Age> 65 yrs
CHINOM Flow Chart Screening Randomization Tel Inda Comb placebo Open label, n 2000 Open label, n 2000 Double n 2000 Blind, n 4000 2w 1m 3m 6m 9m 12m 15m 18m 60m. Follow-up Proportion of active treatment to placebo= 3:2
Study endpoints Primary endpoint: Combined cardiovascular events (nonfatal stroke, nonfatal MI, cardiovascular death)
Sample Size Estimation Estimated primary endpoints in the placebo group: 7 cases/1000pys 25% reduction by active treatment =80%, =0.05 Primary endpoints: 400 cases Sample size: 10000 cases, 6.5yrs follow up (65000pys)
Progress of CHINOM First subject enrollment: Feb. 2008 End of randomization: May. 2012 Number of randomization: 10689 cases Follow up: 70000 pyrs (Dec. 2017)
Baseline data of 10689 subjects in CHINOM Study Variable Results Age (yrs) 58.8±7.5 Sex: Male 5074 (47.5%)
Baseline BP and HR Variable Results SBP(mmHg) 134.8(3.8) DBP(mmHg) 83.2(4.5) HR (bpm) 73.9(7.9)
CVD risk factors Variable Results Smoker 1849 (17.33%) BMI (kg/m2) 25.4±3.0 BMI subgroup <24 3361 (31.51%) 24-28 5192 (48.67%) 28-1924 (18.04%) Alcohol intake current 1990 (18.65%) Previous 367 (3.44%) Never 8221 (77.06%)
CVD risk factors Variable Results Overweight/obese 8201 (76.87%) TC 5.70mmol/L 或 TG 1.70mmol/L or HDL-C <1.03mmol/L 4428 (41.51%) 5.6 FPG<7.0 mmol/l mmol/l or 7.8 OGTT <11.1 mmol/l 3322 (31.14%) NYHF (II) 87 (0.82%) Stable CHD 300 (2.81%) Peripherial aterial disease 40 (0.37%) MA 128 (1.2%) Age>65yrs 1725 (16.17%)
Variable CVD risk factors Results History of hypertension 3846 (36.05%) History of Stroke 1308 (12.26%) History of MI 547 (5.13%) History of Diabetes 751 (7.04%) Metabolic syndrome 5156 (48.33%) No. of risk factors 0 115 (1.08%) 1 3231 (30.29%) 2 3118 (29.23%) 3 2467 (23.13%) 4 1232 (11.55%) 5 383 (3.59%)
Number of primary endpoints until Feb.21, 2018 330 cases
Conclusion In the management of low to moderate risk CVD subjects, evidence supporting antihypertensive agents is scanty. CHINOM study is an outcome trial in subjects of high normal BP with low to moderate CVD risk. Final results of the study is expected.
China Expertise within K.I.T. Group HYPERTENSION BEIJING 2018 27 th Scientific Meeting of the Society of International Hypertension 14 th Asian-Pacific Congress of Hypertension 20-23 September 2018 Beijing International Convention Center www.ish2018.org
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