When should you treat blood pressure in the young?

Transcription

1 ESC Stockholm - Dilemmas in Cardiovascular Disease Prevention in the Young: 30 th August 2010 When should you treat blood pressure in the young? Bryan Williams MD FRCP FAHA FESC Professor of Medicine Department of Cardiovascular Sciences NIHR Cardiovascular Biomedical Research Unit University of Leicester United Kingdom

2 Hypertension in the Young What do we mean by hypertension? BP >140/90mmHg What do we mean by Young? <40 years;

3 Pre-hypertensive Hypertensive + Damage Hypertension + Clinical Disease Treatment Guidelines Drug Treatment Evolution of Disease; yrs Target Organ Damage: LVH and diastolic dysfunction Vascular Structural Damage Systolic Hypertension LV systolic Dysfunction Small Vessel Brain Disease Albuminuria / Declining GFR Surrogate End-points Cardiovascular Disease Risk BP and CVD Risk Number of Drugs Clinical Trials Evolution Younger of Hypertensive Injury Older Hypertension: Lipid Disorder Glucose Disorder BP dysregulation No TOD No CVD Williams B. Lancet. 2006; 368: 6-8 +/- +/- +/- Hard End-points Metabolic syndrome to diabetes Cardiovascular Disease: CHD / CHF Stroke / TIA Dementia Renal Disease Macular degeneration Death

4 Treatment Objectives in Hypertension Younger People: Prevent the Evolution of Disease and Regress Structural Damage Older People: Prevent Clinical Events

5 Dilemmas in Cardiology Williams B. J Am Coll Cardiol. 2007; 50:840-2.

6 Hypertension in the Young: The challenge of proving drug efficacy Regulators and Guideline Developers focus on hard clinical end-points from clinical outcome trials; Young people do not develop hard end-points during the typical duration of a clinical trial; Guidelines advocate global risk assessment but short term risk (10yrs) is powerfully determined by age most young hypertensive people are classified low risk ; Surrogate end-points are usually disregarded but are the only feasible efficacy measure in young people; Surrogate end points = Premature Death Markers.

7 European Society of Hypertension 2003: Cardiovascular Disease Risk Stratification Blood Pressure (mm Hg) Other risk factors and disease history Normal SBP or DBP High normal SBP or DBP Grade 1 SBP or DBP Grade 2 SBP or DBP Grade 3 SBP 180 or DBP 110 No other risk factors Average risk Average risk Low added risk Moderate added risk High added risk 1-2 risk factors Low added risk Low added risk Moderate added risk Moderate added risk Very high added risk 3 or more risk factors or TOD or diabetes Moderate added risk High added risk High added risk High added risk Very high added risk Associated Clinical Conditions High added risk Very high added risk Very high added risk Very high added risk Very high added risk ACC=associated clinical conditions. European Society of Hypertension Guidelines Committee. J Hypertens. 2003;21:

8 Actuarial Survival According to Age and Blood Pressure Women At Age 45 At Age 45 Men Normal 37 Normal / / yrs 140/ / / / At Age 55 At Age 55 Normal 27.5 Normal yrs 130/90 140/ /90 140/ / / Metropolitan Life Insurance Company Actuarial Data; 1961

9 CVD Risk Assessment in Young People with Hypertension Short term absolute risk assessment favours treatment of older people and discriminates against the treatment of younger people; Life-time risk assessment incorporating life years gained by treatment is urgently needed for younger people; Life time risk more accurately estimates longterm, insidious cumulative damage.

10 Treating Hypertension in the Young Can we delay treatment based on the assumption that blood pressure-mediated damage is reversible? Is there anything lost by delaying treatment for years? Is pressure mediated damage reversible? YES and NO

11 Hypertensive Structural Damage Vascular damage Cardiac Damage Brain Damage Renal Damage Small Artery reversible early Large Artery not reversible LVH muscular hypertrophy - reversible Cardiac Fibrosis not reversible Diastolic dysfunction not reversible Small vessel ischaemic damage not reversible Cognitive decline not reversible Increased Albuminuria reversible early Glomerulosclerosis not reversible Decline in GFR not reversible

12 Blood Pressure Profiles According to Age in U.S. Adults Burt VL, et al. Hypertension 1995;25:

13 Pulse Wave Velocity (cm/sec) Augementation Index (%) Aortic Root Size (mm/m 2 ) Intimal Median Thickness (cm) Effects of Aging on Vascular Structure and Function 28 Aortic root size & age B Carotid IMT & age 24 Men Women Age (years) Age (years) 2500 Pulse wave 70 Augmentation velocity & age index & age D Age (years) Age (years) Najjar SS, et al. Hypertension. 2005;46:

14 Hypertension. 2009;54: )

15 J Am Coll Cardiol Delayed treatment and development of aortic stiffness contribute to the development of resistant hypertension; Most people are not born with resistant hypertension it represents delayed treatment and damage treatment failure

16 Julius S. et al. NEJM, 2006

17 TROPHY Study Primary End-Point Development of Hypertension (BP >140/90mmHg or BP requiring Treatment) Julius S. et al. NEJM, 2006

18 Hypertension in the Young Consequences of Delayed Treatment Subtle but irreversible structural damage to vessels, heart, kidney and brain; Development of more severe and resistant hypertension later in life; Risk of developing accelerated hypertension; Reduced life expectancy according to actuarial survival data.

19 Hypertension in the Young: Their future is now People are living longer as a consequence of more effective detection and treatment of BP and CVD risk; The future focus will be on healthy ageing Disease patterns will shift dramatically in next 20 years; Greater disease burden due to insidious structural damage; - Aortic damage: Systolic hypertension; - Cardiac damage: LVH and heart failure and arrhythmias; - Kidney injury: declining function and ESRD; - Brain injury: Stroke, small vessel brain disease and dementia;

20 Earliest reference to the Importance of Early Treatment of Hypertension? A little fire is quickly trodden out; which, being suffered, rivers cannot quench Shakespeare W, Henry VI

21 Blood Pressure Thresholds and Targets in Young People with Hypertension Evidence is lacking with regard to optimal BP thresholds and targets in young people with hypertension consensus statements; Lifestyle intervention in pre-hypertension (systolic BP , Diastolic BP 85-90mmHg); Consider drug treatment when BP: >140/90mmHg; Treatment essential if end-organ damage is evident; Preferred initial therapy: renin-angiotensin system blockade (young patients usually high renin status)

22 Conclusions Objectives of treatment are to prevent the evolution of disease healthy vascular ageing; BP-mediated Cardiovascular damage is mostly not reversible; Life-time risk assessment tools are needed to better appreciate the adverse consequence of delayed treatment in young people; Evidence to support treatment guidance will have to come from studies of intermediate (surrogate) end-points; Research is urgently needed to define optimal means of stratifying young people for treatment, and to define the appropriate therapeutic thresholds and targets.