Clinical Notes : Cardiovascular Disease

129. Isolated Systolic Hypertension

129. systolic-hypertension.jpg

Isolated Systolic Hypertension




Isolated systolic hypertension is defined as systolic blood pressure (BP) >140 mm Hg and diastolic BP <90 mm Hg.(1)


  • most common form of hypertension in the elderly, but not uncommon in young and middle-aged adults.(2)

  • increasing systolic BP in the elderly

    • believed to be secondary to modifiable and hereditary risk factors as well as patho-physiological changes of aging.

    • women, non-Hispanic blacks, and those with only secondary school education are more likely to be affected (3)

  • isolated systolic hypertension is independently associated with future cardiovascular events (4) (5)

    • cardiovascular mortality

    • all-cause mortality

    • stroke

    • cardiac events

    • cardiac failure


  • de novo in­crease in systolic BP secondary to increased arterial stiffness in pre-viously normotensive in-dividuals.(6)

    • type 1 diabetes

    • osteoporosis with vascular calcifications

    • accelerated atherosclerosis from chronic kid­ney disease

    • peripheral vascular disease

    • altered elastin formation during intrauterine fetal growth retardation

    • thyrotoxicosis

    • repaired coarctation of the aorta

    • ageing of the proximal aorta

  • In the elderly

    • reduction in arterial elasticity and compliance leads to a decrease of the lumen-to-wall ratio as wellas increased arterial stiffness (7)

      • changes specially involve predominantly large arteries and the aorta

    • renin-angiotensin-aldosterone system (8)

      • gradual progressive decline in plasma renin activity with age

      • modulated by several other factors such as sodium intake and comorbidities

  • Chronic diseases

    • diabetes mellitus

    • chronic kidney disease

    • hyperlipidemia

    • smoking

isolated syst ht.jpg

Pathophysiologic mechanisms associated with isolated systolic hypertension. RAAS = renin-angiotensin-aldosterone system.


Based on 2013 European Society of Hypertension and of the Euro­pean Society of Cardiology Guidelines for the management of arterial hypertension.(1)

isolated syst ht 2.png
isolated syst ht 4.gif.jpg


Four landmark randomized trials28-31 provided ironclad evidence for treatment of isolated systolic hypertension in the elderly

  • SHEP (9)

  • Sys-Eur (10)

  • Sys-China (11)

  • Hyvet (12)

isolated syst ht 3.jpg

BP = blood pressure

ISH = isolated systolic hyperten­sion

SBP = systolic blood pressure.

ACEi = angiotensin-converting enzyme inhibitors (e.g. 

ARB = angiotensin receptor blockers

CCB = calcium channel blocker

see ROI notes below for meds and combinations available

DASH = Dietary Approaches to Stop Hypertension

Aggressive BP lowering may be harmful in elderly patients with ISH due to the risk for target organ hypoperfusion.

  • Aggressive BP reduction in these patients is accompanied by a fall in diastolic BP as well.(13)

Beta-blockers have little, if any, efficacy in management of hypertension.(14)

  • Beta-blockers exert a pseudo-antihypertensive effect wherein peripheral BP was lowered but central (aortic) BP remained distinctly elevated (15)

    • reduction in heart rate ex­aggerates this effect.(16)

  • beta-blockers can engender a pro-fibrotic effect on the arterial wall, which may contribute to an increase in arterial stiffness (17)


1. 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(28):2159-2219.


2. Bavishi C, Goel S, Messerli FH

Isolated Systolic Hypertension: An Update After SPRINT

The American Journal of Medicine (2016) 129, 1251-1258


3. Liu X, Rodriguez CJ, Wang K.

Prevalence and trends of isolated systolic hypertension among untreated adults in the United States.

J Am Soc Hypertens. 2015;9(3):197-205.


4. Antikainen R, Jousilahti P, Tuomilehto J.

Systolic blood pressure, isolated systolic hypertension and risk of coronary heart disease, strokes, cardiovascular disease and all-cause mortality in the middle-aged population.

J Hypertens. 1998;16(5):577-583.


5. Ettehad D, Emdin CA, Kiran A, et al.

Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387(10022):957-967.


6. Franklin SS.

Elderly hypertensives: how are they different?

J Clin Hypertens (Greenwich). 2012;14(11):779-786


7. Chobanian AV.

Clinical practice. Isolated systolic hypertension in the elderly.

N Engl J Med. 2007;357(8):789-796.


8. Alderman MH, Cohen HW, Sealey JE, Laragh JH.

Plasma renin ac­tivity levels in hypertensive persons: their wide range and lack of suppression in diabetic and in most elderly patients.

Am J Hypertens. 2004;17(1):1-7.


9. Prevention of stroke by antihypertensive drug treatment in older per­sons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group.

JAMA. 1991;265(24):3255-3264.​


10. Staessen JA, Fagard R, Thijs L, et al.

Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

Lancet. 1997;350(9080):757-764.


11. Liu L, Wang JG, Gong L, Liu G, Staessen JA.

Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. Systolic Hypertension in China (Syst-China) Collabo­rative Group.

J Hypertens. 1998;16(12 Pt 1):1823-1829.


12. Beckett NS, Peters R, Fletcher AE, et al.

Treatment of hypertension in patients 80 years of age or older.

N Engl J Med. 2008;358(18): 1887-1898.


13. Messerli FH, Panjrath GS.

The J-curve between blood pressure and coronary artery disease or essential hypertension: exactly how essen­tial?

J Am Coll Cardiol. 2009;54(20):1827-1834.


14. Messerli FH, Grossman E, Goldbourt U.

Are beta-blockers efficacious as first-line therapy for hypertension in the elderly? A systematic re­view.

JAMA. 1998;279(23):1903-1907.


15. Williams B, Lacy PS;

CAFE and the ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) Investigators. Impact of heart rate on central aortic pressures and hemodynamics: analysis from the CAFE (Conduit Artery Function Evaluation) study: CAFE-Heart Rate.

J Am Coll Cardiol. 2009;54(8):705-713.


16. Messerli FHRS, Bangalore S, Bavishi C, Laurent S.

When increase in central pressure overrides benefits of heart rate lowering.

J Am Coll Cardiol. 2016;68(7):754-762.


17. Ong KT, Perdu J, De Backer J, et al.

Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a pro­spective randomised, open, blinded-endpoints trial.

Lancet. 2010;376(9751):1476-1484.


Ireland notes.png

Chlorthalidone is NOT available in Ireland except in combination with a BetaBlocker

(BetaBlocker should be avoided in ISH)

Indapamide is available in Ireland as Coversyl, Pendrex, Natrilix SR

Indapamide plus ACEi (Perindopril) is available in Ireland as Coversyl Plus, Pendrex Plus, Perindopril/Indapamide TEVA

Indapamide plus ACEi (Perindopril) plus CCB (Amlodipine) is available in Ireland as Coverdine

ACEi available in Ireland include :

  • benazepril (Cibacen)

  • captopril (Captor)

  • enalapril (Enap, Innovace)

  • lisinopril (Bizestra, Lestace, Lisopress, Lispril, Zesgen, Zestan, Zestril)

  • perindopril (Coversyl Arginine, Pendrex, Perindopril Kirka, Perindopril Tosilate Teva, Prindace)

  • quinapril (Accupro)

  • ramipril (Ramit, Ramilo, Ramipril Actavis, Ramipril KRKA, Ramitace, Tritace)

  • trandolapril (Odrik)

ARB available in Ireland include :

  • azilsartan (Edarbi)

  • candesartan (Atacand, Biopress, Candist, Catasart)

  • eprosartan (Teveten)

  • irbesartan (Aprovel, Ibersa, Ibersan Clonmel, Iprestan)

  • telmisartan (Micardis, Telmisartan Clonmel, Telmisartan Rowex)

  • valsartan (Diovan, ValsartanActavis, Valsartan Teva, Valtan, Vatan)

  • losartan (Casartal, Cozaar, Cozatan, Losartan Teva, Lotanos)

  • olmesartan (Benetor, Olmesartan Rowex, Omesar)

CCB available in Ireland include :

  • Amlodipine (Amlode, Amlodipine Clonmel, Istin, Istolde)

  • Diltiazem (Adizem,Diltam retard, Dizem)

  • Felodipine (Plendil)

  • Nifedipine (Adalat)

  • Verapamil (Isoptin, Isoptin SR, Verapamiol, Verap, Verisop)

Spironolactone is available in Ireland as (Aldactone)

Eplenerone is available in Ireland as (Eplenerone Rowexa, Inspra)

Doxazocin is available in Ireland as (Cardura, Carsem XL, Doxacar, Doxane XL, Doxatan, Raporsin)

Nebivolol is available in Ireland as (Nebilet, Nebikel, Nebivolol Teva, Nebol)


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