Reduction of diastolic blood pressure: Should hypertension guidelines include a lower threshold target?

Table 2 Comments on studies evaluating blood pressure thresholds

Study	Comment
Studies to target DBP
1967 JAMA	Small sample size
1970 JAMA	Small sample size
1979 Lancet	Small sample size, lacking data on baseline comorbidities
1998 Lancet (HOT)	Event rate lower than expected; difficult to recognize between-group outcomes due to small differences in achieved BP targets among three groups
Studies in the elderly
1991 JAMA (SHEP)	Stepwise titration of Chlorthalidone and addition of Atenolol vs placebo elderly isolated systolic hypertension; reduced all CV events with Rx
1997 Lancet (Syst-Eur)	Stepwise titration of Nifedipine and addition of enalapril and HCTZ vs placebo in elderly isolated systolic hypertension; reduced CV events and mortality but not all-cause mortality with Rx
2008 N Engl J Med (HYVET)	Indapamide ± Perindopril vs placebo; reduction of CVA, all-cause mortality and CHF
2016 JAMA (SPRINT)	Significant reduction in primary and secondary outcomes
Studies in CAD
2005 J Hypertens (ACTION)	Non-significant trends towards higher CV events in normotensives on Nifedipine
2006 Ann Intern Med (INVEST)	J-curve more prominent in DBP; DBP categories of < 60 through > 110 with 10 increments
2009 J Hypertension (ONTARGET)	High risk patients with known CAD or DM with target organ damage; Rx increased CV mortality if baseline SBP < 130; But CVA risk increased with high baseline SBP, but reduced with further BP lowering
2010 Am J Med (INVEST)	Prespecified secondary analysis; Verapamil SR or Atenolol based Rx, add-on ACE-I, HCTZ allowed; J-curve DBP nadir similar in all age groups, while SBP nadir increasing with age
2010 Eur Heart J (TNT)	Exponential increase in primary outcome for SBP < 110-120 or DBP < 60-70 except CVA which was further reduced with lower SBP
2010 Circulation (PROVE IT- TIMI)	All ACS patients; DBP categories of < 60 through >100 with 10 increments exponential increase in outcomes for SBP < 110 or DBP < 70
2011 Circulation (ONTARGET)	High risk patients with known CAD or DM with target organ damage, stratified by % of on-treatment visits in which BP was < 140/90 or < 130/80; no MI benefit for lowering < 130/80; but better CVA outcome with lower BP
2012 Hypertension (SMART)	DBP nadir 82 for all CV events, including CVA; DBP nadir 84 for mortality
2016 Eur Rev Med Pharmacol Sci	Small sample size when randomized to 5 groups; J-Curve for all outcomes except CVA
2016 Eur Heart J (VALUE)	High CV risk patients stratified by % of on-treatment visits in which BP was < 140/90 or < 130/80; data adjusted for baseline covariates by propensity score; worse outcomes with BP lowering < 130/80 except CVA
Studies in DM
1998 BMJ (UKPDS)	All newly diagnosed DM patients; tight vs less tight BP control (target < 150/85 vs 180/105) with Captopril or Atenolol as main agent and follow-up > 8 yr; tight BP control improved mortality and DM complications.
2002 Kidney Int (ABCD)	All diabetic normotensive patients; Rx with ACE-I or CCB vs placebo; achieved DBP of 75 vs 81 after 5 yr
2005 J Am Soc Nephrol (IDNT)	Achieving DBP < 85 associated with a trend towards increased all-cause mortality, a significant increase in risk of MI, but a decrease in risk of CVA
2010 JAMA (INVEST)	J Curve nadir eat SBP < 115 for all cause mortality
2010 N Engl J Med (ACCORD)	SBP < 120 vs < 140 did not further reduce the rate of composite CV outcomes, except CVA
2012 BMJ	All newly diagnosed DM; DBP < 75 and SBP < 110 in CAD patients associated with worse outcome
Epidemiology studies
1991 BMJ (Framingham)	J curve between DBP and CV death only in those with MI, independent of age, sex, BP Rx; J curve not significant for SBP after adjusting for confounders
2003 Ann Intern Med (NHANES II)	J curve between DBP and all mortality in age ≥ 65
2011 J Gen Intern Med (NHANES I)	J-curve for DBP even after adjusting for SBP
2014 J Am Coll Cardiol	DBP categories of < 50 through > 100 with 10 increments; data adjusted for confounders by CCI; DBP nadir lower for DM and age > 70 yr

ABCD: Appropriate Blood Pressure Control in Diabetes; ACCORD: Action to Control Cardiovascular Risk in Diabetes; CV: Cardiovascular; HOT: Hypertension Optimal Treatment; HYVET: Hypertension in the Very Elderly Trial; IDNT: Irbesartan Diabetic Nephropathy Trial; INVEST: International Verapamil SR Trandolapril Study; MI: Myocardial Infarction; NHANES: National Health and Nutrition Examination Survey; ONTARGET: Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial; PROVE IT-TIMI: Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction; RCT: Randomized Controlled Trial; SHEP: Systolic Hypertension in the Elderly Program; SMART: Secondary Manifestations of Arterial Disease; SPRINT: Systolic Blood Pressure Intervention Trial; Syst-Eur: Systolic Hypertension in Europe; TNT: Treating to New Targets; UKPDS: United Kingdom Prospective Diabetes Study; VALUE: Valsartan Antihypertensive Long-term use Evaluation.