Peer-review started: September 1, 2016
First decision: October 26, 2016
Revised: November 20, 2016
Accepted: December 16, 2016
Article in press: December 18, 2016
Published online: February 23, 2017
Processing time: 171 Days and 4.3 Hours
Reduction of diastolic blood pressure to less than 60-80 mmHg does not improve mortality and may lead to adverse cardiovascular events in high risk patient populations. Despite a growing body of evidence supporting the J-curve phenomenon, no major society guidelines on hypertension include a lower threshold target for diastolic blood pressure. Many major society guidelines for hypertension have been updated in the last 5 years. Some guidelines include goals specific to age and co-morbid conditions. The Sixth Joint Task Force of the European Society of Cardiology and the Canadian Hypertension Education Program are the only guidelines to date that have recommended a lower threshold target, with the Canadian guidelines recommending a caution against diastolic blood pressure less than or equal to 60 mmHg in patients with coronary artery disease. While systolic blood pressure has been proven to be the overriding risk factor in hypertensive patients over the age of 50 years, diastolic blood pressure is an important predictor of mortality in younger adults. Post hoc data analysis of previous clinical trials regarding safe lower diastolic blood pressure threshold remains inconsistent. Randomized clinical trials designed to determine the appropriate diastolic blood pressure targets among different age groups and populations with different comorbidities are warranted. Hypertension guideline goals should be based on an individual’s age, level of risk, and certain co-morbid conditions, especially coronary artery disease, stroke, chronic kidney disease, and diabetes.
Core tip: Reduction of diastolic blood pressure to less than 60-80 mmHg appears to lead to adverse cardiovascular events in high risk patient populations. Currently, only two major society guidelines on hypertension include a minimum threshold for diastolic blood pressure. Available studies demonstrating adverse events at lower diastolic blood pressure vary in their cutoff values and patient populations. Randomized controlled trials comparing outcomes across different diastolic blood pressure targets are limited. Hypertension guideline goals should be based on an individual’s age, level of risk, and certain co-morbid conditions, especially coronary artery disease, stroke, chronic kidney disease, and diabetes.
- Citation: Tringali S, Huang J. Reduction of diastolic blood pressure: Should hypertension guidelines include a lower threshold target? World J Hypertens 2017; 7(1): 1-9
- URL: https://www.wjgnet.com/2220-3168/full/v7/i1/1.htm
- DOI: https://dx.doi.org/10.5494/wjh.v7.i1.1
Hypertension remains the most common primary diagnosis for office visits in adult patients[1]. Blood pressure (BP) lowering is associated with reduction in cardiovascular morbidity and mortality[2,3]. A common practice is to aggressively treat BP as “the lower the better”. Generally, guidelines have not cautioned against a lower limit beyond which treatment could be deleterious. A Cochrane review concluded that treating patients to lower than standard BP targets, ≤ 140-160/90-100 mmHg, does not reduce mortality or morbidity[4]. Over-treatment of diastolic blood pressure (DBP) has been associated with adverse cardiovascular (CV) events in patients with coronary artery disease (CAD)[5,6]. In patients at risk of or with established CAD, adverse events appear when DBP is lowered beyond values of 60 to 80 mmHg[7-11]. This J-curve phenomenon, first described by Stewart over 30 years ago[12], continues to be reported in the hypertension literature. Today there is no clear consensus on the ideal range of DBP in various patient groups.
Support for a lower threshold of DBP target is found in the rational assertion that at some point BP is too low to perfuse vital organs. The threshold for organ blood flow autoregulation is elevated in the presence of vascular disease, thus elevated BP may be “essential” for preserving organ function[13]. Compared to systolic blood pressure (SBP), DBP has a greater contribution to mean arterial pressure, which more closely correlates with organ perfusion. Additionally, since coronary perfusion occurs during diastole, a decrease in DBP would likely reduce perfusion and induce ischemia[14].
Many studies have identified a J-curve relationship between low DBP and adverse events (Tables 1 and 2). Existing data from observational and interventional studies have been reviewed previously[13,14]. These represent diverse ages and populations, different cutoff values of BP targets, varying outcome measures, and inconsistent findings[15-18]. Some studies were not appropriately designed to address pre-specified questions, others were underpowered[19-21], and still others lost the beauty of randomization in randomized controlled trials (RCTs) due to re-grouping for post hoc analyses.
Study | Type | n | Age1 | CAD2 | DM2 | CKD2 | CVA2 | Baseline DBP3 | DBP J-curve by outcome | DBP J-curve Nadir3 |
Studies to target DBP | ||||||||||
1967 JAMA | RCT | 143 | 51 | 22 | 6 | 121 | CV events and all-cause mortality | Not observed at 92 | ||
1970 JAMA | RCT | 380 | 51 | 104 | CV events and all-cause mortality | Not observed at 86 | ||||
1979 Lancet | Case-Control | 169 | 51 | 124 | MI | 90 | ||||
1998 Lancet (HOT) | RCT | 18790 | 62 | 6 | 8 | 1 | 105 | CV events; CV and all-cause mortality | 82-86 | |
Studies in the elderly | ||||||||||
1991 JAMA (SHEP) | RCT | 4736 | 72 | 5 | 10 | 1 | 77 | CVA and other CV events; CV mortality | Not observed at 70 | |
1997 Lancet (Syst- Eur) | RCT | 4695 | 70 | 30 | 4 | 86 | CVA and other CV events; all-cause and CV mortality | Not observed at 81 | ||
2008 N Engl J Med (HYVET) | RCT | 3845 | 84 | 12 | 6.8 | 7 | 90 | CVA; all-cause mortality; CV mortality; CVA mortality | Not observed at 84 | |
2016 JAMA (SPRINT) | RCT | 2636 | 80 | 25 | 0 | 44 | 0 | 71 | All CV events; CV mortality; all-cause mortality | Not observed at 65 |
Studies in CAD | ||||||||||
2005 J Hypertens (ACTION) | Post-Hoc | 7661 | 64 | 100 | 15 | 80 | CV mortality; event or procedure; all-cause mortality; CVA | 73 | ||
2006 Ann Intern Med (INVEST) | Post-Hoc | 22576 | 66 | 100 | 29 | 2 | 5 | 87 | All-cause mortality; non-fatal MI or CVA | 84 |
2009 J Hypertension (ONTARGET) | Post-Hoc | 25588 | 66 | 75 | 37 | 21 | 82 | CV mortality and all CV events | 75-79 | |
2010 Am J Med (INVEST) | Post-Hoc | 22576 | 66 | 100 | 29 | 2 | 5 | 87 | All-cause mortality; non-fatal MI or CVA | 70-75 |
2010 Eur Heart J (TNT) | Post-Hoc | 10001 | 60 | 100 | 15 | 5 | 79 | All CV events; CV and all-cause mortality | 81 | |
2010 Circulation (PROVE IT-TIMI) | Post-Hoc | 4162 | 58 | 100 | 18 | 11 | 6 | 75 | All-cause mortality and all CV events | 84-85 |
2011 Circulation (ONTARGET) | Post-Hoc | 12554 | 66 | 75 | 37 | 21 | 82 | CV mortality and all CV events | 80 | |
2012 Hypertension (SMART) | Post-Hoc | 5788 | 57 vs 65 | 60 | 17 | 28 | 82 | CV events and all-cause morality | 82 | |
2016 Eur Rev MedPharmacol Sci | RCT | 369 | 67 | 100 | 7 | 105 | All CV events | 75-80 | ||
2016 Eur Heart J (VALUE) | Post-Hoc | 15244 | 67 | 46 | 32 | 20 | 87 | All CV events; all-cause mortality | 80 | |
Studies in DM | ||||||||||
1998 BMJ (UKPDS) | RCT | 1148 | 56 | 100 | 94 | All cause mortality | Not observed at 83 | |||
2002 Kidney Int (ABCD) | RCT | 480 | 59 | 100 | 84 | GFR changes; CV event; retinopathy; neuropathy | Not observed at 75 | |||
2005 J Am SocNephrol (IDNT) | RCT | 1715 | 59 | 29 | 100 | 100 | 87 | CV events and mortality | 85 | |
2010 JAMA (INVEST) | Post-Hoc | 6400 | 66 | 100 | 100 | 4 | 9 | 85 | All-cause mortality; non-fatal MI or CVA | SBP nadir 115, but no corresponding DBP nadir reported |
2010 N Engl J Med (ACCORD) | RCT | 4733 | 62 | 34 | 100 | 76 | Non-fatal MI or CVA; CV mortality | Not observed at 68 | ||
2012 BMJ | Cohort | 126092 | 67 | 10 | 100 | 83 | All-cause mortality | 75 | ||
Epidemiology studies | ||||||||||
1991 BMJ (Framingham) | Cohort | 5209 | 30-62 | CV mortality; non-CV mortality | 75-79 | |||||
2003 Ann Intern Med (NHANES II) | Cohort | 7830 | 54 | 5 | 82 | All-cause mortality; CV mortality | 79 | |||
2011 J Gen InternMed (NHANES I) | Cohort | 13792 | 25-75 | All-cause mortality | 70-79 | |||||
2014 J Am CollCardiol | Cohort | 398419 | 64 | 19 | 30 | 24 | 8 | 73 | All-cause mortality; ESRD | 60-79 |
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 |
More than half of the studies identifying the DBP J-curve are post-hoc analyses[22-26]. This finding was most consistent among trials where most patients had underlying CAD compared to patients without CAD. Few RCTs have targeted DBP as an intervention. The average achieved DBP in such trials after intervention was greater than 80 mmHg. In the Hypertension Optimal Treatment (HOT) trial, it is difficult to recognize between-group difference due to the small differences in achieved DBP targets among the three groups (85 mmHg vs 83 mmHg vs 81 mmHg). A non-statistical trend towards increased CV events and mortality was observed at DBP valued < 80 mmHg[8].
Various epidemiological studies have found the J-curve phenomenon for DBP in certain patient subgroups. Increased CV death was seen in patients from the Framingham Heart Study cohort when DBP was reduced below 75-79 mmHg[27]. Patients from the National Health and Nutrition Examination Survey (NHANES) I and II both saw an increase in all-cause mortality when DBP was lowered below 70 mmHg[28,29]. A recent cohort of Kaiser 398419 patients showed differences in the j-curve nadir based on age and presence of diabetes[30].
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial achieved the lowest DBP among diabetic trials at 67.5 mmHg without increasing the risk of MI or CV mortality[31]. In a large cohort of 126092 newly diagnosed diabetics with CAD, risk of all-cause mortality increased when DBP was lowered below 75 mmHg[32]. Other studies of standard vs lower BP targets in diabetics have produced mixed results[33-36].
Meta-analyses have been conducted to evaluate lower targets compared to standard targets (Table 3). Generally, these analyses have shown no statistical difference in primary outcomes between targets[4,37-39]. In patients with chronic kidney disease, two meta-analyses showed conflicting results[40,41]. The J-curve effect was seen in one meta-analysis of 49 RCTs. In this study a meta-regression showed the risk of CV mortality increased by 28 percentage points for each 10 mmHg decrease in baseline DBP (P = 0.013), with harm being seen at values less than 78 mmHg[42]. Certain limitations that are germane to meta-analyses may explain why no J-curve was seen in other reports. First, most of these studies evaluated trials that used a dichotomous comparison of below or above a standard target and were not designed to compare different BP intervals. This is typically not possible without individual patient data. Second, selection bias from the individual trials can highly influence the outcome of the meta-analysis. Finally, outcomes across various studies may not be measured or defined using the same criteria.
Study | No. | Trials | DBP J-curve Nadir1 | Findings | Limitations |
2009 Cochrane Database Syst Rev | 22089 | 7 | Not observed at 85 | In hypertensive patients, lower vs standard BP targets (DBP 85 vs < 90) did not improve mortality or CV events | Difference in mean DBP was 3.4 mmHg between groups. In 2 trials, most did not achieve lower DBP targets. Failure to demonstrate harms with “lower targets” may be due to reporting bias |
2011 Ann Intern Med | 2272 | 3 | Not observed at 75-80 | In patient with CKD, lower BP targets (DBP < 75-80) did not improve renal outcomes | Data on deaths and CV disease outcomes were not informative given the lack of ascertainment or low event rate. Included very few patients with CKD; trial duration may have been too short to detect events |
2013 Cochrane Database Syst Rev | 2580 | 4 | Not observed at 76 | In diabetics, comparing lower vs standard DBP targets, no difference observed in CV mortality or CV events. Lower groups showed trend towards reduced non-cardiac mortality | High risk of selection bias for every outcome analyzed in favor of the “lower” DBP target |
2013 CMAJ | 9287 | 11 | Not observed at 75-92 | In patients with CKD, intensive BP lowering, compared to standard therapy, reduced risk of kidney failure, but not the risk of CV events (CV outcome data available only in 5 of 11 trials) | Did not include patient with diabetes. Heterogeneity of individual study limits the strength of conclusions |
2015 Lancet | 44989 | 19 | Not observed at 76 | In high risk patients, intensive vs standard BP therapy reduced major CV events, including CVA; but more intensive BP lowering no further benefits on mortality | Many trials did not achieve target BP levels in most patients. Mean BP in intensive groups was 133/76 |
2015 JAMA | 100354 | 40 | Not observed at 64-83 | In diabetics, BP lowering improved mortality and CV events if baseline SBP > 140, but no outcome benefit if baseline SBP < 140 except CVA and albuminuria | Scarcity of large trials with achieved BP levels of < 70-80 (baseline DBP 70-106) |
2016 BMJ | 73738 | 49 | 78 | In diabetics, if SBP < 140, risk of CV mortality increased by 28 percentage points for each 10 mmHg decrease in baseline DBP (P = 0.013) | Most included trials were not designed to evaluate different BP targets, but randomized patients to drugs or placebo |
Nearly all of the major society guidelines for hypertension have been updated in the last 5 years (Table 4). Some have included discussions regarding the J-curve and whether or not the evidence is strong enough to support minimum thresholds in both DBP and SBP. Yet in the final analysis, none have concluded that there is sufficient evidence to make a recommendation for a minimum diastolic threshold.
Society | Year updated | DBP upper threshold1 | DBP lower threshold1 | Individualized to comorbidities | Discuss | |||
Age | CAD | DM | CKD | J-curve | ||||
ACCF/AHA (elderly) | 2011 | < 90 | - | Yes | - | - | - | Yes |
ADA | 2016 | < 90 | - | Yes | - | - | - | - |
CHEP | 2016 | < 90 (< 80 in diabetes) | 60 in CAD | Yes | Yes | Yes | Yes | Yes |
ESH/ESC | 2013 | < 90 (< 85 in diabetes) | - | Yes | Yes | Yes | Yes | Yes |
ESC | 2016 | < 85 | 80 | Yes | - | Yes | - | Yes |
French | 2013 | < 90 | - | Yes | - | - | - | - |
JNC8 | 2014 | < 90 (including DM and CKD) | - | - | - | - | - | Yes |
KDIGO | 2012 | ≤ 90 ( ≤ 80 if microalbuminuria) | - | Yes | - | Yes | Yes | Yes |
NICE | 2011 | < 85 | - | - | - | - | - | - |
Renal Association (United Kingdom) | 2011 | < 90 (< 80 if proteinuria) | - | - | - | - | Yes | - |
The most robust discussion between the J-curve and the “lower the better” concept was found in the 2013 guidelines of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC)[43]. Following an explanation of the reasons why the J-curve is popular and rational, they cite observational data that both validate and refute the relationship. Regarding patients with overt CAD, they report that there is inconsistent evidence to treat hypertension to a systolic target of < 130 mmHg. These patients may be most affected by a J-curve phenomenon. Prior to the publication of the 2013 ESH/ESC guidelines, the ESH issued a task force document that expanded upon the 2007 guidelines and expanded the discussion of the J-curve[44].
In 2016, the sixth joint task force of the ESC, along with 10 other European societies including the ESH, updated their 2012 guidelines[45]. These are the first to include a lower threshold for both diastolic and systolic BP targets. After reviewing post-hoc analyses that investigate the J-curve, they conclude that this phenomenon cannot be excluded in lower SBP < 130 mmHg, especially in patients with atherosclerosis. They recommend blood pressure goals of 130-139/80-85 mmHg in all hypertensive patients.
The Canadian Hypertension Education Program (CHEP) also debated this topic in their 2013 guidelines[46] but decided to wait for more evidence. A lower threshold was revisited in 2016 and a new recommendation was made for patients with CAD. The authors caution against lowering DBP below 60 mmHg for concern that myocardial ischemia may be exacerbated. This was graded as weak evidence[47].
JNC updated their guidelines in 2014 with the eighth panel[48]. Based largely on the HOT trial, the authors concluded that the evidence shows no benefit in treating patients to DBP goals of < 80 or 85 mmHg, even among diabetics. Their recommendations differed from 2003 when the panel recommended a target of < 80 mmHg in diabetics.
While the United Kingdom’s Renal Associate did not issue any recommendations on a lower threshold for DBP targets, they did make such a recommendation for SBP. They referenced the Irbesartan Diabetic Nephropathy Trial and the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint (ONTARGET) trail, both of which found increased mortality in patients who achieved a SBP of < 120 mmHg. They conclude that (1) antihypertensive therapy should be individualized and (2) in chronic kidney disease patients, there is no evidence to support lower SBP below 120 mmHg[49].
The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical guidelines advised caution in patients with comorbidities, but did not feel the evidence would allow for a specified lower limit for BP lowering[50]. In patients with microalbuminuria, they recommend more aggressive control down to a DBP of 80 mmHg. The American Diabetes Association (ADA) guidelines increased their upper threshold from a maximum DBP of 80 mmHg in 2013 to 90 mmHg in the 2016 guidelines[51,52].
In the elderly, recommended BP goal by guidelines for uncomplicated hypertension remains at < 140/90 mmHg. In an expert consensus, the American College of Cardiology Foundation (ACCF), and the American Heart Association (AHA) recognize that this goal is based more on expert opinion rather than randomized controlled trials[53]. Questions that remain to be answered include target BP across a range of ages and the application of the J-curve in the elderly. The ACCF/AHA discuss a target SBP of 150 mmHg as “the diagnostic criterion for hypertension and the treatment target in octogenarians and beyond”. However, the formal recommendation leaves this as an area of uncertainty. The National Clinical Guideline Centre (United Kingdom) updated their recommendations in 2011 and provide a separate target for people aged 80 years and over of 150/90 mmHg[54]. The French Society of Hypertension made the same recommendation in 2013[55].
Currently, the ESC and CHEP have issued the only guidelines that include goals with a lower threshold for DBP target. While the ESC recommends a DBP 80-85 mmHg, CHEP issues a caution below a lower threshold for DBP target. This threshold is specific to patients with CAD. These are important steps in addressing lower thresholds in general and for specific populations. Other societies, including the International Society of Hypertension and the Latin American Society of Hypertension, are cautious in recommending reduction in SBP to levels below 130 mm Hg, as was accomplished in the SPRINT trial[56,57]. Many questions still exists as to what targets achieve maximal benefit for patients[58].
A J-curve in CV events is most consistently seen in patients with existing CAD. The current evidence for adverse CV events at lower diastolic pressures is based largely on observational and post-hoc analyses. Indeed, the Latin American Society of Hypertension recently reported that only 14 antihypertensive treatment trials have compared the effects of more vs less BP lowering. The ongoing debate between the lower the better concept and the J-curve hypothesis is “a good demonstration that evidence on the issue is lacking[57]”.
Individual comorbid conditions play a significant role in overall CV risk as well as tolerance to lower blood pressures. Sophisticated statistics used in data analyses to adjust for confounders still cannot match the impartiality of well-designed and well-conducted RCTs. Diabetic patients receive an added benefit of reduction in nephropathy as well as CV events when BP is lowered to < 140/80 mmHg[59]. Patients with CAD, especially following acute coronary syndromes, are more affected by the J-curve than patients with stroke[5,60]. Many societies are now publishing guidelines with goals based on age and co-morbid conditions.
In 2003, the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) stated that the relationship between BP and CV events is continuous, consistent, and independent of other risk factors[61]. Observational studies of patients free from CV disease have confirmed this linear relationship in DBP levels as low as 75 mmHg[2]. Yet these finding do not consistently apply to patients with significant comorbid conditions.
While we advocate that major societal guidelines discuss the effect of aggressive BP lowering among different populations, we recognize that there are practical concerns with recommending a lower limit. First, since the cutoffs derived from post-hoc and observational analyses vary widely, as well as the outcomes, it is difficult to define what that lower limit should be. Second, in patients where a J-shaped relationship occurs between DBP and outcomes, specifying a lower limit could encourage targeting (as close to but not below) that limit, leading to unintended overtreatment. Third, the increased pulse pressure with age poses a challenge for clinical decision on achieving balanced therapeutic targets (lowering SBP without over treating DBP). Attempting to further decrease SBP for stroke and chronic kidney disease risk reduction may compromise outcomes for coronary artery disease risk via reduction in DBP. Additionally, while challenging to measure, central BP may correlate more closely with cardiovascular events than brachial BP[62]. Systolic function is lower in the aorta than the peripheral system and can be less responsive to various antihypertensive agents[63].
Reduction of DBP to less than 60-80 mmHg appears to lead to adverse CV events in high risk patient populations. Currently, only two major society guidelines on hypertension include a minimum threshold for diastolic blood pressure. Available studies demonstrating adverse events at lower DBP vary in their cutoff values and patient populations. Randomized controlled trials comparing outcomes across different DBP targets are limited. We anticipate that more guidelines will include recommendations individualized to comorbid conditions as future studies focus on risk factors within specific disease populations, especially CAD, stroke, chronic kidney disease, and diabetes.
Manuscript source: Invited manuscript
Specialty type: Peripheral vascular disease
Country of origin: United States
Peer-review report classification
Grade A (Excellent): 0
Grade B (Very good): B, B, B
Grade C (Good): 0
Grade D (Fair): 0
Grade E (Poor): 0
P- Reviewer: Cheng TH, Papanas N, Sanchez R S- Editor: Qiu S L- Editor: A E- Editor: Lu YJ
1. | Hsiao CJ, Cherry DK, Beatty PC, Rechtsteiner EA. National Ambulatory Medical Care Survey: 2007 summary. Natl Health Stat Report. 2010;1-32. [PubMed] [Cited in This Article: ] |
2. | Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903-1913. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 6631] [Cited by in F6Publishing: 6639] [Article Influence: 301.8] [Reference Citation Analysis (0)] |
3. | Turnbull F, Neal B, Ninomiya T, Algert C, Arima H, Barzi F, Bulpitt C, Chalmers J, Fagard R, Gleason A. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ. 2008;336:1121-1123. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 510] [Cited by in F6Publishing: 491] [Article Influence: 30.7] [Reference Citation Analysis (0)] |
4. | Arguedas JA, Perez MI, Wright JM. Treatment blood pressure targets for hypertension. Cochrane Database Syst Rev. 2009;CD004349. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 66] [Cited by in F6Publishing: 97] [Article Influence: 6.5] [Reference Citation Analysis (0)] |
5. | Messerli FH, Mancia G, Conti CR, Hewkin AC, Kupfer S, Champion A, Kolloch R, Benetos A, Pepine CJ. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med. 2006;144:884-893. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 560] [Cited by in F6Publishing: 522] [Article Influence: 29.0] [Reference Citation Analysis (0)] |
6. | Bangalore S, Messerli FH, Wun CC, Zuckerman AL, DeMicco D, Kostis JB, LaRosa JC. J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial. Eur Heart J. 2010;31:2897-2908. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 261] [Cited by in F6Publishing: 264] [Article Influence: 18.9] [Reference Citation Analysis (0)] |
7. | Kovesdy CP, Bleyer AJ, Molnar MZ, Ma JZ, Sim JJ, Cushman WC, Quarles LD, Kalantar-Zadeh K. Blood pressure and mortality in U.S. veterans with chronic kidney disease: a cohort study. Ann Intern Med. 2013;159:233-242. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 157] [Cited by in F6Publishing: 163] [Article Influence: 14.8] [Reference Citation Analysis (0)] |
8. | Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S, Ménard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998;351:1755-1762. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 3920] [Cited by in F6Publishing: 3524] [Article Influence: 135.5] [Reference Citation Analysis (0)] |
9. | Mancia G, Schumacher H, Redon J, Verdecchia P, Schmieder R, Jennings G, Yusoff K, Ryden L, Liu GL, Teo K. Blood pressure targets recommended by guidelines and incidence of cardiovascular and renal events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET). Circulation. 2011;124:1727-1736. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 124] [Cited by in F6Publishing: 129] [Article Influence: 9.9] [Reference Citation Analysis (0)] |
10. | Tringali S, Oberer CW, Huang J. Low Diastolic Blood Pressure as a Risk for All-Cause Mortality in VA Patients. Int J Hypertens. 2013;2013:178780. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 15] [Cited by in F6Publishing: 16] [Article Influence: 1.5] [Reference Citation Analysis (0)] |
11. | Adler AI, Stratton IM, Neil HA, Yudkin JS, Matthews DR, Cull CA, Wright AD, Turner RC, Holman RR. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. 2000;321:412-419. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1386] [Cited by in F6Publishing: 1272] [Article Influence: 53.0] [Reference Citation Analysis (0)] |
12. | Stewart IM. Relation of reduction in pressure to first myocardial infarction in patients receiving treatment for severe hypertension. Lancet. 1979;1:861-865. [PubMed] [DOI] [Cited in This Article: ] [Cited by in F6Publishing: 1] [Reference Citation Analysis (0)] |
13. | Zanchetti A. Blood pressure targets of antihypertensive treatment: up and down the J-shaped curve. Eur Heart J. 2010;31:2837-2840. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 51] [Cited by in F6Publishing: 51] [Article Influence: 3.6] [Reference Citation Analysis (0)] |
14. | Banach M, Aronow WS. Blood pressure j-curve: current concepts. Curr Hypertens Rep. 2012;14:556-566. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 77] [Cited by in F6Publishing: 71] [Article Influence: 5.9] [Reference Citation Analysis (0)] |
15. | SHEP Cooperative Research Group. 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;265:3255-3264. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2597] [Cited by in F6Publishing: 2219] [Article Influence: 67.2] [Reference Citation Analysis (0)] |
16. | Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhäger WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE. 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;350:757-764. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2083] [Cited by in F6Publishing: 1836] [Article Influence: 68.0] [Reference Citation Analysis (0)] |
17. | Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, Stoyanovsky V, Antikainen RL, Nikitin Y, Anderson C. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887-1898. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2183] [Cited by in F6Publishing: 2039] [Article Influence: 127.4] [Reference Citation Analysis (0)] |
18. | Williamson JD, Supiano MA, Applegate WB, Berlowitz DR, Campbell RC, Chertow GM, Fine LJ, Haley WE, Hawfield AT, Ix JH. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial. JAMA. 2016;315:2673-2682. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 777] [Cited by in F6Publishing: 842] [Article Influence: 105.3] [Reference Citation Analysis (0)] |
19. | Veterans Administration Cooperative Study Group on Antihypertensive Agents. Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA. 1967;202:1028-1034. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 255] [Cited by in F6Publishing: 195] [Article Influence: 3.4] [Reference Citation Analysis (0)] |
20. | Veterans Administration Cooperative Study Group on Antihypertensive Agents. Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA. 1970;213:1143-1152. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1296] [Cited by in F6Publishing: 1105] [Article Influence: 20.5] [Reference Citation Analysis (0)] |
21. | Lu W. Could intensive anti-hypertensive therapy produce the “J-curve effect” in patients with coronary artery disease and hypertension after revascularization? Eur Rev Med Pharmacol Sci. 2016;20:1350-1355. [PubMed] [Cited in This Article: ] |
22. | Lubsen J, Wagener G, Kirwan BA, de Brouwer S, Poole-Wilson PA. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with symptomatic stable angina and hypertension: the ACTION trial. J Hypertens. 2005;23:641-648. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 100] [Cited by in F6Publishing: 107] [Article Influence: 5.6] [Reference Citation Analysis (0)] |
23. | Sleight P, Redon J, Verdecchia P, Mancia G, Gao P, Fagard R, Schumacher H, Weber M, Böhm M, Williams B. Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study. J Hypertens. 2009;27:1360-1369. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 271] [Cited by in F6Publishing: 282] [Article Influence: 18.8] [Reference Citation Analysis (0)] |
24. | Denardo SJ, Gong Y, Nichols WW, Messerli FH, Bavry AA, Cooper-Dehoff RM, Handberg EM, Champion A, Pepine CJ. Blood pressure and outcomes in very old hypertensive coronary artery disease patients: an INVEST substudy. Am J Med. 2010;123:719-726. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 111] [Cited by in F6Publishing: 118] [Article Influence: 8.4] [Reference Citation Analysis (0)] |
25. | Dorresteijn JA, van der Graaf Y, Spiering W, Grobbee DE, Bots ML, Visseren FL. Relation between blood pressure and vascular events and mortality in patients with manifest vascular disease: J-curve revisited. Hypertension. 2012;59:14-21. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 106] [Cited by in F6Publishing: 109] [Article Influence: 8.4] [Reference Citation Analysis (0)] |
26. | Mancia G, Kjeldsen SE, Zappe DH, Holzhauer B, Hua TA, Zanchetti A, Julius S, Weber MA. Cardiovascular outcomes at different on-treatment blood pressures in the hypertensive patients of the VALUE trial. Eur Heart J. 2016;37:955-964. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 75] [Cited by in F6Publishing: 78] [Article Influence: 8.7] [Reference Citation Analysis (0)] |
27. | D’Agostino RB, Belanger AJ, Kannel WB, Cruickshank JM. Relation of low diastolic blood pressure to coronary heart disease death in presence of myocardial infarction: the Framingham Study. BMJ. 1991;303:385-389. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 165] [Cited by in F6Publishing: 171] [Article Influence: 5.2] [Reference Citation Analysis (0)] |
28. | Taylor BC, Wilt TJ, Welch HG. Impact of diastolic and systolic blood pressure on mortality: implications for the definition of “normal”. J Gen Intern Med. 2011;26:685-690. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 58] [Cited by in F6Publishing: 53] [Article Influence: 4.1] [Reference Citation Analysis (0)] |
29. | Pastor-Barriuso R, Banegas JR, Damián J, Appel LJ, Guallar E. Systolic blood pressure, diastolic blood pressure, and pulse pressure: an evaluation of their joint effect on mortality. Ann Intern Med. 2003;139:731-739. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 132] [Cited by in F6Publishing: 138] [Article Influence: 6.6] [Reference Citation Analysis (0)] |
30. | Sim JJ, Shi J, Kovesdy CP, Kalantar-Zadeh K, Jacobsen SJ. Impact of achieved blood pressures on mortality risk and end-stage renal disease among a large, diverse hypertension population. J Am Coll Cardiol. 2014;64:588-597. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 126] [Cited by in F6Publishing: 118] [Article Influence: 11.8] [Reference Citation Analysis (0)] |
31. | Cushman WC, Evans GW, Byington RP, Goff DC, Grimm RH, Cutler JA, Simons-Morton DG, Basile JN, Corson MA, Probstfield JL. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575-1585. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2637] [Cited by in F6Publishing: 2359] [Article Influence: 168.5] [Reference Citation Analysis (0)] |
32. | Vamos EP, Harris M, Millett C, Pape UJ, Khunti K, Curcin V, Molokhia M, Majeed A. Association of systolic and diastolic blood pressure and all cause mortality in people with newly diagnosed type 2 diabetes: retrospective cohort study. BMJ. 2012;345:e5567. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 62] [Cited by in F6Publishing: 70] [Article Influence: 5.8] [Reference Citation Analysis (0)] |
33. | UK Prospective Diabetes Study Group. Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes: UKPDS 40. UK Prospective Diabetes Study Group. BMJ. 1998;317:720-726. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 230] [Cited by in F6Publishing: 205] [Article Influence: 7.9] [Reference Citation Analysis (0)] |
34. | Schrier RW, Estacio RO, Esler A, Mehler P. Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney Int. 2002;61:1086-1097. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 586] [Cited by in F6Publishing: 533] [Article Influence: 24.2] [Reference Citation Analysis (0)] |
35. | Berl T, Hunsicker LG, Lewis JB, Pfeffer MA, Porush JG, Rouleau JL, Drury PL, Esmatjes E, Hricik D, Pohl M. Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial. J Am Soc Nephrol. 2005;16:2170-2179. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 225] [Cited by in F6Publishing: 244] [Article Influence: 12.8] [Reference Citation Analysis (0)] |
36. | Cooper-DeHoff RM, Gong Y, Handberg EM, Bavry AA, Denardo SJ, Bakris GL, Pepine CJ. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA. 2010;304:61-68. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 483] [Cited by in F6Publishing: 447] [Article Influence: 31.9] [Reference Citation Analysis (0)] |
37. | Upadhyay A, Earley A, Haynes SM, Uhlig K. Systematic review: blood pressure target in chronic kidney disease and proteinuria as an effect modifier. Ann Intern Med. 2011;154:541-548. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 249] [Cited by in F6Publishing: 224] [Article Influence: 17.2] [Reference Citation Analysis (0)] |
38. | Arguedas JA, Leiva V, Wright JM. Blood pressure targets for hypertension in people with diabetes mellitus. Cochrane Database Syst Rev. 2013;CD008277. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 31] [Cited by in F6Publishing: 44] [Article Influence: 4.0] [Reference Citation Analysis (0)] |
39. | Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA. 2015;313:603-615. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 538] [Cited by in F6Publishing: 548] [Article Influence: 60.9] [Reference Citation Analysis (0)] |
40. | Lv J, Ehteshami P, Sarnak MJ, Tighiouart H, Jun M, Ninomiya T, Foote C, Rodgers A, Zhang H, Wang H. Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis. CMAJ. 2013;185:949-957. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 191] [Cited by in F6Publishing: 195] [Article Influence: 17.7] [Reference Citation Analysis (1)] |
41. | Xie X, Atkins E, Lv J, Bennett A, Neal B, Ninomiya T, Woodward M, MacMahon S, Turnbull F, Hillis GS. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet. 2016;387:435-443. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 666] [Cited by in F6Publishing: 681] [Article Influence: 85.1] [Reference Citation Analysis (0)] |
42. | Brunström M, Carlberg B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses. BMJ. 2016;352:i717. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 241] [Cited by in F6Publishing: 241] [Article Influence: 30.1] [Reference Citation Analysis (0)] |
43. | Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A. 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;34:2159-2219. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 3156] [Cited by in F6Publishing: 3184] [Article Influence: 289.5] [Reference Citation Analysis (0)] |
44. | Mancia G, Laurent S, Agabiti-Rosei E, Ambrosioni E, Burnier M, Caulfield MJ, Cifkova R, Clément D, Coca A, Dominiczak A. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens. 2009;27:2121-2158. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1060] [Cited by in F6Publishing: 1002] [Article Influence: 71.6] [Reference Citation Analysis (0)] |
45. | Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corrà U, Cosyns B, Deaton C. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention & amp; Rehabilitation (EACPR). Eur J Prev Cardiol. 2016;23:NP1-NP96. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 512] [Cited by in F6Publishing: 579] [Article Influence: 72.4] [Reference Citation Analysis (0)] |
46. | Hackam DG, Quinn RR, Ravani P, Rabi DM, Dasgupta K, Daskalopoulou SS, Khan NA, Herman RJ, Bacon SL, Cloutier L. The 2013 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol. 2013;29:528-542. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 131] [Cited by in F6Publishing: 140] [Article Influence: 12.7] [Reference Citation Analysis (0)] |
47. | Leung AA, Nerenberg K, Daskalopoulou SS, McBrien K, Zarnke KB, Dasgupta K, Cloutier L, Gelfer M, Lamarre-Cliche M, Milot A. Hypertension Canada’s 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Can J Cardiol. 2016;32:569-588. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 320] [Cited by in F6Publishing: 339] [Article Influence: 42.4] [Reference Citation Analysis (0)] |
48. | James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 5429] [Cited by in F6Publishing: 5379] [Article Influence: 537.9] [Reference Citation Analysis (0)] |
49. | MacGregor MS, Taal MW. Renal Association Clinical Practice Guideline on detection, monitoring and management of patients with CKD. Nephron Clin Pract. 2011;118 Suppl 1:c71-c100. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 18] [Cited by in F6Publishing: 21] [Article Influence: 1.6] [Reference Citation Analysis (0)] |
50. | Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. Blood pressure management in CKD ND patients without diabetes mellitus. In: KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012;2:337-414. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 18] [Cited by in F6Publishing: 19] [Article Influence: 0.5] [Reference Citation Analysis (0)] |
51. | American Diabetes Association. Standards of medical care in diabetes--2013. Diabetes Care. 2013;36 Suppl 1:S11-S66. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2371] [Cited by in F6Publishing: 2437] [Article Influence: 221.5] [Reference Citation Analysis (0)] |
52. | American Diabetes Association. Cardiovascular Disease and Risk Management. Diabetes Care. 2016;39 Suppl 1:S60-S71. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 174] [Cited by in F6Publishing: 169] [Article Influence: 21.1] [Reference Citation Analysis (0)] |
53. | Aronow WS, Fleg JL, Pepine CJ, Artinian NT, Bakris G, Brown AS, Ferdinand KC, Ann Forciea M, Frishman WH, Jaigobin C. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension. J Am Soc Hypertens. 2011;5:259-352. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 92] [Cited by in F6Publishing: 87] [Article Influence: 6.7] [Reference Citation Analysis (0)] |
54. | National Clinical Guideline Centre (UK). Hypertension: The Clinical Management of Primary Hypertension in Adults: Update of Clinical Guidelines 18 and 34. London: Royal College of Physicians (UK) 2011; . [PubMed] [Cited in This Article: ] |
55. | Blacher J, Halimi JM, Hanon O, Mourad JJ, Pathak A, Schnebert B, Girerd X. Management of hypertension in adults: the 2013 French Society of Hypertension guidelines. Fundam Clin Pharmacol. 2014;28:1-9. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 56] [Cited by in F6Publishing: 55] [Article Influence: 5.0] [Reference Citation Analysis (0)] |
56. | Weber MA, Poulter NR, Schutte AE, Burrell LM, Horiuchi M, Prabhakaran D, Ramirez AJ, Wang JG, Schiffrin EL, Touyz RM. Is It Time to Reappraise Blood Pressure Thresholds and Targets? A Statement From the International Society of Hypertension-A Global Perspective. Hypertension. 2016;68:266-268. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 14] [Cited by in F6Publishing: 14] [Article Influence: 1.8] [Reference Citation Analysis (0)] |
57. | López-Jaramillo P, Coca A, Sánchez R, Zanchetti A. Hypertension Guidelines: Is It Time to Reappraise Blood Pressure Thresholds and Targets? Position Statement of the Latin American Society of Hypertension. Hypertension. 2016;68:257-262. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 18] [Cited by in F6Publishing: 19] [Article Influence: 2.4] [Reference Citation Analysis (0)] |
58. | Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015;373:2103-2116. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 4453] [Cited by in F6Publishing: 4051] [Article Influence: 450.1] [Reference Citation Analysis (0)] |
59. | UK PDSG. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317:703-713. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 4930] [Cited by in F6Publishing: 4217] [Article Influence: 162.2] [Reference Citation Analysis (0)] |
60. | Bangalore S, Qin J, Sloan S, Murphy SA, Cannon CP. What is the optimal blood pressure in patients after acute coronary syndromes?: Relationship of blood pressure and cardiovascular events in the PRavastatin OR atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction (PROVE IT-TIMI) 22 trial. Circulation. 2010;122:2142-2151. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 165] [Cited by in F6Publishing: 174] [Article Influence: 12.4] [Reference Citation Analysis (0)] |
61. | Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-2572. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 13416] [Cited by in F6Publishing: 13132] [Article Influence: 625.3] [Reference Citation Analysis (0)] |
62. | McEniery CM, Cockcroft JR, Roman MJ, Franklin SS, Wilkinson IB. Central blood pressure: current evidence and clinical importance. Eur Heart J. 2014;35:1719-1725. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 476] [Cited by in F6Publishing: 421] [Article Influence: 42.1] [Reference Citation Analysis (0)] |
63. | 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;54:1827-1834. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 162] [Cited by in F6Publishing: 170] [Article Influence: 11.3] [Reference Citation Analysis (0)] |