Blood pressure target in diabetes mellitus

422 2
Hypertension in diabetic patients increases
the risk of microvascular and macrovascular complications. It is quantitatively
and qualitatively different from the non-diabetic population and characterized
by disturbed circadian rhythm of blood pressure (BP) with increased
variability. It also features frequent nocturnal hypertension with high 24 hour
BP load and impaired auto-regulation of blood flow leading to microvascular
injury.

A large
meta-analysis
of 1 million individuals followed for 14 years showed a
continuous decrease in cardiovascular risk with reduction in BP to as low as
115/75 mmHg. In the absence of RCT data, presuming “lower is better”, BP
targets of < 130/80 mm Hg were traditionally recommended in diabetic
patients. However the hypothesis of a J-shaped relationship with risk
challenges the lower BP targets suggesting that benefits of extreme BP
reductions are smaller than moderate reductions. This seems logical as
physiologically there is a low (as well as high) BP threshold for organ blood
flow auto-regulation. Two diabetic statin trials (TNT
and PROVE
IT-TIMI
) reported a J-shaped relationship between BP and adverse
cardiovascular events, although there were no BP lowering interventions.  Recently, JNC 8 (based on the ACCORD trial,
where the SBP target of < 120 mm Hg could have produced J shaped curve) and
ESH/ESC 2013 (diastolic target based on HOT trial) recommended a
relaxed BP target of < 140/90 mmHg in diabetic patients. These conflicting
recommendations on hypertension targets, from various professional bodies have
created confusion in the minds of physicians.

Comparison of BP
targets (in mm Hg) by different guidelines

 

Age 

Diabetes

Chronic Kidney disease

JNC 8 (2013)

<60 y: <140/90
≥60 y: <150/90

<140/90

<140/90

ESH/ESC (2013)

Elderly <
80y:
SBP 140-150SBP < 140 in fit patientsDBP < 90
 Elderly >
80 y:
SBP 140-150DBP < 90

<140/85

<140/90

ASH/ISH (2014)

< 80 y: <140/90
≥ 80 y: <150/90

<140/90

<140/90

AHA/ACC/CDC (2013)

<140/90
Lower targets may be appropriate in some patients
including the elderly

<140/90
Lower targets may be considered

<140/90
Lower targets may be considered

KDIGO BP guidelines in CKD (2012)

No recommendation for general population. For Elderly
with CKD ND
Tailor BP target based on age and co-morbidities

CKD ND with or without
diabetes

Albuminuria
< 30 mg /24 hr
≤ 140/90
Albuminuria
> 30 mg /24 hr
≤ 130/80 

CKD ND = non-dialysis-dependent CKD
A recent
meta-analysis in JAMA
has reignited the debate of BP targets in patients
with diabetes. Emdin et al analyzed
45 RCT`s (100,354 participants), conducted between Jan 1966 and October 2014,
of BP lowering treatment in patients with diabetes (regardless of presence or
absence of defined hypertension). Trials with predominantly type 1 diabetes
patients were excluded. The researchers examined the associations between
BP-lowering treatment and vascular disease in type 2 diabetes. They found that:
  •  Each 10-mmHg lower systolic BP
    was associated with a lower risk of mortality, cardiovascular disease events,
    coronary heart disease events, stroke, albuminuria and retinopathy.
  • All outcomes, including
    mortality, were reduced when SBP was lowered from elevated baseline of >140
    mm Hg and higher to a range of 130-140 mmHg. 
  •  Further reduction of SBP below
    130 mm Hg yielded lower risk of stroke, retinopathy and progression of
    albuminuria.
  •  Irrespective of drug class, the
    associations between BP-lowering treatments and outcomes were not significantly
    different except for stroke and heart failure.

The authors recommended that for patients
at high risk of stroke, retinopathy or progression of albuminuria, BP treatment
should be commenced at initial SBP level of 140 mmHg and target SBP below 130
mmHg.
The lower risk of stroke with reduction of
SBP below 130 mmHg has been previously reported in the TNT
trial, this meta-analysis
and a subgroup analyses
from the ONTARGET trial
. However, the bigger question is if such lower SBP
target can be achieved without any adverse events in the elderly diabetic
population. The rate of serious adverse events reported in ACCORD trial in
intensive treatment group (achieved BP 119 mmHg) was 2.5 times that of the
control group (achieved BP 133 mmHg). While there is clear benefit in BP
sensitive outcomes like stroke, it is unclear why lower SBP target below 130
mmHg does not benefit other outcomes like heart failure and renal failure. This
could be due to the fact that hypertension trials have a short follow up and
these outcomes occur too late in the disease process to see early benefits. Or
could this be due to J-shaped relationship?
As summed up in a recent commentary titled
Hypertension
Guidelines in need of Guidance
”: We should be more worried about
hypertension, not hypotension. Surely, one would avoid excessive or unwanted
degree of BP lowering in patients with hypertension; it needs only common
sense, not guideline committees.
Which hypertension guidelines do you
follow? And what BP target do you set for your diabetes patients? Will you try
to target these lower SBP if your patient tolerated them? Leave your comments
below.
Amit Langote
Nephrology Fellow, Ottawa

2 comments

  1. I agree with you Swapnil. I think CHEP has maintained a balanced approach by recommending <130/80 mm Hg BP target in diabetics with a caution to watch out for the elderly frail who may not tolerate such low pressures. Unfortunately, the young healthy diabetic who may tolerate these low pressures, are not seen by a Nephrologist. We commonly see the elderly group with comorbid illness in whom the side effects of hypotension can be catastrophic (fall, head injury).
    Having said that, benefit of preventing a hard outcome like stroke with lower target pressures in diabetic`s cannot be neglected. If not prevented, stroke can be equally catastrophic event. Hence it is necessary to individualize the blood pressure targets in diabetic patients based on their risk for stroke.

  2. Hi Amit
    Great post!
    I would liked inclusion of the CHEP and/or CDA or CSN guidelines. They do recommend 130/80 for diabetics (with or without CKD) – after weighing the same evidence. Part of the problem is which outcomes are considered important. Stroke reduction is inarguably a robust benefit at lower blood pressure thresholds – and IMO to just look at mortality (JNC) is somewhat rigid. Lastly, it's the complex interaction/interplay – a 40 yr old diabetic on 2 drugs and BP 128/78 is not the same as the 80 yr old on 4 drugs and BP 148/60!

    Ref:
    CHEP http://www.ncbi.nlm.nih.gov/m/pubmed/24786438/
    CSN
    http://www.ncbi.nlm.nih.gov/m/pubmed/24725980/

    Disclosure: I am part of both those groups cited above.

    Swapnil Hiremath

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