Wednesday, February 25, 2015

Blood pressure target in diabetes mellitus

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:

Swapnil Hiremath said...

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

Amit Langote said...

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.