Physicians' Academy for Cardiovascular Education

Pulse pressure provides additive prognostic utility for CV risk stratification

Literature - Selvaraj S et al., J Am Coll Cardiol 2016

Pulse Pressure and Risk for Cardiovascular Events in Patients With Atherothrombosis
From the REACH Registry


Selvaraj S, Steg G, Elbez Y,et al.
J Am Coll Cardiol 2016;67:392403
 

Background

Pulse pressure reflects stroke volume and arterial wall compliance and represents a cardiovascular risk factor [1]. High pulse pressure is associated with decreased arterial compliance, especially in older patients with atherosclerosis, hypertension, and diabetes, among others [2]. Although there is evidence supporting that pulse pressure is associated with adverse cardiovascular outcomes in special populations [3-4], the predictive value of pulse pressure in a broad population has not been thoroughly studied.
In this study, the relationship between pulse pressure and major adverse cardiovascular events was examined independently of mean arterial pressure, in the Reduction of Atherothrombosis for Continued Health (REACH) registry [5]. Out of 67,888 eligible participants with clinical atherothrombotic disease or risk factors for its development, 45,087 met the inclusion criteria and were analysed in the present study. The mean age of the cohort was 68 ± 10 years and 35% were women.
 

Main results

  • The mean blood pressure was 138 ± 19/79 ± 11 mm Hg, and the mean pulse pressure was 49 ± 16 mm Hg
  • Increasing pulse pressure quartile was associated with worse outcomes including CV death, nonfatal myocardial infarction (MI), nonfatal stroke, all stroke, all MI, CV hospitalisation, and the combined outcome of CV death, MI, stroke, or CV hospitalisation (unadjusted HRs between 1.1 and 1.4 when comparing quartile 4 with quartile 1, P < 0.05 for all comparisons).
  • After adjusting for sex, age, current smoking status, history of hypercholesterolemia, history of diabetes, aspirin use, statin use, blood pressure medication use, and mean arterial pressure, pulse pressure quartile was still associated with all outcomes (adjusted HRs between 1.1 and 1.3 when comparing quartile 4 with quartile 1, P < 0.05 for all comparisons)  except all stroke and CV death.
  • In multiple sensitivity analyses the relationship between pulse pressure and adverse events was studied more extensively, in several subgroups. Participants without established atherothrombotic disease showed a strong relationship for instance, suggesting that despite their lower risk, pulse pressure has prognostic value.

Conclusions

In a broad registry population of subjects with established atherosclerosis or at high risk for this condition, pulse pressure measurement was associated with adverse CV outcomes, independently of mean arterial pressure. Pulse pressure, which can easily be measured in the office setting, can help stratify patients at high risk of CV events.
 

Editorial comment [6]

In this study, pulse pressure was examined in the largest international patient population to date, thus providing the opportunity to conduct all possible meaningful adjustments and to perform several subgroup analyses with high statistical power. However, Franklin and Wong highlight the limitations of the study, in an effort to provide a balanced and useful interpretation of the results in every day clinical practice:
  1. ‘The authors note that there was zero-digit preference bias in 58% for SBP and 60% for DBP, when the expected number was 20%. This highlights the almost universal poor technique of BP measurement by physicians and nurses in an office setting that result in errors in calculating PP accurately.’
  2. ‘In addition, the high prevalence of treatment in the REACH population suggests that widened PP may have been more prevalent in the absence of treatment, given the greater SBP lowering effect (relative to DBP lowering) from antihypertensive treatment.’
  3. ‘Focusing on PP alone does not clarify which physiologic component of elevated BP is contributing to CVD risk, and therefore what approach should be taken to reduce risk.’
  4. ‘Importantly, although elevated PP provides useful prognostic information, the ultimate goal of therapy is dictated by how low to go in reducing SBP. Therefore, the relationship of PP with CVD risk should always be examined in the context of (e.g., stratified by) levels of SBP and ideally in a more treatment-naïve population.’
‘In summary, as shown in the REACH registry study, a widened PP can be a reliable prognostic indicator of CVD risk and the authors are to be applauded for conducting a thorough and comprehensive analysis of this issue. However, a widened PP represents a double-edged swordin terms of potential pitfalls in making diagnostic and therapeutic decisions. In future hypertension guideline development there should be continued discussion of the potential role of PP in further risk stratification beyond traditional staging based on SBP and DBP.‘
 
Find this article online at J Am Coll Cardiol
 

References

1. Safar ME, Blacher J, Jankowski P. Arterial stiffness, pulse pressure, and cardiovascular disease-is it possible to break the vicious circle? Atherosclerosis 2011;218:26371
2. Blacher J, Staessen JA, Girerd X, et al. Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients. Arch Intern Med 2000;160:10859
3. Franklin SS, Khan SA, Wong ND, et al. Is pulse pressure useful in predicting risk for coronary heart disease? The Framingham Heart Study. Circulation 1999;100:35460
4. Lee ML, Rosner BA, Weiss ST. Relationship of blood pressure to cardiovascular death: the effects of pulse pressure in the elderly. Ann Epidemiol 1999;9:1017
5. Ohman EM, Bhatt DL, Steg PG, et al. The Reduction of Atherothrombosis for Continued Health (REACH) registry: an international, prospective, observational investigation in subjects at risk for atherothrombotic events-study design. Am Heart J 2006;151:786.e110
6. Franklin SS, Wong ND. Pulse Pressure: How Valuable as a Diagnostic and Therapeutic Tool? J Am Coll Cardiol 2016;67:404-406