“Patients with CKD have disproportionately high cardiovascular (CV) risk,” explains L. Parker Gregg, MD, MS, “and identifying treatable novel risk factors is critical to improving long-term outcomes in this patient population.” Although visit-to-visit blood pressure variability (BPV) has been shown in prior research to be associated with CV events in the general population and among those with advanced CKD, data are lacking on this association among patients across the entire spectrum of CKD, from stages 1 to 5, she adds. “Furthermore, although prior studies note decreased BPV in patients treated with diuretic medications, none studied whether diuretics modified the association of BPV with long-term outcomes.”

BPV, Diuretics & CV Events Across the CKD Spectrum

For a study published in Hypertension, Dr. Gregg and colleagues set out to determine:

  • Whether thiazide or loop diuretics are associated with decreased BPV compared with non-diuretic antihypertensive medications in patients with non-dialysis CKD stages 1-5
  • If BPV is associated with CV events, death, and ESKD
  • If a diuretic prescription modifies the association of BPV with the above outcomes

“To address these questions, we conducted a retrospective cohort study of national real-world data from the Veterans Affairs hospital system,” says Dr. Gregg. “We identified individuals with CKD stages 1-5 who were already taking one antihypertensive medication and included them in the cohort at the time of prescription of a second antihypertensive agent. We then measured associations between BPV with CV and kidney outcomes and tested whether prescription of a diuretic (n = 31,394) versus a non-diuretic (n = 31,394) as the second agent modified these associations.”

When compared with the first quintile, higher BPV was associated with composite CV events (fatal or nonfatal myocardial infarction or ischemic stroke; heart failure hospitalization) at the second (hazard ratio [HR], 1.79), third (HR, 2.32), fourth (HR, 2.60), and fifth (3.12) quintiles. “Higher BPV was also associated with a higher risk of all-cause death, CV death, myocardial infarction, hospitalization for heart failure, and ischemic stroke in patients with CKD stages 1-5,” adds Dr. Gregg. “However, it was not associated with a higher risk of progression of kidney disease to the point of needing dialysis or kidney transplantation.” When analyzing whether the associations of BPV with each outcome measured in the study differed between those who received diuretics or non-diuretics as their second antihypertensive medication, the researchers found that, among those with the highest BPV, the association was significantly lower for those who were prescribed a diuretic (Table).

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Sensitivity analyses conducted to determine if the observed results were impacted by study inclusion criteria, or how variables were defined, showed that the findings were similar when using BPV as a continuous variable among different subsets of participants, and when looking at outcome events in slightly different ways, explains Dr. Gregg. “This supports that the relationship between BPV and CV events was consistent and robust, and likely not primarily driven by characteristics of who was included or excluded from the study,” she says.

BPV: Marker of CV Health or Treatable Risk Factor?

Dr. Gregg notes the need for future research to identify other interventions that can decrease BPV and to evaluate whether lowering BPV improves long-term CV outcomes in patients with CKD. “Clinical trials will ultimately be crucial to evaluate such effects for interventions supported by sufficient observational evidence,” she adds. “Underlying mechanisms of BPV also need to be better understood to enable identification of targeted interventions.”

Although it is not yet clear whether BPV is primarily a marker of poor underlying CV health or whether it is a promising, potentially treatable risk factor of CV events and death in patients with CKD, explains Dr. Gregg, “high visit-to-visit BPV in the outpatient clinic setting may be useful for long-term prognostication,” she says. “For some patients with very high BPV, prescribing a diuretic may decrease the association of BPV with CV events.”