Checking Cumulative High BP Exposure Hones CV Risk Prediction in Diabetes

Cumulative systolic blood pressure load over time—a measure incorporating both the magnitude and the duration of high BP—may provide a better indication of future risk of major cardiovascular events in patients with type 2 diabetes than do more-standard BP metrics, a study shows.

Adding the measure to models that included traditional CV risk factors provided better discrimination of cardiovascular events compared with the other BP measures, researchers led by Nelson Wang, MD (The George Institute for Global Health UNSW, Sydney, Australia), report in a paper published in the September 20, 2022, issue of the Journal of the American College of Cardiology.

“Although the improvements were modest in size, I think one of the main messages is that if you account for both the duration and the magnitude of blood pressure exposure, you can get better predictive power,” Wang told TCTMD.

“If we think of the exposure to high blood pressure more as something that is going to accumulate over time, . . . it forces clinicians to think about managing and intervening early in the process” to stave off future events, Wang said.

Betul Hatipoglu, MD (University Hospitals Cleveland Medical Center, OH), who was not involved in the study, said she was happy to read the paper because it highlights what is potentially a better way to assess and track patients’ blood pressure compared with the current focus on most-recent readings.

“That practice that we have right now I think needs to change, and the change can only happen if we have different tools that are validated and have been shown to be effective and better,” she commented.

Looking at the cumulative BP load provides a better view of how high BP has affected a patient’s health, Hatipoglu said. She added that “the long-term effect . . . of different insults to the body is important to consider,” noting that prior data on control of blood sugar in patients with type 2 diabetes has shown that doing a good job managing levels earlier in the course of the disease is beneficial.

Additional studies across a broader swath of patients—including those at lower CV risk than patients with diabetes—are needed to establish cumulative BP load as a clinically useful tool, Hatipoglu indicated, but she said there is hope that this will provide clinicians with a better assessment of a patient’s risk, enabling improved management.

Reinforcing the Importance of Early Intervention

When managing BP, the typical approach of looking at the value at a single time point fails to account for what the level was in the past and fluctuations over time, Wang said, adding that, ideally, clinicians would use a metric that captures both the magnitude and the duration of exposure to high BP.

Cumulative BP load—a measure incorporating BP level over a certain threshold (130 mm Hg in this case) multiplied by time—fits that mold, and it can be calculated using a simple formula that could be incorporated into most electronic medical records, Wang said. In a prior small study, cumulative BP load was associated with target-organ damage in patients with essential hypertension.

That practice that we have right now I think needs to change, and the change can only happen if we have different tools that are validated and have been shown to be effective and better. Betul Hatipoglu

For the current study, the investigators calculated cumulative systolic BP load over a 24-month period among participants in the ADVANCE-ON study, a follow-up study conducted after the conclusion of the ADVANCE trial, which assessed the impact of BP-lowering and intensive glucose-lowering on vascular outcomes in patients with type 2 diabetes. They then evaluated the association between cumulative BP load and CV risk. The analysis included 9,338 patients (mean age 65 years; 42% women) who had systolic BP values available from six time points—3, 4, 6, 12, 18, and 24 months.

Over a mean follow-up of 7.6 years, each standard-deviation rise in cumulative systolic BP load was associated with greater risks of the following outcomes, after accounting for traditional risk factors:

• A composite of CV death, MI, or stroke (HR 1.14; 95% CI 1.09-1.20)
• All-cause mortality (HR 1.13; 95% CI 1.13-1.18)
• CV death (HR 1.21; 95% CI 1.13-1.29)
• MI (HR 1.19; 95% CI 1.10-1.29)
• Stroke (HR 1.10; 95% CI 1.02-1.18)

In general, other measures of systolic BP—including mean BP, visit-to-visit variability, and the time spent below the BP goal—also were associated with risk of adverse outcomes. When added to models for predicting CV events and death, however, cumulative BP load provided a bigger boost in discrimination than did the other metrics.

“Although the present study only assessed cumulative systolic BP load over 24 months, clinicians should recognize the importance of cumulative systolic BP load over a lifetime,” Wang et al write. “This approach emphasizes the importance of early BP-lowering interventions, beginning with lifestyle measures and, if needed, pharmacological BP-lowering therapies to reduce the cumulative systolic BP load that each individual experiences over their lifetime.”

More Work Needed

In an accompanying editorial, American Heart Association President Donald Lloyd-Jones, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), discusses both the potential of cumulative BP load as a measure to inform CV risk prediction and the steps that still need to be taken to validate its use in the clinic.

One of the main messages is that if you account for both the duration and the magnitude of blood pressure exposure, you can get better predictive power. Nelson Wang

Research indeed supports the concept of intervening earlier to avoid years of extra exposure to high BP, Lloyd-Jones notes, pointing to one of his group’s prior studies demonstrating that middle-age and older adults who had their BP treated to below 120/80 mm Hg still had double the risk of CVD compared with those who always had levels that low. Data from younger individuals followed for decades suggested that the reason was greater cumulative exposure to high BP and accompanying organ damage, including greater LV mass, increased coronary artery calcification, and worse renal function.

“In other words, there was a price to be paid (in subclinical target-organ damage) for cumulative BP exposure and time spent with BP elevation above optimal that could not be fully reversed by restoration of optimal BP levels with medication,” Lloyd-Jones writes.

The current study provides some insights into the impact of cumulative BP load in a high-risk group of patients, showing a “very modest” increase in discriminating risk of CV events with this metric versus others, he says.

Before integrating cumulative BP load into practice, further research is necessary, Lloyd-Jones indicates, highlighting questions around the populations in which the measure should be used, whether calculating the metric over a longer time period would provide different information, whether it adds value to existing risk-prediction equations, and whether its use improves decision-making and outcomes.

“Ultimately, clinicians should leverage as much information on their patients as possible to understand their BP-related CVD risk, to identify those who may be more likely have occult or emerging subclinical target-organ damage, and to identify those who may have particular net benefit from earlier or more-intensive treatment,” Lloyd-Jones says. “These opportunities are more readily available with integration of data that allow for visualization of longer-term BP patterns and incorporation of home BP monitoring and ambulatory BP monitoring data to monitor out-of-office BP levels and control.”