Anemia Exacerbates Adverse Effects of Hypertension and Blood Urea Nitrogen

A recent cross-sectional study revealed that anemia can moderate the association between blood urea nitrogen (BUN) and hypertension (HTN), exacerbating the adverse effects of both.

HTN is widely known as a catalyst of atherosclerotic cardiovascular disease (ASCVD). Despite the use of antihypertensive therapy to control blood pressure, however, patients with HTN still have a residual cardiovascular risk. Previous studies have shown that antihypertensive therapy is suboptimal for preventing cardiovascular disease. Few studies have examined the lingering risk after therapy.2

“Therefore, our study aimed to investigate the association between BUN, anemia, and the risk of ASCVD in middle-aged hypertensive patients, while also exploring the moderating role of anemia on the association between BUN and ASCVD risk,” wrote Qianqian Yu, department of blood transfusion, the Second Affiliated Hospital of Anhui Medical University, and colleagues.1

Investigators collected data from the National Health and Nutritional Examination Survey (NHANES) from 1999 to 2018. An initial total of 22,250 hypertensive patients ages 40-79 were collected – 4359 with a history of cardiovascular disease were then excluded, as well as patients missing data on BUN measurement, hemoglobin levels, energy intake, ASCVD, and body mass index (BMI). The final total participant count was 15,109.1

The team defined hypertension by either self-reported HTN previously diagnosed by healthcare professionals, use of antihypertensive medications, or elevated biological measurements (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥80 mmHg). Anemia was defined using the WHO criteria, which state that a hemoglobin level <13 g/dL in men and <12 g/dL in women is anemic.1

After accounting for covariates, investigators noted that a BUN level ≥4.69 mmol/L was related to higher odds of ASCVD in HTN patients (odds ratio [OR] = 1.68, 95% CI: 1.51-1.88). Anemia was also associated with higher odds of ASCVD in HTN patients (OR = 1.45, 95% CI: 1.22-1.73). Additionally, in patients without anemia, BUN level ≥4.69 mmol/L was associated with higher odds of ASCVD compared to patients with anemia, BUN level <4.69 mmol/L (OR = 2.95, 95% CI: 2.05-4.25).1

Yu and colleagues noted that the cause for this clear association is most likely multifactorial. Elevated BUN levels may indicate impairment of renal function, which is a well-known risk factor for ASCVD. Elevated BUN levels could also signify increased activity of the sympathetic nervous system and renin-angiotensin-aldosterone system activation, both of which contribute to ASCVD and HTN pathogenesis.1

Importantly, the team indicates that anemia is also associated with increased incidence of ASCVD: this, coupled with its established association with BUN, implies that anemia is exacerbating the adverse effects of elevated BUN levels.1

The team provides several reasons for anemia’s influence on the relationship between BUN and ASCVD. First, patients with HTN are often in a state of persistent low-grade inflammation, which anemia exacerbates by inducing the production of inflammatory cytokines.1

Second, anemia can trigger compensatory mechanisms, increasing cardiac output and peripheral vasoconstriction. This increases the workload on the heart, potentially leading to the development of left ventricular hypertrophy and, eventually, heart failure.1

Finally, anemia simultaneously aggravates tissue hypoxia to reduce oxygen delivery to the kidneys and increases oxidative stress to produce reactive oxygen species and nitrogen excessively.1

Investigators indicated impaired oxygen delivery, chronic inflammation, and bidirectional interactions between HTN, BUN, and ASCVD as the mechanisms underlying these findings. Yu and colleagues call for physicians to consider BUN and hemoglobin levels simultaneously when assessing ASCVD in patients with hypertension.1

“Early detection and treatment of anemia should be incorporated into the comprehensive management strategy for hypertensive patients, aiming to improve oxygen delivery and alleviate the cardiovascular burden,” Yu and colleagues wrote. “However, further prospective studies are needed to establish causality and explore potential therapeutic interventions.”1

References

1. Yu Q, Yu H. Moderating Role of Anemia on the Association between Blood Urea Nitrogen and Atherosclerotic Cardiovascular Disease in Hypertension. Rev Cardiovasc Med. 2025;26(3):26245. Published 2025 Mar 13. doi:10.31083/RCM26245

2. Wang MC, Petito LC, Pool LR, et al. The 2017 American College of Cardiology/American Heart Association Hypertension Guideline and Blood Pressure in Older Adults. Am J Prev Med. 2023;65(4):640-648. doi:10.1016/j.amepre.2023.04.011