Does immunotherapy increase blood pressure?

Does Immunotherapy Elevate Blood Pressure?

Yes, immune checkpoint inhibitor (ICI) therapy is associated with an increased risk of developing hypertension, though the mechanism and incidence differ significantly from traditional chemotherapy agents.

Evidence for Hypertension Risk

The most recent high-quality evidence demonstrates that ICI therapy significantly increases the incidence of new-onset hypertension compared to non-ICI treated cancer patients (13.2% vs 9.7%, with a risk ratio of 1.356 and odds ratio of 1.410, both p<0.001) 1. This represents a 35.6% increased relative risk of developing hypertension within one year of starting ICI therapy.

Clinical Context and Mechanism

The hypertension associated with ICIs differs fundamentally from that seen with antiangiogenic agents:

• Antiangiogenic agents (like bevacizumab and lenvatinib) frequently cause hypertension through direct vascular injury mechanisms 2
• ICIs alone cause hypertension less commonly, but the risk is clinically significant and requires monitoring
• When ICIs are combined with antiangiogenic therapy (common in hepatocellular carcinoma), blood pressure management becomes particularly complex 2

Important Clinical Caveat

High blood pressure is listed as a presenting symptom of immune-related renal toxicity (nephritis/AKI), not as a primary cardiovascular adverse event 3. The ASCO guidelines specifically mention hypertension as a potential manifestation of immune-mediated kidney injury, which occurs in 1-4% of ICI-treated patients 4. This means:

• When hypertension develops during ICI therapy, evaluate for underlying immune-related nephritis
• Check serum creatinine, urinalysis, and consider renal function assessment
• The hypertension may be secondary to renal injury rather than a direct vascular effect

Monitoring Recommendations

Based on guideline evidence:

• Check serum creatinine before every dose of checkpoint inhibitor therapy 3
• Monitor for symptoms of renal toxicity including fluid retention, sudden weight gain, and elevated blood pressure 3
• Maintain low threshold for investigating new hypertension as potential immune-related renal toxicity 4

Historical Note on IL-2 Therapy

Older interleukin-2 immunotherapy (distinct from modern ICIs) actually caused hypotension rather than hypertension, through mechanisms involving increased vascular permeability and vasodilation 5, 6. This is the opposite effect and should not be confused with modern checkpoint inhibitor therapy.

Clinical Management Approach

When hypertension develops during ICI therapy:

1. First, rule out immune-related nephritis: Check creatinine, urinalysis with protein-to-creatinine ratio, electrolytes
2. If nephritis is present: Follow immune-related adverse event protocols with potential ICI discontinuation and corticosteroid therapy 3, 4
3. If isolated hypertension: Treat with standard antihypertensive agents while continuing cancer therapy monitoring
4. In combination therapy regimens (ICI + antiangiogenic): Expect higher rates of hypertension requiring more aggressive blood pressure management 2