Why is cardiovascular disease the leading cause of death among prostate cancer patients?

Why Cardiovascular Disease is the Leading Cause of Death in Prostate Cancer Patients

Cardiovascular disease kills more prostate cancer patients than the cancer itself because most men have pre-existing cardiovascular risk factors at diagnosis, these risk factors are poorly controlled, and androgen deprivation therapy—the mainstay of treatment—directly worsens cardiovascular health through metabolic disruption and direct cardiac effects. 1

The Baseline Cardiovascular Burden

The problem begins before cancer treatment even starts:

• More than half of prostate cancer patients have poorly controlled cardiovascular risk factors at baseline, creating a vulnerable population before any cancer-directed therapy is administered 1
• In a Chinese nationwide study, 27% of newly diagnosed prostate cancer patients already had cardiovascular disease, with 7.2% having two or more cardiovascular conditions 2
• Among US veterans with prostate cancer, 43.1% had hypertension, and half of these patients had poorly controlled blood pressure at the time of cancer diagnosis 2

The Treatment Paradox

Androgen deprivation therapy (ADT), which benefits patients with locally advanced and metastatic disease, creates a cardiovascular toxicity paradox:

Direct Metabolic and Cardiac Effects

• ADT induces metabolic changes that directly impact cardiovascular function, reducing cardiorespiratory fitness and increasing cardiovascular mortality 1
• These therapies cause or worsen pre-existing cardiovascular risk factors and cardiovascular disease 1
• Patients receiving ADT-related therapy demonstrate an originally higher cardiovascular risk profile compared to those not receiving ADT, though this partly reflects that older, more advanced-stage patients are selected for systemic therapy 2

Specific Mechanisms

• GnRH agonists, GnRH antagonists, enzalutamide, and abiraterone can directly or indirectly increase the risk of hypertension through various pathways 3
• The metabolic disruption from androgen receptor targeting therapies creates a cascade of cardiovascular risk amplification 1

The Care Gap Crisis

The most alarming finding is that cardiovascular disease remains underassessed and undertreated despite being the leading cause of death:

• Only 68.1% of veterans with prostate cancer received comprehensive cardiovascular risk factor assessment (blood pressure, cholesterol, and glucose monitoring) 4
• Among those assessed, 54.1% had uncontrolled cardiovascular risk factors 4
• Of those with uncontrolled risk factors, 29.6% were not receiving corresponding cardiac risk-reducing medications 4
• Initiation of ADT was not associated with substantial improvements in cardiovascular risk factor assessment or management, representing a critical missed opportunity 4

The ADT Treatment Gap

• Among Chinese patients undergoing medical castration, only 4% received GnRH antagonists (which have more favorable cardiovascular profiles), despite the heavy cardiovascular disease burden—demonstrating insufficient awareness of cardiovascular protection strategies 2

Why This Matters Clinically

For most prostate cancer patients, death is predominantly from non-cancer-related causes, making cardiovascular optimization during cancer treatment not just important but essential 5. The intersection of:

1. High baseline cardiovascular risk
2. Cardiotoxic cancer treatments
3. Systematic underassessment and undertreatment of modifiable risk factors
4. Lack of multidisciplinary coordination between oncology and cardiology

...creates the perfect storm where cardiovascular disease becomes the primary threat to survival, eclipsing the cancer itself 1, 5.

Common Pitfall: Oncologists focusing solely on cancer control while assuming primary care will manage cardiovascular risk, and primary care providers deferring to oncology during active cancer treatment—resulting in neither adequately addressing the leading cause of death in this population 4, 5.