Chronic high caffeine consumption (>300 mg/day) is associated with elevated systolic blood pressure, increased heart rate, higher plasma interleukin-6 levels, and reduced endothelium-dependent vasodilation during total sleep deprivation, even in the absence of acute caffeine intake.

Long-term high caffeine use keeps adenosine receptors blocked, which reduces the production of a blood vessel-relaxing molecule called nitric oxide. This makes blood vessels stiff and less able to open when needed. At the same time, the body produces more inflammatory signals and oxidative stress, which further damage the lining of blood vessels. These changes worsen during sleep loss, leading to higher blood pressure, faster heart rate, and reduced blood flow through the vessels.