Based upon the physical properties of the cardiovascular system, it can be demonstrated mathematically that fluid retention increases turbulence of blood flow. Turbulence is a risk factor for atherosclerosis. Several medical conditions that cause fluid retention (heart failure, nephrotic syndrome, cirrhosis and obstructive sleep apnea) are associated with an increased risk of adverse cardiovascular events. Numerous medications that cause fluid retention (NSAIDs, COX-2 inhibitors, insulin, sulfonylureas, estrogens, progestins and androgens) are associated with an increased risk of adverse cardiovascular events. The cardiovascular risk of numerous medications that cause fluid retention has never been investigated. The observation that fluid retention increases the risk of adverse cardiovascular events has implications for pharmaceutical manufacturers and pharmaceutical regulatory agencies.
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