NSAIDs, calcineurin inhibitors, and erythropoietin are among the agents that cause BP elevations.
Most patients who have high BP have primary or essential hypertension, the cause of which is as yet unknown. About 5%-10% of adults with hypertension have an identifiable or “secondary” cause of their elevated BP.
Although relatively rare, the diagnosis of secondary hypertension is important because, depending on the source, it may be possible to cure the underlying condition or tailor therapy as a means to achieving optimal BP control.
Features that aid in the diagnosis of secondary hypertension include on-set of hypertension before age 20 or after age 50 years; hypertension refractory to medical therapy and requiring the use of multiple antihypertensive medications from different classes; and specific body habitus and ancillary physical findings.
For example, truncal obesity and purple striae occur with hypercortisolism, and exophthalmos is associated with hyperthyroidism. Biochemical tests may aid the diagnosis by revealing the presence of certain disorders, such as hypercalcemia in hyperparathyroidism and unprovoked hypokalemia in patients with renin-producing tumors.
Many prescription and nonprescription drugs can cause transient or sustained increases in BP. Nicotine in cigarettes, smokeless tobacco, and cigars causes transient increases in BP, although transdermal nicotine preparations do not appear to have this effect.
Caffeine can raise BP acutely, but tolerance develops rapidly, and there appears to be no direct relationship between caffeine intake and chronic hypertension. Chronic overuse of alcohol is a potentially reversible cause of hypertension.
Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease prostaglandin biosynthesis through in-hibition of cyclooxygenase (COX) which exists as two isoforms, COX-1 and COX-2. NSAIDs and COX-2 inhibitors elevate BP via their antiprostaglandin effects on the kidneys (Am J Med. 1999;107[6A]:65S-70S).
The cardiovascular consequences of COX-2 inhibition may include a shift in platelet the aggregation balance toward thrombosis, increases in sodium and water retention, exacerbations of heart failure and hypertension, and loss of the protective effects of COX-2 upregulation in the setting of myocardial ischemia and infarction. Many of these effects are common with all NSAIDs.
NSAIDs may have deleterious effects on kidney function, especially with regard to solute homeostasis and maintenance of renal perfusion and glomerular filtration. The most clinically important adverse renal effects of NSAIDs are decreased sodium and potassium excretion and reductions in renal perfusion. Decreased sodium excretion can result in peripheral edema, BP elevations, and attenuation of the effects of antihypertensive agents.
The cardiovascular safety of COX-2 inhibitors has come under increased scrutiny since rofecoxib was voluntarily withdrawn from the worldwide marketplace in September 2004, following reports of increased risks of MI and stroke.
Studies published since then have reinforced the concerns about the cardiovascular risks of COX-2 inhibitors and have identified an increased cardiovascular risk even with nonselective NSAIDs, raising concerns about the safety of these drugs as well. The FDA requested and received a voluntary market withdrawal of another COX-2 inhibitor, valdecoxib, in April 2005.
The effects of NSAIDs on BP were examined in a meta-analysis of 38 randomized, placebo-controlled trials and 12 randomized but uncontrolled trials comparing two or more NSAIDs (Ann Intern Med. 1994;121:289-300). Analysis of the pooled data revealed that NSAIDs elevated supine mean BP by 5.0 mm Hg but had no effect on other variables.
NSAIDs antagonized the antihypertensive effect of beta blockers (BP elevation, 6.2 mm Hg) more than did vasodilators and diuretics. Among NSAIDs, piroxicam produced the most marked elevation in BP (6.2 mm Hg), whereas sulindac and aspirin had the least hypertensive effect.
It is unknown whether the relatively small BP increases associated with NSAIDs confer an increased risk of cardiovascular complications or if the increments in BP observed following NSAID administration are sustained over time. Risk factors for BP elevation during treatment with NSAIDs have not been documented.
Some data suggest that elderly people and patients with pre-existing hypertension have an increased risk, particularly during antihypertensive treatment. Frequent measurement of BP may be warranted in select patients during the first few weeks of NSAID treatment.