The adrenal glands produce various hormones that are responsible for coordinating and monitoring a variety of physiological activities. These include cortisol, adrenaline, DHEA, estrogen and testosterone. There is concern that caffeine can cause the body to be flooded with excess adrenaline, resulting in an increased heart rate and higher blood pressure. Some authors even suggest that ongoing stimulation of the adrenal glands will eventually cause them "wear out." Although there has been research into the stimulation caused by caffeine, an online search produced no study that addressed the "wearing out" theory.
A 2002 study from the Duke University Medical Center investigated the effects of moderate doses of caffeine on blood pressure and heart rate, urinary excretion of epinephrine, norepinephrine, and cortisol, and self-reported stress during normal activities. This study found that caffeine raised average blood pressure during the workday and evening by 4/3 mm Hg and increased average heart rate by 2 bpm. Caffeine also caused a 32% increase in the levels of epinephrine (a stimulating hormone). In addition, caffeine amplified the increases in blood pressure and heart rate associated with higher levels of stress from daily activities. These effects were undiminished through the evening until bedtime. An Australian study also found that while most data suggest very little excess risk of coronary heart disease among the general population of habitual coffee drinkers, the better controlled data suggest an excess risk on the order of 60% for people drinking five or more cups per day.
In another area of concern, a 2004 study linked moderate to high levels of coffee consumption to increased inflammatory markers. Inflammatory markers are important as predictors of coronary heart disease. Another study published in 2004 found that the combination of caffeine plus smoking cigarettes reduced the flexibility of the aorta more than either substance alone.
However, other work has suggested that response to coffee vs. isolated caffeine is minimal, particularly for habitual drinkers. In 2006, a study was reported in the April 24th Rapid Access issue of Circulation. The authors concluded that "coffee consumption was not associated with an increased risk of Coronary Heart Disease." This study found that total cholesterol, low-density and high-density lipoprotein cholesterol levels in men and women coffee drinkers did not differ in those who drank caffeinated or decaffeinated coffee. CHD risk associated with drinking coffee did not differ in people with or without type 2 diabetes.
So are you off the hook? Er... not so fast. A 2006 study published in the Journal of the American Medical Association found that some people have a genetic mutation of the CYP1A2 enzyme that reduces the rate they metabolize caffeine. For those people, drinking four or more cups a day over for a year had a 64% increased risk of heart attack, compared to less than 1% increased risk for people without the gene mutation. Such genetic differences between participants in a study may explain why it has been hard to determine if there is a clear association between coffee consumption and heart attack risk.