Blood pressure normally reaches its lowest level (dips) during sleep. However, some people with high blood pressure have little or no decline in blood pressure while sleeping, which has been linked to an increased risk for heart attack and stroke. Findings from a large study of hypertensive patients show that "non-dippers" have higher levels of the clotting factor fibrinogen, which could account for at least part of the increased risk.
"To my knowledge, the rise in fibrinogen in non-dippers has not been reported before," says Ramon C. Hermida, Ph.D., lead author of the study and a professor at the University of Vigo in Vigo, Spain. "The results emphasize the importance of adequate blood pressure control throughout the day. Our findings also show that identification of non-dippers is very relevant to prevention of coronary events and death."
Hermida said data from the U.S. National Myocardial Infarction Registry, a large database on heart attack patients, have shown that a 75 mg/dL rise in fibrinogen translates into an 85 percent increased risk for coronary events and mortality.
"Even within the range of normal levels, a 75 mg/dL increase in fibrinogen is very relevant to the risk of coronary events and death," he says. "This is not just a small change but a major increase in risk."
The study also confirmed previous research showing that fibrinogen levels vary over the course of a year and peaks during winter months. The winter peak in fibrinogen levels correlates with annual patterns of coronary events and mortality, which also peak during the coldest months. Several studies have documented elevated fibrinogen levels as a risk factor for heart attack, Hermida notes.
The findings emerged from an investigation that evaluated seasonal variations in fibrinogen among hypertensive patients. Hermida and colleagues in Vigo and at the University of Santiago in Spain compared fibrinogen levels in 741 patients who had mild or moderate hypertension, defined as greater than 140/90 millimeters of mercury (mm Hg) but less than 180/110 mm Hg.
Blood pressure was monitored continuously over 48 hours by ambulatory blood pressure monitoring devices. Blood and urine samples were obtained before monitoring started. Each patient had a single evaluation, and the individual evaluations were distributed throughout the year.
Overall, fibrinogen levels averaged 323 milligrams per liter (mg/dL) in the patients, well within the normal range of 160-400 mg/dL says Hermida. As with previous studies, the results showed a difference of 75 mg/dL between highest and lowest fibrinogen levels. The highest readings occurred in patients evaluated during the winter, peaking in the first week of March.
Results of the 48-hour blood pressure monitoring showed that almost half the patients (365 of 741) were non-dippers, defined by a decrease in nocturnal blood pressure of less than 10 percent. A comparison of fibrinogen levels in dippers and non-dippers showed that non-dippers had a 21 mg/dL higher mean fibrinogen value over the course of the year, which was statistically different from dippers.
The proportion of non-dippers identified in the study conflicts with other research showing that non-dippers account for 15 percent to 20 percent of hypertensive patients. However, Hermida says recent European studies employing continuous ambulatory blood pressure monitoring have consistently shown non-dipper rates of about 40 percent.
"This emphasizes the importance of ambulatory blood pressure monitoring for identification of non-dippers," he says. "Many studies have indicated that ambulatory blood pressure monitoring is a much better predictor of morbidity and mortality, as compared to clinic measurement of blood pressure. The results indicate that ambulatory blood pressure monitoring should be performed in every patient who goes to a blood pressure clinic for the first time."
Findings have strong implications for treating high blood pressure, said Hermida. Specifically, the results imply a need for treatment that provides adequate 24-hour control.
"Antihypertensive drugs have differing effects throughout the day and in terms of the time of day the drugs are taken," he says. "If a patient is a non-dipper and is given a drug that does not have 24-hour coverage, the drug will no longer be active in the early morning hours when the risk is greater. This should be taken into account when planning the treatment for a hypertensive patient."
Co-authors were Carlos Calvo, Diana E. Ayala, and Jose E. Lopez.