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CLINICAL RESEARCH: ENDOTHELIAL FUNCTION IN WOMEN

Prognostic Role of Flow-Mediated Dilation and Cardiac Risk Factors in Post-Menopausal Women

Rosario Rossi, MD^_*,_*, Annachiara Nuzzo, MD^_*, Giorgia Origliani, PhD and Maria Grazia Modena, MD, FACC^_*

^_* Institute of Cardiology, Policlinico Hospital, University of Modena and Reggio Emilia, Modena, Italy
Centro "Bene Essere Donna," Azienda Policlinico di Modena, Modena, Italy.

Manuscript received September 12, 2006; revised manuscript received October 30, 2007, accepted November 8, 2007.

^_* Reprint requests and correspondence: Dr. Rosario Rossi, Institute of Cardiology, Policlinico Hospital, Via del Pozzo, 71-41100 Modena, Italy. (Email: rossi.rosario{at}unimore.it).

Preliminary results of this study were presented at the 55th Annual Scientific Sessions of the American College of Cardiology; Atlanta, Georgia, March 11 to 15, 2006.

Objectives: The aim of this study was to examine the association between brachial artery flow-mediated dilation (FMD) and cardiovascular events in a cohort of initially asymptomatic post-menopausal women, with adjustment for the presence of the major cardiovascular risk factors.

Background: Conventional major cardiovascular risk factors (cigarette smoking, hypercholesterolemia, hypertension, and diabetes) fail to explain nearly 50% of cardiovascular events. Defining the magnitude of future risk for the development of clinical events is a major focus of effective primary prevention. Evaluation of endothelial function, utilizing the noninvasive measurement of the brachial artery FMD, may serve as a screening tool to individualize high-risk patients.

Methods: We conducted a prospective study on 2,264 post-menopausal women, age 54 ± 6 years. The length of the follow-up was 45 ± 13 months (range 6 to 65 months).

Results: During observation, 90 major events were recorded. Risk-adjusted relative risk values resulted 1.0, 1.33 (95% confidence interval [CI] 1.09 to 4.09), and 4.42 (95% CI 2.97 to 8.01) for women in the higher, intermediate, and lower tertile of FMD, respectively (p < 0.0001 for trend). The event rate for women in the lower tertile (FMD 4.5%) was greater than the combined event rate noted in the other 2 tertiles (women in the lower tertile accounted for 51 events [56.6% of total events]). When added to age and other conventional cardiovascular risk factors (smoking habits, presence of hypercholesterolemia, history of diabetes, hypertension), FMD contributed significantly to the model predicting cardiovascular events (likelihood ratio chi-square change: 10.22; p < 0.0001).

Conclusions: In post-menopausal women, the knowledge of FMD provided incremental prognostic information regarding the risk of developing cardiovascular events.

Abbreviations and Acronyms   CV = cardiovascular   CVD = cardiovascular disease   FMD = flow-mediated dilation   NO = nitric oxide   TIA = transient ischemic attack   t-PA = tissue-type plasminogen activator   u-PA = urokinase-type plasminogen activator