Depressive Symptoms Are Related to Higher Ambulatory Blood Pressure in People With a Family History of Hypertension KAREN M. GREWEN,PHD, SUSAN S. GIRDLER,PHD, ALAN HINDERLITER, MD, AND KATHLEEN C. LIGHT,PHD Objective: We investigated whether parental history of hypertension (FH) enhances the impact of depressed mood, indexed by Beck Depression Inventory (BDI), on ambulatory blood pressure (ABP). Methods: Twenty-four– hour ABP, urinary norepineph- rine (NE), and cortisol were obtained in 314 unmedicated normotensive and hypertensive men and women (age 18 – 64 years) who also completed the BDI. Results: Subjects with a positive family history of hypertension (N  177) exhibited significantly greater mean body mass index (BMI) and ABP compared with subjects without (N  137). Importantly, when covarying for age, BMI, gender, and race, linear regressions revealed significant FH by BDI interactions. Higher BDI scores were significantly associated with higher 24-hour ABP in FH subjects, but not in FH participants. Relationships were significantly stronger in those with two hypertensive parents vs. those with one vs. those with no hypertensive parents. Increases in BDI scores were significantly related to greater heart rate (HR) and 24-hour urinary NE in both FH and FH groups, although no evidence of a mediational role for NE in the effect of BDI score on blood pressure (BP) or HR was seen. Conclusions: These findings suggest that depressed mood may be reliably associated with higher BP only among those with an underlying susceptibility to HTN. Key words: depression, ambulatory blood pressure, family history of hypertension, norepinephrine. ABP  ambulatory blood pressure; BDI  Beck Depression Inven- tory; BMI  body mass index; BP  blood pressure; CHD  coronary heart disease; CVD  cardiovascular disease; DBP  diastolic blood pressure; ENRICHD  Enhancing Recovery in Coronary Disease; FH  family history of hypertension; HPA  hypothalamic-pituitary-adrenal; HR  heart rate; HTN  hyperten- sion; MI  myocardial infarction; NE  norepinephrine; SNS  sympathetic nervous system; SADHEART  Sertraline Antidepres- sant Heart Attack Randomized Trial; SBP  systolic blood pressure. INTRODUCTION O ver the last 2 decades, a large body of research has identified clinical and subclinical depression as potent predictors of cardiovascular morbidity and mortality. Both major depressive disorder (1–5) and the milder, more common condition of depressed mood, assessed by the Beck Depres- sion Inventory (BDI), have predicted subsequent cardiac mor- bidity and mortality after myocardial infarction (MI) in men and women (3,6), with greatest risk afforded those in which post-MI depression was not their first episode (7). That de- pression actually precedes cardiovascular disease (CVD) is suggested by findings from prospective studies showing that clinical and subclinical depression in initially healthy subjects relates to significantly greater risk of future coronary artery disease, MI, and mortality 22 to 40 years hence (8,9). There is also growing evidence supporting a relationship of depression to higher blood pressure (BP) levels and hypertension (HTN), which are important precursors to heart and vessel damage. Increases in existing depression have prospectively predicted cardiac events in patients with HTN (10), and increased inci- dence of heart failure (11) and stroke have been reported in depressed compared with nondepressed elderly patients with HTN (12). In initially normotensive men and women, depres- sive symptoms have been related to future incident HTN (13,14) and stroke (15). Incremental increases in mildly de- pressed mood have also been related to an increasing gradient of normotensive BP levels in premenopausal women (16). Studies of the relation of depression to components of auto- nomic regulation identify potential pathways by which de- pressed affect may increase BP and future cardiovascular risk, linking it with several markers of increased sympathetic ner- vous system (SNS) tone (17–20) and to enhanced SNS reac- tivity to physical and mental challenges (18,21,22). It is also widely accepted that BP and susceptibility to HTN are influenced by genetic factors (23,24). Because animal models have demonstrated that environmental stressors cause BP elevations more readily in HTN-prone strains (25–27), investigators have proposed that a genes by environment in- teraction model may more accurately predict HTN. In hu- mans, recent findings suggest that a genes by behavior inter- action may also enhance predictions of BP and HTN development (26,28,29). For example, Light et al. have re- ported that among normotensive young men, high cardiovas- cular responsivity to stressors at initial testing predicted higher BP levels and risk of HTN at 10-year follow-up, but only in subjects reporting parental HTN (FH). Men without familial susceptibility were not at increased risk regardless of earlier stress responsivity patterns. It is important to note here that the generational link in HTN vulnerability is more complex in humans than in other animals, with the impact of parental HTN on future risk most likely the result of shared genes, learned behaviors, shared environments, or various combina- tions thereof. However, based on previous findings, examina- tion of the interactive effects of other behavioral risk factors combined with genetic or familial vulnerability or both to HTN appear warranted. Therefore, in the current study, we investigated whether FH would enhance the impact of depressed mood on am- bulatory BP (ABP) profiles in a biracial sample of unmedi- cated men and women during their daily lives. We hypothe- sized an interaction between FH status and depressive symptoms whereby the predicted association between higher levels of depressed mood and higher BP over the day would be stronger in FH subjects vs. FH subjects. Our secondary From the Department of Psychiatry (K.M.G., S.S.G., K.C.L.), Department of Psychology (S.S.G., K.C.L.), and Medical School (A.H.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Karen Grewen, PhD, University of North Carolina, Medical Research Building A, CB #7175, Chapel Hill, NC 27599-7175. E-mail: karen_grewen@med.unc.edu Received for publication April 15, 2003; accepted July 23, 2003. This work was supported by National Institutes of Health Grants HL31533, HL64927, RR00046, and MH12094. DOI: 10.1097/01.PSY.0000106881.60228.16 9 Psychosomatic Medicine 66:9 –16 (2004) 0033-3174/04/6601-0009 Copyright © 2004 by the American Psychosomatic Society