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Psychosomatic Medicine 66:9-16 (2004)
© 2004 American Psychosomatic Society

ORIGINAL ARTICLES

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

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{at}med.unc.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
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 norepinephrine (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.

Abbreviations: ABP = ambulatory blood pressure;; BDI = Beck Depression Inventory;; 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 = hypertension;; MI = myocardial infarction;; NE = norepinephrine;; SNS = sympathetic nervous system;; SADHEART = Sertraline Antidepressant Heart Attack Randomized Trial;; SBP = systolic blood pressure.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Over 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 Depression Inventory (BDI), have predicted subsequent cardiac morbidity 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 depression 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 incidence 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, depressive symptoms have been related to future incident HTN (13,14) and stroke (15). Incremental increases in mildly depressed 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 autonomic regulation identify potential pathways by which depressed affect may increase BP and future cardiovascular risk, linking it with several markers of increased sympathetic nervous system (SNS) tone (17–20) and to enhanced SNS reactivity 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 interaction model may more accurately predict HTN. In humans, recent findings suggest that a genes by behavior interaction may also enhance predictions of BP and HTN development (26,28,29). For example, Light et al. have reported that among normotensive young men, high cardiovascular 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 combinations thereof. However, based on previous findings, examination 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 ambulatory BP (ABP) profiles in a biracial sample of unmedicated men and women during their daily lives. We hypothesized 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 hypothesis was that, independent of FH status, subjects with more depressive symptoms would exhibit greater heart rate (HR) and BP levels and greater sympathetic and hypothalamic-pituitary-adrenal (HPA) activity during real life challenges, indexed by higher 24-hour urinary catecholamines and cortisol.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Participants
Volunteers (156 men, 158 women) age 18 to 64 years were recruited by public advertisements from the community. Exclusionary criteria were current or recent use of medications affecting SNS activity including antidepressants and antihypertensive drugs, self-report of current or recent depression, and diagnosis of any systemic disease with the exception of HTN. African Americans composed 45% of the sample. The protocol also required that all subjects be employed outside of the home to include ABP monitoring during an 8-hour period at work. FH+ was defined as self-report of one or more hypertensive parents, and subjects were also classified as having no, one, or two hypertensive parents (FH0, FH1, or FH2, respectively). Within the total sample, 15% were identified by our protocol as hypertensive, defined as systolic BP (SBP) greater than 140 or diastolic BP (DBP) greater than 90 mm Hg or both at clinic and ambulatory monitoring appointments (HTN = 47, normotension = 267). Subjects reporting a previous diagnosis of HTN at telephone screening (N = 18) were asked, under the supervision of their physicians, to forego antihypertensive medication for 3 weeks before testing, and prestudy BP in these subjects was also regularly monitored by our staff, with data made available to subjects’ physicians. Of these 18 subjects, 12 exhibited BP in the hypertensive range defined by our protocol after 3 weeks without medication.

Physiologic Measures
Clinic Assessment and 24-Hour Ambulatory Monitoring
Subjects’ eligibility was first assessed during a brief telephone interview. At the subsequent clinic appointment, screened subjects provided informed consent; were assessed for BP, height, and weight; and were given questionnaires to complete. Reported values of clinic BP are the mean of three seated BP measurements taken no less than 1 minute apart by a trained technician using a mercury sphygmomanometer. Subjects returned on the morning of a typical workday and were instrumented with the Accutracker II ambulatory blood pressure monitor (Suntech, Raleigh, NC). Three disposable spot electrocardiogram electrodes (Invisatrace; Con Med, Utiaca, NY) were placed on the chest, and a piezoelectric microphone was used to measure Korotkoff sounds was placed over the brachial artery of the nondominant arm, which was then covered with the BP cuff connected to the ambulatory monitor. A trained technician assessed at least three seated and two standing BP recordings using a mercury sphygmomanometer while simultaneously taking Accutracker BP readings to confirm accuracy of monitor assessments. The monitor was then programmed to take four readings per hour at random intervals during the day, and two readings per hour during sleep. HR was determined from R-waves for each reading. Subjects were then sent to work wearing the instrument for the ensuing 24 hours. All subjects were required to undergo monitoring while at work outside the home for at least 8 hours. On completion, BP and HR data were downloaded into computer files and edited to exclude readings accompanied by error codes, and artifactual readings were determined according to the method described by Harshfield et al. (30).

Biochemical Assays
For two 24-hour periods consisting of the monitoring day and an additional workday within that week, subjects collected 24-hour samples of urine, using bottles containing sodium metabisulfite preservative. Reported urinary cortisol and norepinephrine (NE) levels are the averages of both days (µg/24 h). Aliquots were pipetted and frozen at -80°C until assay. NE levels were measured using reverse-phase high-performance liquid chromatography. This assay is sensitive to NE levels as low as 5 pg/ml, with interassay and intra-assay coefficient of variation (CV) less than 10%. Urinary cortisol levels were assessed using a commercially available radioimmunoassay kit (ICN Pharmaceuticals; sensitivity = 0.07 µg/dl, intra-assay and interassay CV =< 8%).

Instruments
Beck Depression Inventory
The BDI is a 21-item self-report scale that assesses cognitive, affective, and somatic depressive symptoms that have occurred over the previous week. This scale measures depressed mood, is not used as a diagnostic tool to assess major depressive disorder, has acceptable test–retest reliability (r = 0.79) in nonclinical populations, and demonstrates concurrent validity (r = 0.67–0.79) in clinical and nonclinical samples (31).

Statistical Analysis
For descriptive analyses, unpaired t tests were used to examine FH+ vs. FH- group differences in mean BP, HR, age, body mass index (BMI), BDI score, and urinary NE and cortisol. The {chi}2 statistic was used to test group differences in gender, race, and HTN status. Each subject’s ambulatory data were averaged across the 24-hour period to provide a mean total 24-hour value. Mean ABP was also calculated during work, sleep, and awake periods; however, mean total 24-hour SBP, DBP, and HR are the focus of this report.

Linear regression analyses were used to examine the main effects and interaction of FH status and BDI score on mean ambulatory SBP, DBP, HR, and mean urinary NE and cortisol. Age, BMI, gender, race, and FH status were entered in step 1 to create the reduced model. When added as a covariate, menopausal status was not a significant predictor of ABP and therefore was not included in the model. BDI score and the FH by BDI interaction were entered in step 2 to create the full model. The F tests of the significance of the uniqueness indices attributable to step 2 ({Delta}R2) were performed using the procedure described by Hatcher and Stepanski (32). These regressions were performed first on the complete sample (N = 314) and again on a subset (N = 267) from which all subjects with HTN (N = 47) were removed. Categorical predictor variables were represented as dummy variables, and continuous predictor variables were centered with the method described by Aiken and West (33) for testing interactions. Separate correlations, adjusted for covariates, were then plotted for predicted mean 24-hour SBP and DBP with BDI score in the FH0, FH1, and FH2 groups. For mediational analyses, urinary NE and cortisol values were added separately to BP and HR models as additional potential covariates to assess their possible role as mediators in the effects of depression, according to the method described by Baron and Kenny (34).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Descriptive Data on Groups With and Without Family History of Hypertension
Characteristics of participants, categorized by FH status, are presented in Table 1. No significant group difference in age, BDI score, mean urinary NE, or cortisol was seen. Although the distribution of BDI scores across the entire sample was positively skewed (mean, 5.67; median, 4.00; range, 0–29), both FH+ and FH- groups displayed similar top (FH+, 15–28; FH-, 14–29) and bottom (FH+, 0; FH-, 0) quartiles, and the independent variables (mean 24-hour SBP and DBP) were normally distributed at both the top and bottom quartiles of BDI. The FH+ group exhibited significantly greater BMI and higher SBP and DBP both in the clinic and across all ambulatory measurement periods. The FH+ group also contained a significantly greater percentage of African Americans, women, and subjects with HTN (based on seated BP assessed at both clinic and ambulatory monitoring visits). As previously described, all effects of the FH group by BDI interaction were examined with age, BMI, FH, race, and gender as covariates in the model to adjust for any effects of these group differences. The range of BDI scores was similar in both groups (FH+, 0–29; FH-, 0–28).


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  		TABLE 1. Subject Characteristics in 314 Men and Women by FH
 
Differences in Clinic and Ambulatory Blood Pressure by Family History Status and Depressive Symptoms
As predicted, significant FH by BDI interaction effects were observed on mean total SBP and DBP values averaged across the ambulatory monitoring period when covarying for age, BMI, race, and gender (SBP, F(7,306) = 16.71; DBP, F(7,306) = 21.49, respectively; p values <.0001). These results, presented in Table 2, show that the inclusion of BDI and the FH by BDI interaction (step 2) accounted for a significant and unique portion of the variance ({Delta}R2) in mean SBP and DBP during the total 24-hour session (p values <.01). The effects of the interaction were essentially unchanged when hypertensive status was included as a covariate (SBP, t = 2.73; DBP, t = 2.21; p values <.05). These analyses were also repeated excluding the 47 subjects with BP levels in the hypertensive range as per our protocol (SBP >140 and/or DBP >90) to ensure that this relation was not driven solely by subjects with HTN within the sample. Similar significant FH by BDI interactions were obtained for both SBP (t = 2.56, p <.05) and DBP (t = 2.55, p <.05) on this smaller normotensive sample. Work, nonwork waking, and sleep periods were also examined separately to detect whether the influence of the FH by BDI interaction was stronger during a particular part of the day. Significant FH by BDI interaction effects were observed for mean work (SBP, t = 2.32; DBP, t = 2.10; p values <.05) and nonwork waking (SBP, t = 2.73, p <.01; DBP, t = 2.25, p <.05) periods. This pattern was weaker for SBP (t = 2.02, p <.05) and nonsignificant for DBP during sleep. In contrast with mean ABP patterns, clinic SBP and DBP were not predicted by BDI score or the FH by BDI interaction.


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  		TABLE 2. FH by BDI Interaction in Multiple Regression Analyses Predicted Mean ABP
 
Differences in Ambulatory Blood Pressure by Family History Status and Depressive Symptoms in Younger vs. Older Subjects
The broad age range spanned by the sample (18–64 years) may have allowed greater variability in parental HTN diagnosis, with younger volunteers more likely to be classified as false-negatives, reporting FH- when they would actually be FH+ if their parents were given time to reach the age of older subjects’ parents. A {chi}2 analysis of the FH status of older vs. younger subjects (<=40 vs. >40 years) did not confirm this, with no significant differences in the percentage of FH0 (38% vs. 49%), FH1 (46% vs. 39%), and FH2 (17% vs. 12%) in younger (N = 181) and older (N = 169) groups ({chi}2 = 3.71, p >.15). When separate analyses regressing mean ABP on our predictors were run for younger vs. older subjects, significant FH by BDI interactions were found for mean 24-hour SBP (t = 2.45, p <.05) in the younger group, whereas marginal effects for mean 24-hour SBP ((t = 1.82, p <.08) and DBP (t = 1.74, p <.09) were seen in the older group.

Differences in Ambulatory Blood Pressure by Depressive Symptoms in Subjects With Zero, One, and Two Hypertensive Parents
Further inspection revealed that higher BDI was related to higher mean SBP and DBP in FH+ subjects. In contrast, this relationship was weak to nonexistent in FH- subjects. When subjects were categorized by the number of hypertensive parents (FH0, FH1, or FH2) reported, both groups of FH+ subjects showed a positive relationship between BDI score and ABP after controlling for the covariates described. Figure 1 illustrates that greater partial r values between BDI and predicted mean SBP were observed in FH1 and FH2 (r values = 0.36 and 0.58, p values <.001) groups compared with the FH0 group (r = 0.19, p <.05). The Fisher z statistic revealed marginal to significant differences in the magnitude of these correlation coefficients, with FH0 less than FH1 less than FH2 groups (FH0 vs. FH1, z = 1.49, p <.08; FH1 vs. FH2, z = 2.19, p <.05). Figure 2 illustrates the same pattern of significant positive correlations between BDI and predicted total mean DBP, adjusted for covariates, observed in both FH1 and FH2 (r values = 0.31 and 0.51, p values <.001) groups. This association was not seen in the FH0 group (r values = -0.11, p = NS). Again, the Fisher z statistic revealed that these correlation coefficients were reliably different from each other (FH0 vs. FH1, z = 1.61, p <.06; FH1 vs. FH2, z = 3.47, p <.0002).



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  		Fig. 1. Correlations of predicted 24-hour mean SBP adjusted for age, BMI, race, and gender with BDI in subjects reporting two normotensive parents (FH0) or one (FH1) or two (FH2) hypertensive parents. ****p < .0001, ***p < .001, **p < .01, *p < .05.

 


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  		Fig. 2. Correlations of predicted 24-hour mean DBP adjusted for age, BMI, race, and gender with BDI in subjects reporting two normotensive parents (FH0) or one (FH1) or two (FH2) hypertensive parents. ****p < .0001, ***p < .001, **p < .01, *p < .05.

 
FH1 did not differ from FH2 in mean BDI score (FH1, 6.07; FH2, 6.20), age (FH1, 38.61; FH2, 39.18), BMI (FH1, 27.18; FH2, 27.68), mean urinary NE (FH1, 38.72; FH2, 36.14), or cortisol (FH1, 181.31; FH2, 165.04) levels. However, compared with FH1, FH2 demonstrated significantly higher mean 24-hour SBP (FH1, 126.88; FH2, 133.19) and DBP (FH1, 78.41; FH2, 83.03).

Differences in Ambulatory Heart Rate by Family History Status and Depressive Symptoms
No significant differences in mean ambulatory HR were seen between FH+ and FH- groups. The FH by BDI interaction did not predict mean HR and was therefore omitted from the model. After controlling for age, BMI, race, and gender, linear regression analyses of mean HR on BDI revealed that higher BDI scores were significantly related to higher ambulatory HR values, accounting for significant amounts of the variance in mean HR across the measurement period (Table 3).


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  		TABLE 3. BDI In Multiple Regression Analyses Predicted Mean HR
 
Differences in 24-Hour Urinary Norepinephrine and Cortisol by Family History Status and Depressive Symptoms
No significant differences in 24-hour urinary NE or cortisol were observed between FH+ and FH- groups. The FH by BDI interaction did not predict mean NE or cortisol and was therefore omitted from the model. Linear regression of NE on BDI revealed that higher BDI scores were significantly related to higher NE values (b = 640.53, ß = 13.4, t = 2.48, p <.05). Figure 3 illustrates the relationship between BDI score and predicted mean urinary NE after controlling for age, BMI, race, and gender (r = 0.44, p <.0001). Higher mean NE values were also related to female gender; greater age and BMI; and higher SBP, DBP, and HR across all periods, and were unrelated to race. In contrast, 24-hour urinary cortisol was unrelated to any BP or HR measure or to BDI. Significantly higher cortisol values were seen in men vs. women (F(3,310) = 8.02, p <.005) and in white subjects vs. black subjects (F(3,310) = 14.05, p <.001).



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  		Fig. 3. Correlation of mean 24-hour urinary NE (µg/24h) with BDI adjusted for age, BMI, race, and gender in 311 men and women. ****p < .0001.

 
Mediational Analyses Involving Norepinephrine
Although NE measures were significantly correlated with BP and with depression scores, all reported effects of BDI and the FH by BDI interaction on BP and HR remained unchanged after covarying urinary NE levels, thus failing to provide supportive evidence for NE as a mediator of the effects of depressed mood on BP levels in FH+ participants.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
ACKNOWLEDGMENTS
 REFERENCES
 
In this heterogeneous sample, the FH by BDI interaction was a unique predictor of mean ambulatory SBP and DBP in men and women across a day that included assessment while at work and at home and during sleep. A unique contribution is the finding that higher depressive symptoms were linked to higher mean BP in subjects throughout the day, but only if they also had a familial (genetic and shared environment) susceptibility to HTN. Moreover, the strength of this depression-BP association increased across the gradient of FH status: it was weak to nonsignificant in those reporting two normotensive parents, moderate in those with one hypertensive parent, and strongest in those with two hypertensive parents. In addition, results were essentially identical when participants with BP levels within the hypertensive range were excluded from the analyses, suggesting that this pattern may precede the development of HTN. In contrast, neither BDI score nor the FH by BDI interaction predicted clinic BP, and the interaction was least predictive of BP levels during sleep, suggesting that the influence of depression on BP in FH+ subjects is manifested during responses to the stresses and strains of everyday living. These observations add to previous work suggesting that genetic vulnerability to HTN may enhance or synergize the impact of other well-known risk factors on BP in nonpatient samples (35,30).

Based on previous research relating depression to markers of chronically elevated sympathetic cardiovascular tonic control (16–18,37), we hypothesized that, independent of family history, depressed mood would be associated with enhanced SNS activity. This was confirmed by findings that higher BDI scores were related to higher mean urinary NE and to higher mean ambulatory HR, adjusted for age, BMI, race, and gender. However, our attempts to define a mediator role for sympathetic activity through use of NE measures were unsuccessful. Nonetheless, the conclusion that sympathetic activity is not a mediator of depression’s effect on BP may be premature. Urinary NE levels, reflecting a mixture of nerve terminal overflow, reuptake, adrenal release, and renal clearance, are an imperfect index that may not completely capture the complex balance of factors determining the degree of sympathetic stimulation to cardiac and vascular tissue (38). For example, previously, Light et al. (39) reported that plasma catecholamine levels in response to a laboratory speech stressor were enhanced in some but not other high BP responders (high cardiac but not high vascular reactors). This was true even though we are confident, based on other studies involving adrenergic blockade (40), that the vascular reactivity also involved increased sympathetic activity. Similar findings have recently been reported in a sample of young men (41), with greater 24-hour urinary epinephrine levels and plasma epinephrine stress responses in those with predominantly cardiac vs. vascular responses to stress, with no differences in plasma or urinary NE between reactor types. Therefore, our failure to show sympathetic mediation of BP elevations related to higher depressive symptoms may have been caused by lack of a better index of overall sympathetic activity. Nevertheless, the fact that higher BDI scores were linked to urinary NE levels encourages further study of a potential contributory role of sympathetic activity in the cardiovascular effects of depressive symptoms.

Because dysregulation at all levels of the HPA axis has been related to depression (42,43), we also expected that depressive symptoms would be related to aberrant urinary cortisol levels in our subjects. However, we did not find differences in mean 24-hour urinary cortisol related to depressive symptoms, BP, or HR in any group based on urinary excretion averaged over two 24-hour periods and verified by creatinine clearance. The accuracy of this measure depends in large part on subject compliance, which is difficult to assess, and which may have differed as a function of depressive symptom level. However, urinary NE levels did correlate with BP in all groups, and with depression symptom scores. Additionally, creatinine clearance of samples retained for analyses all met standards. These results suggest that people with mildly depressed mood may not consistently show the dysregulated HPA activity seen in clinical depression but instead may more typically exhibit autonomic imbalance characterized by greater SNS activity. Alternatively, a different index of HPA activity, such as free cortisol measured in salivary samples, may be more responsive to symptoms of depressed mood compared with the 24-hour urinary total cortisol that we assessed.

A strength of the current investigation is the use of 24-hour ABP measurement, which has been identified as superior to clinic BP in predicting target organ damage and daily cardiovascular load (44,45). FH+ men and women with higher depressive symptoms demonstrated higher ABP in their work and home environments. Because this group difference was not apparent in clinic BP, identification of a potentially vulnerable subgroup (FH+/high depressive symptoms) would have been missed without ABP assessment. A reservation is that although the BDI is the most widely used tool for assessing depressive symptoms, it was never intended for use as a trait measure, but instead is a measure of transient state affect at any given time point. In future studies, multiple assessments of depressed affect over a period of months or years would strengthen confidence in findings concerning relationships between depressive symptoms and BP. Also, because a focus of the current study was the influence of mildly depressed mood on BP levels in interaction with familial HTN, the exclusion of volunteers with current or recent clinical depression may have contributed to the positive skew in the BDI distribution scores in this sample. Although both FH groups exhibited similar top (FH+, 15–28; FH-, 14–29) and bottom (FH+, 0; FH-, 0) quartiles of BDI scores, our subsequent ability to apply the probability levels associated with reported regression results from this sample to the general population may be weakened.

A more major reservation is the use of self-report of parental HTN as an index of genetic susceptibility. A related issue is the broad age range of our sample, which may have added variability to the parental HTN diagnoses. However, we found equal proportions of FH- and FH+ subjects in groups classified as younger than 40 years compared with those 40 and older. Also of concern is that parents of older subjects are more likely to have been diagnosed with systolic vs. diastolic HTN; however, we are unable to examine such differences in our current sample. Despite these limitations, because familial hypertension is a well-documented risk factor for HTN and is used by physicians to infer patient risk, it is arguably a valid variable of interest despite the likelihood of some false-positive and negative data. Consistent with expectations, self-report of FH+ status was associated with higher BP and HTN prevalence, and a gradient of higher clinic and ambulatory BP was related to a gradient of FH status; this pattern was not different in younger vs. older groups of subjects. In addition, HTN is a heterogeneous disorder attributable to any number of weak genetic factors in gene–gene or gene–environment combinations, or both (28). Therefore, the FH status variable remains a useful, if imprecise, composite of susceptibilities caused by multiple components of genetic vulnerability and environmental influences shared by family members. In addition, the broad age range of our sample may have added variability to the parental HTN diagnoses.

Finally, it must be emphasized that depression has been strongly linked to coronary heart disease (CHD) morbidity and mortality, particularly after MI. The present study in no way minimizes the importance of efforts to reduce depression as a means of relieving suffering, improving quality of life, and possibly lowering CHD risk in those with and without FH+. However, based on the recent ENRICHD trial and the SADHEART study, Sheps et al. (46) and Glassman et al. (47) emphasize that although there may be no uniform method by which to reduce cardiovascular risk in patients with depression, we need further investigations to examine different treatment alternatives and to identify patient subgroups who may derive greater cardiac benefit. Similarly, attempts to discern a link between subclinical depressed mood and elevated BP in medically healthy subjects have produced inconsistent results (48–50). The current findings suggest that depressive symptoms not considered serious enough to warrant a mental health problem may increase BP more consistently in those with familial or genetic risk factors. Thus, behavioral interventions that reduce depressive symptoms may be more effective in lowering risk of HTN in these genetically prone people. Future studies aimed at reconfirming the association of depressed mood with elevated BP or at using behavioral interventions to modify these symptoms should consider stratifying by FH.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
REFERENCES
 
This work was supported by National Institutes of Health Grants HL31533, HL64927, RR00046, and MH12094.

Received for publication April 15, 2003.

Accepted for publication July 23, 2003.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 

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