Depression and cardiovascular risk: does blood pressure play a role?

Population aging represents an achievement of improved life conditions and progress in healthcare and therapeutical interventions. However, it represents also a major challenge for the increasing burden of disability and for the more complex interplay between the comorbid clinical conditions affecting older individuals, conditions usually appearing isolated at younger ages. Depressive disorders are among the most common comorbidities in elderly individuals [1]. Depressive symptoms, even in the absence of a clinical diagnosis of depression, are accompanied by increased morbidity and mortality for cardiovascular events both in individuals with [2,3] or without [4–6] history of cardiovascular disease. However, depression has often been regarded merely as the reflection of the severity of medical conditions and poor social support. Indeed, a higher occurrence of diabetes and prevalent cardiovascular disease in depressed individuals has been reported [6]. Nonetheless, studies in individuals with heart failure showed that the effects of depression on poor cardiovascular outcomes were independent of left ventricular function and other established cardiovascular risk factors [7] – thus suggesting that depression is secondary to more severe illness. Elevated blood pressure (BP), an established potent risk factor for cardiovascular disease, is highly prevalent at older ages [8,9]. Therefore, it is reasonable to ask whether two common conditions in older individuals – depression and elevated BP – interact or share, or both, a common pathway contributing to the higher likelihood of cardiovascular events. Under this context, in the present issue of Journal of Hypertension an interesting study [10] exploring the effect of depression on BP levels is published. The Three City Study confirmed that both depression and hypertension are extremely common in older individuals. However, the findings of the Three City Study are apparently counterintuitive. In fact, it has been observed that average levels for systolic and diastolic BP were lower (approximately 3 mmHg for systolic and 1 mmHg for diastolic BP) in depressed than in nondepressed older individuals. This was true for both men and women, and it was independent of the use of antihypertensive or psychotropic medications. For those thinking that a 3 mmHg difference in systolic BP is clinically not relevant, particularly at older ages, it may be important to remember that a difference in usual systolic BP even within the 120–140 mmHg range has been associated with an annual difference in absolute risk that is nearly ten times more in individuals aged 80 years and older than that at ages 50–59 years [11]. Lower average levels of BP may certainly reflect a higher proportion of individuals with low BP as a consequence of heart failure. Indeed, history of heart failure was more frequent among depressed individuals than in nondepressed ones in both sexes in the Three City Study [10]. Nonetheless, when history of heart failure was added as covariate to multiple linear regression models, the association between depression and lower BP levels remained virtually unchanged. An alternative possibility is represented by a higher occurrence of hypotensive episodes in individuals with depression. In fact, hypoperfusion and increased cerebral blood flow pulsatility are associated with higher prevalence and severity of cerebral white matter lesions [12,13] and this brain vascular damage may be causative for depression and poor outcome in depressed individuals [14–16]. The present hypothesis opens another appealing scenario – depression alters the circadian BP profile. Of course, the cross-sectional design of the Three City Study does not allow speculation about mechanisms linking depression and BP regulation. Anyway, a stone has been thrown into the stagnant water. Depression can no longer be considered exclusively a psychiatric disorder. A multidisciplinary approach to depressive symptoms is required to disentangle the pathways leading to increased cardiovascular risk in depressed individuals, to identify adequate management of older individuals with comorbidities, and to understand the safety and effectiveness of specific antidepressant therapy in depressed individuals with high cardiovascular risk. Although the broadening of scientific and clinical interest in depression is welcome, it requires a fundamental preliminary methodological consideration – which screening test for depression should be considered the gold standard? As previously reported, different tests had been adopted to measure depression or depressive symptoms [17]. However, appropriateness, specificity, and sensitivity of the variety of adopted screening methods are questionable. In this regard, the Three City Study is also relevant. In fact, BP differences between depressed and nondepressed older individuals changed according to the test adopted to define depression [10]. Additionally, no evidence of cross-classification of older individuals among different definitions of depression has been provided [10].