Chronic depression symptoms, hypertension and renal impairment in a bi-ethnic sex cohort : the SABPA study
Abstract
Motivation: Although elevated renin levels are associated with volume-loading hypertension, African ethnicities are prone to develop low-renin hypertension. Chronic depressive symptoms were associated with vascular dysfunction and may disrupt the renin-angiotensin-aldosterone-system (RAAS). This may underscore a plausible mechanism for the association between depressive symptoms, sensitization of the RAAS in facilitating hypertension and renal dysfunction.
Objectives: The aim of this study was to investigate prospective changes and independent associations between depression symptoms, RAAS mediators (renin, aldosterone), blood pressure and estimated glomerular filtration rate (eGFR) in a bi-ethnic sex cohort from South Africa.
Methodology: This sub study forms part of the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study, conducted in 2008 and 2009. The study sample consisted of 359 participants with comparable socio-economic status, who participated in both legs of sampling. All users of hypertensive medication were excluded, as were participants diagnosed with diabetes or HIV infection. The final study population thus consisted of 195 participants (33 black men, 54 white men, 35 black women, and 73 white women). The study was approved by the Ethics Review Board of the North-West University and adhered to the requirements set in the Declaration of Helsinki.
Clinical measurements included ambulatory blood pressure (ABPM) and electrocardiogram (ECG) measures using the Cardiotens CE120® and interpreted with the Cardiovisions 1.19 software. A psychological battery of questionnaires was administered under supervision of registered psychologists. The battery included the Patient Health Questionnaire-9 (PHQ-9) used to determine the number of depression symptoms in participants. Physical activity recorded total energy expenditure (kcal/24h), considering resting metabolic rate and body surface area (m2) measurements were also obtained.
An 8-hour overnight midstream urine sample was collected to determine estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study equation. Fasting blood samples were collected by a registered nurse. All blood and urine samples were dealt with and stored according to secure standardized methods. Serum samples were analyzed for creatinine, glucose, and cholesterol, serum C-reactive protein (CRP), and gamma glutamyl transferase (γ-GT), serum cotinine levels, and glycosylated A1C (HbA1C). Plasma renin and plasma aldosterone were also measured.
Statistica 13.0 and IBM SPSS v 23 were used for all statistical analyses of the data. A priori covariates included age, body surface area, physical activity γ-GT and cotinine. A priori hypotheses were tested for all cardiovascular risk markers independent of baseline a priori and respective baseline risk markers. Normal distribution of data was tested, and box-cox logarithmic transformations were done for physical activity, cotinine, γ-GT, CRP, estradiol, renin, aldosterone, eGFR, PHQ, SBP, DBP and pulse pressure (PP) data.
Independent t-tests and Chi-square tests were used to describe the study population. Chi-square tables determined prevalence, while dependent sample t-tests determined differences over time. McNemar chi-square equations were used to calculate Odds Ratios and obtain p-values.
Multiple linear regression analyses were computed to determine the adjusted associations of changes over time in depressive symptoms, BP and eGFR in the bi-ethnic sex cohort, independent of baseline a priori covariates, estradiol, and baseline values of the respective cardiovascular risk markers. Statistical significance level was set at p < 0.05 (two-tailed). Optimal cut points 1) of depression symptoms associated with chronic diastolic hypertension (DBP-HTN) and 2) of renin values associated with moderately severe depression were computed from the maximum of the Youden index (J) (sensitivity + specificity − 1) using non-parametric receiver operating characteristic (ROC) curves. The statistical significance level was set at p ≤ 0.05 (two-tailed).
Results: Africans (Blacks) had more depressive symptoms and a mean hypertensive state, as well as lower plasma renin levels than Caucasians (Whites). Ethnic differences adjusted for a priori covariates were apparent for depressive symptoms (F1, 198 = 24.529), eGFR (F1, 198 = 14.360), SBP (F1, 198 = 13.929), DBP (F1, 198 = 13.998), and renin (F1, 196 = 11.286) (p < 0.001).
Forward stepwise multiple regression analyses and receiver operating characteristics were used to assess associations. An inverse association between depression and renin levels [Adj R2 0.38; β -0.27 (-0.5, -0.1), p = 0.009] with [AUC=0.61 (0.47-0.74); sensitivity/specificity 63.6/61.0%] was found in Blacks only. Chronic depression symptoms were associated with chronic DBP-HTN [AUC =0.58 (0.45-0.72); sensitivity/specificity 72.4/46.2%]. Similar findings were not traced for the White cohort.
Conclusions: Chronic depression symptoms may desensitize the RAAS by maintained activation of central neural control centers. Neural control may compensate by lowering renin and improving renal function to protect against volume-loading hypertension in Blacks. These findings emphasize the impact of depression on low renin and hypertension in Blacks in terms of prevention, diagnosis and treatment.
Chronic depression symptoms predicted chronic 24-hour DBP-HTN and may suggest a desensitization of the RAAS over time. Protection by central neural control centers may lower renin levels to protect against volume-loading hypertension and renal impairment
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