Cardiovascular risk factors and major depressive disorder: a cross-sectional study in São Paulo, Brazil

ABSTRACT BACKGROUND: Cardiovascular risk factors can mediate the association between depression and cardiovascular diseases. OBJECTIVE: To evaluate cardiovascular risk factors in adult individuals with and without histories of major depression in the metropolitan region of São Paulo, Brazil. DESIGN AND SETTING: Cross-sectional study in São Paulo (SP), Brazil. METHODS: This study evaluated 423 individuals without any lifetime diagnosis of major depression and 203 individuals with a previous diagnosis of major depression (n = 626). The participants underwent a psychiatric evaluation using a structured clinical interview (SCID-1), an anthropometric evaluation and a clinical evaluation that included blood pressure measurement and assessment of fasting blood glucose, lipid profile and physical activity levels. RESULTS: Individuals with histories of major depression were more likely to be female (P < 0.0001). Individuals with lifetime diagnoses of major depression were more likely to be current smokers (odds ratio, OR 1.61; 95% confidence interval, CI 1.01-2.59) and to have diabetes (OR 1.79; 95% CI 1.01-3.21); and less likely to be obese (OR 0.58; 95% CI 0.35-0.94). CONCLUSION: Individuals with major depression had higher odds of presenting tobacco smoking and diabetes, and lower odds of being obese. Healthcare professionals need to be aware of this, so as to increase the rates of diagnosis and treatment in this population.


INTRODUCTION
Cardiovascular diseases are the leading cause of death worldwide and in Brazil. 1 Mortality rates relating to cardiovascular diseases have also been found to be higher in a psychiatric population than in an age-matched general population, with a hazard ratio (HR) of 4.16 (95% confidence interval, CI 1. 22-14.25). 2 There is reasonable data describing the association between depressive disorders and cardiovascular disease incidence and mortality, especially with regard to coronary heart diseases. 3,4 Nicholson et al. reviewed 54 observational studies and conducted a meta-analysis regarding depression as an etiological factor among individuals with coronary heart diseases. They found that depression increased the risk of incident coronary heart disease (pooled relative risk, RR 1.81; 95% CI 1.53-2.15). 5 Individuals' profile of cardiovascular risk factors can explain, at least partially, the higher incidence of coronary heart disease and related mortality among individuals with depressive disorders. Appleton et al. evaluated 8,138 men and found higher incidence of cardiovascular diseases in individuals with depressive disorders (HR 2.36; 95% CI 1.39-4.0). However, the association lost significance after cardiovascular risk factors were included in the model for adjustment (HR 1.73; 95% CI 0.99-2.99). 2 Therefore, cardiovascular risk factors might be important mediators of the causal model linking depressive disorders and cardiovascular mortality.
Depressed individuals might have unhealthier lifestyles than the general population, with higher rates of smoking and greater physical inactivity. 6,7 Strine et al. evaluated 217,379 individuals in a survey in the United States and found that individuals with previous major depression had higher odds of current smoking (odds ratio, OR 1.9; 95% CI 1.8-2.1) and physical inactivity (OR 1.3; 95% CI 1.2-1.4). 7 There are also data showing higher prevalence of metabolic syndrome in patients with major depression 8 and, more consistently, in depressed women. 9,10 Studies that have evaluated the relationship between cardiovascular risk factors and depressive disorders in the general population are less common, especially in low and middle-income countries.

OBJECTIVE
The aim of this study was to evaluate cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, obesity and metabolic syndrome) and their association with lifetime major depression in a subsample of individuals from the São Paulo Megacity Mental Health Survey, in the metropolitan area of São Paulo, Brazil.

Study design
The São Paulo Megacity Mental Health Survey is a population-

Study sample
The current study was based on a subsample of the Brazilian WMH, with a cross-sectional design and was conducted in parallel with the main household survey. Out of the 5,037 individuals who were evaluated in their households, a random subsample of 780 individuals was selected. Eight individuals (1%) with symptoms that needed emergency evaluation, who did not complete the protocol, were excluded. We also excluded 146 (18.7%) who had substance use disorders or eating disorders and, thus, 626 individuals (80.3%) remained included in the final analysis (Figure 1).
The only missing data consisted of body mass index (BMI) values for individuals. The remainder of the data was 100% complete.

Psychiatric and clinical assessments
In the hospital outpatient setting, trained psychiatrists assessed participants through the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). 12 The SCID-I makes it possible to generate current and lifetime diagnoses on psychiatric conditions. For this analysis, we only included individuals with lifetime diagnoses of major depressive disorder (MDD), with or without associated anxiety disorders.
In addition, the onsite evaluation included a questionnaire that was used to collect the following sociodemographic data: age, sex, marital status, number of years of formal education (measured as number of school years), current job status (worker, housekeeper, student, retired or other) and annual household income. A clinical evaluation focusing on cardiovascular risk factors and cardiovascular diseases was performed by two physicians. All subjects were asked about smoking status (never, past or current), alcohol intake and personal histories of hypertension, diabetes, coronary heart disease or cerebrovascular disease. The level of physical activity was measured using the long version of the International Physical Activity Questionnaire (IPAQ). 13 Inadequate physical activity was defined as being sedentary or insufficiently active according to the IPAQ, considering two domains separately: leisure-time and journey-to-work (commuting) physical activity.

Definition of cardiovascular risk factors
Hypertension was defined as mean systolic blood pressure ≥ 140 mmHg, mean diastolic blood pressure ≥ 90 mmHg, medical history of hypertension and/or current use of medication to treat hypertension. 14 Diabetes was defined as fasting blood glucose ≥ 126 mg/dl, medical history of diabetes and/or use of medication to treat diabetes. 15 Individuals were considered to have dyslipidemia if they had one or more lipid profile alterations: high-density lipoprotein-cholesterol (HDL-c) levels lower than 40 mg/dl for men and lower than 50 mg/dl for women; triglyceride (TG) levels higher than 150 mg/dl; or low-density lipoprotein-cholesterol (LDL-c) levels higher than 130 mg/dl. Metabolic syndrome was defined as the presence of three or more of the following criteria: abdominal obesity (waist circumference ≥ 102 centimeters (cm) in men and ≥ 88 cm in women); TG blood level ≥ 150 mg/dl; HDL-c cholesterol blood levels lower than 40 mg/dl in men or lower than 50 mg/dl

Anthropometric and blood pressure measurements
The anthropometric evaluation (weight, height and waist circumference) was performed using standardized equipment and techniques. 17 Blood pressure was measured three times using a standardized technique in the seated position after a five-minute rest. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. 18 Overweight was defined as BMI between 25 and 29.9 kg/m 2 . Obesity was defined as BMI greater than or equal to 30 kg/m 2 .

Laboratory measurements
Venous blood samples were obtained after a 12-hour overnight fast.
LDL-c values were obtained using the Friedewald formula. 16

Statistical analysis
Data entry was carried out twice and a validity check was done in order to identify and correct any data entry errors. Groups were compared using the chi-square test or Fisher's exact test for categorical data, whenever applicable. Continuous variables were tested for normality, and one-way ANOVA (analysis of variance) or nonparametric tests were performed, whenever applicable. We used logistic regression to evaluate comparisons among individuals with and without depression and the results were presented crudely and adjusted for age and sex. The significance level was set at 0.05. We used the SPSS for Windows software, version 16.0 (SPSS Inc., Chicago, United States), and the R software, version 3.0.0 (Vienna, Austria) for the analyses.

Ethical considerations
The Institutional Review Board of Hospital das Clínicas, Universidade de São Paulo approved the study under the protocol number 234/03 (on April 24, 2003), and all the participants signed a written informed consent statement. sion were more likely to be current smokers than were individuals who had never been depressed, with borderline significance (20.3% versus 13.0%; P = 0.056) ( Table 1).

Among
There were no differences between the individuals with and without lifetime diagnoses of major depressive disorder regarding  Table 2).
In the age and sex-adjusted logistic regression model, individuals with lifetime major depression had higher odds of being current smokers (OR 1.61; 95% CI 1.01-2.59) and higher odds of presenting diabetes (OR 1.79; 95% CI 1.01-3.21). In addition, individuals with lifetime major depression had lower odds of presenting obesity (OR 0.58; 95% CI 0.35-0.94). No differences were found for other cardiovascular risk factors (hypertension, dyslipidemia, metabolic syndrome and physical activity) ( Table 2). Further adjustment for cardiovascular risk factors did not change the results (data not shown).

DISCUSSION
In our study, we found that current smoking and diabetes showed associations with lifetime histories of major depression. We also found lower odds of being obese among individuals with lifetime histories of major depression, compared with nondepressed individuals.
Our study found that individuals with lifetime major depression had higher odds of being diabetic. Most studies have found this same association between diabetes and major depression, including evidence for a bidirectional association. 19 24 Mezuk et al. found that diabetes could enhance the risk of incident depression (OR 1.15; 95% CI 1.02-1.30). They also found higher risk of new-onset diabetes among depressed subjects (RR 1.60; 95% CI 1.37-1.88). 23 There are multiple explanations for the association between diabetes and depression, as mediated by long-term use of antidepressants 25 and increased inflammation and insulin resistance. 26 The recent discussion on syndemics has indicated that the association between diabetes and depression is more complex than it would seem through explanations that invoke exclusive biological pathways. The dynamics of poverty and sociocultural contexts influence lifestyle and the health and disease process that links these two diseases. [27][28][29][30] Because the present study was a cross-sectional analysis, it is impossible to draw any conclusions relating to causality. Nevertheless, our data confirm the presence of this association in a Brazilian population sample.  7 Goodwin et al. found that among smokers the prevalence of past-year depression was 10.45%, compared with 5.51% among never-smokers. 32 Previous Brazilian studies confirmed the association between tobacco smoking and depressive symptoms. 33,34 Borçói et al. found a prevalence ratio of 2.69 (95% CI 1.62-4. 46) for being a current smoker, among individuals with depressive disorder in a sample at a primary care service in a Brazilian municipality (Alegre, Espírito Santo). 33  We found lower odds of obesity among individuals with lifetime histories of major depression. The results in the medical literature regarding this association are divergent, with positive results, 35,36 negative results [37][38][39] and inverse associations. 40 41 The Brazilian National Health Survey (Pesquisa Nacional de Saúde, PNS 2013) also found a bidirectional association between depression and obesity. 42 Paulitsch et al. found that the association of depression and obesity was mediated by weight perception, i.e. believing oneself to be fat. They also found that some groups were more vulnerable: being non-single, having more schooling and not engaging in physical activity. 43 Our data contrasted with different Brazilian studies showing regional heterogeneity. In our study, the association between higher rates of commuting-related physical activity and lifetime history of MDD lost its significance after adjustment. Because our sample had a higher number of women than of men and commuting physical activity occurs more frequently among men than among women, 44,45 our results probably lost significance after adjustment for sex.
Our study had some methodological strengthens. Trained psychiatrists made the psychiatric diagnoses of all participants, using a gold-standard instrument (SCID-I). The cardiovascular risk factors were evaluated using medical history and using clinical and laboratory assessments from onsite evaluation made by trained physicians.
The results from the study highlight the importance of diagnosing and treating depression within primary and secondary care. 46 Depression is an important risk factor for noncompliance with treatment of chronic diseases. Therefore, for effective control of cardiovascular risk factors, it is mandatory to recognize and treat depression. Depressive individuals are less active, with higher frequency of smoking and less adherence to prescribed medication. 47 In addition, practicing physical activity can also be part of depression treatment.
On the other hand, the effect of treating depression can have some impact regarding weight gain, which has been shown to have an important relationship with depression and cardiovascular risk factors and chronic diseases. Healthcare professionals can manage treatment of depression using better cardiovascular-profile drugs or considering other treatment options, such as psychotherapy, whenever possible. 48 Our study also had some limitations, given that the cross-sectional study design did not permit evaluation of causality. Moreover, the diagnosis of diabetes was made based on only one measurement of fasting plasma glucose, as a consequence of budget limitations and logistic limitations on performing some laboratory tests such as hemoglobin A1c. Another important point is that our sample was young, with a mean age of around 40 years. The prevalence of cardiovascular risk factors increases with age, which may explain the lower frequency in our sample. In addition, although the sample in the first phase of the study with home interviews was representative of the population living in the metropolitan region of São Paulo, only a subsample of participants was invited in the second phase, and many of them refused to participate, thus introducing some selection bias. However, even considering the young age, we reported that there was higher prevalence of diabetes and smoking among the depressive participants than among the nondepressed participants.

CONCLUSIONS
In this sample of individuals living in the metropolitan region of São Paulo, the biggest city in Brazil, we found that individuals with lifetime major depression had higher odds of current tobacco use and of presenting diabetes mellitus. They also had lower odds of being obese, compared with nondepressed individuals. Healthcare professionals need to increase their awareness of the diagnosis of cardiovascular risk factors among individuals with major depression, in order to enhance preventive strategies and thus reduce morbidity and mortality in this high-risk group.