Itamar S. Santos

Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015

Importance Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Results Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). Loss of disability-adjusted life-years (DALYs) associated with SBP of at least 110 to 115 mm Hg increased from 148 million (95% UI, 134-162 million) to 211 million (95% UI, 193-231 million), and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

Effects of Depression, Anxiety, Comorbidity, and Antidepressants on Resting-State Heart Rate and Its Variability: An ELSA-Brasil Cohort Baseline Study

OBJECTIVE Increases in resting-state heart rate and decreases in its variability are associated with substantial morbidity and mortality, yet contradictory findings have been reported for the effects of the mood and anxiety disorders and of antidepressants. The authors investigated heart rate and heart rate variability in a large cohort from Brazil, using propensity score weighting, a relatively novel method, to control for numerous potential confounders. METHOD A total of 15,105 participants were recruited in the Brazilian Longitudinal Study of Adult Health. Mood and anxiety disorders were ascertained using the Portuguese version of the Clinical Interview Schedule-Revised. Heart rate and its variability were extracted from 10-minute resting-state electrocardiograms. Regressions weighted by propensity scores were carried out to compare participants with and without depressive or anxiety disorders, as well as users and non-users of antidepressants, on heart rate and heart rate variability. RESULTS Use of antidepressants was associated with increases in heart rate and decreases in its variability. Effects were most pronounced for the tricyclic antidepressants (Cohens d, 0.72-0.81), followed by serotonin and norepinephrine reuptake inhibitors (Cohens d, 0.42-0.95) and other antidepressants (Cohens d, 0.37-0.40), relative to participants not on antidepressants. Only participants with generalized anxiety disorder showed robust, though small, increases in heart rate and decreases in its variability after propensity score weighting. CONCLUSIONS The findings may, in part, underpin epidemiological findings of increased risk for cardiovascular morbidity and mortality. Many factors that have an adverse impact on cardiac activity were controlled for in this study, highlighting the importance of cardiovascular risk reduction strategies. Further study is needed to examine whether, how, and when such effects contribute to morbidity and mortality.

Carotid intima–media thickness value distributions in The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

OBJECTIVE Carotid intima-media thickness (IMT) is a noninvasive measurement of early atherosclerosis. Most IMT studies have involved populations with low rates of racial blending. The aim of the present article is to describe IMT value distributions and analyze the influence of sex and race on IMT values in a large Brazilian sample, a setting with a high rate of racial admixture. METHODS The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a multicenter cohort of 15,105 adult (aged 35-74 years) civil servants in six Brazilian cities. Baseline assessment included IMT measurements in both common carotid arteries. Race was self-reported. We studied the association between sex and race with IMT values using multiple linear regression models. We conducted analyses in all and low-risk individuals, defined as those without classical cardiovascular risk factors. RESULTS We analyzed complete IMT data from 10,405 ELSA-Brasil participants. We present nomograms by age for all and low-risk individuals, stratified by sex and race. We found that men had significantly higher maximal IMT values compared with women (β = 0.058; P < 0.001). This association remained for low-risk individuals (β = 0.027; P = 0.001). In addition, Brown and White individuals had lower maximal IMT values compared with Black individuals for all (β = -0.034 and β = -0.054, respectively; P < 0.001) and low-risk individuals (β = -0.027; P = 0.013 and β = -0.035; P < 0.001, respectively). CONCLUSION We found significantly higher IMT values in men. We found significantly higher IMT values in Black individuals than White and Brown individuals. These results persisted when analyses were restricted to low-risk individuals.

Resistant hypertension: risk factors, subclinical atherosclerosis, and comorbidities among adults-the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

The frequency of resistant hypertension—defined as blood pressure (BP) ≥140/90 mm Hg with proven use of three antihypertensive medications, or as the use of four antihypertensive drug classes regardless of BP—is unknown in low‐middle–income countries. Using data from the Brazilian Longitudinal Study of Adult Health, a cohort of 15,105 civil servants aged 35 to 74 years, the authors identified 4116 patients taking treatment for hypertension, 11% of who had resistant hypertension. These participants were more likely to be older, black, less educated, poorer, and obese. The adjusted prevalence ratios (95% confidence intervals) were diabetes, 1.44 (1.20–1.72); glomerular filtration rate (<60 mL/min/1.72 m2), 1.95 (1.60–2.38); albumin‐to‐creatinine ratio (>300 mg/g), 2.43 (1.70–3.50); carotid‐femoral pulse‐wave velocity, 1.07 m/s (1.03–1.11 m/s); common carotid intima‐media thickness, 2.57 mm (1.64–4.00 mm); left ventricular hypertrophy, 2.08 (1.21–3.57); and atrial fibrillation, 3.55 (2.02–6.25). Thus, the prevalence of resistant hypertension in Brazil is high and associated with subclinical markers of end‐organ cardiovascular damage.

Low Impact of Traditional Risk Factors on Carotid Intima-Media Thickness The ELSA-Brasil Cohort

Objective—There is little information about how much traditional cardiovascular risk factors explain common carotid artery intima-media thickness (CCA-IMT) variance. We aimed to study to which extent CCA-IMT values are determined by traditional risk factors and which commonly used measurements of blood pressure, glucose metabolism, lipid profile, and adiposity contribute the most to this determination in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort baseline. Approach and Results—We analyzed 9792 individuals with complete data and CCA-IMT measurements. We built multiple linear regression models using mean left and right CCA-IMT as the dependent variable. All models were stratified by sex. We also analyzed individuals stratified by 10-year coronary heart disease risk and, in separate, those with no traditional risk factors. Main models’ R2 varied between 0.141 and 0.373. The major part of the explained variance in CCA-IMT was because of age and race. Indicators of blood pressure, lipid profile, and adiposity that most frequently composed the best models were pulse pressure, low-density lipoprotein/high-density lipoprotein ratio, and neck circumference. The association between neck circumference and CCA-IMT persisted significant even after further adjustment for vessel sizes and body mass index. Indicators of glucose metabolism had smaller contribution. Conclusions—We found that >60% of CCA-IMT were not explained by demographic and traditional cardiovascular risk factors, which highlights the need to study novel risk factors. Pulse pressure, low-density lipoprotein/high-density lipoprotein ratio, and neck circumference were the most consistent contributors.

Cardiovascular risk in individuals with depression

Depression and cardiovascular diseases (CVD) are both common illnesses. Several studies demonstrated that depressed individuals have higher mortality compared to age- and gender-matched population, with an excess of cardiovascular deaths. There is a bidirectional association between depression and CVD. Several factors can interact and influence this relationship: poverty and social inequality, reduced accessibility to health care, biological alterations (as reduced heart rate variability, endothelial dysfunction, increased inflammation and platelet function, and hyperactivity of hypothalamic-pituitary-adrenal axis), side effects of psychiatric medication, lower adherence to medical treatments, and higher frequency of cardiovascular risk factors (higher tobacco use, physical inactivity, obesity, diabetes mellitus). This article aims to update the current evidence of the possible mechanisms involved in the association between depression and CVD.

Relationship among Medical Student Resilience, Educational Environment and Quality of Life

Context Resilience is a capacity to face and overcome adversities, with personal transformation and growth. In medical education, it is critical to understand the determinants of a positive, developmental reaction in the face of stressful, emotionally demanding situations. We studied the association among resilience, quality of life (QoL) and educational environment perceptions in medical students. Methods We evaluated data from a random sample of 1,350 medical students from 22 Brazilian medical schools. Information from participants included the Wagnild and Young’s resilience scale (RS-14), the Dundee Ready Educational Environment Measure (DREEM), the World Health Organization Quality of Life questionnaire – short form (WHOQOL-BREF), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Results Full multiple linear regression models were adjusted for sex, age, year of medical course, presence of a BDI score ≥ 14 and STAI state or anxiety scores ≥ 50. Compared to those with very high resilience levels, individuals with very low resilience had worse QoL, measured by overall (β=-0.89; 95% confidence interval =-1.21 to -0.56) and medical-school related (β=-0.85; 95%CI=-1.25 to -0.45) QoL scores, environment (β=-6.48; 95%CI=-10.01 to -2.95), psychological (β=-22.89; 95%CI=-25.70 to -20.07), social relationships (β=-14.28; 95%CI=-19.07 to -9.49), and physical health (β=-10.74; 95%CI=-14.07 to -7.42) WHOQOL-BREF domain scores. They also had a worse educational environment perception, measured by global DREEM score (β=-31.42; 95%CI=-37.86 to -24.98), learning (β=-7.32; 95%CI=-9.23 to -5.41), teachers (β=-5.37; 95%CI=-7.16 to -3.58), academic self-perception (β=-7.33; 95%CI=-8.53 to -6.12), atmosphere (β=-8.29; 95%CI=-10.13 to -6.44) and social self-perception (β=-3.12; 95%CI=-4.11 to -2.12) DREEM domain scores. We also observed a dose-response pattern across resilience level groups for most measurements. Conclusions Medical students with higher resilience levels had a better quality of life and a better perception of educational environment. Developing resilience may become an important strategy to minimize emotional distress and enhance medical training.

Low Impact of Traditional Risk Factors on Carotid Intima-Media Thickness

Objective—There is little information about how much traditional cardiovascular risk factors explain common carotid artery intima-media thickness (CCA-IMT) variance. We aimed to study to which extent CCA-IMT values are determined by traditional risk factors and which commonly used measurements of blood pressure, glucose metabolism, lipid profile, and adiposity contribute the most to this determination in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort baseline. Approach and Results—We analyzed 9792 individuals with complete data and CCA-IMT measurements. We built multiple linear regression models using mean left and right CCA-IMT as the dependent variable. All models were stratified by sex. We also analyzed individuals stratified by 10-year coronary heart disease risk and, in separate, those with no traditional risk factors. Main models’ R2 varied between 0.141 and 0.373. The major part of the explained variance in CCA-IMT was because of age and race. Indicators of blood pressure, lipid profile, and adiposity that most frequently composed the best models were pulse pressure, low-density lipoprotein/high-density lipoprotein ratio, and neck circumference. The association between neck circumference and CCA-IMT persisted significant even after further adjustment for vessel sizes and body mass index. Indicators of glucose metabolism had smaller contribution. Conclusions—We found that >60% of CCA-IMT were not explained by demographic and traditional cardiovascular risk factors, which highlights the need to study novel risk factors. Pulse pressure, low-density lipoprotein/high-density lipoprotein ratio, and neck circumference were the most consistent contributors.

Association between psoriasis and coronary calcium score

BACKGROUND Emerging data suggests that chronic inflammatory disease, such as psoriasis, may be associated to coronary artery disease (CAD). OBJECTIVE Analyze the association between psoriasis and subclinical atherosclerosis using coronary calcium score (CAC). METHODS We investigated 221 participants with psoriasis and 718 age- and sex-matched controls without prior known CAD. All participants completed a questionnaire and underwent laboratory tests and a CAC exam. Logistic regression models adjusted for Framingham risk score (FRS) and C-reactive protein (hs-CRP) were built. CAC was included in the models as a binary variable with different cut off values. RESULTS Body-mass index, race, hypertension, HDL, LDL and hs-CRP were significantly associated with psoriasis presence and severity. Psoriasis severity was significantly associated with CAC (p = 0.04), particularly for very high CAC (>400) (p < 0.01). The OR for severe psoriasis and CAC >400 was 2.45 (95%CI: 1.26-4.75) in unadjusted models. In a model adjusted for the FRS, this association was no longer significant, but a trend was noted (p = 0.09). No significant changes in the association were noted after the inclusion of hs-CRP in the model. CONCLUSION Psoriasis is associated with higher CAC values, mainly in individuals with severe psoriasis. The current findings also suggest the potential involvement of other mechanisms beyond classical cardiovascular risk factors and inflammation in this association.

Associations of life course socioeconomic position and job stress with carotid intima-media thickness. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

RATIONALE The association between life course socioeconomic position (SEP) and subclinical atherosclerosis is not consistent across studies. Socioeconomic adversities early in life are related to an increased probability of a low occupational grade and more stressful jobs in adulthood. However, the role of job stress in explaining the life course social gradient in subclinical atherosclerosis is unknown. OBJECTIVES To examine whether life course SEP is associated with carotid intima-media thickness (IMT) and to investigate whether this association is partially mediated by job stress. METHODS This study used baseline data (2008-2010) for 8806 current workers from ELSA-Brasil. Maternal education, social class of first occupation and social class of current occupation were used to evaluate childhood, youth and adulthood SEP, respectively. Accumulation of risk across the life course was also evaluated. Job stress was assessed by the Swedish Demand-Control-Support Questionnaire. Directed acyclic graph and linear regression models were used. RESULTS Low childhood SEP was associated with increased IMT only in women, but low youth and adulthood SEP were associated with higher IMT in both genders. The simultaneous adjustment for all SEP indicators showed that only adulthood SEP continued to be associated with IMT. However, higher IMT values were observed among men and women sequentially exposed to low SEP in more than one period of life. High-strain jobs and low job control were not associated with IMT independent of SEP. CONCLUSION Our results support a model of the cumulative effects of exposures to SEP across the life span because the highest IMT values were observed in individuals sequentially exposed to low SEP in more than one period of life. We did not find that job stress explained the association between life course SEP and IMT, suggesting that strategies to address socioeconomic inequalities in CVD should target additional steps beyond reducing job stress.