Introduction

According to the National Health Survey (ENSANUT MC) 2016, 25.5% of Mexican adults have hypertension¹,². Hypertension causes functional and structural alterations in blood vessels, especially affecting arteries of medium and small caliber, which predominate in some organs like brain³. Several studies have established a causal relationship between hypertension and brain diseases such as stroke, vascular dementia, and recently Alzheimer's disease⁴. Due to factors that are not yet completely clear, vascular damage induced by hypertension seems to be more aggressive in the frontal lobe, which could lead to executive dysfunction⁵.

Executive functions refer to a collection of cognitive abilities that enable and drive adaptive, goal-oriented behavior. These include the ability to generate thought and think flexibly, to update and manipulate information mentally, to inhibit what is irrelevant to current goals, to self-monitor, and to plan and adjust behavior as appropriate to the present context. Executive dysfunction impairs efficient performing of daily activities and increases the risk of morbidity and mortality by accidents inside and outside the home, increases dependence on caregivers, limits productive activities, and reduces quality of life⁶,⁷. Chronicity and aging can worsen brain damage caused by hypertension⁸. Executive dysfunction may be one of the first manifestations of brain damage⁹, especially in patients who do not achieve control despite consuming pharmacological treatment¹⁰.

In most cases, brain damage is irreversible⁶, so it is an important early diagnosis. Young and middle-aged hypertensive people usually have not symptoms of a cognitive impairment, however, there are standardized tools to evaluate the executive function¹¹. The aim of this study was to compare the executive cognitive function in middle-aged hypertensive and no hypertensive Mexican adults and related with some epidemiological data.

Methods

It is an observational and analytical study.

Patients were recruited at the Unit of Social Insertion (UUIS) of University of Yucatán, México. This institution provides medical care to approximately 1179 users annually. The sample size was non-probabilistic and included all patients with and without hypertension, men and women from 41 to 60 years, with and without diagnosis of hypertension, and with minimum secondary schooling who attended the external consultation from October 2018 to December 2018. All selected patients with hypertension had at least 5 years of diagnosis to ensure chronicity period. To avoid biases on interpretation of cognitive function, results were excluded patients with a history of cerebral vascular event, known brain diseases, with obesity (body mass index [BMI] > 30), dyslipidemias, and hypo or hyperthyroidism. Motor, visual or auditory dysfunction, or under neurological or psychiatric treatment were not included in the study. Ninety-two people agreed to participate and met the selection criteria.

We eliminated patients who at the time of the evaluation had mild cognitive deterioration and/or depressive symptomatology. Seven people were eliminated due to symptoms of depression and/or cognitive impairment.Forty-one hypertensive and 44 normotensive patients were included in final analysis.

Results

The results presented below correspond to 85 adults. Table 1 describes its main characteristics, grouped as a control group (not hypertensive) and hypertension group.

We found similar distribution of sex, age and BMI in both groups.

There were no differences in BP between men and women, neither in the hypertension group nor in the control group. DSST values in the hypertension group were lower than the control group. Hypertensive men performed less than women did (p = 0.007). In the control group, there was no sex difference (p = 0.15).

Diagnostic average duration in the hypertension group was 11.9 ± 5 years, on men was 11.31 ± 5.5 years and woman 12.28 ± 4.7 (p = 0.55). Most hypertensive patients (82.9%) were receiving some form of pharmacological treatment, 17% of patients had abandoned treatment or had never consumed drugs for it. About 97% of patients with treatment were taking one drug, 3% taken two or more. About 76% consuming angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, 11.7% were taking beta-blockers, and 12% receiving calcium antagonist or diuretics. Table 2 shows the results of controlled and uncontrolled hypertensive patients.

In the hypertension group, there was a negative correlation between the DSST score with age (y = −1.139*x + 82.76, R² = 0.24, p = 0.001), with SBP (y = −0.292*x + 61.75, R² = 0.16, p = 0.008), and DBP (y = −0.357*x + 51.69, R² = 0.09, p = 0.045). No correlation was found between the DSST score and the duration of hypertension. The control group showed no correlation (data not shown).

Discussion

This study showed that hypertension in middle-aged Mexican adults is associated with lower scores in the DSST, a validated test with a high sensitivity to detect variations in executive function¹⁶,¹⁹. Hypertension is a well-known risk factor for numerous adverse cardiovascular outcomes². Given their impact in brain vessels vasodilatory capacity, it could decrease biological efficacy to execute some cognitive functions³. Although there is a normal increase in the BP while aging due to calcification and atherosclerosis, hypertension in younger subjects suggests a possible genetic predisposition negatively modulated by environmental and lifestyle factors such as obesity and elevated salt intake and others²⁰.

Mean duration of hypertension in participants in our study was higher than that reported by the National Health Survey, which states that most hypertensive individuals in Mexico had 4-10 years with the diagnosis¹. This could be explained by our selection criteria only allowed people with at least 5 years with hypertension. About 83% of hypertensive participants in our study had pharmacological treatment, similar with 79.3% reported in other studies for Mexican hypertensive patients¹. There is evidence that lack of pharmacological treatment in hypertensive people increases their risk of ischemic heart disease, heart failure, stroke, and kidney diseases²¹.

Although the treatment of hypertension is cheap and simple compared to other chronic diseases, their asymptomatic nature can cause patients to refuse to undergo lifelong treatment or reduce their adherence. Remarkably, only 50% of patients with treatment had achieved therapeutic goals. Mexican National Health Survey reported a hypertensive control proportion of 45.6%¹. Most hypertensive patients in our study consume antihypertensive drugs in monotherapy, and though this approach facilitates compliance, it is well documented that few patients achieve adequate hypertensive control without two or more drugs²²,²³. We observed an important number of patients receiving beta-blockers, which, according to recent guidelines should not be used as first choice antihypertensive drugs because they promote the development of dyslipidemias, impair glucose tolerance and hinder weight reduction²³,²⁴. It is important to analyze individual patient conditions to offer the best treatment in each case and achieve therapeutic goals.

Our findings show that hypertensive patients have a worse performance in the DSST compared with normotensive people. Cognitive impairment is a gradual process and having hypertension could accelerate this process. Controversial results of the effect of hypertension on cognitive function have been found²⁴,²⁵. In our study, SBP was responsible for 16% of the variance in DSST scores in the hypertensive patients.

Some studies have found a better executive performance in men²⁶; however, we found that men hypertensive obtained lower scores in DSST compared with woman hypertensive or normotensive people. There is evidence that in women, prenatal exposition to different hormonal concentrations promotes the overdevelopment of specific neuronal pathways and the neurotrophic effects of estrogens are well described²⁷. The patients in this study were around 50 years old, so the women were in the menopausal period; consequently, it is likely that they maintained some degree of neurotrophic estrogenic stimulation and better cerebral blood flow compared to man²⁸.

The mechanisms that regulate arterial BP are similar in men and women; however, there are physiological differences at the molecular, cellular, and tissue levels between the sexes that contribute to differences in disease onset, susceptibility, prevalence, and treatment responses. The sympathetic nervous system, the renin-angiotensin-aldosterone system, and the immune system are differentially activated in males and females. Sex hormones such as estrogens or testosterone as well as sex chromosome complement likely contribute to sex differences in BP and cardiovascular disease. At the cellular level, differences in cell senescence pathways may contribute to increased longevity in women and may limit brain damage caused by hypertension²⁹. Therefore, this may be an explanation because the women in our study were less affected in their executive function. In addition, many lifestyles and environmental factors such as smoking, alcohol consumption, and diet, they are usually different in men and women, as well as their possible effect on BP and brain function, were not evaluated in the present study.

SBP and DBP were higher than those reported in the previous studies in Mexico¹, and higher BP readings were correlated with lower DSST scores. Uncontrolled hypertension increases vascular stiffness which rises pulse pressure. Increased BP is a risk factor for white matter lesions and subclinical hemorrhages that can cause cognitive alterations³⁰. In concordance with other authors³¹, we could not find differences in executive function between controlled or uncontrolled hypertensive patients, maybe due to the small sample size. Several studies have reported that an elevated BP during middle age predicts cognitive impairment 20-30 years later³²,³³ and SBP control since middle age reduces this risk²⁷,³⁴.

Many studies have reported intense prefrontal activation during DSST resolution using functional MRI and electroencephalography³⁵,³⁶, these areas are particularly vulnerable to subclinical ischemia because they depend on distal blood supply. Vasomotor dysfunction characteristic of hypertension impairs their capacity for compensatory redistribution of blood flow in response to cognitive challenge⁹. DSST is a powerful tool to explore the executive cognitive domain associated with brain regions most affected by hypertensive vasculopathy. On the hypertensive group, we found an inverse correlation between age and DSST performance, which is consistent with the previous reports²¹,³⁷. Motor dexterity decline through aging may contribute to this consistent finding and hypertension could accelerate this process. Although we guarantee a minimum level of education in our inclusion criteria, we did not specifically explore the influence of the educational level on DSST performance. However, the previous reports state that there is no relationship between education and DSST performance probably due to their iconographic nature, making it useful in poor educated populations like ours⁸. As opposed to most studies revised, we could not observe a significant correlation between DSST scores and duration of disease. The duration of hypertension is relevant because there is evidence that their neurodegenerative effects are accumulative³⁸.

Effective hypertension management requires a substantial amount of self-planning and adherence to pharmacological and non-pharmacological treatment. Thus, we propose that executive dysfunction may worsen self-care on hypertensive patients. Assessing executive function since middle age with easy administrated tests like the DSST in primary health-care settings could promote early interventions that preserve the functional independence of hypertensive patients.

Conclusion

In conclusion, mature adults with hypertension had less efficiency in the executive function test. Men showed worse test performance compared to women. In this population the control of hypertension and the duration of the disease did not affect the performance of the executive function.