Effects of Confounding Factors on Blood Pressure in Hypertensive Patients: A Cross Sectional Study

this study to investigate confounding factors in who


Introduction
Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. (1) A recent analysis of data from European registries (2) has shown that on average only 39% of hypertensive patients achieve an adequate blood pressure (BP) control.Improvement in BP control rates is probably one of the most bene cial steps that can improve life expectancy and the quality of life for millions of people with immediate and measurable results. The lifetime burden of hypertension remains substantial and highlights the need for new strategies. (3) There are studies explaining the negative effect of manyreasons/factors on BP control. Among these reasons/factors, late or ineffective treatment, leading to irreversible or di cult to reverse adaptations of the cardiovascular system, may play a role. (4) Smoking is also one of these factors. Patients without a history of tobacco use had faster and better BP control than current or former tobacco users. This nding is concerning because of the increased cardiovascular risk associated with tobacco use. (5,6) Lower income is another factor. Patients with higher income have better control of BP. Lower income may be associated with increased risk for mental disorders. (7) Modi able risk factors including lack of physical exercise and adding salt into meals were signi cantly and independently associated with poor BP control. (8) Higher BP was associated with higher alcohol consumption, higher body-mass index, diet high in sugar-sweetened beverages and diet high in sodium. (9) A study which investigated BP, sleep quality and fatigue in shift working police o cers showed that there was a signi cant increase in systolic BP after shift work, while BP and fatigue levels were strongly related. (10) BP is in uenced by biopsychosocial factors such as physical, environmental, emotional, cognitive and behavioral in hypertensive patients. (11) Pessimistic and anxious adults had higher BP levels and felt more negative and less positive than did optimists or low anxious adults. (12) Happiness, anger, and anxiety increase BP to differing degrees and emotional effects may be greater with more labile BP. (13) A meta-analysis supported that depression was probably an independent risk factor for hypertension as a confounding factor. (14) Emotional state (happiness, anger, or anxiety) signi cantly contributed to the variation of BP in this sample of borderline hypertensive patients. The comparison of the pressures during each reported emotional state show that anger and anxiety increase BP more than happiness.
(13)Anger, rather than fear, produced the greatest overall increases in BP and was distinctly opposite from relaxation. (15) Sadness produced a distinct pattern with moderate increases in BP and vascular resistance and a decrease in cardiac output compared with changes during neutral imagery. (16) Fear, action, and joy produced similar BP changes in which systolic pressure increased and diastolic pressure was relatively unchanged. (16)A confounding factor such as a traumatic life event should also be kept in mind in case of inadequate BP control in hypertensive patients. (11) The current study investigates confounding factors in hypertensive patients who have poor BP control.

Sample
According the data from National Household Health Survey-Prevalence of Noncommunicable Disease Risk Factors in Turkey 2017, the prevalence of hypertension in Turkey was 16.2% in 2017. (17) Sample size was calculated by using theprevalence of hypertension and the nal required sample size was 207.

Research design and setting
This study was designed as a cross-sectional study.Our sample was 407 patients with hypertension in Rize, a Northern city in the Black Sea Region of Turkey. Instudy group, there were 207 hypertensive patients who had admission to emergency department due to high BP. In control group, there were 200 hypertensive patients visiting family physician,who de ned themselves as having regulated BP over the past six months.Only hypertensive patients receiving medicines for BP control included in the study and patients with other chronic conditions (such as psychological disorders, diabetes mellitus, hypothyroidism, hypercholesterolemia, heart disease, chronic heart failure, history of heart or cerebral attacks etc.) were excluded.
In this study, confounding factors that caused high BP in hypertensive patients were investigated. Firstly, we tried to reveal confounding factors of the patients in study group. They completed the questionnaire including sociodemographic data, lifestyle behaviors, health risks and confounding factors. The questionnaires were completed face-to-facejust after their BP reduced by medicine and they calmed down. We noted their systolic and diastolic BPat the beginning of admission to emergency department. Hypertensive patients in control group also completed the questionnaire via the face-to-face interview method. Research was completed between August 2020 to December 2020.All participants gave informed written informed consent.

Data collection tool
The data collection tool used in this study included a questionnaire. We designed the questionnaire including patients' age, gender, socioeconomic status, tobacco use, alcohol consumption, exercise, healthy diet and confounding factors. We revealed confounding factorsof the patients who had admission to emergency department due to high BP. We asked them 'Do you think there was a special reason or factor that might increase your BP?' just after medicine (example; captopril) reduced BP and they calmed down. Before the treatment of hypertensive patients who had admission to emergency department, we noted their systolic and diastolic BP. We also revealed confounding factors of the patients in control group.

Data analysis
Data was analyzed using the SPSS 26 statistical analysis program. Age, systolic and diastolic BP were analyzed as mean, standard deviation, minimum and maximum score. The normality of the data was examined using the Kolmogorov-Smirnov test. Descriptive statistics, including number and percentage, were used to describe sociodemographic characteristics, lifestyle behaviors, confounding factors and health risks of participants. The Regression Analysis test was used to determine the impact of confounding factors on the meansystolic and diastolic BP. The Chi-Square test was used to determine the homogeneity of study and control groups in terms of their sociodemographic characteristics, lifestyle behaviors, confounding factors and health risks. The independent samples t-test and the ANOVA testwere used for analysis of independent samples.The level of signi cance was set as p<0.05.

Ethical approval
Formal permission was obtained from the Ethics Committee of the Faculty of Medicine of Recep Tayyip Erdogan University (Identi cation number: 2020/179).

Sociodemographic data
Sociodemographic characteristics, lifestyle behaviors and health risks of participants are shown in Table  1. There were no signi cant differences between the groups in terms of their sociodemographic characteristics (p>0.05).The mean± standard deviation age of participants was 52.1 ± 13.3in the study group and 50.5 ± 12.1 in the control group. Of the participants, 57.5% (n=119) of the study group and 54.5% (n=109) of the control group were female.About one third of the participants (32.9% of the study group and 38.0% of the control group) stated their socioeconomic status as 'moderate'. Of the participants, 11.1% (n=23) of the study group and 9.5% (n=19) of the control group were smokers.The rate of alcohol consumption was 6.3% (n=13) of the study group and 4.5% (n=9) of the control group.Of the participants, only 3.4% (n=7) of the study group and 5.0% (n=10) of the control group were doing regular exercise more than 150 minutes per week, with 60.9% (n=126) of the study group and 65.5% (n=131) of the control group having healthy nutritional habits. When we asked the patients of study group questions to reveal their confounding factors,21.3% (n=44) stated 'anger', 12.6%(n=26) 'sadness',11.1% (n=23) 'anxiety', 10.6% (n=22) 'depressed', 9.2% (n=19) 'unhealthy diet', 7.2% (n=15)'fatigue and poor sleep quality', and 3.9% (n=8) 'irregular medication' ( Table  2).

Confounding factors and BP
Impact of confounding factors on systolic and diastolic BP in the study group is shown in Table 3. Mean systolic and diastolic BP were signi cantly higher in hypertensive patients having confounding factors than those without confounding factors (p=0.001, p=0.001, respectively).
Regression analysis also showed signi cant impact of confounding factors on mean systolic and diastolic BP in the study group (p<0.001; R 2 =0.164 and p<0.001; R 2 =0.101, respectively).  . Mean systolic BP of hypertensives who stated their confounding factor as 'anger' was signi cantly higher than those the remaining groups. Mean systolic BP of hypertensives who stated their confounding factor as 'sadness' was signi cantly lower than those the remaining groups (p<0.001, Post Hoc Test, Tukey).

Discussion
In this study, the effect of confounding factors on BP in hypertensives with high BP was investigated by comparing those in hypertensives with regulated BP. More than three quarter of the hypertensive patients who had admission to emergency department due to high BP had confounding factors. In the control group, about one-third of hypertensives with regulated BP had confounding factors. There was asigni cant difference between thehypertensives of study and control groups in terms of their confounding factors.So, this study suggested that confounding factors impair BP control in patients with hypertension. A confounding factorshould be kept in mind in case of poor BP control in hypertensive patients. (7,8,(11)(12)(13)(14)(15) Mean systolic and diastolic BP were signi cantly higher in hypertensives having confounding factors than those without confounding factors in the study group. Furthermore, each confounding factor had signi cantly different effect on BP in hypertensives having confounding factors in the study group. In a study which investigated the in uence of happiness, anger, and anxiety on the blood pressure of borderline hypertensives; happiness, anger, and anxiety increase BP to differing degrees. (13) Mean systolic BP of hypertensives who stated their confounding factor as 'anger' was signi cantly higher, and 'sadness' was signi cantly lower than those the remaining groups. Our nding was consistent with literature. The comparison of the pressures during each reported emotional state show that anger increase BP more than happiness. (13) In a study which investigated cardiovascular differentiation of happiness, sadness, anger, and fear, it was shown that anger, rather than fear, produced the greatest overall increases in BP. (15) In a research which investigated cardiovascular differentiation of emotions showed that sadness produced a distinct pattern with moderate increases in BP. (16) We found that anxiety, anger, sadness, fatigue, poor sleep quality, unhealthy diet, depressed, and irregular medication seem to be confounding factors for elevated BP. In addition, mentioned as 'others' in this study, happiness, feeling tense, panic, sense of worthlessness, and sense of cheerless also were confounding factors for elevated BP.
In this study, anxiety was a confounding factor for elevated BP. Our nding was consistent with literature.Anxiety can activate the sympathetic nervous system, increase cardiac output, constrict blood vessels, and raise arterial BP. (18) First, anxiety increases BP in the short term, and the white coat effect derived from anxiety is a typical example. (19,20) In a study which investigated association between anxiety and hypertension has shown that there was an association between anxiety and increased risk of hypertension. (21) It has been reported that patients with hypertension on antidepressant medications have lower BPs compared to those not on these medications possibly due to decreased barore ex sensitivity and altered neuro-endocrine pathways. (22,23) In this study, about one-tenth of hypertensives in the study group were depressed. Depression is common in patients with uncontrolled hypertension and may interfere with BP control. In a study about hypertension, depression was a risk factor for poor BP control in hypertensive patients. (24) In another study about hypertension, it was shown that despite antihypertensive treatment, mean systolic and diastolic BP in patients with moderate/severe depression was signi cantly higher, than in group of patients without depression. (25) In this study, we revealed 'fatigue' as confounding factor for elevated BP. On the contrary, in a research which investigated the relationship between fatigue and cardiac functioning, fatigue was not associated with BP at rest and no signi cant differences were found in heart rate or BP response between the various fatigue groups. (26) In this study, poor sleep quality was a confounding factor for elevated BP and our nding was consistent with literature.Obstructive sleep apnea is common in patients with resistant hypertension, which is de ned as BP that remains uncontrolled with three or more medications. (27) Insomnia with objective short sleep duration also is associated with increased hypertension risk. (27) Periodic limb movements in sleep increases BP, especially when associated with arousals. (27) It was important to nd that,especially after diet high in sodium, about one-tenth of hypertensives in the study group had admission to emergency department due to high BP. Adding salt into meals was signi cantly and independently associated with poor BP control. (8) Higher BP was associated with higher alcohol consumption, diet high in sugar-sweetened beverages and diet high in sodium. (9) Adherence to the Mediterranean diet pattern can be correlated with BP control. (28) Sodium reduction resulted in a signi cant decrease in BP of 3.5% in patients with hypertension. (29) Conclusion This study has shown that confounding factors impair BP control in patients with hypertension.
Confounding factors should be kept in mind and revealed in case of poor BP control in hypertensive patients. This study has also shown that systolic and diastolic BP were signi cantly higher in hypertensives having confounding factors than those without confounding factors. Furthermore, each confounding factor had signi cantly different effect on BP in hypertensives.

Limitations
Confounding factors were revealed based on patient's self-assessment.However, as we know, there is not a scale to reveal confounding factors yet, which Turkish validity and reliability study was performed. Figure 1 Interaction of confounding factors, systolic and diastolic BPof hypertensives having confounding factors in the SG (n=168)