Blood pressure control and its associated factors among patients with heart failure in Jordan

Uncontrolled blood pressure (BP) has been associated with increased risk of cardiovascular events including heart failure. This study aimed to explore the factors associated with poor BP control among patients with heart failure at two major outpatient cardiology clinics in Jordan. Variables including socio-demographics, biomedical variables, in addition to disease and medication characteristics were collected using medical records and custom-designed questionnaire. The validated 4-item Medication Adherence Scale was used to assess medication adherence. Binary logistic regression analysis was conducted to explore the significant and independent predictors of poor BP control. Regression analysis results revealed that being not satisfied with the prescribed medication (OR = 2.882; 95% CI: 1.458–5.695; P < 0.01), reporting moderate medication adherence (OR = 0.203; 95% CI: 22 0.048–0.863; P < 0.05), not receiving digoxin (OR = 3.423; 95% CI: 1.346–8.707; P < 0.05), and not receiving aldosterone antagonist (OR = 2.044; 95% CI: 1.038-4.025; P < 0.05) were associated with poor BP control. Future interventions should focus on increasing medication satisfaction and enhancing medication adherence, in order to improve BP control among patients with heart failure.


INTRODUCTION
Heart Failure (HF) is a progressive cardiovascular disease (CVD) that results from any structural or functional abnormality of the heart, causing an impairment in ventricular filling or ejection of blood.Subsequently, the heart cannot pump enough blood to meet the demands of the body [1].Globally, CVDs including HF are the highest leading cause of morbidity and mortality, with approximately 64 million people estimated to have HF worldwide, and its prevalence is expected to rise by 46% from 2012 to 2030 [2].Earlier statistics reported that CVDs including HF are responsible for 37% of all deaths in Jordan [3].HF cost in 2012 is approximately estimated to reach 30 billion dollars.The cost is expected to reach 69.7 billion dollars by 2030 [4].
Uncontrolled blood pressure (BP) was found to lead to the development of CVDs including HF [5].It has been reported that most longstanding hypertension ultimately leads to HF, and patients with HF very commonly have a history of hypertension.During up to 20 years of follow-up, the Framingham Heart Study which was conducted on 5143 subjects found that hypertension preceded the development of HF in 91% of all newly diagnosed HF patients [6].Hypertension has been found to affect one billion people worldwide, with an estimated 4 million deaths every year; making it the third leading cause of death, with a mortality rate of 13% [5].Furthermore, approximately one-third of the adult Jordanians are classified hypertensive, with an alarming rate of optimal BP control [7].
According to the Framingham cohort, the lifetime risk of HF has been estimated to be 20%, which is doubled for patients with BP of 160/100 mmHg when compared with those with BP reading of 140/90 mmHg [8].Earlier studies reported that lowering BP was associated with reduced incidence and mortality from different CVDs such as HF [9,10].Despite the presence of effective treatments for BP control, there is an evidence that considerable number of patients still have uncontrolled BP [11,12].Data in the literature revealed that 79% of people with hypertension do not have controlled BP [13].The Third National Health and Nutrition Survey in the United States showed that only 14-25% of the treated hypertensive adults had achieved effective BP control of <130/80 mmHg [14].
Inconsistent data have been reported with regard to the factors affecting BP control in patients with hypertension.A study conducted in America found a variety of economic, social, and lifestyle barriers for BP control including alcoholism, use of illicit drugs, social isolation, unemployment, and lack of health insurance [15].Another study found that obesity, dyslipidemia, and diabetes were associated with increased risk of poor BP control across Europe.[16].Korean patients with hypertension were found to have lower rates of BP control if they were overweight, alcoholic, or stressed [17].
Due to the sparse of such information in HF based community, the present study, which is the first one in Jordan, was conducted to explore the factors associated with poor BP control among patients with HF in Jordan.The study findings are critically important to provide insight for the development of future interventions which aim at improving BP control and health outcomes among patients with HF.

PATIENTS AND METHODS Study design and settings
The current cross-sectional study was conducted on patients who attended the outpatient cardiology clinics at King Abdullah University Hospital and Al Bashir Hospital in the period from August 2021 through April 2022.

Sampling
All patients who had HF and hypertension for at least 6 months, aged 18 years or older, were receiving at least one HF medication, and agreed to sign a consent form were included in the study.The diagnosis of HF was established by the cardiologists after utilizing the HF diagnostic tests including echocardiography and the elevated pro-NT-BNP (≥125 pg/mL for age <75 yr and ≥450 pg/mL for age ≥75 yr) [18].The cardiologists also follow the new ACC/AHA blood pressure (BP) management guidelines, in which the patients were considered to have hypertension if they were in stage I hypertension demonstrated by systolic blood pressure (SBP) of 130-139 mmHg or diastolic blood pressure (DBP) of 80-89 mmHg, or in stage II hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg) [19].The patients who had HF and hypertension were identified for inclusion in the study from the confirmed diagnosis as reported in the medical record of each patient.Patients with an acute decompensation of HF or an active listing for heart transplantation and patients who had cognitive impairment were excluded from the study.Patients who were eligible to participate were informed that participation is voluntary, and they have the right to withdraw from the study at any time.They were also informed that the collected data will only be used for research purposes and will be kept at the Principal Investigator's office to ensure confidentiality.

Data collection and study instruments
A custom-designed questionnaire and the medical records were used to collect information about the participants' sociodemographic data such as age, gender, body mass index, marital status, place of residency, living arrangements, education, occupation status, monthly income, smoking status, physical activity, and family history of CVDs.The collected information also included duration of HF, NYHA classification of HF, the presence and number of other comorbidities, total number of medications, number of HF medications, frequency of taking medications, medications' side effects, the concerns about medications' side effects, patient satisfaction with the prescribed medications, and receiving medications for HF management.The medical records were also used to obtain various biomedical and laboratory data including low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, total cholesterol, glycosylated hemoglobin A1c, random blood glucose, SBP, DBP, ejection fraction (EF), serum creatinine, white blood cells count, red blood cells count and hemoglobin.On the day of the clinic visit, the certified nurse specialist measured the blood pressure for each patient using a mercury sphygmomanometer at room temperature, in a calm, appropriate setting, after they had rested for three to five minutes, in a seated position without crossing their legs and after ensuring that they had not smoked or consumed any caffeine before the measurement.The arm cuff was kept at the level of the heart, and special care was taken to ensure that it was not fastened over bulky shirts or coats, and the upper arm was not compressed by tucking up sleeves.The mean of the readings was recorded after two measurements separated by one to two minutes, and additional measurement was performed if two measurements differed by more than 5 mmHg [20].According to the new ACC/AHA BP management guidelines, the target for BP control in patients with HF is less than 130/80 mmHg.Accordingly, the patients were considered to have uncontrolled hypertension if they had BP readings of ≥130/80 mmHg [19].
Patients' adherence to the prescribed medications was evaluated by the validated Arabic version of the 4-item Medication Adherence Scale [21].This simple survey includes the potential forms of medication non-adherence such as forgetfulness, being carelessness, and stop taking the medication when feeling better or worse [22].One score was given for each 'yes' response, and each 'no' response was given a score of zero.The scores were ranging from 0 to 4. According to the Morisky classification, adherence was divided into three groups: high for those scoring zero, medium for those scoring one or two, and low for those scoring three or four.The questionnaire was self-completed, and patients who encountered difficulty in completing the questionnaire for different reasons, had the questionnaire read to them without giving any interpretation of the questions.Each patient interview took approximately 10-15 min to be completed.

Data analysis
The Statistical Package for the Social Sciences (SPSS) version 26 was used for descriptive and analytical statistics.Continuous and categorical variables were presented using descriptive analyses in term of the mean (standard deviations), and frequencies (percentages), respectively.The difference between study sample with regard to hypertension control were tested using the independent sample t-test for normally distributed continuous variables, and Mann-Whitney U-test for non-normally distributed continuous variables.Pearson Chi-square test was conducted to find the association between different categorical variables and hypertension control.Variables with a P-value < 0.2 at the univariate analysis were entered into the binary logistic regression in order to investigate the significant and independent predictors of the study outcome.The Rule of Events Per Variable criterion (EPV) ≥ 10 (293) was used to calculate the sample required to conduct the binary logistic regression analysis.As the model included 15 variables, the smallest required group should include at least 150 patients.In the present study, the smallest group included 157 patients (the controlled BP group), therefore the minimum required sample size was met.

RESULTS
Out of 550 patients with HF, a total of 428 patients agreed to participate in the study, which was conducted for multiple purposes, one of which was the factors associated with BP control.Out of the 428 HF patients, a total of 330 patients were diagnosed with hypertension and therefore they were included in the present study.The mean age of the participants was 64 ± 11.The majority were males (61.8%), married (94.8%), living with their families (95.5%), living in the city (66.7%), did not complete their education (71.2%), unemployed or retired (79.1%), had low monthly income (69.4%),non-smokers (71.8%), and were physically inactive (89.4%).Other characteristics of the study participants are presented in Table 1.
As shown in Table 5, results of the regression analysis showed that patients who were not satisfied with their medications had higher odds to be in the uncontrolled hypertension group when compared with those who were satisfied (OR = 2.882; 95% CI: 1.458-5.695;P < 0.01).Patients who reported moderate medication adherence had lower odds to have uncontrolled hypertension than those who reported low medication adherence (OR = 0.203; 95% CI: 0.048-0.863;P < 0.05).Patients who were not taking digoxin (OR = 3.423; 95%, CI: 1.346-8.707;P < 0.05) or aldosterone antagonist (OR = 2.044; 95% CI: 1.038-4.025;P < 0.05) had higher  odds to be in the uncontrolled hypertension group when compared with those who received digoxin and aldosterone therapy, respectively.

DISCUSSION
The coexistence of hypertension with HF has become a frequently observed issue over time.High BP increases left ventricular afterload and peripheral vascular resistance leading to an increased load on the heart and structural remodeling of its tissues, which would further make the situation worse for the already exhausted heart [6].According to the current guidelines, BP elevation in patients with HF should be treated with medications that have compelling indications in HF to reach a target BP of less than 130/80 mmHg [19].For the best of our knowledge, a very limited number of studies have investigated the factors associated with poor BP control in patients with HF, which was the current study purpose.Hypertension was diagnosed in 77% of the patients in the present study, from which, 52.6% were having uncontrolled hypertension.Similarly, over 68% of the HF patients enrolled in a retrospective cohort study were found to have uncontrolled BP based on the 2017 ACC/AHA guidelines [23].Other studies reported uncontrolled BP in most of the participating patients with other chronic diseases such as chronic kidney disease [24], type 2 diabetes mellitus [25], and coronary heart disease [26], which highlight the need for revealing the factors that hinder BP control in patients with chronic diseases, particularly HF, due the negative impact of uncontrolled BP on these patients as evidenced in several observational studies that found a positive relationship between SBP and all-cause and cardiovascular mortality in patients with HF [27][28][29].
The current study found several variables that were significantly associated with BP control in patients with HF, including medication satisfaction, medication adherence, taking digoxin, and taking aldosterone antagonist.Patients who were unsatisfied with their medications were found to have significantly lower BP control than those who were satisfied.Therefore, patients' satisfaction with the prescribed medications should be enhanced by empowering the patient in the treatment plan development and considering the patient's values, preferences and circumstances [30].
Medication non-adherence has been associated with a negative impact on both patients and society including higher rates of hospital admissions, poor health outcomes, increased morbidity and mortality, and increased health care costs [31].Medication non-adherence was found to be associated with poor disease control in several chronic diseases including hypertension [32], type 2 diabetes mellitus [33], asthma [34], and HF [35].Similarly, poor medication adherence was found to negatively impact BP control in the present study.Consistent findings were reported in a study that examined baseline data from the Systolic Blood Pressure Intervention Trial to investigate the relationship between medication adherence and SBP among patients who aged 50 years or older, with SBP ≥ 130 mmHg, and with or at increased risk for CVD [36].The study found that patients who had moderate medication adherence had significantly lower SBP than those with low adherence [37].Centers for Disease Control and Prevention analyzed data from the National Health and Nutrition Examination Survey 2003-2010 that focused on US adults with uncontrolled hypertension reported that failure of individuals to adhere to the prescribed antihypertensive medication was one of the most common factors that contributed to poor BP control [38].These findings shed the light on the importance of medication adherence in controlling BP, which is an important determinant of disease control in patients with HF.
Digoxin has usually been used to manage symptoms of HF in combination with other medications after failure of the standard pharmacotherapy to control HF symptoms [39].The present study results revealed that patients who were receiving digoxin were less likely to have uncontrolled BP than their counterparts.The literature reported contradictory findings regarding the effect of digoxin on BP readings.A randomized controlled trial conducted on normotensive patients with mild congestive HF reported that digoxin significantly decreased DBP and increased SBP during overnight sleep, but had no effect on BP readings during daytime [40].The latter study justified the reduction in DBP by the reduction of the sympathetic activity or the increase in the parasympathetic activity, and the increase in SBP by the positive inotropic effect of digoxin.Consistent results were also reported in another study conducted on healthy individuals [41].The paucity of the studies concerning the relationship between digoxin use and blood pressure control necessitates conducting more studies in order to fully understand this relationship and to provide stronger evidence of the effect of digoxin on BP control.
Aldosterone receptor antagonists are group of medications used for the treatment of HF symptoms by removing excess fluid that buildup in the body and thus easing the pumping function of the heart [42].Patients who were not taking aldosterone antagonist were more likely to have uncontrolled BP in the present study.The mechanism of action of this medication, which involves the blockage of aldosterone effects through the blockage of reabsorption of sodium that encourages water loss, subsequently reducing blood volume and blood pressure, and enhancing BP control in HF patients, could justify the present study finding [43].A meta-analysis reported that aldosterone antagonists have also proven their efficacy in controlling BP even in patients with resistant hypertension when used as an add-on therapy [44], which further strengthening the current study finding.The current guidelines suggest that aldosterone antagonist should be used in patients with NYHA class III or IV HF in the absence of contraindications, but further studies are needed to confirm the benefits of aldosterone antagonists in patients with NYHA class I or II HF [45].

Table 1 .
Demographic characteristics of the study participants (n = 330).
SD standard deviation, JD Jordanian Dinar, CVD cardiovascular diseases.

Table 2 .
Disease and medication characteristics of the study participants (n = 330).
SD Standard deviation, NYHA The New York Heart Association Classification, ACEIs Angiotensin-converting enzyme inhibitors, ARBs Angiotensin-receptor blockers.

Table 4 .
Univariate analysis of the factors associated with blood pressure control (n = 330).

Table 5 .
Multivariate analysis of variables associated with hypertension control.