Abstract
The current hypertension guideline emphasizes combination therapy, especially single‐pill combination therapy (SPC). However, few studies compared the prevalence and factors associated with initial therapy choice across heterogeneous age groups in a current population. First, the authors consecutively identified 964 treatment naïve hypertensive patients in a large academic hospital from 01/31/2019 to 01/31/2020. All patients were grouped into (1) young aged, age < 55; (2) middle‐aged, 55≤age < 65; and (3) older aged, age ≥65. The multivariable regression model examined the factors associated with the combination therapy by age group. Overall, 80 (8.3%) were young, 191 (19.8%) were middle, and 693 (71.9%) were older aged. Compared with older age, younger patients were more likely to be male, highly educated, regularly exercised, have metabolic syndrome, and less likely to have cardiovascular‐related comorbidities, with a lower systolic but higher diastolic pressure. Only one in five patients used SPC, and the prevalence decreased with age. Besides hypertension grade, young patients without catheterization or echo test were less likely to receive multiple therapies, while older patients who were male with lower weight and lower risk levels were less likely to receive multiple therapies. In conclusion, combination therapy, especially SPC, was underused in the targeted hypertensive population. Our contemporary population study showed that young patients (<55) without a history of catheterization or echo examination and male older‐aged (≥65) patients with low‐risk classification were the population most likely to be neglected. Such information can help triage medical care resources in improving SPC use.
Keywords: age, combination therapy, hypertension, influential factors
1. INTRODUCTION
Uncontrolled hypertension (HTN) is one of the most significant public health problems today. It is related to a significantly elevated risk of stroke, myocardial infarction, heart failure, and renal failure. 1 Data from national surveys suggest that globally only 1/3 of patients with HTN have their blood pressure controlled to recommended levels, 2 , 3 although a difference in BP of 20/10 mmHg is associated with a 50% difference in cardiovascular risk. 4 The situation is even worse in developing countries. According to China Hypertension Survey, the crude rate of hypertension in the population aged 18 and above in China is 27.9%. A recent survey showed that only 40% of hypertensive people received treatment; among them, only 16.8% of those who received anti‐hypertensive treatment in China met the blood pressure standard. 5 , 6
All the current guidelines suggest considering initial hypertension therapy with combination therapy. 7 , 8 , 9 Since the 2017 ACC/AHA guideline, SPC or combination therapy has been recommended. 8 The most recent 2021 World Health Organization (WHO) hypertension guideline updated its pharmacological treatment recommendation, preferably with an SPC as an initial treatment. 7 Initial therapy with single‐pill combinations provided more than 50% better hypertension control in the first year than monotherapy. 10 Since 2017, 5 years have passed. Yet, few studies have examined the contemporary patients' initial therapy pattern in treatment‐naïve patients in the current context of updated guidelines. 7 , 8 , 9 Furthermore, little data compared the difference in associated factors by age. Therefore, it would be important to obtain solid evidence on factors associated with the combination choice initiation for hypertension in the current population.
Therefore, our study was conducted on the most current hospitalized treatment naïve hypertensive patients of all ages. We temped to examine (1) baseline characteristics, including related psychosocial characteristics of the current hypertensive population and their differences between various age groups; (2) investigate the initial treatment pattern differed by age; (3) determine the factors associated with the use of combination therapy and compared the differences of associated factors by ages. Findings from the study would help generate insights on improving the prevalence of combination therapy and SPC in the hypertension population, both young and older age groups. This is the first study in the updated guideline era examining the initial anti‐hypertensive therapy pattern and its associated factors by age.
2. MATERIALS AND METHODS
2.1. Study design and participants
Our present medical research was conducted according to the principles expressed in the Declaration of Helsinki. This retrospective study included 964 patients with hypertension admitted to one large academic hospital in Shanghai. The Ethics Commission of the studied Hospital approved this study. Written informed consent was waived for the retrospective study.
According to the International Society of Hypertension (ISH) guidelines 2020 hypertension guideline, the diagnosis of hypertension was the patient's blood pressure over 140/90 mmHg in three measurements on different days. 11 Inclusion criteria were 18 years or older, treatment naïve hypertensive patients consecutively seen in the cardiology unit from January 31st, 2019 to January 31st, 2021. 8 Patients with severe acute or inter‐recurrent acute comorbidities disease requiring hospital admission or medical rest with incomplete medical records (e.g., transfer to other hospitals) were excluded from the analysis.
2.2. Data collection
Data were collected including patient demographic information, information about sociodemographic data such as age, sex, occupation, education level, alcohol consumption, sedentary lifestyle, depression, family history of hypertension, family history of cardiovascular disease, comorbidities such as abnormal glucose metabolism or diabetes, dyslipidemia, hyperuricemia, cerebrovascular disease, coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), peripheral artery disease, obstructive sleep apnea syndrome (OSAS), thyroid dysfunction, hypertension complications such as cardiac hypertrophy by electrocardiogram (ECG), retinopathy, clinical characteristics such as heart rate, blood pressure, height, weight, body mass index (BMI), laboratory data, hypertension grade, primary or secondary hypertension, and therapeutic interventions (anti‐hypertensive medication and other concomitant medication), examination for cardiac such as ECG, catheterization or echography examination during the hospitalization were extracted from documented medical history. The in‐hospital treatments were collected from medical records. Details of medical history and care measure processes were collected using an online standardized data collection form. All data were double‐checked against source documents by two independent researchers.
2.3. Definition
The occupation was grouped into unemployed, employed, and self‐employed. Education was grouped into uneducated, less than high school, high school, and beyond. Alcoholic consumption was classified as (1) None, no alcohol consumption in the past year; (2) Occasional, alcohol consumption less than once a week on average in the past year; and (3) Often, alcohol consumption once a week or more on average in the past year. A sedentary lifestyle was defined as engaging in less than 150 min of moderate‐intensity physical activity per week. Abnormal glucose metabolism is defined as fasting blood glucose (FBG) ≥5.56 mmol/L (≥100 mg/dL). For historical BP, we have carefully extracted the data from general practitioners' documentation. In Shanghai, citizens were accepting physical examinations routinely by general practitioners in a community clinic, and such electronic data was shared with our hospital. The clinician's BP was measured under standardized conditions using the validated self‐inflating oscillometric device HEM‐705 CP (Omron, HealthCare, Bannockburn, IL, USA), and hypertension was diagnosed according to International Society of Hypertension (ISH) guidelines 2020 (140/90 mmHg in three measurements on different days). Therefore, the clinician reported our historical BP and unstandardized measurement was avoided. Hypertension grade was determined by historical BP according to the International Society of Hypertension (ISH) guidelines 2020 guideline. Baseline blood pressure (SBP/DPB) was categorized as normotension (SBP/DPB 130/80 mmHg), grade 1 hypertension (140–159/90–99 mmHg), grade 2 hypertension (160–179/100–109 mmHg), and grade 3 hypertension (more than 180/110 mmHg).
2.3.1. Age groups
Patients were classed into three groups: (1) young aged, age < 55 years old; (2) middle aged, 55≤age < 65 years old; (3) older aged, age ≥65 years old.
2.3.2. Medication use definition
Anti‐hypertensive medication use pattern was defined as medication prescription at the first administration among treatment‐naïve patients during hospitalization. Combination therapy was defined as more than two categories of anti‐hypertensive treatment or single‐pill combination therapy.
2.4. Statistical analysis
Continuous variables were expressed as the median and interquartile range (IQR), and categorical variables were expressed as numbers and percentages (%). For quantitative data, normality tests are performed first, and the distribution shape is determined through a comprehensive analysis using histograms. If the data follows or approximately follows a normal distribution, the three group differences are compared using ANOVA. If the data does not follow a normal distribution, the three group differences are compared using nonparametric rank sum tests. For qualitative data, non‐ordered categorical variables are compared using the contingency table chi‐square test, and ordered categorical variables are compared using nonparametric rank sum tests. Finally, among patients with a systolic blood pressure of more than 150 mmHg, we tested the probability of in‐hospital combination therapy among the young, medium, and old age groups by univariate and multivariate logistic regression analysis. Variables with significant statistical differences in the single‐factor analysis, based on whether there is index hypertensive therapy as the outcome variable, are included in a multivariate stepwise logistic regression model to obtain the odds ratio (OR), 95% confidence interval (CI), and p‐value.
Multivariable adjustment includes age, sex, BMI, comorbidities (cerebrovascular disease, HF, CAD, diabetes, AF, peripheral artery disease, hyperuricemia), hypertension complications (cardiac hypertrophy by ECG and retinopathy), hypertension grade, alcohol consumption amount, and blood pressure measurement at community or office. A two‐side α less than 0.05 was considered statistically different. Data were analyzed in R‐3.6.3 (R Foundation for Statistical Computing, Vienna, Austria) and SPSS Statistics (version 26.0, IBM, Armonk, NY, USA).
3. RESULTS
3.1. Baseline characteristics of hypertension patients
This study cohort began with 1032 patients who visited a hospital exclusively to manage hypertension in Shanghai, China. From this cohort, we excluded the following: 43 with severe acute or inter‐recurrent acute comorbidities disease requiring hospital admission, 25 with incomplete medical records (e.g., transfer to other hospitals). Our analysis' final population consisted of 964 patients enrolled from January 31st, 2019 to January 31st, 2021.
Overall and per‐group baseline characteristics are presented in Table 1. Among these 964 patients, 80 (8.3%) were young‐aged, 191 (19.8%) middle‐aged, and 693 (71.9%) older aged. Baseline characteristics showed an overall median (IQR) age of 71 (IQR [70.9, 72.5]) and female (43.7%). Family history of abnormal glucose metabolism (34.7%), hypertension (30.5%), and cerebrovascular disease (26.1%) were the most frequent comorbidities.
TABLE 1.
Baseline clinical and biochemical characteristics of different age groups.
| Classification | All | <55 | 55–65 | ≥65 | p value | |
|---|---|---|---|---|---|---|
| Numbers | 964 | 80 (8.3%) | 191(19.8%) | 693 (71.9%) | – | |
| Age (years) | 71 (64,82.8) | 49 (40,52) | 61 (59,63) | 77 (70,85) | <.001 | |
| Sex | Female | 421 (43.7%) | 20 (25.0%) | 67 (35.1%) | 334 (48.2%) | <.001 |
| Height (cm) | 164 (158.0,170.0) | 173 (166.5,175.5) | 168 (160.0,172.0) | 162 (158.0,170.0) | <.001 | |
| Weight (kg) | 66 (60.0,75.0) | 75 (68.8,85.0) | 70 (62.0,75.0) | 65 (60.0,70.0) | <.001 | |
| BMI | 24.2 (22.5,26.4) | 25.4 (23.4,28.9) | 24.4 (22.9,26.9) | 24.2(22.3,26.1) | <.001 | |
| Employment | Unemployed | 694 (72.9%) | 18 (24.3%) | 128 (68.1%) | 548 (79.4%) | <.001 |
| Employed | 135 (14.2%) | 25 (33.8%) | 34 (18.1%) | 76 (11.0%) | ||
| Self‐employed | 21 (2.2%) | 12 (16.2%) | 4 (2.1%) | 5 (0.7%) | ||
| Others | 102 (10.7%) | 19 (25.7%) | 22 (11.7%) | 61 (8.8%) | ||
| Education level | Uneducated | 267 (27.7%) | 16 (20.0%) | 40 (20.9%) | 211 (30.4%) | <.001 |
| Below high school | 386 (40.1%) | 9 (11.2%) | 71 (37.2%) | 306 (44.2%) | ||
| High school or above | 310 (32.2%) | 55 (68.8%) | 80 (41.9%) | 175 (25.3%) | ||
| Alcohol | Never | 859 (89.2%) | 70 (87.5%) | 148 (77.9%) | 641 (92.5%) | <.001 |
| Occasionally | 18 (1.9%) | 0 (0%) | 8 (4.2%) | 10 (1.4%) | ||
| Now | 86 (8.9%) | 10 (12.5%) | 34 (17.9%) | 42 (6.1%) | ||
| Sedentary lifestyle | 480 (49.8%) | 34 (42.5%) | 75 (39.5%) | 371 (53.5%) | .001 | |
| Psychology health | Good | 827 (85.9%) | 72 (90.0%) | 176 (92.6%) | 579 (83.6%) | .003 |
| Family history of HBP | 292 (30.5%) | 35 (43.8%) | 70 (37.0%) | 187 (27.2%) | .001 | |
| Family history of DM | 123 (12.9%) | 14 (17.5%) | 26 (13.8%) | 83 (12.1%) | .357 | |
| Family history of early CAD | 118 (12.3%) | 12 (15.0%) | 27 (14.2%) | 79 (11.4%) | .426 | |
| DM | 332 (34.7%) | 20 (25.3%) | 58 (30.7%) | 254 (36.8%) | .056 | |
| Hyperuricemia | 76 (8.0%) | 6 (7.6%) | 15 (8.0%) | 55 (8.0%) | .992 | |
| Cerebrovascular disease | 251 (26.1%) | 3 (3.8%) | 30 (15.8%) | 218 (31.5%) | <.001 | |
| CHD | 269 (27.9%) | 5 (6.3%) | 42 (22.1%) | 222 (32.0%) | <.001 | |
| AF | 70 (7.3%) | 0 (0%) | 8 (4.2%) | 62 (9.0%) | .003 | |
| HF | 108 (11.2%) | 4 (5.0%) | 9 (4.7%) | 95 (13.7%) | <.001 | |
| Peripheral artery disease | 13 (1.4%) | 1 (1.3%) | 0 (0%) | 12 (1.7%) | .186 | |
| OSAS | 4 (0.4%) | 1 (1.3%) | 1 (0.5%) | 2 (0.3%) | .433 | |
| Abnormal thyroid function | 21 (2.2%) | 4 (5.0%) | 3 (1.6%) | 14 (2.0%) | .184 | |
| ECG test | 931 (96.7%) | 76 (95.0%) | 182 (95.8%) | 673 (97.1%) | .454 | |
| LVH | 53 (5.5%) | 2 (2.5%) | 5 (2.6%) | 46 (6.6%) | .047 | |
| Retinopathy | 29 (3.0%) | 3 (3.8%) | 4 (2.1%) | 22 (3.2%) | .687 | |
| Heart rate (bpm) | 76.0 (70.0,80.0) | 78.0 (72.0,86.4) | 78.0 (72.0,82.0) | 76.0 (70.0,80.0) | .004 | |
| Respiratory rate (per min) | 18.0 (17.0,20.0) | 18.0 (18.0,20.0) | 18.0 (17.0,20.0) | 18.0 (17.0,20.0) | .537 | |
| Potassium (mmol/L) | 3.9 (3.7,4.2) | 3.8 (3.7,4.1) | 3.9 (3.6,4.2) | 3.9 (3.7,4.2) | .377 | |
| Sodium (mmol/L) | 140.7 (138.0,142.2) | 140.7 (139.0,142.0) | 141.0 (138.0,142.8) | 140.4 (138.0,142.3) | .596 | |
| Chlorine (mmol/L) | 103.6 (101.0,106.0) | 102.6 (101.0,104.0) | 103.3 (101.1,105.0) | 104.0 (101.0,106.0) | .074 | |
| Blood uric acid (umol/L) | 341.5 (278.0,415.8) | 382.0 (332.0,442.3) | 342.0 (282.0,414.6) | 336.0 (270.0,410.0) | .001 | |
| Homocysteine (umol/L) | 12.6 (10.1,16.2) | 11.2 (8.4,14.6) | 11.6 (9.4,14.1) | 13.1 (10.7,16.9) | <.001 | |
| Scr (umol/L) | 73.0 (59.0,90.0) | 69.5 (61.0,80.0) | 70.0 (57.0,82.0) | 75.0 (60.0,93.0) | .006 | |
| eGFR | 62.7 (34.5,93.2) | 82.0 (63.0,105.9) | 65.7 (39.3,90.8) | 58.4 (28.5,92.0) | <0.001 | |
| TC (mmol/L) | 4.5 (3.7,5.3) | 4.9 (4.2,5.6) | 4.8 (4.0,5.5) | 4.4 (3.6,5.2) | <.001 | |
| LDL (mmol/L) | 2.8 (2.2,3.4) | 3.2 (2.6,3.6) | 3.0 (2.3,3.5) | 2.6 (2.1,3.3) | <.001 | |
| HDL (mmol/L) | 1.2 (1.0,1.5) | 1.7 (0.9,1.3) | 1.2 (0.9,1.5) | 1.2 (1.0,1.5) | .002 | |
| TG (mmol/L) | 1.6 (1.1,2.28) | 1.9 (1.4,2.5) | 1.7 (1.2,2.6) | 1.5 (1.0,2.2) | <.001 | |
| ALT (u/L) | 19.0 (14.0,28.0) | 30.0 (20.0,39.8) | 21.0 (16.0,29.0) | 18.0 (13.0,26.0) | <.001 | |
| AST (u/L) | 21.0 (17.0,27.0) | 23.0 (18.0,30.3) | 21.0 (17.0,26.60) | 21.0 (17.0,27.0) | .209 | |
| FBG (mmol/L) | 5.8 (5.2,7.0) | 5.7 (5.1,6.9) | 5.8 (5.3,7.0) | 5.8 (5.2,7.0) | .924 | |
| HbA1c (mg/dL) | 6.2 (5.8,7.1) | 6.0 (5.7,6.8) | 6.1 (5.7,6.9) | 6.3 (5.8,7.1) | .227 | |
| Aspirin/Clopidogrel | 358(37.1%) | 7(8.8%) | 60(31.4%) | 291(42.0%) | <.001 | |
| Statin | 324(33.6%) | 15(18.8%) | 84(44.0%) | 225(32.5%) | <.001 | |
| Glucose lowering | 289(30.0%) | 16(20.0%) | 46(24.1%) | 227(32.8%) | <.001 |
Abbreviations: AF, atrial fibrillation; ALT, glutamic‐pyruvic transaminase; AST, aspertate aminotransferase; BMI, body mass index; ECG, electrocardiogram; eGFR, glomerular filtration rate; FBG, fasting blood glucose; HbA1c, glycosylated hemoglobin; HDL, high‐density lipoprotein; HF, heart failure; LDL, low‐density lipoprotein; LVHV, left ventricular high voltage; OSAS, obstructive sleep apnea; Scr, serum creatinine; TC, total cholesterol; TG, Triglycerides.
The median (IQR) age for the three groups was 49 (40, 52) for young aged (<55), 61 (59, 63) for middle‐aged (55–64), and 77 (70, 85) for old aged (≥65). Compared with the older‐aged group, the younger‐aged group was more likely to be male, employed, highly educated, regular alcoholic, regularly exercised, have a higher BMI, family history of high blood pressure (HBP) and early cardiovascular disease (CVD), have comorbidities such as diabetes mellitus (DM), OSAS, and thyroid dysfunction, less likely to have a sedentary life, depression, cerebrovascular disease, CAD, AF, and HF. For lab results, younger patients were more likely to have hyperuricemia and dyslipidemia with higher total cholesterol (TC), triacylglycerol (TG), higher low‐density lipoprotein (LDL), lower high‐density lipoprotein (HDL), and higher glutamic‐pyruvic transaminase (ALT) levels but less likely to have left ventricular hypertrophy (LVH). In short, compared with older aged patients, younger patients diagnosed with hypertension were more likely to be male, highly educated, regularly exercised, have metabolic syndrome, and less likely to have cardiovascular‐related comorbidities such as CAD, AF, and HF.
3.2. Hypertension characteristics
Regarding hypertension history and data, 91.7% had a history of hypertension, and 1.4% were secondary hypertension. For hypertension grades, grades 1, 2, and 3 had 58 (6.1%), 187 (19.7%), and 704 (74.2%) patients, respectively. For risk classification, the low, medium, high, and very high‐risk percentage was 2.0%, 6.1%, 17.9%, and 73.9%, respectively. With age increased, the percentage of higher hypertension grades increased. (Grade 3: young vs. medium vs. old: 70.3% vs. 71.1% vs. 75.4%, p = .332), and higher risk classification also increased (Very high risk: young vs. medium vs. old, 73.0% vs. 70.4% vs. 75.0%, p = .364) (Table 2).
TABLE 2.
Hypertensive characteristics by age groups.
| Variable | All | <55 | 55–65 | ≥65 | p value | |
|---|---|---|---|---|---|---|
| History of hypertension | Yes | 877 (91.1%) | 62 (77.5%) | 164 (86.3%) | 651 (93.9%) | <.001 |
| Hypertension classification | Grade1 | 58 (6.1%) | 7 (9.5%) | 12 (6.4%) | 39 (5.7%) | .332 |
| Grade2 | 187 (19.7%) | 15 (20.3%) | 42 (22.5%) | 130 (18.9%) | ||
| Grade3 | 704 (74.2%) | 52 (70.3%) | 133 (71.1%) | 519 (75.4%) | ||
| Risk stratification | Low | 19 (2.0%) | 5 (6.8%) | 4 (2.2%) | 10 (1.5%) | .364 |
| Middle | 58 (6.1%) | 5 (6.8%) | 14 (7.5%) | 39 (5.7%) | ||
| High | 169 (17.9%) | 10 (13.5%) | 37 (19.9%) | 122 (17.8%) | ||
| Extremely high | 698 (73.9%) | 54 (73.0%) | 131 (70.4%) | 513 (75.0%) | ||
| Secondary hypertension | Yes | 13 (1.4%) | 2 (2.5%) | 4 (2.1%) | 7 (1.0%) | .334 |
| Highest clinic‐based systolic pressure in history a | 180.0 (160.0,196.5) | 170.0 (160.0,190.0) | 180.0 (160.0,200.0) | 180.0 (170.0,198.0) | .010 | |
| Highest clinic‐based diastolic pressure in history a | 100.0 (90.0,110.0) | 108.5 (100.0,118.5) | 100.0 (96.0,110.0) | 100.0 (90.0,110.0) | <.001 | |
| Hypertension duration (y) | 10.0 (7.0,20.0) | 4.0 (2.0,10.0) | 10.0 (5.0,14.0) | 12.0 (9.0,20.0) | <.001 | |
| Clinic systolic pressure a | 140.0 (130.0,160.0) | 140.0 (130.0,160.0) | 142.0 (130.0,160.0) | 140.0 (130.0,160.0) | .731 | |
| Clinic diastolic pressure a | 80.0 (74.0,90.0) | 90.0 (80.0,99.3) | 84.0 (80.0,91.8) | 80.0 (72.0,90.0) | <.001 | |
| Home systolic pressure a | 135.0 (129.0,150.0) | 140.0 (125.0,150.0) | 140.0 (130.0,150.0) | 134.0 (130.0,150.0) | .426 | |
| Home diastolic pressure a | 80.0 (70.0,85.0) | 85.0 (80.0,90.0) | 80.0 (75.0,90.0) | 80.0 (70.0,82.0) | <.001 | |
| ACEI | 23 (2.4%) | 1 (1.2%) | 6 (3.1%) | 16 (2.3%) | .63 | |
| ARB | 374 (38.8%) | 34 (42.5%) | 80 (41.9%) | 260 (37.5%) | .43 | |
| CCB | 571 (59.2%) | 45 (56.2%) | 113 (59.2%) | 413 (59.6%) | .85 | |
| Diuretic | 80 (8.3%) | 3 (3.8%) | 14 (7.3%) | 63 (9.1%) | .23 | |
| Adrenergic alpha antagonists | 16 (1.7%) | 1 (1.2%) | 1 (0.5%) | 14 (2.0%) | .34 | |
| Beta‐receptor‐blocking agent | 252 (26.1%) | 23 (28.7%) | 52 (27.2%) | 177 (25.5%) | .77 | |
| Single therapy | 542 (56.2%) | 51 (63.8%) | 120 (62.8%) | 371 (53.5%) | .03 | |
| SPC | 238 (24.7%) | 27 (33.8%) | 52 (27.2%) | 159 (22.9%) | .07 | |
| SPC or two or more drugs | All | 542 (56.2%) | 51 (63.7%) | 120 (62.8%) | 371 (53.5%) | .03 |
| SBP > 150 a | 230 (71.4%) | 23 (79.3%) | 49 (72.1%) | 158 (70.2%) | .59 |
Unit: mmHg.
There were significant differences between age groups in the history of hypertension, historical systolic blood pressure, historical diastolic blood pressure, years of hypertension history, and clinical and family diastolic blood pressure (all p < .001). Compared with the old‐aged group, the younger‐aged group had a lower highest systolic pressure but higher highest diastolic pressure in history. Similarly, the younger group had lower clinical and family systolic pressure records but higher clinical and family diastolic pressure records (p < .001) (Table 2).
3.3. Hypertensive treatment
The most commonly used treatments in anti‐hypertension treatment were angiotensin receptor blockers (ARB) 38.8% and calcium entry blockers (CCB) 59.2%. Other medications were angiotensin‐converting enzyme inhibitors (ACEI) treatment was 2.4%, diuretics 8.3%, beta‐blocker 26.1%, and alpha‐blocker 1.7% (Table 2).
3.4. SPC
Among overall patients, 24.7% patients were receiving SPC therapy. The probability of using SPC decreased with age (<55, 33.8% vs. 55−64, 27.2% vs. ≥65, 22.9%, p = .07).
3.5. ≥2 combined therapies
Among overall patients, 56.2% were receiving ≥2 combination therapies. There were significant differences between young and old groups in using ≥2 combination therapies. Similarly, the younger, the more (<55, 63.7% vs. 55−64, 62.8% vs. ≥65, 53.5%, p = .027).
Among those with a systolic blood pressure of over 150 mmHg, 71.4% received≥2 combination therapies. The younger, the more (<55, 79.3% vs. 55−64, 72.1% vs. ≥65, 70.2%, p = .59).
3.6. ≥3 combined therapies
Among overall patients, 23.1% were receiving ≥3 combined therapies. Similarly, the use of ≥3 combined therapies decreased with age increased. (<55, 28.7%% vs. 55−64, 24.1% vs. ≥65, 22.2%, p = .59) (Table 2).
3.7. Factors associated with single therapy, ≥2 combined therapies, and ≥3 combined therapies
3.7.1. Single therapy
Multifactor analysis showed that factors associated with single drug treatment were occupation, weight, hypertension grade, and systolic community pressure. Specifically, compared with unemployed, employed patients were 3.04 times less likely to be treated with a single therapy, and self‐employed were 8.62 times less likely to be treated with a single therapy. Compared with Grade 1 hypertensive patients, Grade 3 hypertensive patients were nine times less likely to receive single therapy. Every 1 mmHg increase in clinical systolic pressure was 1.02 times less likely to receive single therapy (Table 3).
TABLE 3.
Predictors for multiple therapies by ages.
| Variables | <55 (80/51) | 55–65 (191/120) | ≥65 (693/371) | ||||
|---|---|---|---|---|---|---|---|
| OR (95% CI) | p | OR (95% CI) | p | OR (95% CI) | p | ||
| Hypertension grade | One | — | — | — | |||
| Two | 2.7 (0.2,30.7) | .43 | 3.8 (0.4,35.1) | .24 | 13.8 (1.6,119.5) | .017 | |
| Three | 11.6 (1.1,121.6) | .04 | 12.8 (1.5,111.1) | .021 | 17.3 (2.0,147.2) | .009 | |
| Catheterization or echo examination | 4.1 (1.1,15.4) | .04 | |||||
| Sex | 0.4 (0.3,0.7) | .001 | |||||
| Sedentary lifestyle | 0.5 (0.3,0.8) | .002 | |||||
| Family history of hypertension | 0.6 (0.4,1.0) | .031 | |||||
| Weight | 1.0 (1.0,1.1) | .002 | |||||
| Systolic pressure in clinic | 1.0 (1.01,1.03) | <.001 | |||||
| Highest diastolic pressure in history | 1.1 (1.0,1.1) | .010 | |||||
| Risk classification | Low | — | |||||
| Medium | — | ||||||
| High | 2.0 (0.6,7.3) | .29 | |||||
| Very high | 4.2 (1.2,14.5) | .03 | |||||
3.7.2. ≥2 combined therapies
For overall patients, hypertension grade (Class 2 vs. Class 1, 9.4, [2.1, 42.9], Class 3 vs. Class 1, 11.4, [2.5, 52.6]), historical highest clinical systolic pressure (1.0 [1.01, 1,02]), family systolic pressure (1.0, [1.001, 1.03]), age (0.98, [0.96, 0.994] for everyone increase), and risk classification (very high risk vs. medium, 3.4, [1.3, 8.7]) were independent factors associated with ≥2 combined therapies.
Among those whose systolic blood pressure was >150 mmHg, we again examined the factors associated with ≥2 combination therapy. It turned out that BMI and clinic systolic blood pressure were independent factors associated with the choice of ≥2 combined treatments. Specifically, patients with higher BMI were more likely to use ≥2 combined therapies (adjusted OR, 1.1 [1.0, 1.2] for everyone increase in BMI). Also, patients with higher clinical systolic blood pressure were more likely to receive ≥2 combined therapies (adjusted OR, 1.02 [1.01, 1.04] for everyone increase in systolic blood pressure) (Table 3).
3.7.3. ≥3 combined therapies
Among all patients, we examined the factors associated with ≥3 combination therapy. Hypertension grade (Grade 3 vs. 2, adjusted OR, 5.1 [2.1, 12.1]), highest systolic blood pressure in history (adjusted OR, 1.01 [1.004, 1.024]), and clinical systolic blood pressure (adjusted OR, 1.02 [1.01, 1.03]) were independent factors associated with ≥3 combination therapy (Table 3).
3.7.4. Associated factors for single therapy by ages
In hypertensive patients with all blood pressure ranges, we examined the difference in factors associated with single therapy. In young aged (<55) patients, hypertension grade (Grade 3 vs. Grade 2, adjusted OR 0.1 [0.0, 0.9]) and catheterization procedure (0.2, [0.1, 0.9]) were independent influential factors. In the medium‐aged group, hypertension grade (Grade 3 vs. Grade 2, adjusted OR 0.1 [0.0, 0.7]) and historical highest diastolic pressure (0.9, [0.9, 1.0]) were independent influential factors. In old aged group, sex (male vs. female, 2.3 [1.4, 3.6]), weight (1.0, [0.94, 0.99]), clinic systolic pressure (0.98, [0.97, 0.99]), hypertension grade (Grade 2 vs. Grade 1, 0.1, [0.0, 0.6], Grade 3 vs. Grade 2, 0.1, [0.0, 0.5]), and risk classification (very high risk vs. high risk, 0.2, [0.1, 0.8]). In short, besides hypertension grade, young patients without catheterization or echographic test were more likely to receive single therapy (less likely to receive multiple therapies). In contrast, older male patients with lower weight and risk were more likely to receive single therapy (less likely to receive multiple therapies).
4. DISCUSSION
In our contemporary study of patients hospitalized with primary hypertension, we found that (1) compared with old aged patients, young patients were more likely to have metabolic syndrome, and older patients were more likely to have comorbidities such as CAD, AF, and HF; (2) the anti‐hypertensive treatment prescription pattern differed between young and older patients, the younger, the more aggressively treated; (3) young patients without catheterization or echo test were more likely to receive single therapy (less likely to receive multiple therapies) while older patients who were male with lower weight, and lower risk were more likely to receive single therapy (less likely to receive multiple therapies). Factors associated with the use of combination therapy were different in young and old groups. Physicians may need to focus on various facets of patients of different ages to improve the use of combination therapy, particularly in enhancing SPC prevalence.
Our study first delved into the social characteristic factors such as occupation, education level, alcohol consumption, sedentary lifestyle, and depression to describe hypertension baseline characteristics. Our study showed that (1) almost 30% of the overall population were aged <65 years old; (2) Compared with older aged patients, younger patients diagnosed with hypertension were more likely to be male, highly educated, regularly exercised, have metabolic syndrome, and less likely to have depression, cardiovascular‐related comorbidities such as CAD, AF, and HF; (3) Compared with older patients, young patients were more likely to have lower systolic pressure but higher diastolic pressure. Our study population was similar to previous large‐cohort registry studies regarding patients' characteristics by age. Similar to our study, a prospective cohort study of 71 245 patients showed that with the decrease of hypertension onset age, the proportions of ever‐smokers and ever‐drinkers and body mass index, metabolic syndrome such as dyslipidemia, and estimated glomerular filtration rate (eGFR) gradually increased. 12 On the other hand, comorbidities related to older age, such as CAD, HF, and AF, were more common in older patients. 13 Moreover, our study echoes previous studies that the diastolic pressure rises in young patients with higher cardiac pumping ability. In contrast, older patients had higher systolic pressure rises because of stiffened arteries. 14
Our study is novel in examining the social‐psychological factors by age and showed that psychosocial stressors, depression, and chronic disease burdens such as cardiovascular comorbidities were more common in the older aged group. Meanwhile, Psychosocial stressors and a history of depression were important risk factors for hypertension. 15 , 16 Besides, psychosocial stress and major psychiatric disorders increased the cardiovascular risk, 11 particularly in patients with hypertension, suggesting the importance of BP control in depressed patients. 15 , 16 Our study showed that although the psychosocial stressor, depression, and cardiovascular comorbidities were more common in the older aged group compared with younger patients, yet the use of combination therapy was much lower in this group of patients. One reason may be clinical fear that elderly patients are more prone to adverse drug effects than younger patients. 17 Still, such low use of combination therapy patterns in older patients implied these patients' undertreatment status.
The combined therapy was strikingly low in our current population. First, our result showed that less than 25% of patients used single‐pill combination therapy, while the 2021 WHO guideline recommends initiating all patients who need treatment with single‐pill combination therapy. 7 Next, as the previous guideline emphasized, we examined combination therapy in patients whose systolic pressure was over 150 mmHg. 8 , 11 Our results showed that 71% of patients received guideline‐recommended combination therapy, and such proportion decreased with age increased. Our study mirrored a previous global study examing patients from 1990 to 2015 in that although only 35% of patients had their blood pressure controlled, the control rates were lowest in the oldest age group. 18 Of note, our study population was enrolled in 2019−2021, 5 years after the 2017 ACC/AHA guideline was published, and in Shanghai, one of the most developed cities in China. The use of combination therapy was still low, let alone SPC. Our treatment pattern also reflected the real‐world anti‐hypertensive treatment among elderly patients. Diuretic use was low, less than 10% since physicians are reluctant to use diuretics with the caution of its impact on electrolytes imbalance and glucose metabolism, resulting in hypokalemia and high glucose level. Early studies have showed that the use of an ARB or low‐dose diuretic (i.e., 12.5 mg HTCT) had a lower incidence of hypokalemia and hyperglycemia. 19 , 20 China is a country with excessive salt consumption. Previous studies have confirmed that about 20%−40% of the general population is sensitive to salt. In patients with essential hypertension, salt sensitivity is as high as 60%. 21 Low diuretic use is responsible for suboptimal blood pressure control, particularly in the elderly population. Although we did not examine the blood pressure control rate, we did explore the number of medicine types to resemble the aggressiveness of the treatment. For two and three combination therapies, the treatment prevalence decreased with age increased. Real‐world studies confirmed that patients with worse BP control were treated less aggressively with fewer medications than their younger counterparts despite older hypertension. 22 Yet the guidelines have recommended controlling BP to at least <130/80 mmHg regardless of age. 8 , 9 , 11 Our study is comparable with the previous research that so‐called “very old” individuals with hypertension, despite having worse BP control, higher systolic hypertension rates, and more cardiovascular comorbidity, are being treated less aggressively than younger patients. 22 Such phenomenon existed 15 years ago and still today, despite strong evidence that has evolved over the past 15 years for hypertension treatment, which now recommends similar approaches to hypertension management regardless of age. Our study showed that the treatment controversy in elderly patients (>= 65 years) remains among current real‐world patients.
Factors associated with the combination therapy differed by age. Our study showed that those with no history of catheterization or echo examination for young‐aged patients were most likely to be neglected in combination therapy. On the other hand, males with low weight and low‐risk stratification were the group of patients neglected in combination therapy for older patients. Although previous studies showed that most aged patients (age ≥ 80 years) were being treated less aggressively with fewer medications. 22 For young patients, a previous study showed that young males were less likely to have hypertension well‐controlled than other age groups of patients. 23 Our study emphasized that young patients who did not undergo catheterization were also the group most likely to be undertreated. For the first time, our study identified different focus of patients by age. Since the ESC, ACC, and the International Society of Hypertension (ISH) guidelines emphasize that most patients, regardless of age, will require more than one anti‐hypertensive drug to achieve control. 8 , 9 , 11 Furthermore, guidelines recommend an identical treatment target for young and old patients. Physicians should focus on age and specific patient factors to improve the initial use of single‐pill combination therapy for hypertension in treatment‐naïve patients, which is currently underused even 5 years after being recommended in guidelines. Our study showed that young patients (<55) who have no history of catheterization examination and male older aged patients (≥65) with low risk classification were the population most likely to be neglected. Such information can guide the triage of medical care resources in improving the use of SPC and combination therapy.
4.1. Limitation
The present study also has several potential limitations. First, our analysis was performed in a large academic hospital in Shanghai with patients with good access to medical care and medication. Therefore, findings may not be generalized to other geographic settings. However, our age‐related hypertensive characteristics, such as age range, BMI, heart rate, alcohol consumption, and comorbidities, were similar to large cohort hypertensive studies in China and the global registry. 2 , 6 , 12 Second, we did not examine physicians' willingness to prescribe the medications. However, in our study, clinicians were all from one hospital with similar access to anti‐hypertensive treatment medications. Third, we captured the aggressiveness of treatment by counting the number of medications, yet the dose, duration of therapy, and pressure control rate had not been studied. But because we examined the initial treatment pattern in patients without anti‐hypertensive treatment history, whether or not BP goals have been reached should not impact the initial treatment pattern. Therefore, our results would probably not change appreciably. Fourth, we excluded patients with severe acute or inter‐recurrent acute comorbidities disease requiring hospital admission or medical rest with incomplete medical records (e.g., transfer to other hospitals) whose anti‐hypertensive treatment may be influenced by acute disease. Yet, these patients were a small percentage, only 2.4% of our study population. Last, we did not have information on nonadherence or side effects, which might influence the therapy choice, and account for undertreatment in elderly patients. Of note, studies have shown that elderly patients were more likely to benefit from SPC than single treatment with an increased dose. 24
AUTHOR CONTRIBUTIONS
Jianfei Xiong and Li Wang contributed to the conception and design of the study, the data analysis, the data interpretation, the manuscript drafting, and the critical revision of the manuscript; Chuanxi Yang and Hengye Huang contributed to the data analysis, the data interpretation, the manuscript drafting, and the critical revision of the manuscript; Lan Shen, Ben He, and Feng Su contributed to the data interpretation, the manuscript drafting, and the critical revision of the manuscript. All authors have read and approved the manuscript.
CONFLICT OF INTEREST STATEMENT
The authors declare that they have no competing interests.
ACKNOWLEDGMENTS
This research was supported by the National Natural Science Foundation of China to L. Shen (81900308), Youth Program of National Natural Science Foundation of China to C.X. Yang (82200379) and the Informatization Development Project of Shanghai Municipal Commission of Economy and Informatization (202002009).
Xiong J, Wang L, Yang C, et al. Age‐specific differences in hypertension combination management and associated factors influencing treatment choice. J Clin Hypertens. 2023;25:545–554. 10.1111/jch.14668
Jianfei Xiong, Li Wang, Chuanxi Yang, and Hengye Huang contributed equally to this work and share the first authorship.
Drs. Lan Shen and Feng Su provided mentorship and served as corresponding authors.
Contributor Information
Lan Shen, Email: shenlan_shanghai@163.com.
Feng Su, Email: sufenga@163.com.
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