Association between hypertension and pressure ulcer: A systematic review and meta‐analysis

Abstract

This review aims to systematically evaluate the association between hypertension and pressure ulcer (PU). PubMed, Embase, Web of Science, and Cochrane Library were searched for studies from their inception until September 12, 2023. Literature search, data extraction, and quality assessment were conducted independently by two researchers. The random‐effects model was used to calculate the combined odds ratio (OR) and corresponding 95% confidence interval (CI) of hypertension in patients with PU; subgroup analyses were performed to explore the source of between‐study heterogeneity; sensitivity analysis was used to test the robust of the combined result; and funnel plot and Egger's test were used to assess the publication bias. Finally, a total of 19 studies with 564 716 subjects were included; the overall pooled result showed no significant association between hypertension and risk of developing PU (OR = 1.15, 95% CI = 0.90–1.47, p = 0.27); and the sensitivity analysis and publication bias analysis showed robust of the combined result. Subgroup analysis indicated a significant association between hypertension and PU when the primary disease was COVID‐19 (OR = 1.73, 95% CI = 1.35–2.22, p < 0.0001). No association between hypertension and PU was seen in subgroup analysis on the patient source and study design. In sum, there is no significantly statistical association between hypertension and the occurrence of PU in most cases, while the risk of PU significantly elevates among COVID‐19 patients combined with hypertension regardless of patient source and study design.

1. INTRODUCTION

It is reported by the China Patient‐Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project, that nearly half of Chinese adults aged 35–75 years suffer from hypertension and fewer than one in twelve are in control of their blood pressure. ¹ Hypertension is known to be related not only to cardiovascular events such as coronary heart disease, arrhythmia and heart failure but also to a positive association with Alzheimer's disease, ² and a direct relationship with cancer incidence and mortality. ³ Recent studies showed that hypertension is associated with non‐alcoholic fatty liver and imbalances of intestinal flora. ⁴ , ⁵ However, it remains unclear whether hypertension causes any other diseases.

Pressure ulcer (PU) is a common health issue, particularly among older people who are physically limited or bedridden. Several contributing or confounding factors, such as the patient's underlying pathologies, severity of primary illness, comorbidities, functional state, nutritional status and degree of social and emotional support, are also associated with PU. ⁶ With the growth of the aging population and nursing home residents, as well as poorly understood biology and a dismal track record of clinical research, PU will bring an increasing burden and challenge to personal impact and public healthcare management. ⁷

It was previously believed that pressure was the main cause of PU, other risk factors included prolonged immobilization, sensory deficits, circulatory disturbances and poor nutrition. ⁸ However, current knowledge ⁹ confirms that PU develops due to sustained mechanical loading leading to soft tissue deformation. Specifically, excessive shear strain or stress exposures can cause superficial skin damage, while high pressures in combination with shear at the surface over bony prominences or under stiff medical devices can result in deeper PU. ⁹ However, the role of hypertension in PU formation is still unclear. Some studies ¹⁰ , ¹¹ , ¹² suggest that hypertension is a significant risk factor for PU, while others ¹³ show an inverse association. To resolve this controversy and provide evidence‐based medical recommendations for the prevention of PU, a systematic review and meta‐analysis were conducted.

2. METHODS

Literature search, data extraction and quality assessment were conducted independently by two professional researchers. Disagreements between the two investigators was resolved through discussion with the third reviewer.

2.1. Study registration and reporting

This systematic review and meta‐analysis were carried out using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA2020) checklist. ¹⁴ Additionally, the review protocol was registered at PROSPERO‐the international prospective register of systematic reviews (www.crd.york.ac.uk/PROSPERO; CRD42023460528).

2.2. Search strategy

We performed systematic literature search in PubMed, the Cochrane library, Web of Science and EMBASE databases from the inception to September 12, 2023 using subject headings (MeSH and Emtree) and text words related to hypertension and pressure ulcers to retrieve potentially eligible studies. In addition, the references of reviews and major studies were searched to avoid omissions. A detailed electronic search strategy is presented in Supplementary material 1 for PubMed database.

2.3. Inclusion and exclusion criteria

Inclusion criteria: (1) clinical studies included history of hypertension among patients with PU; (2) the control group included history of hypertension among patients without PU; (3) study design: cohort or case–control study; (4) relationship between hypertension and PU was used as an outcome indicator; and (5) only studies published in English were considered to meet our inclusion criteria.

Exclusion criteria: (1) Repeated published literature; (2) animal experiments, review literature, conference reports, case reports, reviews, notes, replies and comments; (3) studies which did not provide sufficient information for odds ratios (OR) and their 95% confidence intervals (CI); (4) studies without full text available; (5) Newcastle‐Ottawa scale (NOS) score ≤4 points.

2.4. Study selection

We used the EndNote X9 software to manage literature, duplicate studies were first removed by using this software, and then ineligible studies were excluded based on the title and abstract screening. Finally, we determine eligible studies that met our eligibility criteria based on full‐text screening of the remaining studies. If published papers had inadequate or unclear data, the study authors were contacted for further information or clarification.

2.5. Data extraction and quality assessment

Data extraction for the included studies was performed independently by two researchers according to a pre‐designed table. The extracted contents included:

First author, year of publication, nationality, study design, sex, age, the number of hypertension cases in the PU group and non‐PU group, primary disease, and the relationship between hypertension and PU as outcome indicators. The quality evaluation of the literature included in the study was completed independently by two investigators using the NOS with a maximum score of 9 representing the highest quality. ¹⁵ In this tool, each study was scored independently according to selection of study groups, comparability of groups and ascertainment of exposure and outcomes, with a total score ranging from 0 to 9. A study was considered to be of high methodological quality if the total score was ≥5 stars. ¹⁶

2.6. Statistical analysis

Meta‐analysis was performed using Review Manager 5.3. The OR and corresponding 95% CI were used to express the combined result. The Mantel–Haenszel method was used for pooling ORs in each study. Statistical heterogeneity among the included studies was evaluated using the I ² index. If p < 0.1 and/or I ² > 50.0%, statistical heterogeneity between studies were considered significant, and the random‐effect model was used for meta‐analysis; otherwise, the fixed‐effects model was used. Subgroup analyses were performed on patient source, study design and primary disease to explore the source of between‐study heterogeneity.

2.7. Sensitivity analysis and publication of bias

STATA version 14 was used for sensitivity analysis and evaluation of publication of bias. Sensitivity analysis was used to evaluate the impact of omitting each study on the overall effect size of the association between hypertension and PU. Funnel plot and Egger's test were performed to assess the publication bias when there were more than 10 articles in this meta‐analysis.

3. RESULTS

3.1. Study selection

The literature search yielded 6060 reports. After de‐duplication, 4873 titles and abstracts were screened, where a further 4828 articles were excluded, mainly because they were reviews, case reports, in vitro studies, meeting abstracts, or irrelevant to our analysis. Full‐text screening was conducted for the remaining 45 studies, where a further 26 studies were excluded for the following reasons: no extracted data, cross sectional study, no control group and group mismatch. Ultimately, 19 studies were eligible for inclusion in our meta‐analysis. A flowchart showing the study selection is presented in Figure 1.

FIGURE 1.

Flowchart of study search and selection.

3.2. Study characteristics and quality assessment

As mentioned in Table 1, the 19 studies comprised data on 564 716 subjects across 12 countries were included. Of these studies, 10 were case–control studies and 9 were cohort studies. The continents in which the studies were performed were as follows: Asia (n = 13, including China, Qatar, Turkey, Singapore, Iran, Japan, Thailand and Saudi Arabia) and non‐Aisa (n = 6, including USA, Switzerland, Portugal and Brail). The average age of the patients ranged between 37.4 and 83.0 years, and the percentage of men ranged from 27.3% to 100.0%. Across these 19 studies, there were 17 142 and 547 574 subjects in the PU and non‐PU groups, in which contains 11 160 and 386 627 PU patients, respectively. The primary diseases of these subjects in included studies mainly contains stroke (n = 2), COVID‐19 (n = 3), ICU patients (n = 4), geriatric diseases (n = 3) and surgical diseases (operation or non‐operation, n = 7). The NOS scores of eligible studies are listed in the Table 1, with a minimum score of 5 and a maximum score of 8, all included studies showed acceptable quality. NOS scoring details for each study are available in supplementary material 2.

TABLE 1.

Characteristics of the included studies.

			Age (years, mean)		Sex (male, %)		PU group		Non‐PU group
	Patient source	Study design	PU	Non‐PU	PU	Non‐PU	Events	Total	Events	Total	Primary disease	NOS
Jiang 2022 17	China	Cohort	68.0	58.0	65.5%	68.3%	25	58	129	205	ICU patients	7
Mehaffey 2017 18	USA	Case–control	70.1	66.5	54.2%	58.2%	10 462	15 877	373 878	522 930	Vascular surgical patients	5
Rabadi 2011 19	USA	Case–control	60.0	59.0	100%	96.7%	11	27	32	60	Traumatic spinal cord injury	7
Nadukkandiyil 2020 20	Qatar	Case–control	76.7	81.5	62.2%	66.7%	37	45	33	45	Elderly patients	6
Gengenbacher 2002 23	Switzerland	Case–control	80.3	82.2	27.3%	27.5%	10	22	20	40	Elderly patients	8
Yurt 2022 24	Turkey	Case–control	80.05	76.22	66.7%	53.7%	40	54	47	54	Stroke	7
Lei 2022 25	China	Case–control	50.9	49.5	61.9%	52.4%	22	42	37	84	General anaesthetized patients	7
Aloweni 2019 12	Singapore	Case–control	≥75 43.8%	≥75 16.4%	45.0%	55.6%	48	80	68	189	Surgical patients	6
Siotos 2023 26	USA	Case–control	≥70 62.7%	≥70 27.0%	45.8%	52.1%	60	83	2431	4507	COVID‐19	6
Farahbakhsh 2023 27	Iran	Cohort	37.4	42.2	78.2%	73.2%	3	87	202	2698	Traumatic spinal fractures	6
Vaz 2023 10	Portugal	Cohort	63.2	60.3	79.7%	63.2%	72	118	41	87	COVID‐19	7
Okuwa 2006 28	Japan	Cohort	83.0	84.0	45.5%	23.2%	12	33	63	226	Bedfast older patients	8
Techanivate 2021 29	Thailand	Case–control	60.6	62.4	32.9%	37.6%	44	82	126	218	Spine surgical patients	7
Liao 2019 30	China	Case–control	75	67	46.4%	61.8%	66	97	7843	12 318	Acute ischemic stroke patients	5
Shimura 2022 22	Japan	Cohort	70.5/69.3	66.0/66.1	61.0%	63.1%	34	77	1120	2759	ICU patients	6
Jiang 2020 32	China	Cohort	67.5	66	73.2%	57.7%	49	82	165	267	ICU patients	7
Shi 2023 11	China	Cohort	>65 48.9%	>65 32.7%	51.2%	47.6%	23	43	133	370	Surgical patients	6
Ramalho 2023 21	Brazil	Cohort	71.9	61.2	77.2%	77.7%	122	202	233	466	COVID‐19	6
Tayyib 2016 31	Saudi Arabia	Cohort	65.45	NR	54.5%	74.5%	20	33	26	51	ICU patients	6

Abbreviations: ICU, intensive care unit; NOS, Newcastle–Ottawa Scale; NR, not reported; PU, pressure ulcers; USA, United States of America.

3.3. Association between hypertension and PU

A total of 19 studies with the sample size of 564 716 were included. Heterogeneity assessment showed significantly statistical heterogeneity among the 19 studies (I ² = 81%, p < 0.00001), so we selected the random‐effects model to perform meta‐analysis. Pooled result from meta‐analysis showed that there was no significantly statistical association between hypertension and the risk of PU (OR = 1.15, 95% CI = 0.90–1.47, p = 0.27, Figure 2). ¹⁰ , ¹¹ , ¹² , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ , ²¹ , ²² , ²³ , ²⁴ , ²⁵ , ²⁶ , ²⁷ , ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² Furthermore, as shown in Figure 3, the results of sensitivity analysis using the leave‐one‐out strategy showed that the pooled result of the current meta‐analysis was robust.

FIGURE 2.

Forest plot for association between hypertension and PU.

FIGURE 3.

Sensitivity analysis on the association between hypertension and PU.

3.4. Subgroup analysis

To detect the source of heterogeneity that affects the pooled effect size of association between hypertension and PU, subgroup analyses were performed on patient source, research design and primary disease (Table 2). In the subgroup analysis of patient source, the meta‐analysis results indicated no significant association between hypertension and PU in Asia group (OR = 1.12, 95% CI = 0.83–1.50, I ² = 63%, p = 0.46) ¹¹ , ¹² , ¹⁷ , ²⁰ , ²² , ²⁴ , ²⁵ , ²⁷ , ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² and Non‐Asia group (OR = 1.20, 95% CI = 0.75–1.94, I ² = 88%, p = 0.45). ¹⁰ , ¹⁸ , ¹⁹ , ²¹ , ²³ , ²⁶ In the subgroup analysis of study design, the results also showed no significant association between hypertension and PU in cohort study (OR = 1.16, 95% CI = 0.84–1.61, I ² = 63%, p = 0.36) ¹⁰ , ¹¹ , ¹⁷ , ²¹ , ²² , ²⁷ , ²⁸ , ³¹ , ³² and case–control study (OR = 1.14, 95% CI = 0.79–1.64, I ² = 82%, p = 0.49). ¹² , ¹⁸ , ¹⁹ , ²⁰ , ²³ , ²⁴ , ²⁵ , ²⁶ , ²⁹ , ³⁰ Due to the primary disease difference, subgroup analysis was performed based on primary disease, and the results showed that there was a significant association between hypertension and PU in COVID‐19 patients(OR = 1.73, 95% CI = 1.35–2.22, I ² = 0%, p < 0.0001), ¹⁰ , ²¹ , ²⁶ whereas no association was found in stroke patients(OR = 0.80, 95% CI = 0.29–2.18, I ² = 72%, p = 0.66), ²⁴ , ³⁰ geriatric disease (OR = 1.32, 95% CI = 0.78–2.24, I ² = 0%, p = 0.30), ²⁰ , ²³ , ²⁸ ICU patients(OR = 0.89, 95% CI = 0.56–1.42, I ² = 61%, p = 0.62) ¹⁷ , ²² , ³¹ , ³² and surgical patients (OR = 1.10, 95% CI = 0.70–1.73, I ² = 82%, p = 0.68). ¹¹ , ¹² , ¹⁸ , ¹⁹ , ²⁵ , ²⁷ , ²⁹ The impact of heterogeneity slightly decreased for the subgroup of primary disease, which indicated that primary disease might be the source of heterogeneity.

TABLE 2.

Subgroup metanalyses of the association between hypertension and PU by study variables.

	Number of studies	OR (95% CI)	I 2 for heterogeneity (%)	p value for heterogeneity
Patient source
Asia	13	1.12 (0.83–1.50)	63	0.001
Non‐Asia	6	1.20 (0.75–1.94)	88	0.00001
Study design
Cohort	9	1.16 (0.84–1.61)	63	0.006
Case–control	10	1.14 (0.79–1.64)	82	0.00001
Primary disease
Stroke	2	0.80 (0.29–2.18)	72	0.06
COVID‐19	3	1.73 (1.35–2.22)	0	0.45
Geriatric disease	3	1.32 (0.78–2.24)	0	0.59
ICU patients	4	0.89 (0.56–1.42)	61	0.05
Surgical disease	7	1.10 (0.70–1.73)	82	0.00001

Abbreviations: CI, confidence intervals; OR, odds ratios.

3.5. Publication bias

A funnel plot was evaluated for all 19 studies, and the result suggests the possibility of a visual bias in publishing (Figure 4). Egger’ test detected statistically significant publication bias (p = 0.008). However, the trim‐and‐fill method indicated no missing studies (Figure 5).

FIGURE 4.

Funnel plot for association between hypertension and PU.

FIGURE 5.

Funnel plot adjusted with trim‐and‐fill methods for association between hypertension and PU.

4. DISCUSSION

Our meta‐analysis comprised 19 articles that met the eligibility criteria and included a total of 564 716 participants. The pooled results indicated that there was no significant association found between hypertension and PU. However, when we conducted a subgroup analysis based on the primary disease, we found a significant association between hypertension and PU in patients with COVID‐19. This means that COVID‐19 patients who have hypertension are more likely to develop PU than those without hypertension.

To the best of our knowledge, this is the first meta‐analysis to systematically assess the association between hypertension and PU. Previous study had shown an inverse association between hypertension and PU, ¹³ while several studies have observed no association, ²² , ²⁵ , ²⁷ the other evidence even suggests that hypertension is a risk factor of PU. ¹⁰ , ¹¹ , ¹² The overall result of our meta‐analysis indicates no association between hypertension and PU, the preliminary conclusion that we draw can provide clinicians with some references for prevention of PU. In the subgroup analysis for primary disease, we further found COVID‐19 patients with hypertension is at higher risk of PU than these without hypertension, this may have been an important source of heterogeneity among these studies, the further conclusion remained that we should pay great attention to prevent PU among COVID‐19 patients with hypertension. Currently, there are not many studies about the association between hypertension and PU among COVID‐19 patients, the pathophysiological mechanism underlying the relationship between hypertension and PU among COVID‐19 patients is still uncertain. In a recent retrospective cohort study in Iran, Alamdari ³³ found that PU were observed significantly more in metabolic syndrome group (including hypertension) compared with non‐metabolic syndrome group among COVID‐19 patients. Additionally, in a recent meta‐analysis about COVID‐19 and PU, Adrienn ³⁴ suggested that both intrinsic factors (e.g, comorbidities, including hypertension) and extrinsic factors can further increase the risk of Hospital‐Acquired Pressure Injuries for patients with COVID‐19. Due to the uneven approach to testing, the reviews do not give qualitative conclusions; however, the results indirectly support our findings. On one hand, hypertension was shown by several studies as the most common comorbidity of cardiovascular disease, and it seemed to significantly increase the risk of severity and death in patients with COVID‐19, ³⁵ , ³⁶ , ³⁷ the reason for which was possibly due to the proinflammatory state of this chronic illness in addition to the hypercytokinaemia that occurs in COVID‐19. ³⁸ On the other hand, in another retrospective cohort study in Brazil, Oliveira ³⁹ found that the incidence of PU was significantly higher in COVID‐19 patients compared with non‐COVID‐19, it may mainly due to hypoxemia, inflammatory status and vasculopathy. Hypertension eventually leads to the occurrence of PU through aggravating the progression of COVID‐19 and its effect to blood circulation, which result in higher risk of PU among COVID‐19 patients with hypertension, and this may be one of the potential pathways that hypertension interacts with PU. Of course, this speculation and the specific mechanism in these processes needs to be confirmed by further investigations.

However, it is still important to recognize the limitations of the current meta‐analysis when interpreting its results. First, a limited number of studies were included, and the quality of the included studies varied widely, which have a great impact on the results and may affect the reliability of the meta‐analysis. Second, this review did not assess the severity of PU, grade of hypertension, use of antihypertensive drug and control of blood pressure due to the lack of detailed information, which may lead the omission of some subgroup analysis results, and even cause different results. Third, since only English articles were included in the literature search, there might be a language bias.

5. CONCLUSION

Based on the current evidence, we conclude that there is no significantly statistical association between hypertension and the occurrence of PU in most cases, while the risk of PU significantly elevates among COVID‐19 patients combined with hypertension regardless of patient source and study design. However, considering the extremely limited quality of included studies, more researches of higher quality are needed to confirm these conclusions, as well as to further improve personal health and decrease the economic burden.

FUNDING INFORMATION

There was no source of funding for this systematic review study.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

ETHICS STATEMENT

Not applicable.

Supporting information

Supplementary material 1.

Supplementary material 2.

Huang Y, Zhou W, Du H. Association between hypertension and pressure ulcer: A systematic review and meta‐analysis. Int Wound J. 2024;21(3):e14829. doi: 10.1111/iwj.14829

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.