Higher blood pressure may have a protective effect against the development of pathological scars, including keloids and hypertrophic scars, according to new findings that challenge previous research.
The study, published in Frontiers in Medicine, utilized genetic variants as instrumental variables to explore the causal relationship between blood pressure and pathological scars.
The researchers employed a two-sample Mendelian randomization design, utilizing genome-wide association study data from large-scale meta-analyses. For blood pressure-related events, data were obtained from a meta-analysis of 810,865 individuals of European ancestry. Hypertension data came from the UK Biobank. Keloid data were derived from a meta-analysis including 668 keloid patients and 481,244 controls of European descent. Hypertrophic scar data were from the FinnGen database, comprising 766 patients and 207,482 controls.
Instrumental variables were selected using stringent criteria, including a genome-wide significance threshold of P < 1.0 × 10^–8 for blood pressure–related events and P < 5.0 × 10^–6 for pathological scars. Linkage disequilibrium pruning was performed with a threshold of r^2 < 0.001 and a window size of 10,000 kb.
The primary analysis employed the inverse-variance weighted method, supplemented by weighted median and MR-Egger methods. Heterogeneity was assessed using Cochran's Q statistics, and horizontal pleiotropy was evaluated using MR-Egger intercept and MR-PRESSO global tests.
Reverse Mendelian randomization analysis and Steiger's directionality test were conducted to assess potential reverse causality. Results consistently indicated no significant reverse causal relationship between hypertension and pathological scars.
Key findings included:
- Diastolic blood pressure: Odds ratio (OR) per standard deviation increase = 0.67 (95% Confidence Interval [CI] = 0.49–0.99) for keloids
- Systolic blood pressure: OR per standard deviation increase = 0.66 (95% CI = 0.46–0.93) for keloids
- Hypertension: Pooled OR = 0.39 (95% CI = 0.18–0.85) for keloids
- Hypertension: Pooled OR = 0.31 (95% CI = 0.11–0.89) for hypertrophic scars
The study's findings contradicted previous research suggesting that hypertension promoted pathological scar formation through mechanisms such as extracellular matrix imbalance, inflammation-induced hypoxia, and elevated angiotensin II levels. The researchers hypothesized that slight increases in blood pressure may enhance blood flow in certain areas, potentially boosting oxygen supply and influencing wound healing.
However, the researchers acknowledged several limitations of their study, including that the results were not consistent across all Mendelian randomization methods, unrecognized confounders could not be completely eliminated, and there was potential sample overlap between keloid and hypertension-related event data in the meta-analysis. Further, proposed hypotheses had not been validated through basic experimental studies and GWAS data were derived solely from individuals of European ancestry, limiting generalizability.
The researchers noted the study aimed to provide a fresh perspective on the complex relationship between blood pressure, wound healing, and pathological scarring rather than overturn previous findings. They suggested that further research may be needed to confirm these results and explore potential clinical implications for blood pressure management in patients at risk of pathological scarring.
The study authors declared the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.