The Association Between Blood Pressure and Coronary Plaque Morphology

Technical Summary: The Association Between Blood Pressure and Coronary Plaque Morphology

Problem Statement
Hypertension is a well-established major determinant of coronary artery disease (CAD), contributing to vascular injury through sustained mechanical and biochemical stress. While the link between elevated blood pressure (BP) and coronary artery calcification (CAC) is recognized in macroscopic studies using computed tomography (CT), the microscopic structural consequences of BP elevation within coronary plaques remain poorly understood. Specifically, the relationship between BP parameters (systolic and diastolic) and detailed plaque morphology—particularly features of plaque vulnerability such as thin-cap fibroatheroma (TCFA) and lipid-rich plaques—has not been thoroughly investigated. This study addresses the gap in understanding how hypertension influences the microstructural composition of coronary plaques as visualized by optical coherence tomography (OCT).

Methodology
This was a retrospective, multicenter, cross-sectional study conducted across five institutions in Japan. The study enrolled 293 patients who underwent OCT-guided percutaneous coronary intervention (PCI) between August 2019 and September 2024. Patients with in-stent restenosis, poor OCT image quality, or those on hemodialysis were excluded.

• Data Collection: Clinical data and OCT images were extracted from the "Yamagata OCT Registry." Blood pressure was measured in the supine position prior to PCI.
• Categorization: Patients were stratified by hypertension stage (Normotensive, Stage 1, Stage 2) and by tertiles of systolic blood pressure (SBP) and diastolic blood pressure (DBP).
• OCT Analysis: Three independent investigators, blinded to clinical data, performed qualitative and quantitative assessments. Key metrics included:
  • Qualitative: Presence of TCFA, lipid-rich plaque, macrophage accumulation, microvessels, cholesterol crystals, layered plaque, thrombus, and ruptured plaque.
  • Quantitative: Maximal lipid arc, maximal calcification arc, lipid index, calcium index, layer index, minimum lumen area (MLA), and percent area stenosis.
• Statistical Analysis: Associations between BP parameters and OCT findings were assessed using multivariable generalized linear models, adjusting for confounders including age, sex, clinical presentation (ACS vs. CCS), comorbidities (diabetes, atrial fibrillation, anemia), and medication use.

Key Results
The study population had a median age of 70 years, with 80.2% male. The median SBP was 130 mmHg and DBP was 76 mmHg.

1. Association with Calcification:

   • Hypertension Stage: There was a significant positive trend between hypertension stage and the maximal calcification arc (Normotensive: 69° vs. Stage 1: 110° vs. Stage 2: 144°; p for trend < 0.001). Similarly, the proportion of lesions with a calcium score ≥ 3 increased with hypertension stage.
   • SBP and DBP: Both SBP and DBP were significantly associated with a greater maximal calcification arc and higher calcium scores. In multivariable analysis, each tertile increment in SBP and DBP remained significantly associated with increased maximal calcification arc after adjustment.
   • Clinical Presentation: The association between BP and coronary calcification was more pronounced in patients presenting with Acute Coronary Syndrome (ACS) compared to those with Chronic Coronary Syndrome (CCS).

2. Lack of Association with Plaque Vulnerability:

   • Contrary to the findings for calcification, BP parameters were not consistently associated with OCT-defined features of plaque vulnerability.
   • While the prevalence of lipid-rich plaques and ruptured plaques decreased in higher hypertension stages, there was no significant association between BP and the presence of TCFA or macrophage accumulation in the multivariable models.
   • The maximal lipid arc was inversely correlated with SBP, but this did not translate to a consistent association with vulnerable plaque features.

3. Specific Findings:

   • In the ACS subgroup, SBP was associated with smaller minimum lumen area and greater percent area stenosis, whereas these associations were not evident in CCS.
   • DBP was associated with the maximal calcium arc only in the ACS subgroup.

Significance and Claims
The paper claims that elevated blood pressure is specifically reflected in the extent of coronary calcification at the microstructural level, rather than in the features typically associated with plaque vulnerability (such as TCFA or lipid-rich cores).

• Microstructural Insight: The study suggests that BP-related hemodynamic stress preferentially contributes to calcific plaque remodeling. This supports the concept that coronary calcification serves as an imaging marker for cumulative BP burden, even at a microscopic level.
• Clinical Implications: The findings highlight that even Stage 1 hypertension is associated with measurable calcific changes, reinforcing the importance of early and rigorous BP control.
• Mechanistic Context: The authors propose that sustained mechanical stress from elevated BP may induce endothelial dysfunction and oxidative injury, triggering the phenotypic modulation of vascular smooth muscle cells toward osteoblastic states, thereby promoting calcification without necessarily enhancing the formation of vulnerable, rupture-prone plaques.
• Limitations: The authors acknowledge that the retrospective, cross-sectional design precludes causal inference. Additionally, the reliance on a single BP measurement, the predominance of Japanese patients, and the exclusion of biomarkers for mineral metabolism limit the generalizability and depth of mechanistic exploration.

In conclusion, the study establishes a robust link between blood pressure parameters and the degree of coronary calcification visualized by OCT, while finding no significant evidence that BP directly drives the specific morphological features of plaque vulnerability in this cohort.