Mechanisms underlying the J-curve for diastolic blood pressure: Subclinical myocardial injury and immune activation

Abstract

Background: Low diastolic blood pressure (DBP) is associated with increased risk of cardiovascular events. In patients with coronary artery disease (CAD), limitations in coronary blood flow and immune activity are implicated mechanisms, but evidence is lacking. We investigated the association between DBP, biomarkers of myocardial injury, inflammation, immune activation and incident events in patients with CAD.

Methods: We studied 2448 adults (mean age 65 ± 12 years, 68% male, median follow-up 4.5 years) with CAD. DBP was categorized into 10 mm Hg increments. Biomarkers of myocardial injury (high sensitivity cardiac troponin-I [hs-cTnI]) and immune activity/inflammation (soluble urokinase plasminogen activator receptor [suPAR]) were dichotomized at their median values. DBP 70-79 mm Hg was used as the referent group, and individuals were followed prospectively for adverse outcomes.

Results: After adjusting for demographic and clinical covariates, individuals with DBP < 60 mm Hg had increased odds of elevated levels of hs-cTnI (OR = 1.68; 95% CI = 1.07, 2.65) and suPAR (OR = 1.71; 95% CI = 1.10, 2.65) compared to the referent group. Additionally, DBP < 60 mm Hg was associated with increased adjusted risk of cardiovascular death or MI (HR = 2.04; 95% CI = 1.32, 3.16) and all-cause mortality (HR = 2.41; 95% CI = 1.69, 3.45).

Conclusion: In patients with CAD, DBP < 60 mm Hg is associated with subclinical myocardial injury, immune/inflammatory dysregulation and incident events. Aggressive BP control may be harmful in these patients, and further investigation is warranted to determine appropriate BP targets in patients with CAD.

Keywords: Blood pressure; Coronary artery disease; High-sensitivity troponin; J-curve; Soluble urokinase plasminogen activator receptor.

Figure 1.. Association between diastolic blood pressure and biomarkers of myocardial injury.

Restricted cubic spline regression with 4 knots modeling odds ratio estimates for (A) hscTnI >5 pg/mL and (B) suPAR >3 ng/mL along a continuous spectrum for diastolic blood pressure (DBP) from the 1^st to the 99^th percentile of DBP. Dotted lines and shaded areas represent the 95% confidence interval. Histograms of the distribution of DBP are presented below each spline. Models are adjusted for age, race, sex, body mass index, systolic blood pressure, smoking, hyperlipidemia, heart failure with preserved ejection fraction, diabetes, ACEi/ARB use, beta blocker use, statin use, aspirin use, and estimated eGFR. Models for suPAR are additionally adjusted for white blood cell count.

Figure 2.. Association between diastolic blood pressure and incident events.

Restricted cubic spline regression with 4 knots modeling hazard ratio estimates for (A) all-cause death and (B) cardiovascular death or non-fatal MI along a continuous spectrum for DBP, from the 1^st to the 99^th percentile of DBP. Dotted lines and shaded areas represent the 95% confidence interval. Histograms of the distribution of DBP are presented below each spline. Models are adjusted for age, race, sex, body mass index, systolic blood pressure, smoking, hyperlipidemia, heart failure with preserved ejection fraction, diabetes, ACEi/ARB use, beta blocker use, statin use, aspirin use, and estimated eGFR.