Association of apolipoprotein B and apolipoprotein A1 levels with social determinants of health and coronary artery disease mortality in the United Kingdom Biobank - is there a need for consideration?

BACKGROUND: A higher prevalence of cardiovascular risk factors has previously been shown to be associated with adverse social determinants of health (SDoH) and to explain some of their impact on cardiovascular risk. Whether there is a relationship between lipid parameters, specifically apolipoprotein B (apoB), apolipoprotein A1 (apoA1), their ratio (apoB/apoA1), and SDoH, and whether coronary artery disease (CAD) mortality risk associated with circulating apoB and apoA1 is modified by SDoH was unclear. METHODS: We investigated associations of apoA1, apoB, and apoB/apoA1 with the level of education and household income and their joint impact on CAD mortality in participants of the UK Biobank (UKB) with and without prevalent CAD at enrollment. Hazard ratios for CAD mortality were estimated after adjusting for SDoH and clinical covariates. RESULTS: In 292 804 participants without established CAD, apoB, and the apoB/apoA1 ratio were inversely associated with level of education and household income, whereas apoA1 was positively associated with household income. Adjustment for education level and household income coupled with the number of people living in the household did not attenuate the association between the apolipoprotein levels and incident CAD mortality rates. In a cohort of 13 826 participants with prevalent CAD, apoA1 levels were inversely associated with level of education. Higher apoB levels were only associated with greater CAD mortality risk after adjustment for risk factors. Risk estimation for CAD death through circulating apoA1 levels requires accounting for significant differences by sex. CONCLUSION: Circulating lipid parameters are associated with SDoH in individuals without CAD. CAD mortality risk estimation through apoA1 and apoB levels does not require accounting for SDoH.

Long-Term Outcomes in Patients With Chronic Total Occlusion.

Although a chronic total occlusion (CTO) in the setting of an acute coronary syndrome is associated with greater risk, the prognosis of patients with a CTO and stable coronary artery disease (CAD) remains unknown. This study aimed to investigate adverse event rates in patients with stable CAD with and without a CTO. In 3,597 patients with stable CAD (>50% coronary luminal stenosis) who underwent cardiac catheterization, all-cause mortality, cardiovascular mortality, and the composite major adverse cardiac event (MACE) rates for cardiovascular death, myocardial infarction, and heart failure hospitalization were evaluated. Cox proportional hazards and Fine and Gray subdistribution hazard models were used to compare event-free survival in patient subsets after adjustment for covariates. Event rates were higher in patients with CTOs than in those without CTOs after adjusting for demographic and clinical characteristics (cardiovascular death hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.05 to 1.57, p = 0.012). Patients with CTO revascularization had lower event rates than those of patients without CTO revascularization (cardiovascular death HR 0.43, CI 0.26 to 0.70, p = 0.001). Those with nonrevascularized CTOs were at particularly great risk when compared with those without CTO (cardiovascular death HR 1.52, CI 1.25 to 1.84, p <0.001). Moreover, those with revascularized CTOs had similar event rates to those of patients with CAD without CTOs. Patients with CTO have higher rates of adverse cardiovascular events than those of patients with significant CAD without CTO. This risk is greatest in patients with nonrevascularized CTO.

N terminal pro-brain natriuretic peptide level and benefits of chronic total occlusion revascularization.

BACKGROUND: The management of revascularization of chronic total occlusions (CTOs) remains controversial. Whether specific patients gain survival benefit from CTO revascularization remains unknown. OBJECTIVES: We investigated whether (i) patients with CTO have higher N terminal pro-brain natriuretic peptide (NT pro-BNP) levels than patients without CTO, (ii) in patients with CTO, NT pro-BNP levels predict adverse events, and (iii) those with elevated levels benefit from revascularization. METHODS: In 392 patients with stable, significant coronary artery disease (CAD) and CTO undergoing coronary angiography, rates of all-cause mortality, cardiovascular death, and a composite (cardiovascular death, myocardial infarction and heart failure hospitalizations) were investigated. Unadjusted and adjusted Cox proportional and Fine and Gray sub-distribution hazard models were performed to determine the association between NT pro-BNP levels and incident event rates in patients with CTO. RESULTS: NT pro-BNP levels were higher in patients with, compared to those without CTO (median 230.0 vs. 177.7 pg/mL, p ≤0.001). Every doubling of NT pro-BNP level in patients with CTO was associated with a > 25% higher rate of adverse events. 111 (28.5%) patients underwent CTO revascularization. In patients with elevated NT pro-BNP levels (> 125 pg/mL), those who underwent CTO revascularization had substantially lower adverse event rates compared to patients without CTO revascularization (adjusted cardiovascular death hazard ratio 0.29, 95% confidence interval (0.09-0.88). However, in patients with low NT pro-BNP levels (≤ 125 pg/mL), event rates were similar in those with and without CTO revascularization. CONCLUSION: NT pro-BNP levels can help identify individuals who may benefit from CTO revascularization.

Circulating Progenitor Cells and Coronary Collaterals in Chronic Total Occlusion.

BACKGROUND: The role of circulating progenitor cells (CPC) in collateral formation that occurs in the presence of chronic total occlusions (CTO) of a coronary artery is not well established. In stable patients with a CTO, we investigated whether CPC levels are associated with (a) collateral development and (b) ischemic burden, as measured by circulating high sensitivity troponin-I (hsTn-I) levels. METHODS: CPCs were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34 and both CD34 and CD133 epitopes. The association between CPC counts and both Rentrop collateral grade (0, 1, 2, or 3) and hsTn-I levels were evaluated using multivariate regression analysis, after adjusting for demographic and clinical characteristics. RESULTS: In 89 patients (age 65.5, 72% male, 27% Black), a higher CPC count was positively associated with a higher Rentrop collateral grade; [CD34+ adjusted odds ratio (OR) 1.49 95% confidence interval (CI) (0.95, 2.34) P = 0.082] and [CD34+/CD133+ OR 1.57 95% CI (1.05, 2.36) P = 0.028]. Every doubling of CPC counts was also associated with lower hsTn-I levels [CD34+ ß -0.35 95% CI (-0.49, -0.15) P = 0.002] and [CD34+/CD133+ ß -0.27 95% CI (-0.43, -0.08) P = 0.009] after adjustment. CONCLUSION: Individuals with higher CPC counts have greater collateral development and lower ischemic burden in the presence of a CTO.

Vitamin D Deficiency, Inflammation, and Diminished Endogenous Regenerative Capacity in Coronary Heart Disease.

Background: Vitamin D deficiency (VDD) is associated with coronary heart disease (CHD) and poor outcomes, but supplementation does not improve prognosis. VDD has been implicated in and may promote greater risk through inflammation and impaired progenitor cell function. Objectives: The authors examined VDD, high-sensitivity C-reactive protein (hsCRP), circulating progenitor cell (CPC) counts, and outcomes in patients with CHD. They hypothesized that the higher risk with VDD is mediated by inflammation and impaired regenerative capacity. Methods: A total of 5,452 individuals with CHD in the Emory Cardiovascular Biobank had measurement of 25-hydroxyvitamin D, subsets of whom had hsCRP measurements and CPCs estimated as CD34-expressing mononuclear cell counts. Findings were validated in an independent cohort. 25-hydroxyvitamin D <20 ng/mL was considered VDD. Cox and Fine-Gray models determined associations between marker levels and: 1) all-cause mortality; 2) cardiovascular mortality; and 3) major adverse cardiovascular events, a composite of adverse CHD outcomes. Results: VDD (43.6% of individuals) was associated with higher adjusted cardiovascular mortality (HR: 1.57, 95% CI: 1.09-2.28). There were significant interactions between VDD and hsCRP and CPC counts in predicting cardiovascular mortality. Individuals with both VDD and elevated hsCRP had the greatest risk (HR: 2.82, 95% CI: 2.16-3.67). Only individuals with both VDD and low CPC counts were at high risk (HR: 2.25, 95% CI: 1.46-3.46). These findings were reproduced in the validation cohort. Conclusions: VDD predicts adverse outcomes in CHD. Those with VDD, inflammation and/or diminished regenerative capacity are at a significantly greater risk of cardiovascular mortality. Whether targeted supplementation in these high-risk groups improves risk warrants further study.