Dataset Information

Circulating PCSK9 Level and Risk of Cardiovascular Events and Death in Hemodialysis Patients.

ABSTRACT: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for the prevention of cardiovascular (CV) events. However, the clinical significance of circulating PCSK9 is unclear in hemodialysis (HD) patients. A total of 353 HD patients were prospectively enrolled from June 2016 to August 2019 in a K-cohort. Plasma PCSK9 level was measured at the time of study enrollment. The primary endpoint was defined as a composite of CV event and death. Plasma PCSK9 level was positively correlated with total cholesterol level in patients with statin treatment. Multivariate linear regression analysis revealed that baseline serum glucose, albumin, total cholesterol, and statin treatment were independent determinants of circulating PCSK9 levels. Cumulative rates of composite and CV events were significantly higher in patients with tertile 3 PCSK9 (p = 0.017 and p = 0.010, respectively). In multivariate Cox-regression analysis, PCSK9 tertile 3 was associated with a 1.97-fold risk of composite events (95% CI, 1.13-3.45), and it was associated with a 2.31-fold risk of CV events (95% CI, 1.17-4.59). In conclusion, a higher circulating PCSK9 level was independently associated with incident CV events and death in HD patients. These results suggest the importance of future studies regarding the effect of PCSK9 inhibition.

SUBMITTER: Hwang HS

PROVIDER: S-EPMC7019341 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Circulating PCSK9 Level and Risk of Cardiovascular Events and Death in Hemodialysis Patients.

Hwang Hyeon Seok HS Kim Jin Sug JS Kim Yang Gyun YG Lee So-Young SY Ahn Shin Young SY Lee Hong Joo HJ Lee Dong-Young DY Lee Sang Ho SH Moon Ju Young JY Jeong Kyung Hwan KH

Journal of clinical medicine 20200117 1

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for the prevention of cardiovascular (CV) events. However, the clinical significance of circulating PCSK9 is unclear in hemodialysis (HD) patients. A total of 353 HD patients were prospectively enrolled from June 2016 to August 2019 in a K-cohort. Plasma PCSK9 level was measured at the time of study enrollment. The primary endpoint was defined as a composite of CV event and death. Plasma PCSK9 level was positively co ...[more]

PMID: 31963408

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Project description:Background Beyond the controlled setting of trials, scarce information exists on the burden, predictors, and outcomes associated with elevated hs CRP (high-sensitivity C-reactive protein) in "real-world" patients with myocardial infarction ( MI ). Methods and Results We included all-coming MI survivors undergoing hs CRP testing >30 days after an MI during routine health care in Stockholm, Sweden (2006-2011). hs CRP tests measured during hospitalization/emergency department visits, followed by antibiotics or indicative of acute illness, were excluded, together with patients with ongoing/recent cancer, chronic infections, or immunosuppression. Inflammation was defined over a 3-month baseline window and associated with subsequent death and major adverse cardiovascular events (composite of MI, ischemic stroke, or cardiovascular death). Included were 17 464 patients (63% men; mean age, 72.6 years) with a median hs CRP level of 2.2 (interquartile range, 1.0-6.0) mg/L and a median of 2.2 (interquartile range, 0.8-4.9) years since their MI . Most (66%) had hs CRP ≥2 mg/L, and 40% had hs CRP >3 mg/L. Lower hemoglobin, lower estimated glomerular filtration rate, and comorbidities (eg, heart failure, peripheral vascular disease, stroke, atrial fibrillation, diabetes mellitus, and rheumatoid diseases) were associated with higher odds of hs CRP ≥2 mg/L. Conversely, previous percutaneous coronary intervention, ongoing renin-angiotensin blockade, and statins were associated with lower hs CRP ≥2 mg/L odds. Patients with hs CRP ≥2 mg/L were at higher risk of major adverse cardiovascular events (n=3900; adjusted hazard ratio, 1.28; 95% CI, 1.18-1.38) and death (n=4138; adjusted hazard ratio, 1.42; 95% CI, 1.31-1.53). Results were robust across subgroups of patients and after exclusion of events occurring during the first 6 to 12 months. On a continuous scale, the association between hs CRP and outcomes was linear until hs CRP >5 mg/L, plateauing thereafter. Conclusions Most patients with MI exhibit elevated hs CRP levels. Besides identifying populations at high-inflammatory risk, this study extends the prognostic validity of this biomarker from trial evidence to real-world healthcare settings.

Project description:Background and objectivesParathyroid hormone, calcium, and phosphate have been independently associated with cardiovascular event risk. Because these parameters may be on the same causal pathway and have been proposed as quality measures, an integrated approach to estimating event risks is needed.Design, setting, participants, & measurementsPrevalent dialysis patients were followed from August 31, 2005 to December 31, 2006. A two-stage modeling approach was used. First, the 16-month probabilities of death and composite end point of death or cardiovascular hospitalization were estimated and adjusted for potential confounders. Second, patients were categorized into 1 of 36 possible phenotypes using average parathyroid hormone, calcium, and phosphate values over a 4-month baseline period. Associations among phenotypes and outcomes were estimated and adjusted for the underlying event risk estimated from the first model stage.ResultsOf 26,221 patients, 98.5% of patients were in 22 groups with at least 100 patients and 20% of patients were in the reference group defined using guideline-based reference ranges for parathyroid hormone, calcium, and phosphate. Within the 22 most common phenotypes, 20% of patients were in groups with significantly (P<0.05) higher risk of death and 54% of patients were in groups with significantly higher risk of the composite end point relative to the in-target reference group. Increased risks ranged from 15% to 47% for death and from 8% to 55% for the composite. More than 40% of all patients were in the three largest groups with elevated composite end point risk (high parathyroid hormone, target calcium, and high phosphate; target high parathyroid hormone, target calcium, and high phosphate; and target high parathyroid hormone, target calcium, and target phosphate).ConclusionAfter adjusting for baseline risk, phenotypes defined by categories of parathyroid hormone, calcium, and phosphate identify patients at higher risk of death and cardiovascular hospitalization. Identifying common high-risk phenotypes may inform clinical interventions and policies related to quality of care.

Dataset Information

Circulating PCSK9 Level and Risk of Cardiovascular Events and Death in Hemodialysis Patients.

Publications

Circulating PCSK9 Level and Risk of Cardiovascular Events and Death in Hemodialysis Patients.

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