Coronary Artery Disease
Relationship Between Serum Low-Density Lipoprotein Cholesterol and In-hospital Mortality Following Acute Myocardial Infarction (The Lipid Paradox)

https://doi.org/10.1016/j.amjcard.2014.12.006Get rights and content

Lipoprotein levels are currently recognized as independent risk factors for long-term cardiovascular events after acute myocardial infarction (AMI). During the acute-phase reaction after AMI, previous studies have reported trends of decreased low-density lipoprotein cholesterol (LDL-C), increased triglycerides, and variable high-density lipoprotein cholesterol (HDL-C) levels. However, the association between LDL-C and HDL-C levels and in-hospital mortality has not been well established following AMI. The relationship between lipid levels and in-hospital all-cause mortality in 115,492 patients hospitalized for AMI (July 2002 to December 2006), registered in the National Registry of Myocardial Infarction (NRMI) 4b–5, was evaluated using multivariable-adjusted logistic regression models. Mean LDL-C was 104 ± 38, HDL-C was 41 ± 14, and triglycerides 143 ± 83 mg/dl. Compared with the lowest quartile of LDL-C (<77 mg/dl), the risk of in-hospital mortality in the second to fourth quartiles was decreased (adjusted odds ratio 0.79, 0.80, and 0.85, respectively). For HDL-C, only those in the lowest quartile (<31 mg/dl) had higher risk of in-hospital mortality (odds ratio 1.20) compared with the highest quartile (≥47 mg/dl). Results from NRMI 4b–5 suggest a lipid paradox, with lower LDL-C levels associated with increased risk of in-hospital mortality, contrary to findings outside the acute setting. Consistent with previous analyses, lowest HDL-C levels were associated with increased in-hospital mortality. In conclusion, further explorations of the relationship between very low levels of LDL-C, myocardial necrosis, and subsequent adverse cardiovascular events are warranted.

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Methods

NRMI (a prospective, observational study of AMI hospitalizations in the United States from 1990 to 2006, including more than 2,100 hospital sites and 2.5 million patients records; in-hospital data only were collected with no postdischarge records) served as the data source.5 NRMI has been described in detail previously.6, 7 Records from the NRMI 4b–5 cohort were considered, including 404,830 patients presenting with AMI from 836 hospitals from July 2002 to December 2006. Patients were excluded

Results

Baseline characteristics are summarized in Table 1. LDL-C levels were fairly normally distributed (Figure 2). Compared with the Adult Treatment Panel III guideline targets for high-risk and very high-risk patients,8 more than half in this cohort had LDL-C levels above the 100 mg/dl target and >75% were above the more aggressive goal of 70 mg/dl, respectively (Figure 2). The reference group used for the LDL-C regression analysis was the lowest LDL-C quartile (<77 mg/dl) because it represents

Discussion

To date, this is the largest known cohort evaluated for the relation between in-hospital plasma lipid levels and in-hospital CV outcomes following admission for AMI. The LDL-C results were unexpected, indicating that the lowest levels of LDL-C are associated with highest risk of in-patient mortality following AMI. The relationship between post-AMI LDL-C levels and in-hospital mortality was not linear, with levels in the second and third quartiles associated with slightly decreased risk compared

Acknowledgment

Editorial support, from concept for the writing of the manuscript and preparation of the manuscript for submission, was provided by Saira Ansari, PhD, MediTech Media, United Kingdom, funded by F. Hoffmann-La Roche AG.

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