Tracking of high-sensitivity C-reactive protein after an initially elevated concentration: the JUPITER Study
Robert J Glynn1, Jean G MacFadyen, Paul M Ridker
1Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. rglynn@rics.bwh.harvard.edu
Insights
High-sensitivity C-reactive protein (hsCRP) levels demonstrate strong tracking in individuals, indicating that elevated hsCRP concentrations generally persist over time without statin intervention.
Area of Science:
- Cardiovascular Medicine
- Biomarker Research
- Preventive Cardiology
Background:
- The JUPITER trial indicated high-sensitivity C-reactive protein (hsCRP) utility in statin therapy decisions for primary vascular disease prevention.
- Previous studies suggested hsCRP as a reliable longitudinal marker, but its tracking consistency after an initial elevation was uncertain.
Purpose of the Study:
- To evaluate the longitudinal tracking of hsCRP concentrations in individuals with initially elevated hsCRP levels who did not receive statin therapy.
- To compare the tracking of hsCRP with other cardiovascular risk factors like blood pressure and lipid profiles.
Main Methods:
- Analysis of hsCRP tracking in 8901 JUPITER trial participants randomized to placebo, with hsCRP measured at multiple time points over 4 years.
- Nonparametric evaluation of longitudinal trends using box plots and Spearman correlations.
- Repeated-measures regression models to estimate intraclass correlation of hsCRP, with and without covariate adjustment.
Main Results:
- Median hsCRP showed modest regression to the mean, decreasing from 3.8 mg/L to 3.4 mg/L over 4 years.
- hsCRP tracking correlations were comparable to blood pressure and LDL cholesterol, but lower than HDL, triglycerides, and total cholesterol.
- Intraclass correlation for hsCRP was 0.54 (unadjusted) and 0.50 (adjusted), indicating strong tracking.
Conclusions:
- Elevated hsCRP concentrations exhibit strong tracking in individuals, even after initial selection for high values.
- In the absence of statin therapy, persistently high hsCRP levels are generally observed over time.
Background:
The JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) trial suggests that increased high-sensitivity C-reactive protein (hsCRP) concentrations may be useful in decisions about the initiation of statin therapy for primary prevention of vascular disease. Although studies of specific populations have suggested that hsCRP is a reliable longitudinal marker, it is unclear how strongly hsCRP tracks in individuals after a single increased concentration.
Methods:
We evaluated tracking of hsCRP in 8901 individuals randomized to placebo in the JUPITER trial. These individuals had screening LDL cholesterol concentrations <130 mg/dL (<3.37 mmol/L) and hsCRP concentrations > or =2 mg/L, with subsequent hsCRP measurements made before randomization; at 13 weeks; 1, 2, 3, and 4 years later; and at trial termination. Longitudinal trends and associations were evaluated nonparametrically with box plots and Spearman correlations. After data transformation to achieve normality, repeated-measures regression models estimated the intraclass correlation of hsCRP, with and without controlling for known demographic, lifestyle, and medical determinants of hsCRP concentration. For comparison, we evaluated tracking of systolic and diastolic blood pressure; total, LDL, and HDL cholesterol; and fasting triglycerides.
Results:
The median hsCRP concentration in these untreated individuals showed modest regression to the mean over time, declining from 3.8 mg/L at randomization to 3.4 mg/L at 4 years. Tracking correlations for hsCRP over time were comparable to those for blood pressure and LDL cholesterol, but lower than those for HDL, fasting triglycerides, and total cholesterol. The intraclass correlation for repeated hsCRP measurements was 0.54 (95% CI, 0.53-0.55) without covariate adjustment and 0.50 (95% CI, 0.49-0.51) after adjustment for demographic, lifestyle, and comorbidity determinants.
Conclusions:
Concentrations of hsCRP show strong tracking, even after selection of individuals with initially high values. Without statin therapy, increased concentrations of hsCRP generally remain high over time.
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