Neutrophil lymphocyte ratio significantly improves the Framingham risk score in prediction of coronary heart disease mortality: Insights from the National Health and Nutrition Examination Survey-III
Introduction
Cardiovascular disease is the leading cause of death in United States. Statistics from 2009 show nearly 600,000 annual deaths due to cardiovascular disease, out of which 385,000 deaths were due to coronary heart disease (CHD) [1]. The annual cost attributed to CHD in US is around $109 billion [1]. CHD has a long latent period during which the subjects remain asymptomatic. In order to reduce the burden of CHD, an important step is to institute appropriate primary prevention measures in asymptomatic, apparently healthy population at risk. Traditional risk assessment strategies for CHD like the Framingham risk score (FRS) rely on markers like age, sex, hypertension, diabetes, hyperlipidemia and smoking. Unfortunately, conventional risk prediction models like FRS often fail to identify a considerable proportion of individuals at risk of developing CHD. Almost half of individuals who develop CHD have only 1 or none of these traditional risk factors [2], [3]. Hence there is a need to improve the currently existing risk assessment models for more accurate prediction of CHD risk, so that targeted preventive measures can be instituted.
The 2010 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines [4] recommend that initially global risk scores like FRS should be applied to all asymptomatic individuals for risk assessment. Persons at low risk do not need any further testing. Persons at high risk should be subjected to intensive preventive measures. Persons at intermediate risk may be considered to undergo further stratification by using either serum or radiologic markers, as long as these tests are cost effective [4]. The serum markers proposed by ACCF/AHA [4] include C-reactive protein (CRP), brain natriuretic peptide (BNP), hemoglobin A1c and lipoprotein associated phospholipase A2. The role of neutrophil lymphocyte ratio (NLR) as a biomarker for CHD in asymptomatic individuals is not clear. NLR is a simple ratio of the absolute neutrophil and lymphocyte counts obtained on the differential section of leukocyte count of a complete blood count (CBC) and is a marker of inflammation. NLR has been shown to be associated with worse outcomes in patients with acute coronary syndromes and established CHD [5], [6], [7], [8], [9], [10], [11], [12]. However, there is a lack of data regarding its role in healthy individuals free from CHD at baseline. We sought to study the value of NLR to predict CHD related mortality in the National Health and Nutrition Examination Survey-III (NHANES-III) cohort which is representative of a healthy US general population cohort.
Section snippets
Study sample and design
NHANES-III, conducted by the National Center for Health Statistics, includes data from oral surveys and general health examinations. It was designed to assess the demographic, socioeconomic, dietary and overall health status of a representative sample from all 50 States. Of the individuals selected to participate, 30,818 subjects (with 19,215 adults ≥ 18 years age) completed the health examination [13].
Our study inclusion criteria were subjects aged 30–79 years who did not have a history of
Results
We included 7363 subjects, who took part in NHANES-III from 1988 to 1994. This was representative of 89,80,0451 (almost 9 million) US general population. The mean follow up period was 14.1 ± 3.2 years. The number of CHD related deaths over this period was 231 (3.14%), signifying overall low risk in the population.
Discussion
Our study showed that neutrophil lymphocyte ratio (NLR) is an independent predictor of cardiovascular mortality in a nationally representative general population cohort. Moreover, NLR accurately reclassified those in the intermediate risk category of the Framingham Risk Score (FRS) as having lower or higher probability of cardiovascular mortality. NLR has been shown to be predictive of all cause and cardiovascular mortality in patients with acute coronary syndromes (ACS) [5], [6], [7], [8], [9]
Conclusions
NLR is a potential independent predictor of CHD mortality in a cross sectional US population. Adding NLR to the Framingham risk score model marginally improves model discrimination and significantly improves model calibration. There is significantly better reclassification of individuals in intermediate risk category of FRS with NRI of 10.1% and upward reclassification of 5.6%. NLR fulfills the criteria to be considered as a biomarker for predicting future CHD risk in asymptomatic, apparently
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