C-reactive protein and parental history improve global cardiovascular risk prediction: the Reynolds Risk Score for men.
BACKGROUND
High-sensitivity C-reactive protein and family history are independently associated with future cardiovascular events and have been incorporated into risk prediction models for women (the Reynolds Risk Score for women); however, no cardiovascular risk prediction algorithm incorporating these variables currently exists for men.


RESULTS
Among 10 724 initially healthy American nondiabetic men who were followed up prospectively over a median period of 10.8 years, we compared the test characteristics of global model fit, discrimination, calibration, and reclassification in 2 prediction models for incident cardiovascular events, one based on age, blood pressure, smoking status, total cholesterol, and high-density lipoprotein cholesterol (traditional model) and the other based on these risk factors plus high-sensitivity C-reactive protein and parental history of myocardial infarction before age 60 years (Reynolds Risk Score for men). A total of 1294 cardiovascular events accrued during study follow-up. Compared with the traditional model, the Reynolds Risk Score had better global fit (likelihood ratio test P<0.001), a superior (lower) Bayes information criterion, and a larger C-index (P<0.001). For the end point of all cardiovascular events, the Reynolds Risk Score for men reclassified 17.8% (1904/10 724) of the study population (and 20.2% [1392/6884] of those at 5% to 20% 10-year risk) into higher- or lower-risk categories, with markedly improved accuracy among those reclassified. For this model comparison, the net reclassification index was 5.3%, and the clinical net reclassification index was 14.2% (both P<0.001). In models based on the Adult Treatment Panel III preferred end point of coronary heart disease and limited to men not taking lipid-lowering therapy, 16.7% of the study population (and 20.1% of those at 5% to 20% 10-year risk) were reclassified to higher- or lower-risk groups, again with significantly improved global fit, larger C-index (P<0.001), and markedly improved accuracy among those reclassified. For this model, the net reclassification index was 8.4% and the clinical net reclassification index was 15.8% (both P<0.001).


CONCLUSIONS
As previously shown in women, a prediction model in men that incorporates high-sensitivity C-reactive protein and parental history significantly improves global cardiovascular risk prediction.
Ridker
Paul M
PM
Donald W. Reynolds Center for Cardiovascular Research, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. pridker@partners.org
Paynter
Nina P
NP
Rifai
Nader
N
Gaziano
J Michael
JM
Cook
Nancy R
NR
D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology; D008019:Life Style; D016013:Likelihood Functions; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012727:Sex Characteristics
D015415:Biomarkers; D002097:C-Reactive Protein