***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background and Purpose — Ultrasound of carotid arteries provides measures of intima media thickness ( IMT ) and plaque , both widely used as surrogate measures of cardiovascular disease . Although IMT and plaques are highly intercorrelated , the relationship between carotid plaque and IMT and cardiovascular disease has been conflicting . In this prospect i ve , population -based study , we measured carotid IMT , total plaque area , and plaque echogenicity as predictors for first-ever myocardial infa rct ion ( MI ) . Methods —  IMT , total plaque area , and plaque echogenicity  were measured in 6226 men and women aged 25 to 84 years with no previous MI . The subjects were followed for 6 years and incident MI was registered . Results — During follow-up , MI occurred in 6.6 % of men and 3.0 % of women . The adjusted relative risk ( RR ; 95 % CI ) between the highest plaque area tertile versus no plaque was 1.56 ( 1.04 to 2.36 ) in men and 3.95 ( 2.16 to 7.19 ) in women . In women , there was a significant trend toward a higher MI risk with more echolucent plaque . The adjusted RR ( 95 % CI ) in the highest versus lowest IMT quartile was 1.73 ( 0.98 to 3.06 ) in men and 2.86 ( 1.07 to 7.65 ) in women . When we excluded bulb IMT from analyses , IMT did not predict MI in either sex . Conclusions — In a general population , carotid plaque area was a stronger predictor of first-ever MI than was IMT . Carotid atherosclerosis was a stronger risk factor for MI in women than in men . In women , the risk of MI increased with plaque echolucency Abstract — Plasma levels of C-reactive protein ( CRP , a marker of the reactant plasma protein component of the inflammatory response ) and of fibrin D-dimer ( a marker of cross-linked fibrin turnover ) have each been associated in recent studies with the risk of future ischemic heart disease ( IHD ) . Previous experimental studies have shown that fibrin degradation products , including D-dimer , have effects on inflammatory processes and acute-phase protein responses . In the Speedwell Prospect i ve Study , we therefore measured  CRP and D-dimer levels  in stored plasma sample s from 1690 men aged 49 to 67 years who were followed-up for incident IHD for an average of 75±4 months ( mean±SD ) and studied their associations with each other , with baseline and incident IHD , and with IHD risk factors . CRP and D-dimer levels were each associated with age , plasma fibrinogen , smoking habit , and baseline evidence of IHD . CRP was associated with D-dimer ( r = 0.21 , P < 0.00001 ) . On univariate analyses , both CRP and D-dimer were associated with incident IHD . The incidence of IHD increased with CRP independently of the level of D-dimer ( P = 0.0002 ) and also increased with D-dimer independently of the level of CRP ( P = 0.048 ) . In multivariate analyses , inclusion of D-dimer and conventional risk factors reduced the strength of the association between CRP and incident IHD ; likewise , inclusion of CRP and conventional risk factors reduced the strength of the association between D-dimer and incident IHD . We conclude that although these respective markers of inflammation and fibrin turnover show modest association with each other in middle-aged men , they may have additive associations with risk of incident IHD . Further larger studies are required to test this hypothesis BACKGROUND A high serum total homocysteine ( tHcy ) concentration is a risk factor for death , but the strength of the relation in patients with type 2 ( non-insulin-dependent ) diabetes mellitus compared with nondiabetic subjects is not known . A cross-sectional study suggested that the association between tHcy and cardiovascular disease is stronger in diabetic than in nondiabetic subjects . We therefore prospect ively investigated the combined effect of hyperhomocysteinemia and type 2 diabetes on mortality . METHODS AND RESULTS Between October 1 , 1989 , and December 31 , 1991 , serum was saved from 2484 men and women , 50 to 75 years of age , who were r and omly selected from the town of Hoorn , The Netherl and s.  Fasting serum tHcy concentration was measured in 171 subjects who died ( cases ; 76 of cardiovascular disease ) and in a stratified r and om sample of 640 survivors ( control subjects ) .  Mortality risks were calculated over 5 years of follow-up by means of logistic regression . The prevalence of hyperhomocysteinemia ( tHcy > 14 micromol/L ) was 25 . 8 % . After adjustment for major cardiovascular risk factors , serum albumin , and HbA(1c ) , the odds ratio ( 95 % CI ) for 5-year mortality was 1.56 ( 1.07 to 2.30 ) for hyperhomocysteinemia and 1.26 ( 1.02 to 1 . 55 ) per 5-micromol/L increment of tHcy . The odds ratio for 5-year mortality for hyperhomocysteinemia was 1.34 ( 0.87 to 2.06 ) in nondiabetic subjects and 2.51 ( 1.07 to 5.91 ) in diabetic subjects ( P=0.08 for interaction ) . CONCLUSIONS Hyperhomocysteinemia is related to 5-year mortality independent of other major risk factors and appears to be a stronger ( 1.9-fold ) risk factor for mortality in type 2 diabetic patients than in nondiabetic subjects In this nested case-control study , lipoprotein ( a ) [ Lp(a ) ] concentrations and apo(a ) isoform size were measured in serum sample s obtained from men participating in the prospect i ve Multiple Risk Factor Intervention Trial ( MRFIT ) . Serum from men aged 35 to 57 years and stored for up to 20 years were analyzed for Lp(a ) levels ( n=736 ) and isoform size ( n=487 ) , respectively . Cases involved nonfatal myocardial infa rct ions ( MI ; n=98 ) , documented during the active phase of the study that ended on February 28 , 1982 and coronary heart disease ( CHD ) deaths ( n=148 ) monitored through 1990 . Median Lp(a ) levels did not differ between cases and controls and mean apo(a ) size did not vary between cases and controls in the entire study population . When adjusted for age and Lp(a ) concentration , logistic regression analysis indicated that small apo(a ) isoforms were associated with CHD deaths among smokers ( OR 3.31 ; 95 % CI 1.07 - 10.28 ) BACKGROUND Epidemiologic studies have shown that C-reactive protein ( CRP ) is a risk factor for coronary heart disease . Whether routine measurement of CRP has a role in the prediction of future coronary disease in everyday clinical practice has not yet been investigated . METHODS Within the Rotterdam Study , a population -based cohort study of 7983 men and women 55 years and older , we conducted a nested case-control study to investigate the value of CRP in coronary disease prediction . Data are based on 157 participants who experienced a myocardial infa rct ion during follow-up and 500 r and omly selected controls .  High-sensitivity CRP and traditional cardiovascular risk factors were measured at baseline . RESULTS The age- and sex-adjusted relative risk of myocardial infa rct ion for subjects in the highest quartile of the population distribution of CRP compared with the lowest quartile was 2.0 ( 95 % confidence interval , 1.1 - 3.4 ) . After additional adjustment for traditional cardiovascular risk factors , the increase in risk largely disappeared ( odds ratio , 1.2 ; 95 % confidence interval , 0.6 - 2.2 ) . Adding CRP to a coronary disease risk function based on risk factors that are routinely assessed in clinical practice or to the Framingham risk function did not improve the area under the receiver operating characteristic curve of these risk functions . Sensitivity and specificity of both risk functions , computed after dichotomizing the estimated disease probabilities using prespecified cutoff points , hardly improved when CRP was added . CONCLUSION Measurement of  CRP in elderly people has no additional value in coronary disease risk prediction when traditional cardiovascular risk factors are known BACKGROUND We examined the relationship between granulocyte , lymphocyte and monocyte counts and risk of coronary heart disease ( CHD ) and cardiovascular disease ( CVD ) in men and women . There is paucity of data on the differential leucocyte count and its relationship with the risk of CHD and CVD . METHODS This prospect i ve study comprised 7073 men and 9035 women who were 45 - 79 years of age and were residents of Norfolk . United Kingdom . RESULTS During an average of 8 years of follow-up we identified 857 incident CHD events and 2581 CVD incident events . Increased total leucocyte count was associated with increased risk for both CHD and CVD . The highest quartile of granulocyte count was associated with increased risk when compared to lowest quartile for CHD ( men HR 1.70 95 % CI : 1.30 - 2.21 ; women HR 1.24 95 % CI : 0.91 - 1.69 ) and for CVD ( men HR 1.46 95 % CI : 1.24 - 1.71 ; women HR 1.20 95 % CI : 1.02 - 1.42 ) . The association remained unchanged when the analyses were restricted to nonsmokers and when risk was assessed for every 1000 cells L(-1 ) increase in cell count . In multivariable models , despite adjusting for C-reactive protein ( CRP ) , the granulocyte count remained an independent predictor of CHD and CVD risk , especially amongst men . Lymphocyte or monocyte counts were not significantly associated with increased risk . In all analyses , additionally adjusting for CRP did not affect the results material ly . CONCLUSIONS In conclusion , we found that the higher risk for CHD and CVD associated with increased total leucocyte count seems to be accounted for by the increased granulocyte count The relation of serum total homocysteine and lipoprotein(a ) ( Lp(a ) ) with the incidence of atherosclerotic disease was investigated among 7424 men and women aged 40 - 64 years free of atherosclerotic disease at baseline in 1977 . During the 9-year follow-up , 134 male and 131 female cases with either myocardial infa rct ion or stroke were identified . For each case a control subject was selected belonging to the same sex and 5-year age group .  Serum sample s collected in 1977 were stored at -20 degrees C and analyzed in 1991 . The mean serum homocysteine concentration of male cases and controls was 9.99 mumol/l and 9.82 mumol/l at baseline and that of female cases and controls 9.58 mumol/l and 9.24 mumol/l , respectively . The median serum Lp(a ) concentration of male cases and controls was 73 mg/l and 108 mg/l and that of female cases and controls 113 mg/l and 91 mg/l , respectively . The differences between cases and controls were not statistically significant . There was also no significant association between either homocysteine or Lp(a ) and atherosclerotic disease , myocardial infa rct ion or stroke in logistic regression analyses . The odds ratios varied from 1.00 to 1.26 for homocysteine and from 0.81 to 1.06 for Lp(a ) . The results of this prospect i ve population -based study do not support the hypotheses that serum homocysteine or Lp(a ) are risk factors for atherosclerotic disease . The lack of association between serum homocysteine and atherosclerotic disease may be due to the exceptionally low gene frequency predisposing to homocysteinemia in Finl and In 1998 , the American Heart Association convened Prevention Conference V to examine strategies for the identification of high-risk patients who need primary prevention . Among the strategies discussed was the measurement of markers of inflammation.1  The Conference concluded that “ many of these markers ( including inflammatory markers ) are not yet considered applicable for routine risk assessment because of : ( 1 ) lack of measurement st and ardization , ( 2 ) lack of consistency in epidemiological findings from prospect i ve studies with endpoints , and ( 3 ) lack of evidence that the novel marker adds to risk prediction over and above that already achievable through the use of established risk factors . ” The National Cholesterol Education Program Adult Treatment Panel III Guidelines identified these markers as emerging risk factors,1a which could be used as an optional risk factor measurement to adjust estimates of absolute risk obtained using st and ard risk factors . Since these publications , a large number of peer- review ed scientific reports have been published relating inflammatory markers to cardiovascular disease ( CVD ) . Several commercial assays for inflammatory markers have become available . As a consequence of the exp and ing research base and availability of assays , the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly . Despite this , there has been no consensus from professional societies or governmental agencies as to how these assays of markers 
    Output:
    
This sequential approach provides a direct measure of the number or proportion of intermediate-risk persons who could be reclassified by the new test .
This type of analysis provides the best information about the clinical effect of using the new test to further stratify intermediate-risk patients .