Abstract Background Body composition predicts cardiovascular outcomes, but it is uncertain whether anthropometric measures can replace the more expensive serum total cholesterol for cardiovascular risk stratification in low resource settings. Purpose The purpose of the study was to compare the additive prognostic ability of serum total cholesterol with that of body mass index (BMI), waist/hip ratio (WHR), and estimated fat mass (EFM, calculated using a validated prediction equation), individually and combined. Methods We used data from the MORGAM (MONICA, Risk, Genetics, Archiving, and Monograph) Prospective Cohort Project, an international pooling of cardiovascular cohorts, to determine the relationship between anthropometric measures, serum cholesterol, and cardiovascular events, using multivariable Cox proportional-hazards regression analysis. We further investigated the ability of these measures to enhance prognostication beyond a simpler prediction model, consisting of age, sex, smoking status, systolic blood pressures, and country, using comparison of area under the receiver operating characteristics curve (AUCROC) derived from binary logistic regression models. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of death from coronary heart disease, myocardial infarction, or stroke. Results The study population consisted of 52,188 apparently healthy subjects (56.3% men) aged 47±12 years ranging from 20 to 84, derived from 37 European cohorts, with baseline between 1982–2002 all followed for 10 years during which MACE occurred in 2465 (4.7%) subjects. All anthropometric measures (BMI: hazard ratio (HR) 1.04 [95% confidence interval (CI): 1.03–1.05] per kg/m2; WHR: HR 7.5 [4.0–14.0] per unit; EFM: HR 1.02 [1.01–1.02] per kg) as well as serum total cholesterol (HR 1.20 [1.16–1.24] per mmol/l) were significantly associated with MACE (P<0.001 for all), independently of age, sex, smoking status, systolic blood pressures, and country. The addition of serum cholesterol significantly improved the predictive ability of the simple model (AUCROC 0.818 vs. 0.814, P<0.001), as did the combination of WHR, BMI, and EFM (AUCROC 0.817 vs. 0.814, P=0.004). When assessed individually, BMI (AUCROC 0.816 vs. 0.814, P=0.004) and WHR (AUCROC 0.815 vs. 0.814, P=0.02) improved model performance, while EFM narrowly missed significance (AUCROC 0.815 vs. 0.814, P=0.06). There was no significant difference in the predictive ability of a model including serum cholesterol versus that including all three anthropometric measures (AUCROC 0.818 vs. 0.817, P=0.13). The figure shows the pertinent areas under the ROC curve in predicting MACE. Conclusion In this large population-based cohort study, the addition of a combination of anthropometric measures, i.e. BMI, WHR, and EFM, raised the predictive ability of a simple prognostic model comparable to that obtained by the addition of serum total cholesterol. Figure 1 Funding Acknowledgement Type of funding source: None
Aims The aim of this study was to examine whether high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble urokinase plasminogen activator receptor (suPAR) carried incremental prognostic value in predicting cardiovascular morbidity and mortality beyond traditional risk factors in apparently healthy individuals. Methods and results This was a prospective population-based cohort study comprising 1951 subjects included in the 10-year follow-up of the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, between 1993 and 1994. The principal endpoint was death from cardiovascular causes. Secondary endpoints were death from any cause, coronary artery disease, heart failure, and cerebrovascular disease. Predictive capabilities of each of the three biomarkers were tested using Cox proportional-hazards regression, Harrell’s concordance index (C-index), and net reclassification improvement (NRI). Study participants were aged 41, 51, 61, or 71 years, and equally distributed between the two sexes. During a median follow-up of 18.5 years (interquartile range: 18.1–19.0), 177 (9.1%) subjects died from a cardiovascular cause. Hs-CRP (adjusted standardized hazard ratio (HR): 1.37, 95% confidence interval (CI): 1.17–1.60), NT-proBNP (HR: 1.90, 95% CI: 1.58–2.29), and suPAR (HR: 1.35, 95% CI: 1.17–1.57) were all significantly associated with cardiovascular deaths after adjustment for age, sex, smoking status, systolic blood pressure, and total cholesterol ( p < 0.001 for all). Furthermore, all three biomarkers were significantly associated with significant NRI. However, only NT-proBNP significantly raised the C-index in predicting death from cardiovascular causes when added to the risk factors (C-index 0.860 versus 0.847; p = 0.02). Conclusions Hs-CRP, suPAR, and particularly NT-proBNP predicted cardiovascular death and may enhance prognostication beyond traditional risk factors in apparently healthy individuals.
Purpose of review There is an increasing need for improved risk stratification to better individualize cardiovascular preventive measures. Although age and sex are strong and easily obtained cardiovascular risk factors (CVRFs), their influence on the prognostic importance of other CVRF, circulating biomarkers and other markers of subclinical cardiovascular damage has not previously been systematically and critically appraised. Therefore, we have revisited the European MORGAM and the Danish MONI10 cohorts. Recent findings Theoretically, the relative risk of many CVRF is expected to be lower in older healthy individuals due to a combination of selection bias by disease, higher absolute risk primarily due to older age, and the fact that the CVRF and markers may primarily influence or reflect early parts of the cardiovascular disease process. This influence of age may vary between sexes, as the cardiovascular disease process is delayed and possibly different in women compared with men. Summary Adjusted for the remaining Systematic COronary Risk Evaluation (SCORE) CVRF, higher SBP, serum cholesterol, soluble urokinase-type plasminogen activator receptor, left ventricular mass index and atherosclerotic plaques were more closely associated with outcomes in individuals younger than 52 years with some sex-specific differences, whereas higher N-terminal pro-brain natriuretic peptide and urine albumin/creatine ratio were more closely associated with outcomes in subjects aged 61 or 71 years.
The Reference Values for Arterial Stiffness Collaboration has derived an equation using age and mean blood pressure to estimated pulse wave velocity (ePWV), which predicted cardiovascular events independently of Systematic COoronary Risk Evaluation (SCORE) and Framingham Risk Score. The study aim was to investigate the independent association between ePWV and clinical outcomes in 107 599 apparently healthy subjects (53% men) aged 19 to 97 years from the MORGAM Project who were included between 1982 and 2002 in 38 cohorts from 11 countries. Using multiple Cox-regression analyses, the predictive value of ePWV was calculated adjusting for country of inclusion and either SCORE, Framingham Risk Score, or traditional cardiovascular risk factors (age, sex, smoking, systolic blood pressure, body mass index [BMI], total and high-density lipoprotein cholesterol). Cardiovascular mortality consisted of fatal stroke, fatal myocardial infarction, or coronary death, and the composite cardiovascular end point consisted of stroke, myocardial infarction, or coronary death. Model discrimination was assessed using Harrell’s C -statistic. Adjusting for country and logSCORE or Framingham Risk Score, ePWV was associated with all-cause mortality (hazard ratio, 1.23 [95% CI 1.20–1.25] per m/s or 1.32 [1.29–1.34]), cardiovascular mortality (1.26 [1.21–1.32] or 1.35 [1.31–1.40]), and composite cardiovascular end point (1.19 [1.16–1.22] or 1.23 [1.20–1.25]; all P <0.001). However, after adjusting for traditional cardiovascular risk factors, ePWV was only associated with all-cause mortality (1.15 [1.08–1.22], P <0.001) and not with cardiovascular mortality (0.97 [0.91–1.03]) nor composite cardiovascular end point (1.10 [0.97–1.26]). The areas under the last 3 receiver operator characteristic curves remained unchanged when adding ePWV. Elevated ePWV was associated with subsequent mortality and cardiovascular morbidity independently of systematic coronary risk evaluation and Framingham Risk Score but not independently of traditional cardiovascular risk factors.
Objective: The aim of this study was to evaluate the impact of age on the associations between hemodynamic components derived from 24-h ambulatory blood pressure (24-h ABPM) and target organ damage, in apparently healthy, nonmedicated individuals. Methods: Twenty-four-hour ABPM and target organ damage (left ventricular mass index, pulse wave velocity, urine albumin : creatinine ratio and carotid atherosclerotic plaques) were evaluated in 1408 individuals. Associations were examined in regression models, stratified for age [middle-aged (41 or 51 years) or elderly (61 or 71 years)], and adjusted for sex, smoking status, and total-cholesterol. Results: In middle-aged individuals, an increase of 10 mmHg in 24-h SBP was independently associated with an increase of 3.8 (2.7–4.8) g/m2 in LVMI. The effect was nearly doubled in the elderly subgroup, where the same increase resulted in an increase in LVMI of 6.3 (5.0–7.6) g/m2 (P for interaction <0.01). An increase of 10 mmHg of 24-h SBP was associated with a 6.7% increase in pulse wave velocity in middle-aged individuals and with an 9.1% increase in elderly individuals (P for interaction <0.01). An independent association between 24-h ABPM and urine albumin : creatinine ratio was only observed in the elderly subgroup. Associations between the presence of atherosclerotic plaques and components from 24-h ABPM except 24-h DBP were not modified by age (all P for interaction >0.26). Conclusion: Age enhances the associations between hemodynamic components obtained from 24-h ABPM and measures of arterial stiffness, microvascular damage, and cardiac structure, but not atherosclerosis.
