scholarly journals 888Discriminating between risk discriminators: OPERA, AUC, and polygenic variance

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
John Hopper ◽  
James Dowty
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Standard Deviation ◽  
Risk Model ◽  
Disease Risk ◽  
Cumulative Distribution ◽  
Receiver Operating Curve ◽  
Pedigree Data ◽  
Adjusted Risk ◽  
Risk Estimates

Abstract Focus of Presentation Epidemiological risk estimates are often adjusted for age (and, if necessary, sex) by design or analysis, and for other factors. Consequently, risk estimates do not pertain to the crude risk factor, but to its population residual after adjusting for age, sex and other covariates. For disease risk, the change in Odds PER Adjusted standard deviation (OPERA) estimates the risk gradient on an appropriate scale; log(OPERA) is the natural measure to compare estimates. Findings Under a multiplicative risk model for a normally distributed (adjusted) risk factor, log(OPERA) = the difference in mean between cases and controls. The area under the receiver operating curve (AUC) = □(log(OPERA)/√2), where □ is the standard normal cumulative distribution function. The risk discrimination from combining risk factors can be predicted from their OPERAs. The polygenic standard deviation estimated from pedigree data = log(OPERA). The OPERA for knowing all familial risk factors can be calculated. Conclusions/Implications We present examples from the breast cancer literature where the wrong conclusions can be made by not using the OPERA concept. We give examples of the value of OPERA estimates in predicting the risk discrimination of their combination and demonstrate why the better one predicts the disease the harder it is to predict it better. Key messages OPERA overcomes problems about interpreting risk factors, and combinations of risk factors, in a way not apparent using changes in AUC. OPERA also puts an upper bound on the role of genetic factors in explaining differences in risk across the population.

scholarly journals Utility of single versus sequential measurements of risk factors for prediction of stroke in Chinese adults

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew Chun ◽  
Robert Clarke ◽  
Tingting Zhu ◽  
David Clifton ◽  
Derrick Bennett ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Temporal Trends ◽  
Single Visit ◽  
Risk Estimates ◽  
Incident Cases ◽  
Single Versus ◽  
Sequential Measurements

Abstract Absolute risks of stroke are typically estimated using measurements of cardiovascular disease risk factors recorded at a single visit. However, the comparative utility of single versus sequential risk factor measurements for stroke prediction is unclear. Risk factors were recorded on three separate visits on 13,753 individuals in the prospective China Kadoorie Biobank. All participants were stroke-free at baseline (2004–2008), first resurvey (2008), and second resurvey (2013–2014), and were followed-up for incident cases of first stroke in the 3 years following the second resurvey. To reflect the models currently used in clinical practice, sex-specific Cox models were developed to estimate 3-year risks of stroke using single measurements recorded at second resurvey and were retrospectively applied to risk factor data from previous visits. Temporal trends in the Cox-generated risk estimates from 2004 to 2014 were analyzed using linear mixed effects models. To assess the value of more flexible machine learning approaches and the incorporation of longitudinal data, we developed gradient boosted tree (GBT) models for 3-year prediction of stroke using both single measurements and sequential measurements of risk factor inputs. Overall, Cox-generated estimates for 3-year stroke risk increased by 0.3% per annum in men and 0.2% per annum in women, but varied substantially between individuals. The risk estimates at second resurvey were highly correlated with the annual increase of risk for each individual (men: r = 0.91, women: r = 0.89), and performance of the longitudinal GBT models was comparable with both Cox and GBT models that considered measurements from only a single visit (AUCs: 0.779–0.811 in men, 0.724–0.756 in women). These results provide support for current clinical guidelines, which recommend using risk factor measurements recorded at a single visit for stroke prediction.

Abstract MP74: Long Term Risk-Factor Profiles for Chronic Kidney Disease in the Framingham Heart Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Gearoid M McMahon ◽  
Sarah R Preis ◽  
Shih-Jen Hwang ◽  
Caroline S Fox
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Kidney Disease ◽  
Framingham Heart Study ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Standard Deviation Increase ◽  
Heart Study ◽  
Increased Risk

Background: Chronic Kidney Disease (CKD) is an important public health issue and is associated with an increased risk of cardiovascular disease. Risk factors for CKD are well established, but most are typically assessed at or near the time of CKD diagnosis. Our hypothesis was that risk factors for CKD are present earlier in the course of the disease. We compared the prevalence of risk factors between CKD cases and controls at time points up to 30 years prior to CKD diagnosis. Methods: Participants were drawn from the Framingham Heart Study Offspring cohort. CKD was defined as an estimated glomerular filtration rate of ≤60ml/min/1.73m2. Incident CKD cases occurring at examination cycles 6, 7, and 8 were age- and sex-matched 1:2 to controls. Risk factors including systolic blood pressure (SBP), hypertension, lipids, diabetes, smoking status, body mass index (BMI) and dipstick proteinuria were measured at the time of CKD diagnosis and 10, 20 and 30 years prior. Logistic regression models, adjusted for age, sex, and time period, were constructed to compare risk factor profiles at each time point between cases and controls Results: During follow-up, 441 new cases of CKD were identified and these were matched to 882 controls (mean age 69.2 years, 52.4% women). Up to 30 years prior to CKD diagnosis, those who ultimately developed CKD were more likely to have hypertension (OR 1.74, CI 1.21-2.49), be obese (OR 1.74, CI 1.15-2.63) and have higher triglycerides (OR 1.43, CI 1.12-1.84, p=0.005 per 1 standard deviation increase). Each 10mmHg increase in SBP was associated with an OR of 1.22 for future CKD (95% CI 1.10-1.35) Additionally, cases were more likely to have diabetes (OR 2.90, CI 1.59-5.29) and be on antihypertensive therapy (OR 1.65, CI 1.14-2.40, p=0.009) up to 20 years prior to diagnosis. Increasing HDLc was associated with a lower risk of CKD (OR 0.84, CI 0.81-0.97 per 10mg/dl). Conclusions: As many as 30 years prior to diagnosis, risk factors for CKD are identifiable. In particular, modifiable risk factors such as obesity, hypertension and dyslipidemia are present early in the course of the disease. These findings demonstrate the importance of early identification of risk factors in patients at risk of CKD through a life-course approach.

scholarly journals Identification of Endothelial Proteins in Plasma Associated With Cardiovascular Risk Factors

2021 ◽  
Author(s):  
Maria J. Iglesias ◽  
Larissa D. Kruse ◽  
Laura Sanchez-Rivera ◽  
Linnea Enge ◽  
Philip Dusart ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Body Mass Index ◽  
Risk Factor ◽  
Total Cholesterol ◽  
Body Mass ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cardiovascular Disease Risk Factor ◽  
Venous Disease

Objective: Endothelial cell (EC) dysfunction is a well-established response to cardiovascular disease risk factors, such as smoking and obesity. Risk factor exposure can modify EC signaling and behavior, leading to arterial and venous disease development. Here, we aimed to identify biomarker panels for the assessment of EC dysfunction, which could be useful for risk stratification or to monitor treatment response. Approach and Results: We used affinity proteomics to identify EC proteins circulating in plasma that were associated with cardiovascular disease risk factor exposure. Two hundred sixteen proteins, which we previously predicted to be EC-enriched across vascular beds, were measured in plasma samples (n=1005) from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study) pilot. Thirty-eight of these proteins were associated with body mass index, total cholesterol, low-density lipoprotein, smoking, hypertension, or diabetes. Sex-specific analysis revealed that associations predominantly observed in female- or male-only samples were most frequently with the risk factors body mass index, or total cholesterol and smoking, respectively. We show a relationship between individual cardiovascular disease risk, calculated with the Framingham risk score, and the corresponding biomarker profiles. Conclusions: EC proteins in plasma could reflect vascular health status.

scholarly journals Trends in cardiovascular risk factors and treatment goals in patients with diabetes in Singapore-analysis of the SingHealth Diabetes Registry

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259157
Author(s):  
Liang Feng ◽  
Amanda Lam ◽  
David Carmody ◽  
Ching Wee Lim ◽  
Gilbert Tan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Glycated Hemoglobin ◽  
Temporal Trends ◽  
Vascular Complications ◽  
Housing Type ◽  
Risk Factor Control ◽  
Mixed Effect ◽  
Diabetes Registry ◽  
Adjusted Risk

Background Asian populations are at high risk of diabetes and related vascular complications. We examined risk factor control, preventive care, and disparities in these trends among adults with diabetes in Singapore. Methods The sample included 209,930 adults with diabetes aged≥18 years from a multi-institutional SingHealth Diabetes Registry between 2013 and 2019 in Singapore. We performed logistic generalized estimating equations (GEEs) regression analysis and used linear mixed effect modeling to evaluate the temporal trends. Results Between 2013 and 2019, the unadjusted control rates of glycated hemoglobin (4.8%, 95%CI (4.4 to 5.1) and low-density lipoprotein cholesterol (LDL-C) (11.5%, 95%CI (11.1 to 11.8)) improved, but blood pressure (BP) control worsened (systolic BP (SBP)/diastolic BP (DBP) <140/90 mmHg: -6.6%, 95%CI (-7.0 to -6.2)). These trends persisted after accounting for the demographics including age, gender, ethnicity, and housing type. The 10-year adjusted risk for coronary heart disease (CHD) (3.4%, 95% (3.3 to 3.5)) and stroke (10.4%, 95% CI (10.3 to 10.5)) increased. In 2019, the control rates of glycated hemoglobin, BP (SBP/DBP<140/90 mmHg), LDL-C, each, and all three risk factors together, accounted for 51.5%, 67.7%, 72.2%, and 24.4%, respectively. Conclusions Trends in risk factor control improved for glycated hemoglobin and LDL-C, but worsened for BP among diabetic adults in Singapore from 2013 to 2019. Control rates for all risk factors remain inadequate.

scholarly journals Reversal Rate of Clustering of Cardiovascular Disease Risk Factors of Metabolic Syndrome in the General Population: The Niigata Preventive Medicine Study

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Shinsuke Okada ◽  
Akiko Suzuki ◽  
Hiroshi Watanabe ◽  
Toru Watanabe ◽  
Yoshifusa Aizawa
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Disease Risk ◽  
Fasting Blood Glucose ◽  
Reversal Rate ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
The Metabolic Syndrome

The reversal rate from clustering of cardiovascular disease (CVD) risk factors—components of the metabolic syndrome (MetS) is not known.Methods and Results. Among 35,534 subjects who received the annual health examinations at the NiigataHealth Foundation (Niigata, Japan), 4,911 subjects had clustering of 3 or more of the following CVD risk factors: (1) body mass index (BMI) ≥25 Kg/m2, (2) blood pressure ≥130 mm Hg in systolic and/or ≥85 mm Hg in diastolic, (3) triglycerides ≥150 mg/dL, (4) high-density lipoprotein cholesterol ≤40 mg/dL in men, ≤50 mg/dL in women, and (5) fasting blood glucose ≥100 mg/dL. After 5 years 1,929 subjects had a reversal of clustering (39.4%). A reversal occurred more often in males. The subjects with a reversal of clustering had milder level of each risk factor and a smaller number of risk factors, while BMI was associated with the least chance of a reversal.Conclusion. We concluded that a reversal of clustering CVD risk factors is possible in 4/10 subjects over a 5-year period by habitual or medical interventions. Gender and each CVD risk factor affected the reversal rate adversely, and BMI was associated with the least chance of a reversal.

scholarly journals Sex Difference in Risk Factors, GRACE Scores, and Management among Post-Acute Coronary Syndrome Patients in Sri Lanka

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Priyadarshani Galappatthy ◽  
Vipula Bataduwaarachchi ◽  
Priyanga Ranasinghe ◽  
Gamini Galappatthy ◽  
Upul Senerath ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Coronary Syndrome ◽  
Risk Factor ◽  
Sri Lanka ◽  
Disease Risk ◽  
Management Strategies ◽  
Significant Proportion ◽  
Coronary Syndrome ◽  
One Year ◽  
Grace Score

Objective. To assess sex-based differences in the prevalence of risk factor, their management, and differences in the prognosis among acute coronary syndrome (ACS) in Sri Lanka. Methods. Patients diagnosed with ACS were recruited from hospitals throughout the island. The Joint European Societies guidelines were used to assess recommended targets for coronary heart disease risk factors, and the GRACE score was used to assess the post-ACS prognosis. Age-adjusted regression was performed to calculate odds ratios for men versus women in risk factor control. Results. A total of 2116 patients, of whom 1242 (58.7%) were men, were included. Significant proportion of women were nonsmokers; OR = 0.11 (95% CI 0.09 to 0.13). The prevalence of hypertension (p<0.001), diabetes (p<0.001), and dyslipidemia (p=0.004) was higher in women. The LDL-C target was achieved in a significantly higher percentage of women (12.6%); OR = 0.33 (95% CI 0.10 to 1.05). When stratified by age, no significant differences were observed in achieving the risk factor targets or management strategies used except for fasting blood sugar (p<0.05) where more men achieved control target in both age categories. Majority of the ACS patients had either high or intermediate risk for one-year mortality as per the GRACE score. In-hospital and 1-year mean mortality risk was significantly higher among men of less than 65 years of age (p<0.05). Conclusions. Smoking is significantly lower among Sri Lankan women diagnosed with ACS. However, hypertension, diabetes, and dyslipidemia were more prevalent among them. There was no difference in primary and secondary preventive strategies and management in both sexes but could be further improved in both groups.

Ethnicity and hepatocellular carcinoma risk factors in New Mexico: A retrospective analysis over a 12-year period.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 269-269
Author(s):  
Khine Zar Win ◽  
Diaa Osman ◽  
Ruofei Du ◽  
Yehuda Z. Patt
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Risk Factor ◽  
New Mexico ◽  
American Indians ◽  
Pairwise Comparison ◽  
Hcv Infection ◽  
Cancer Center ◽  
Adjusted Risk ◽  
Geographic Regions

269 Background: Common hepatocellular carcinoma (HCC) risk factors, such as hepatitis C virus (HCV) and hepatitis B virus infections, heavy exposure to alcohol and non-alcoholic steatohepatitis (NASH), vary in relation to gender, ethnicity, and geographic regions. New Mexico (NM) has the highest adjusted risk ratio of 1.27 for HCC when compared with other US geographic regions. The population of Hispanic Whites (HW), non-Hispanic Whites (NHW) and American Indians (AI) in NM provides a unique opportunity to study the prevalence of the known HCC risk factors among different ethnicities. Methods: We identified about 550 patients who were diagnosed and/or received treatment for HCC at the University of New Mexico (UNM) Hospital and the UNM Cancer Center from 2003 to 2015, using ICD 9/10 codes. Following approval by institutional review board, a retrospective chart review was conducted to correlate the known HCC risk factors and ethnicity of patients. This is a preliminary report of the findings in a randomly selected 226 of the 550 patients, and we expect to complete the analysis by the time of the GI ASCO symposium. A logistic regression with pairwise comparison was conducted to determine the distribution of the HCC risk factors among different ethnicities. Results: Among NHW, HCV is the most prevalent risk factor for HCC. AI have lower proportion of HCV infection, compared to NHW (35% vs 74%; P= 0.0008). However, DM and NASH were more frequently observed among AI than NHW, 54% vs 27% and 27% vs 9% ( P= 0.025 and 0.038) respectively. Table 1: Proportion of HCV, diabetes, NASH among AI, NHW and HW and pairwise comparison between ethnic groups. Conclusions: Among AI, the major risk factors for HCC seem diabetes mellitus and NASH. However, among NHW, chronic HCV infection is the most prevalent risk factor for HCC.[Table: see text]

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