Abstract 16890: Coronary Artery Calcium for Personalizing Antihypertensive Therapy: A Pooled Cohort Analysis

Background: The 2017 American College of Cardiology/American Heart Association high blood pressure (BP) guidelines recommend risk assessment of atherosclerotic cardiovascular disease (CVD) to inform hypertension (HTN) treatment in adults with elevated BP or low-risk stage 1 HTN. Use of coronary artery calcium (CAC) score, an excellent imaging risk-prediction tool, to guide HTN therapy has not been well studied. Methods: Participants free of CVD were pooled from three population cohort studies; 1) Multiethnic Study of Atherosclerosis, 2) Coronary Artery Risk Development in Young Adults and 3) Jackson Heart Study. Risk for incident CVD events (heart failure, stroke or cardiovascular mortality) by the CAC status and the BP treatment group was assessed. Multivariable Cox proportional hazards models were used to estimate the hazard ratios. The 10-year number needed to treat to prevent a single CVD event was also estimated. Results: This study included 11,499 participants (mean age 56 years; 55.2% women; 42.1% blacks). CAC score was non-zero in 38.2% of the participants. Over a median follow-up of 8.5 years, 910 incident CVD events occurred. Compared to those with zero CAC, participants with non-zero CAC score had a higher CVD incidence rate (per 1000 person-years) at all BP levels (elevated BP/low-risk stage 1 HTN: 14.5 vs 2.7; high-risk stage 1 or stage 2 HTN: 27.1 vs 8.8). Multivariable adjusted hazards of adverse CVD events displayed similar patterns ( Figure ). Among those with zero CAC, the 10-year number needed to treat to prevent 1 CVD event was 154 for those with elevated BP/low-risk stage 1 HTN and 47 for those with high-risk stage 1 or stage 2 HTN. Among those with non-zero CAC score, the number needed to treat was lower, 33 and 18 respectively. Conclusions: Utilization of CAC score may be an effective precision medicine approach to personalize HTN therapy in elevated BP or low-risk stage 1 HTN when treatment is not recommended by the current guidelines.

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Coronary Artery Calcium Score for Personalization of Antihypertensive Therapy

Hypertension ◽

10.1161/hypertensionaha.120.16689 ◽

2021 ◽

Vol 77 (4) ◽

pp. 1106-1118

Author(s):

Vibhu Parcha ◽

Gargya Malla ◽

Rajat Kalra ◽

Peng Li ◽

Ambarish Pandey ◽

...

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery ◽

High Risk ◽

Cardiovascular Event ◽

Coronary Artery Calcium ◽

Cardiovascular Events ◽

Low Risk ◽

Stage I ◽

Number Needed To Treat ◽

Hypertension Therapy

The 2017 American College of Cardiology/American Heart Association high blood pressure (BP) guidelines recommend risk assessment of atherosclerotic cardiovascular disease to inform hypertension treatment in adults with elevated BP or low-risk stage I hypertension. The use of coronary artery calcium (CAC) score to guide hypertension therapy has not been adequately evaluated. Participants free of cardiovascular disease were pooled from Multi-Ethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, and Jackson Heart Study. The risk for incident cardiovascular events (heart failure, stroke, coronary heart disease), by CAC status (CAC-0 or CAC>0) and BP treatment group was assessed using multivariable-adjusted Cox regression. The 10-year number needed to treat to prevent a single cardiovascular event was also estimated. This study included 6461 participants (median age 53 years; 53.3% women; 32.3% Black participants). Over a median follow-up of 8.5 years, 347 incident cardiovascular events occurred. Compared with those with normal BP, the risk of incident cardiovascular event was higher among those with elevated BP/low-risk stage I hypertension and CAC>0 (hazard ratio, 2.4 [95% CI, 1.7–3.4]) and high-risk stage I/stage II hypertension (BP, 140–160/80–100 mm Hg) with CAC>0 (hazard ratio, 2.9 [95% CI, 2.1–4.0]). A similar pattern was evident across racial subgroups and for individual study outcomes. Among those with CAC-0, the 10-year number needed to treat was 160 for elevated BP/low-risk stage I hypertension and 44 for high-risk stage I or stage II hypertension (BP, 140–160/80–100 mm Hg). Among those with CAC>0, the 10-year number needed to treat was 36 and 22, respectively. Utilization of the CAC score may guide the initiation of hypertension therapy and preventive approaches to personalize cardiovascular risk reduction among individuals where the current guidelines do not recommend treatment.

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Risk results from screening for a high cardiovascular disease risk by means of traditional risk factor measurement or coronary artery calcium scoring in the ROBINSCA trial

European Heart Journal ◽

10.1093/ehjci/ehaa946.2959 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Van Der Aalst ◽

S.J.A.M Denissen ◽

M Vonder ◽

J.-W.C Gratema ◽

H.J Adriaansen ◽

...

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery ◽

High Risk ◽

Risk Score ◽

Coronary Artery Calcium ◽

Preventive Treatment ◽

Low Risk ◽

Funding Source ◽

Cvd Risk ◽

Increased Risk

Abstract Aims Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease (CHD)-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or Coronary Artery Calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial. Methods and results Individuals at expected elevated CVD risk were randomized (1:1:1) into the control arm (n=14,519; usual care); screening arm A (n=14,478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n=14,450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. 12,185 participants (84.2%) in arm A and 12,950 (89.6%) in arm B were screened. 48.7% were women, and median age was 62 (InterQuartile Range 10) years. SCORE screening identified 45.1% at low risk (SCORE<10%), 26.5% at intermediate risk (SCORE 10–20%), and 28.4% at high risk (SCORE≥20%). According to CAC screening, 76.0% were at low risk (Agatston<100), 15.1% at high risk (Agatston 100–399), and 8.9% at very high risk (Agatston≥400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%). Conclusion We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated. ROBINSCA flowchart Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Advanced Research Grant

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Screening for cardiovascular disease risk using traditional risk factor assessment or coronary artery calcium scoring: the ROBINSCA trial

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa168 ◽

2020 ◽

Vol 21 (11) ◽

pp. 1216-1224 ◽

Cited By ~ 2

Author(s):

Carlijn M van der Aalst ◽

Sabine J A M Denissen ◽

Marleen Vonder ◽

Jan Willem C Gratama ◽

Henk J Adriaansen ◽

...

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery ◽

High Risk ◽

Risk Score ◽

Coronary Artery Calcium ◽

Preventive Treatment ◽

Low Risk ◽

Relative Reduction ◽

Cvd Risk ◽

Increased Risk

Abstract Aims Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or coronary artery calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial. Methods and results Individuals at expected elevated CVD risk were randomized into screening arm A (n = 14 478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n = 14 450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. A total of 12 185 participants (84.2%) in arm A and 12 950 (89.6%) in arm B were screened. In total, 48.7% were women, and median age was 62 (interquartile range 10) years. SCORE screening identified 45.1% at low risk (SCORE < 10%), 26.5% at intermediate risk (SCORE 10–20%), and 28.4% at high risk (SCORE ≥ 20%). According to CAC screening, 76.0% were at low risk (Agatston < 100), 15.1% at high risk (Agatston 100–399), and 8.9% at very high risk (Agatston ≥ 400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%). Conclusion We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated. Trial registration number NTR6471.

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A novel signature of two long non-coding RNAs in BRCA mutant ovarian cancer to predict prognosis and efficiency of chemotherapy

10.21203/rs.3.rs-28390/v1 ◽

2020 ◽

Author(s):

Yinglian Pan ◽

LiPing Jia ◽

Yuzhu Liu ◽

Yiyu Han ◽

Qian Li ◽

...

Keyword(s):

Ovarian Cancer ◽

High Risk ◽

Proportional Hazards ◽

Cox Regression ◽

Risk Groups ◽

Cox Proportional Hazards ◽

Low Risk ◽

Patient Choice ◽

The Cancer Genome Atlas ◽

Chemotherapy Treatment

Abstract Background: Ovarian cancer (OV) is the most common type of primary female reproductive cancer. BRCA1/2 gene is an important biomarker for evaluating the risk of OV, breast cancer and other related tumors and influences patient choice of individualized treatment. A powerful signature to predict OV prognosis and improve treatment personalization is urgently needed. This study aimed to identify a novel OV-related lncRNA prognostic biomarker.Methods: A Univariate Cox proportional-hazards and multivariate Cox regression analyses were used to identifying prognostic factors from The Cancer Genome Atlas (TCGA) database. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was assessed, and the sensitivity and specificity of the prediction model were determined.Results: The signature consisting of two long noncoding RNAs(lncRNAs), Z98885.2 and AC011601.1, was selected as a criterion for classifying patients into high and low-risk groups (median survival: 7.2 years vs. 2.3 years). The 3-year overall survival (OS) rates for the high- and low-risk groups were approximately 38% and 100%, respectively. Chemotherapy treatment survival rates indicated that high-risk groups had significantly shorter OS rates with adjuvant chemotherapy than the low-risk groups. The OS of 1-, 3- and 5- years were 100%, 40%, and 15% in the high-risk groups respectively. The survival rate of the high-risk group declined rapidly after two years of OA chemotherapy treatment. In addition, multivariate Cox regression associated with other traditional clinical factors showed that the 2-lncRNA model could be used as an independent OV prognostic factor. Analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) indicated that these signatures are pivotal to cancer development.Conclusion: In conclusion, Z98885.2 and AC011601.1 comprise a novel prognostic signature for OV patients with in BRCA1/2 mutations to predict prognosis and chemotherapy efficiency.

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Detecting prognostic biomarkers of breast cancer by regularized Cox proportional hazards models

Journal of Translational Medicine ◽

10.1186/s12967-021-03180-y ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Lingyu Li ◽

Zhi-Ping Liu

Keyword(s):

Breast Cancer ◽

High Risk ◽

Proportional Hazards ◽

Risk Group ◽

External Validation ◽

Cox Proportional Hazards ◽

High Risk Group ◽

Low Risk ◽

Functional Enrichment ◽

Prognostic Biomarkers

Abstract Background The successful identification of breast cancer (BRCA) prognostic biomarkers is essential for the strategic interference of BRCA patients. Recently, various methods have been proposed for exploring a small prognostic gene set that can distinguish the high-risk group from the low-risk group. Methods Regularized Cox proportional hazards (RCPH) models were proposed to discover prognostic biomarkers of BRCA from gene expression data. Firstly, the maximum connected network with 1142 genes by mapping 956 differentially expressed genes (DEGs) and 677 previously BRCA-related genes into the gene regulatory network (GRN) was constructed. Then, the 72 union genes of the four feature gene sets identified by Lasso-RCPH, Enet-RCPH, $$L_{0}$$ L 0 -RCPH and SCAD-RCPH models were recognized as the robust prognostic biomarkers. These biomarkers were validated by literature checks, BRCA-specific GRN and functional enrichment analysis. Finally, an index of prognostic risk score (PRS) for BRCA was established based on univariate and multivariate Cox regression analysis. Survival analysis was performed to investigate the PRS on 1080 BRCA patients from the internal validation. Particularly, the nomogram was constructed to express the relationship between PRS and other clinical information on the discovery dataset. The PRS was also verified on 1848 BRCA patients of ten external validation datasets or collected cohorts. Results The nomogram highlighted that the importance of PRS in guiding significance for the prognosis of BRCA patients. In addition, the PRS of 301 normal samples and 306 tumor samples from five independent datasets showed that it is significantly higher in tumors than in normal tissues ($$P<0.05$$ P < 0.05 ). The protein expression profiles of the three genes, i.e., ADRB1, SAV1 and TSPAN14, involved in the PRS model demonstrated that the latter two genes are more strongly stained in tumor specimens. More importantly, external validation illustrated that the high-risk group has worse survival than the low-risk group ($$P<0.05$$ P < 0.05 ) in both internal and external validations. Conclusions The proposed pipelines of detecting and validating prognostic biomarker genes for BRCA are effective and efficient. Moreover, the proposed PRS is very promising as an important indicator for judging the prognosis of BRCA patients.

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Sex differences in coronary artery calcium progression: The Korea Initiatives on Coronary Artery Calcification (KOICA) registry

PLoS ONE ◽

10.1371/journal.pone.0248884 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0248884

Author(s):

Wonjae Lee ◽

Yeonyee E. Yoon ◽

Sang-Young Cho ◽

In-Chang Hwang ◽

Sun-Hwa Kim ◽

...

Keyword(s):

Coronary Artery ◽

Coronary Artery Calcium ◽

Risk Group ◽

Multivariable Analysis ◽

Low Risk ◽

Progression Rate ◽

Atherosclerotic Cardiovascular Disease ◽

Ascvd Risk ◽

Male Sex

Even with increasing awareness of sex-related differences in atherosclerotic cardiovascular disease (ASCVD), it remains unclear whether the progression of coronary atherosclerosis differs between women and men. We sought to compare coronary artery calcium (CAC) progression between women and men. From a retrospective, multicentre registry of consecutive asymptomatic individuals who underwent CAC scoring, we identified 9,675 men and 1,709 women with follow-up CAC scoring. At baseline, men were more likely to have a CAC score >0 than were women (47.8% vs. 28.6%). The probability of CAC progression at 5 years, defined as [√CAC score (follow-up)—√CAC score (baseline)] ≥2.5, was 47.4% in men and 29.7% in women (p<0.001). When we stratified subjects according to the 10-year ASCVD risk (<5%, ≥5% and <7.5%, and ≥7.5%), a sex difference was observed in the low risk group (CAC progression at 5 years, 37.6% versus 17.9%; p<0.001). However, it became weaker as the 10-year ASCVD risk increased (64.2% versus 46.2%; p<0.001, and 74.8% versus 68.7%; p = 0.090). Multivariable analysis demonstrated that male sex was independently associated with CAC progression rate among the entire group (p<0.001). Subgroup analyses showed an independent association between male sex and CAC progression rate only in the low-risk group. The CAC progression rate is higher in men than in women. However, the difference between women and men diminishes as the 10-year ASCVD risk increases.

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Efficacy of three BCG strains (Connaught, TICE and RIVM) with or without secondary resection (re-TUR) for intermediate/high-risk non-muscle-invasive bladder cancers: results from a retrospective single-institution cohort analysis

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03571-0 ◽

2021 ◽

Author(s):

Francesco Del Giudice ◽

Gian Maria Busetto ◽

Martin S. Gross ◽

Martina Maggi ◽

Alessandro Sciarra ◽

...

Keyword(s):

High Risk ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cohort Analysis ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Secondary Resection ◽

Urological Oncology ◽

Muscle Invasive

Abstract Purpose (I) To evaluate the clinical efficacy of three different BCG strains in patients with intermediate-/high-risk non-muscle-invasive bladder cancer (NMIBC). (II) To determine the importance of performing routine secondary resection (re-TUR) in the setting of BCG maintenance protocol for the three strains. Methods NMIBCs who received an adjuvant induction followed by a maintenance schedule of intravesical immunotherapy with BCG Connaught, TICE and RIVM. Only BCG-naïve and those treated with the same strain over the course of follow-up were included. Cox proportional hazards model was developed according to prognostic factors by the Spanish Urological Oncology Group (CUETO) as well as by adjusting for the implementation of re-TUR. Results n = 422 Ta-T1 patients (Connaught, n = 146; TICE, n = 112 and RIVM, n = 164) with a median (IQR) follow-up of 72 (60–85) were reviewed. Re-TUR was associated with improved recurrence and progression outcomes (HRRFS: 0.63; 95% CI 0.46–0.86; HRPFS: 0.55; 95% CI 0.31–0.86). Adjusting for CUETO risk factors and re-TUR, BGC TICE and RIVM provided longer RFS compared to Connaught (HRTICE: 0.58, 95% CI 0.39–0.86; HRRIVM: 0.61, 95% CI 0.42–0.87) while no differences were identified between strains for PFS and CSS. Sub-analysis of only re-TUR cases (n = 190, 45%) showed TICE the sole to achieve longer RFS compared to both Connaught and RIVM. Conclusion Re-TUR was confirmed to ensure longer RFS and PFS in intermediate-/high-risk NMIBCs but did not influence the relative single BCG strain efficacy. When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to the other strains for RFS outcomes.

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