scholarly journals Longitudinal Plasma Measures of Trimethylamine N‐Oxide and Risk of Atherosclerotic Cardiovascular Disease Events in Community‐Based Older Adults

2021 ◽  
Author(s):  
Yujin Lee ◽  
Ina Nemet ◽  
Zeneng Wang ◽  
Heidi T. M. Lai ◽  
Marcia C. de Oliveira Otto ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Renal Function ◽  
Impaired Renal Function ◽  
Proportional Hazards ◽  
Dietary Habits ◽  
Experimental Studies ◽  
Cox Proportional Hazards ◽  
Atherosclerotic Cardiovascular Disease ◽  
Community Based ◽  
Stable Isotope Dilution

Background Trimethylamine N‐oxide (TMAO) is a gut microbiota‐dependent metabolite of dietary choline, L‐carnitine, and phosphatidylcholine‐rich foods. On the basis of experimental studies and patients with prevalent disease, elevated plasma TMAO may increase risk of atherosclerotic cardiovascular disease (ASCVD). TMAO is also renally cleared and may interact with and causally contribute to renal dysfunction. Yet, how serial TMAO levels relate to incident and recurrent ASCVD in community‐based populations and the potential mediating or modifying role of renal function are not established. Methods and Results We investigated associations of serial measures of plasma TMAO, assessed at baseline and 7 years, with incident and recurrent ASCVD in a community‐based cohort of 4131 (incident) and 1449 (recurrent) older US adults. TMAO was measured using stable isotope dilution liquid chromatography–tandem mass spectrometry (laboratory coefficient of variation, <6%). Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, sudden cardiac death, or other atherosclerotic death) was centrally adjudicated using medical records. Risk was assessed by multivariable Cox proportional hazards regression, including time‐varying demographics, lifestyle factors, medical history, laboratory measures, and dietary habits. Potential mediating effects and interaction by estimated glomerular filtration rate (eGFR) were assessed. During prospective follow‐up, 1766 incident and 897 recurrent ASCVD events occurred. After multivariable adjustment, higher levels of TMAO were associated with a higher risk of incident ASCVD, with extreme quintile hazard ratio (HR) compared with the lowest quintile=1.21 (95% CI, 1.02–1.42; P ‐trend=0.029). This relationship appeared mediated or confounded by eGFR (eGFR‐adjusted HR, 1.07; 95% CI, 0.90–1.27), as well as modified by eGFR ( P ‐interaction <0.001). High levels of TMAO were associated with higher incidence of ASCVD in the presence of impaired renal function (eGFR <60 mL/min per 1.73 m 2 : HR, 1.56 [95% CI, 1.13–2.14]; P ‐trend=0.007), but not normal or mildly reduced renal function (eGFR ≥60 mL/min per 1.73 m 2 : HR, 1.03 [95% CI, 0.85–1.25]; P ‐trend=0.668). Among individuals with prior ASCVD, TMAO associated with higher risk of recurrent ASCVD (HR, 1.25 [95% CI, 1.01–1.56]; P ‐trend=0.009), without significant modification by eGFR. Conclusions In this large community‐based cohort of older US adults, serial measures of TMAO were associated with higher risk of incident ASCVD, with apparent modification by presence of impaired renal function and with higher risk of recurrent ASCVD.

scholarly journals Longitudinal Measures of Trimethylamine N-oxide and Incident Atherosclerotic Cardiovascular Disease Events in Older Adults: The Cardiovascular Health Study

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1434-1434
Author(s):  
Yujin Lee ◽  
Zeneng Wang ◽  
Heidi Lai ◽  
Marcia de Oliveira Otto ◽  
Rozenn Lemaitre ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Older Adults ◽  
Renal Function ◽  
Cystatin C ◽  
Impaired Renal Function ◽  
Cardiovascular Health ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Atherosclerotic Cardiovascular Disease ◽  
Community Based

Abstract Objectives Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite of dietary choline, L-carnitine and phosphatidylcholine-rich animal foods. Based on experimental studies and cohorts with prevalent disease, elevated TMAO may increase risk of atherosclerotic cardiovascular disease (ASCVD). TMAO is also renally cleared and may interact with and causally contribute to renal dysfunction and elevated cystatin-C. Yet, the associations of serial TMAO levels with incident ASCVD in a community-based prospective cohort, and the potential mediating and modifying role of renal function, are not established. Methods We investigated the associations of serial measures of plasma TMAO, assessed at baseline and 7 years post baseline, with incident ASCVD among 4144 older adults in the Cardiovascular Health Study (CHS). TMAO was measured using stable isotope dilution LC/MS/MS (lab CV &lt;6%). Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, sudden cardiac death, or other atherosclerotic death) was centrally adjudicated using medical records. Risk was assessed by multivariable Cox proportional hazards regression including time-varying demographics, lifestyle factors, medical history, and laboratory and dietary variables. We assessed potential mediating effects and interaction by renal function estimated by cystatin-C. Results During a median 15 years follow-up, 1757 ASCVD events occurred. After multivariable adjustment, TMAO was associated with a higher risk of ASCVD, with an extreme quintile HR (95% CI) of 1.22 (1.04, 1.44), P-trend = 0.01. This relationship appeared further mediated or confounded by estimated glomerular filtration rate (eGFR): adjusting for cystatin-C-based eGFR, the HR (95% CI) was 1.06 (0.98–1.25). Significant interaction was also observed by renal function (P-interaction &lt; 0.001), with TMAO associated with higher risk of ASCVD among individuals with impaired renal function (eGFR ≤ 60) [1.63 (1.03–2.59)], but not normal baseline renal function (eGFR &gt; 60) [1.15 (0.96–1.37)], even with further adjustment for continuous eGFR. Conclusions In this large community-based cohort of older US adults, higher serial measures of TMAO were associated with an elevated risk of ASCVD, in particular among those with impaired renal function. Funding Sources NIH, NHLBI.

scholarly journals Cluster Analysis of Cardiovascular Phenotypes in Patients With Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Potential Approach to Precision Medicine

2021 ◽  
Author(s):  
Abhinav Sharma ◽  
Yinggan Zheng ◽  
Justin A. Ezekowitz ◽  
Cynthia M. Westerhout ◽  
Jacob A. Udell ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cluster Analysis ◽  
Proportional Hazards ◽  
Cardiovascular Death ◽  
Cox Proportional Hazards ◽  
Machine Learning Algorithms ◽  
Atherosclerotic Cardiovascular Disease ◽  
Asian Patients

<b>Objective:</b> Phenotypic heterogeneity among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) is ill defined.<b> </b>We used cluster analysis machine learning algorithms to identify phenotypes among trial participants with T2DM and ASCVD. <p><b>Research Design and Methods:</b><i> </i>We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n=14,671), a cardiovascular outcome safety trial comparing sitagliptin with placebo in patients with T2DM and ASCVD (median follow-up 3.0 years). Cluster analysis using 40 baseline variables was conducted, with associations between clusters and the primary composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina) assessed by Cox proportional hazards models. We replicated the results using the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial.</p> <p><b>Results:</b><i> </i>Four distinct phenotypes were identified: cluster I included Caucasian men with a high prevalence of coronary artery disease; cluster II included Asian patients with a low body mass index; cluster III included women with non-coronary ASCVD disease; and cluster IV included patients with heart failure and kidney dysfunction. The primary outcome occurred respectively in 11.6%, 8.6%, 10.3%, and 16.8% of patients in clusters I to IV. The crude difference in cardiovascular risk for the highest versus lowest risk cluster (cluster IV vs. II) was statistically significant (HR, 2.74; 95% CI, 2.29-3.29). Similar phenotypes and outcomes were identified in EXSCEL. </p> <p><b>Conclusions:</b><i> </i>In patients with T2DM and ASCVD, cluster analysis identified four clinically distinct groups. Further cardiovascular phenotyping is warranted to inform patient care and optimize clinical trial designs.</p>

scholarly journals Why is renal impairment associated with poorer cancer specific survival in breast cancer patients?: a comparison with patients with other comorbidities

2020 ◽  
Vol 25 (10) ◽  
pp. 1786-1792
Author(s):  
Andy Evans ◽  
Russell Petty ◽  
Jane Macaskill
Keyword(s):  
Breast Cancer ◽  
Renal Function ◽  
Impaired Renal Function ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Study Group ◽  
Cancer Specific Survival ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
The Poor

Abstract Background Our aim is to assess whether the poor breast cancer specific survival (BCSS) seen in women with breast cancer and impaired renal function can be explained by associations with other prognostic factors. Methods The study group was a consecutive series of patients undergoing breast ultrasound (US) who had invasive breast cancer (n = 1171). All women had their US diameter and mean stiffness (kPa) at shear wave elastography (SWE) recorded. The core biopsy grade and receptor status were noted. Core biopsy of abnormal axillary nodes and the patient referral source was also noted. Survival including cause of death was ascertained. Comorbidities at diagnosis were recorded. Patients were divided into those with a GFR<60 (“renal group”), those with other comorbidities and those with none. BCSS was assessed using Kaplan–Meier survival curves and Cox proportional hazards regression. Results One thousand, one hundred and forty-one patients constituted the study group. 107 (9%) patients had impaired renal function, 182 (16%) had other comorbidities while 852 (75%) had no comorbidities. Mean follow-up was 5.8 years. 109 breast cancer and 122 non-breast cancer deaths occurred. BCSS in the renal group was significantly worse than the other groups. Women with renal comorbidity were older, more likely to present symptomatically, have a pre-operative diagnosis of axillary metastases, and have larger and stiffer cancers. Cox proportional hazards regression showed that renal impairment maintained independent significance. Conclusion The poor BCSS in women with impaired renal function is partially explained by advanced tumour stage at presentation. However, impaired renal function maintains an independent prognostic effect.

scholarly journals Cluster Analysis of Cardiovascular Phenotypes in Patients With Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Potential Approach to Precision Medicine

2021 ◽  
Author(s):  
Abhinav Sharma ◽  
Yinggan Zheng ◽  
Justin A. Ezekowitz ◽  
Cynthia M. Westerhout ◽  
Jacob A. Udell ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cluster Analysis ◽  
Proportional Hazards ◽  
Cardiovascular Death ◽  
Cox Proportional Hazards ◽  
Machine Learning Algorithms ◽  
Atherosclerotic Cardiovascular Disease ◽  
Asian Patients

<b>Objective:</b> Phenotypic heterogeneity among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) is ill defined.<b> </b>We used cluster analysis machine learning algorithms to identify phenotypes among trial participants with T2DM and ASCVD. <p><b>Research Design and Methods:</b><i> </i>We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n=14,671), a cardiovascular outcome safety trial comparing sitagliptin with placebo in patients with T2DM and ASCVD (median follow-up 3.0 years). Cluster analysis using 40 baseline variables was conducted, with associations between clusters and the primary composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina) assessed by Cox proportional hazards models. We replicated the results using the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial.</p> <p><b>Results:</b><i> </i>Four distinct phenotypes were identified: cluster I included Caucasian men with a high prevalence of coronary artery disease; cluster II included Asian patients with a low body mass index; cluster III included women with non-coronary ASCVD disease; and cluster IV included patients with heart failure and kidney dysfunction. The primary outcome occurred respectively in 11.6%, 8.6%, 10.3%, and 16.8% of patients in clusters I to IV. The crude difference in cardiovascular risk for the highest versus lowest risk cluster (cluster IV vs. II) was statistically significant (HR, 2.74; 95% CI, 2.29-3.29). Similar phenotypes and outcomes were identified in EXSCEL. </p> <p><b>Conclusions:</b><i> </i>In patients with T2DM and ASCVD, cluster analysis identified four clinically distinct groups. Further cardiovascular phenotyping is warranted to inform patient care and optimize clinical trial designs.</p>

Association of Impaired Fasting Glucose with Cardiovascular Disease in the Absence of Risk Factor

2021 ◽  
Author(s):  
Yingting Zuo ◽  
Xinsheng Han ◽  
Xue Tian ◽  
Shuohua Chen ◽  
Shouling Wu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Impaired Fasting Glucose ◽  
Proportional Hazards ◽  
Fasting Glucose ◽  
Cox Proportional Hazards ◽  
Atherosclerotic Cardiovascular Disease ◽  
Primordial Prevention ◽  
Increased Risk ◽  
Ascvd Risk

Abstract Background The association between impaired fasting glucose (IFG) and cardiovascular disease (CVD) in participants without atherosclerotic cardiovascular disease (ASCVD) risk factors based on current definitions is unclear. The study aimed to examine the association of fasting glucose levels with CVD and its subtypes in persons without ASCVD risk factors. Methods This study included 38,297 participants (men, 62.1%; mean age, 47.9 [12.9] years) who were free of a history of CVD, absent of ASCVD risk factors, and had a fasting plasma glucose (FPG) level between 70 to 125 mg/dl at baseline from Kailuan Study during 2006 to 2007, participants were followed up until new-onset CVD event, death or December 31, 2017. Cox proportional hazards models were performed to evaluate the associations. Results During a median follow-up of 11.0 years (interquartile range, 10.7-11.2 years), we observed 1,217 incident CVD events. Compared with participants with FPG 70 to 99 mg/dl, the multivariable adjusted hazard ratios for CVD among participants with FPG 100 to 109 mg/dl and 110 to 125 mg/dl were 1.18 (95% confidence interval [CI], 1.02-1.38) and 1.27 (95%CI, 1.03-1.55), respectively. Multivariable-adjusted spline regression model showed a J-shaped association between FPG and the risk of CVD. Conclusions We found that among individuals without diabetes or other traditional ASCVD risk factors, there is an increased risk of incident CVD with increasing abnormal FPG levels. These results highlight the importance of primordial prevention for FPG level increases along with other traditional ASCVD risk factors.

scholarly journals The Association of Plasma Trimethylamine N-Oxide With All-Cause and Cardiovascular Mortality: The Multi-Ethnic Study of Atherosclerosis

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 63-63
Author(s):  
Meng Wang ◽  
Xinmin Li ◽  
Zeneng Wang ◽  
Marcia de Oliveira Otto ◽  
Rozenn Lemaitre ◽  
...  
Keyword(s):  
Renal Function ◽  
Proportional Hazards ◽  
Healthy Eating Index ◽  
Cox Proportional Hazards ◽  
Ethnic Community ◽  
Cvd Risk ◽  
Community Based ◽  
Ethnic Study ◽  
All Cause Mortality ◽  
Cvd Mortality

Abstract Objectives Trimethylamine N-oxide (TMAO) is a gut-microbiota generated metabolite of dietary phosphatidylcholine, choline, and carnitine. TMAO has been suggested to play a role in the pathogenesis of multiple diseases. Yet, studies of TMAO and mortality were conducted in convenience samples of patients with prevalent diseases and lacked socioeconomic and lifestyle data, raising the likelihood of selection bias and residual confounding. To address these research gaps, we investigated the associations of plasma TMAO levels with all-cause and cardiovascular disease (CVD) mortality in a prospective multi-ethnic community-based cohort. Methods The study included 6776 participants from the Multi-Ethnic Study of Atherosclerosis. TMAO was measured at baseline using mass spectrometry. Adjudicated CVD deaths included death due to coronary heart disease, stroke, other atherosclerotic diseases, or other CVDs. Multivariable Cox proportional hazards models assessed associations with adjustment for baseline sociodemographic, lifestyle, diet, and traditional CVD risk factors (BMI, blood pressure, lipids, diabetes, CRP, medications). We also assessed pre-specified interactions by age, sex, race/ethnicity, low vs. high adherence to Alternate Healthy Eating index, and renal function measured by creatinine-based estimated glomerular filtration rate (eGFR). Results During median follow-up of 15.9 years, 1548 participants died, 362 from CVD. Higher TMAO levels were associated with higher risk of both all-cause mortality (HR = 1.09, 95%CI: 1.04 - 1.13, per inter-quintile range increase, 7.5 µM/L) and CVD mortality (HR = 1.10, 95%CI: 1.02 - 1.19). Interaction by renal function was observed for all-cause mortality (P-interaction &lt; 0.005), with a positive association between TMAO and risk in those with impaired renal function (eGFR &lt; 60) [HR = 1.15, 95%CI: 1.09 -1.21], but not normal or mildly reduced renal function (eGFR ≥ 60) [HR = 1.02, 95%CI: 0.95 - 1.08]. No other significant interactions were observed. Conclusions In this multi-ethnic community-based cohort of US adults, higher plasma TMAO levels were associated with a higher risk of all-cause and CVD mortality. The mechanisms of interaction by renal function need to be further studied, especially given that TMAO is renally cleared. Funding Sources NIH

scholarly journals Serum Calcification Propensity and Clinical Events in CKD

2019 ◽  
Vol 14 (11) ◽  
pp. 1562-1571 ◽  
Author(s):  
Joshua D. Bundy ◽  
Xuan Cai ◽  
Rupal C. Mehta ◽  
Julia J. Scialla ◽  
Ian H. de Boer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Proportional Hazards ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cox Proportional Hazards ◽  
Atherosclerotic Cardiovascular Disease ◽  
Calciprotein Particles ◽  
All Cause Mortality ◽  
Prospective Longitudinal

Background and objectivesPatients with CKD are at high risk for cardiovascular disease, ESKD, and mortality. Vascular calcification is one pathway through which cardiovascular disease risks are increased. We hypothesized that a novel measure of serum calcification propensity is associated with cardiovascular disease events, ESKD, and all-cause mortality among patients with CKD stages 2–4.Design, setting, participants, & measurementsAmong 3404 participants from the prospective, longitudinal Chronic Renal Insufficiency Cohort Study, we quantified calcification propensity as the transformation time (T50) from primary to secondary calciprotein particles, with lower T50 corresponding to higher calcification propensity. We used multivariable-adjusted Cox proportional hazards regression models to assess the associations of T50 with risks of adjudicated atherosclerotic cardiovascular disease events (myocardial infarction, stroke, and peripheral artery disease), adjudicated heart failure, ESKD, and mortality.ResultsThe mean T50 was 313 (SD 79) minutes. Over an average 7.1 (SD 3.1) years of follow-up, we observed 571 atherosclerotic cardiovascular disease events, 633 heart failure events, 887 ESKD events, and 924 deaths. With adjustment for traditional cardiovascular disease risk factors, lower T50 was significantly associated with higher risk of atherosclerotic cardiovascular disease (hazard ratio [HR] per SD lower T50, 1.14; 95% confidence interval [95% CI], 1.05 to 1.25), ESKD within 3 years from baseline (HR per SD lower T50, 1.68; 95% CI, 1.52 to 1.86), and all-cause mortality (HR per SD lower T50, 1.16; 95% CI, 1.09 to 1.24), but not heart failure (HR per SD lower T50, 1.06; 95% CI, 0.97 to 1.15). After adjustment for eGFR and 24-hour urinary protein, T50 was not associated with risks of atherosclerotic cardiovascular disease, ESKD, and mortality.ConclusionsAmong patients with CKD stages 2–4, higher serum calcification propensity is associated with atherosclerotic cardiovascular disease events, ESKD, and all-cause mortality, but this association was not independent of kidney function.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_10_28_CJN04710419.mp3

scholarly journals Association between milk and yogurt intake and mortality: a community-based cohort study (Yamagata study)

BMC Nutrition ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Akiko Nakanishi ◽  
Erika Homma ◽  
Tsukasa Osaki ◽  
Ri Sho ◽  
Masayoshi Souri ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Hazard Analysis ◽  
Total Mortality ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Milk Intake ◽  
Community Based ◽  
Hazards Model ◽  
Kaplan Meier

Abstract Background Dairy products are known as health-promoting foods. This study prospectively examined the association between milk and yogurt intake and mortality in a community-based population. Methods The study population comprised of 14,264 subjects aged 40–74 years who participated in an annual health checkup. The frequency of yogurt and milk intake was categorized as none (< 1/month), low (< 1/week), moderate (1–6/week), and high (> 1/day) intake. The association between yogurt and milk intake and total, cardiovascular, and cancer-related mortalities was determined using the Cox proportional hazards model. Results During the follow-up period, there were 265 total deaths, 40 cardiovascular deaths and 90 cancer-related deaths. Kaplan–Meier analysis showed that the total mortality in high/moderate/low yogurt intake and moderate/low milk intake groups was lower than that in none group (log-rank, P < 0.01). In the multivariate Cox proportional hazard analysis adjusted for possible confounders, the hazard ratio (HR) for total mortality significantly decreased in high/moderate yogurt intake group (HR: 0.62, 95% confidence interval [CI]: 0.42–0.91 for high intake, HR: 0.70, 95%CI: 0.49–0.99 for moderate intake) and moderate milk intake group (HR: 0.67, 95% CI: 0.46–0.97) compared with the none yogurt and milk intake groups. A similar association was observed for cancer-related mortality, but not for cardiovascular mortality. Conclusions Our study showed that yogurt and milk intake was independently associated with a decrease in total and cancer-related mortalities in the Japanese population.

scholarly journals Added value of cardiovascular calcifications for prediction of recurrent cardiovascular events and cardiovascular interventions in patients with established cardiovascular disease

2021 ◽  
Author(s):  
Cilie C. van ’t Klooster ◽  
◽  
Yolanda van der Graaf ◽  
Hendrik M. Nathoe ◽  
Michiel L. Bots ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Heart Valve ◽  
Cardiovascular Events ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Added Value ◽  
Cvd Risk ◽  
Major Cardiovascular Events ◽  
Cox Proportional Hazards Models ◽  
Cardiovascular Interventions

AbstractThe purpose is to investigate the added prognostic value of coronary artery calcium (CAC), thoracic aortic calcium (TAC), and heart valve calcium scores for prediction of a combined endpoint of recurrent major cardiovascular events and cardiovascular interventions (MACE +) in patients with established cardiovascular disease (CVD). In total, 567 patients with established CVD enrolled in a substudy of the UCC-SMART cohort, entailing cardiovascular CT imaging and calcium scoring, were studied. Five Cox proportional hazards models for prediction of 4-year risk of MACE + were developed; traditional CVD risk predictors only (model I), with addition of CAC (model II), TAC (model III), heart valve calcium (model IV), and all calcium scores (model V). Bootstrapping was performed to account for optimism. During a median follow-up of 3.43 years (IQR 2.28–4.74) 77 events occurred (MACE+). Calibration of predicted versus observed 4-year risk for model I without calcium scores was good, and the c-statistic was 0.65 (95%CI 0.59–0.72). Calibration for models II–V was similar to model I, and c-statistics were 0.67, 0.65, 0.65, and 0.68 for model II, III, IV, and V, respectively. NRIs showed improvement in risk classification by model II (NRI 15.24% (95%CI 0.59–29.39)) and model V (NRI 20.00% (95%CI 5.59–34.92)), but no improvement for models III and IV. In patients with established CVD, addition of the CAC score improved performance of a risk prediction model with classical risk factors for the prediction of the combined endpoint MACE+ . Addition of the TAC or heart valve score did not improve risk predictions.

scholarly journals Risk and Timing of Cardiovascular Disease After Androgen-Deprivation Therapy in Men With Prostate Cancer

2015 ◽  
Vol 33 (11) ◽  
pp. 1243-1251 ◽  
Author(s):  
Sean O'Farrell ◽  
Hans Garmo ◽  
Lars Holmberg ◽  
Jan Adolfsson ◽  
Pär Stattin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cardiovascular Disease ◽  
Androgen Deprivation Therapy ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Androgen Deprivation ◽  
Gnrh Agonists ◽  
Cvd Risk ◽  
Comparison Cohort ◽  
Using Data

Purpose Findings on the association between risk of cardiovascular disease (CVD) and the duration and type of androgen-deprivation therapy (ADT) in men with prostate cancer (PCa) are inconsistent. Methods By using data on filled drug prescriptions in Swedish national health care registers, we investigated the risk of CVD in a cohort of 41,362 men with PCa on ADT compared with an age-matched, PCa-free comparison cohort (n = 187,785) by use of multivariable Cox proportional hazards regression models. Results From 2006 to 2012, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio [HR] of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 95% CI, 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 95% CI, 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months of GnRH agonist therapy of 1.91 (95% CI, 1.66 to 2.20), an HR of CVD with AA of 1.60 (95% CI, 1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (95% CI, 1.16 to 2.76) versus the comparison cohort. Conclusion Our results support that there should be a solid indication for ADT in men with PCa so that benefit outweighs potential harm; this is of particular importance among men with a recent history of CVD.

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