Correlation of KRAS status with clinical outcome in patients (pts) with metastatic colorectal cancer (mCRC) treated first-line with FOLFOX6 + cetuximab (FX+C) or FOLFIRI + cetuximab (FF+C): The CECOG/CORE1.2.001 trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4055-4055
Author(s):  
I. Koza ◽  
F. Wrba ◽  
D. Vrbanec ◽  
J. Ocvirk ◽  
T. E. Ciuleanu ◽  
...  
Keyword(s):  
Hazard Analysis ◽  
Progression Free Survival ◽  
Prolonged Survival ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Kras Status ◽  
Significant Difference ◽  
The Impact ◽  
Early Occurrence

4055 Background: Previous retrospective analyses of KRAS mutation status from the randomized CECOG/CORE 1.2.001 phase II trial has shown that treatment with cetuximab plus standard chemotherapy (CT) in pts with KRAS wild-type (wt) tumors leads to significantly better progression-free survival (PFS) and overall survival (OS) compared with KRAS mutant (mt) tumors. Methods: CECOG investigators performed a post-study survival update, re-assessing the impact of KRAS status and other possible predictive factors for OS using multivariable Cox proportional hazard methods. Results: KRAS-evaluable tissue was available from 117 (77%) of 151 pts in the ITT population. KRAS wt status was detected in 53% (n=62) of tumors (34/57 and 28/60 in the FX+C and FF+C arm, respectively). After a median follow up of 29 months (mo), OS in pts with KRAS wt tumors was significantly improved compared to pts with KRAS mt tumors (median 20.8 vs 15.9 mo; hazard ratio (HR)=1.62; p=0.0296). OS analysis by treatment arm revealed a statistically significant difference in favor of pts with KRAS wt tumors in the FX+C arm (median 22.5 vs 15.2; HR=2.06; p=0.0201) and no significant differences in the FF+C arm. Exploratory multivariable Cox proportional hazard analysis showed that as well as KRAS wt status (vs KRAS mt), an acne-like rash of grade 2/3 (vs grade 0/1) in the first 6 weeks and no prior treatment (vs prior neo-/adjuvant treatment) were the strongest independent predictors for prolonged survival (each p<0.005). Conclusions: This analysis confirmed the results of previous studies: treatment with cetuximab plus standard CT in pts with KRAS wt tumors leads to significantly better OS compared to pts with KRAS mt tumors. The early occurrence of a cetuximab-related grade 2/3 acne-like rash seems to be an independent predictor for prolonged survival in addition to KRAS status. The relevance of the lower predictive value of KRAS status noted for OS in the FF+C arm pts vs the significant effect in the FX+C arm is undetermined due to the low sample size of the subgroup analyses. [Table: see text]

Baseline neutrophil-to-eosinophil ratio (NER) and its association with clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (CPI).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16569-e16569
Author(s):  
Deepak Ravindranathan ◽  
Yuan Liu ◽  
Dylan J. Martini ◽  
Jacqueline T Brown ◽  
Bassel Nazha ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Clinical Benefit ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
P Value ◽  
Proportional Hazard ◽  
Free Survival ◽  
Cox Proportional Hazard ◽  
Significant Difference

e16569 Background: Inflammatory markers have been studied as prognostic markers in patients with mRCC treated with CPIs. Recently, eosinophilia has been found to be associated with improved survival of patients with melanoma treated with CPIs. We reported baseline NER in patients with mRCC treated with CPIs and its association with clinical outcomes. Methods: We conducted a retrospective analysis of patients with mRCC treated with CPIs at Winship Cancer Institute from 2015-2018. Clinical outcomes were measured as overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). OS and PFS were calculated from CPI-initiation to date of death and radiographic or clinical progression, respectively. Patients with baseline NER were categorized into high or low; high defined as NER > 49.2 and low defined as NER < 49.2. Univariate (UVA) and multivariate (MVA) analyses were carried out for OS and PFS using Cox proportional hazard model. Results: A total of 184 patients were studied with a median follow up of 25.4 months. Median age was 63 years old with 72% male and 20% black. About 25% were in high NER group. The high NER patients had significantly shorter OS in both UVA (HR: 0.58, p-value=0.017) and MVA (HR: 0.62, p-value=0.046) (Table). There was no significant difference between groups for PFS. Clinical benefit was seen in 47.3% of patients with low baseline NER and 40% with high NER. Conclusions: High baseline NER was associated with worse OS in patients with mRCC treated with CPIs. Larger, prospective studies are warranted to validate this hypothesis generating data.[Table: see text]

scholarly journals Microalbuminuria After Kidney Transplantation Predicts Cardiovascular Morbidity

2021 ◽  
Vol 8 ◽  
Author(s):  
Dana Bielopolski ◽  
Ruth Rahamimov ◽  
Boris Zingerman ◽  
Avry Chagnac ◽  
Limor Azulay-Gitter ◽  
...  
Keyword(s):  
Hazard Analysis ◽  
Cardiovascular Morbidity ◽  
Urine Collection ◽  
Proportional Hazard ◽  
Cvd Risk ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Cardiovascular Morbidity And Mortality ◽  
Independent Association

Background: Microalbuminuria is a well-characterized marker of kidney malfunction, both in diabetic and non-diabetic populations, and is used as a prognostic marker for cardiovascular morbidity and mortality. A few studies implied that it has the same value in kidney transplanted patients, but the information relies on spot or dipstick urine protein evaluations, rather than the gold standard of timed urine collection.Methods: We revisited a cohort of 286 kidney transplanted patients, several years after completing a meticulously timed urine collection and assessed the prevalence of major cardiovascular adverse events (MACE) in relation to albuminuria.Results: During a median follow up of 8.3 years (IQR 6.4–9.1) 144 outcome events occurred in 101 patients. By Kaplan-Meier analysis microalbuminuria was associated with increased rate of CV outcome or death (p = 0.03), and this was still significant after stratification according to propensity score quartiles (p = 0.048). Time dependent Cox proportional hazard analysis showed independent association between microalbuminuria and CV outcomes 2 years following microalbuminuria detection (HR 1.83, 95% CI 1.07–2.96).Conclusions: Two years after documenting microalbuminuria in kidney transplanted patients, their CVD risk was increased. There is need for primary prevention strategies in this population and future studies should address the topic.

scholarly journals Prognosis of hemodialysis patients with progressive aortic stenosis: a prospective cohort study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yoriko Horiguchi ◽  
Kaoru Uemura ◽  
Naoyoshi Aoyama ◽  
Shinichi Nakajima ◽  
Tomoki Asai ◽  
...  
Keyword(s):  
Aortic Stenosis ◽  
Cardiac Death ◽  
Hazard Analysis ◽  
Hemodialysis Patients ◽  
Proportional Hazard ◽  
Cardiac Events ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
All Cause Mortality

Abstract Background Whether progressive mild to moderate aortic stenosis in hemodialysis patients influences their prognosis has not been elucidated. This prospective cohort study explored whether progressive aortic stenosis predicted the rate of cardiac events and mortality in those patients. Methods A total of 283 consecutive hemodialysis patients (no aortic stenosis, 248; progressive aortic stenosis, 35) underwent echocardiography for assessment of aortic stenosis, with a median follow-up period of 4.1 years. Study endpoints were cardiac events, all-cause mortality, and cardiac death. Kaplan–Meier analysis and multivariate Cox proportional hazard analysis were performed to estimate cardiac events, all-cause mortality, and cardiac death. Results Cumulative cardiac event rate, all-cause mortality rate, and the rate of cardiac death at 3-year follow-up were 44.9%, 40.5%, and 26.4% in patients with progressive aortic stenosis and 22.1%, 19.0%, and 7.5% in those without aortic stenosis, respectively. Kaplan–Meier analysis demonstrated the cumulative rates of cardiac events and all-cause mortality. And cardiac death was significantly higher in patients with progressive aortic stenosis than in those without aortic stenosis. Multivariate Cox proportional hazard analysis revealed that progressive aortic stenosis was predictive of cardiac events (adjusted hazard ratio 2.47; 95% confidence interval 1.38–4.39) and cardiac death (adjusted hazard ratio 4.21; 95% confidence interval 2.10–8.46). Age, physical activity, C-reactive protein, and serum albumin levels—but not progressive aortic stenosis—predicted all-cause mortality. Conclusions The rates of cardiac events and cardiac death were higher in hemodialysis patients with progressive aortic stenosis than in those without aortic stenosis. Furthermore, progressive aortic stenosis predicted cardiac events and cardiac death. Compared with those without aortic stenosis, patients with progressive aortic stenosis had higher all-cause mortality, which was related to their comorbidities. Trial registration This study was retrospectively registered with University Hospital Medical Information Network Clinical Trials Registry (registration number, UMIN 000024023) at September 12th, 2016.

scholarly journals Relationship between social support status and mortality in a community-based population: a prospective observational study (Yamagata study)

2020 ◽  
Author(s):  
Tsutomu Uzuki ◽  
Tsuneo Konta ◽  
Ritsuko Saito ◽  
Ri Sho ◽  
Tsukasa Osaki ◽  
...  
Keyword(s):  
Social Support ◽  
Social Relationships ◽  
Cardiovascular Mortality ◽  
Prospective Observational Study ◽  
Hazard Analysis ◽  
Vital Role ◽  
Proportional Hazard ◽  
Community Based ◽  
Cox Proportional Hazard

Abstract Background: Social support, defined as the exchange of support in social relationships, plays a vital role in maintaining healthy behavior and mitigating the effects of stressors. This study investigated whether functional aspect of social support is related to 5-year mortality in health checkup participants.Methods: This study recruited 16,651 subjects (6,797 males, 9,854 females). Social support was evaluated using five-component questions: Do you have someone 1) whom you can consult when you are in trouble? 2) whom you can consult when your physical condition is not good? 3) who can help you with daily homework? 4) who can take you to hospital when you don't feel well? and 5) who can take care of you when you are ill in bed? The association between the component of social support and all-cause and cardiovascular mortality was examined using Cox proportional hazard analysis.Results: The percentage of subjects without social support components was 7.7%-15.0%. They were more likely to be male, non-elderly, and living alone. During the follow-up period, there were 166 all-cause and 38 cardiovascular deaths. Cox proportional analysis adjusted for confounders showed that only the lack of support for transportation to hospital was significantly associated with all-cause (hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.26-3.05) and cardiovascular mortality (HR 3.30, 95% CI 1.41-6.87). These associations were stronger in males than females.Conclusion: This study showed that the lack of social support for transportation to the hospital was independently associated with all-cause and cardiovascular mortality in a community-based population.

scholarly journals Relationship between social support status and mortality in a community-based population: a prospective observational study (Yamagata study)

2020 ◽  
Author(s):  
Tsutomu Uzuki ◽  
Tsuneo Konta ◽  
Ritsuko Saito ◽  
Ri Sho ◽  
Tsukasa Osaki ◽  
...  
Keyword(s):  
Social Support ◽  
Social Relationships ◽  
Cardiovascular Mortality ◽  
Prospective Observational Study ◽  
Hazard Analysis ◽  
Vital Role ◽  
Proportional Hazard ◽  
Community Based ◽  
Cox Proportional Hazard

Abstract Background: Social support, defined as the exchange of support in social relationships, plays a vital role in maintaining healthy behavior and mitigating the effects of stressors. This study investigated whether functional aspect of social support is related to 5-year mortality in health checkup participants. Methods: This study recruited 16,651 subjects (6,797 males, 9,854 females). Social support was evaluated using five-component questions: Do you have someone 1) whom you can consult when you are in trouble? 2) whom you can consult when your physical condition is not good? 3) who can help you with daily homework? 4) who can take you to hospital when you don’t feel well? and 5) who can take care of you when you are ill in bed? The association between the component of social support and all-cause and cardiovascular mortality was examined using Cox proportional hazard analysis. Results: The percentage of subjects without social support components was 7.7%-15.0%. They were more likely to be male, non-elderly, and living alone. During the follow-up period, there were 166 all-cause and 38 cardiovascular deaths. Cox proportional analysis adjusted for confounders showed that only the lack of support for transportation to hospital was significantly associated with all-cause (hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.26-3.05) and cardiovascular mortality (HR 3.30, 95% CI 1.41-6.87). These associations were stronger in males than females. Conclusion: This study showed that the lack of social support for transportation to the hospital was independently associated with all-cause and cardiovascular mortality in a community-based population.

Maintenance therapy with bevacizumab with or without erlotinib in metastatic colorectal cancer (mCRC) according to KRAS: Results of the GERCOR DREAM phase III trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3515-3515 ◽  
Author(s):  
Christophe Tournigand ◽  
Benoist Chibaudel ◽  
Benoit Samson ◽  
Werner Scheithauer ◽  
Gérard Lledo ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Phase Iii Trial ◽  
Kras Status ◽  
Secondary Endpoints ◽  
The Impact ◽  
Egfr Tki

3515 Background: The primary analysis of DREAM demonstrated that a maintenance therapy (MT) with bevacizumab (Bev) + EGFR TKI erlotinib (E) significantly improved progression-free survival (PFS) after a 1st-line Bev-based induction therapy (IT) in patients (pts) with unresectable mCRC. Methods: Pts were randomized to MT after an IT with FOLFOX-bev or XELOX-bev or FOLFIRI-bev between Bev alone (Bev 7.5 mg/kg q3w; arm A) or Bev+E (Bev 7.5 mg/kg q3w, E 150 mg/d ; arm B) until PD or unacceptable toxicity. Primary endpoint was PFS on MT. Secondary endpoints included PFS from inclusion, overall survival (OS) and safety. The impact of KRAS tumor status on treatment efficacy was evaluated in an exploratory analysis. Results: 700 pts were registered and 452 pts were randomized (228 in arm A, 224 in arm B). KRAS status was available for 413/452 (91%) pts. The median duration of MT was 3.6 m. Results for MT are presented below (Table). In the registered population, median OS was 24.9m (22.5 – 27.3). Conclusions: Maintenance treatment with bev + erlotinib increases PFS over maintenance with bev alone in pts with mCRC but does not prolong OS. Further follow-up will determine the impact of 2nd or 3rd line anti-EGFR Mabs in this study. Contrasting with anti-EGFR Mabs, KRAS tumor status is not mandatory to select pts with mCRC for treatment with erlotinib. Clinical trial information: NCT00265824. [Table: see text]

scholarly journals The impact of catheter ablation for patients with asymptomatic atrial fibrillation: subanalysis of kansai plus atrial fibrillation (kpaf) registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Pak ◽  
A Kobori ◽  
S Shizuta ◽  
Y Sasaki ◽  
T Toyota ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Primary Endpoint ◽  
Hazard Analysis ◽  
Secondary Endpoint ◽  
Asymptomatic Patients ◽  
Significant Difference ◽  
Secondary Endpoints ◽  
The Impact

Abstract Background Catheter ablation (CA) of atrial fibrillation (AF) for symptomatic patients improves the quality of life and prognosis of patients with heart failure. However, the impact of CA for asymptomatic patients is still controversial. Purpose We aimed to investigate the clinical outcomes of CA of AF for asymptomatic patients compared to those for symptomatic patients. Methods A total of 5,013 patients from the Kansai Plus Atrial Fibrillation (KPAF) Registry who underwent CA were screened. The patients were divided into three groups by type of AF; paroxysmal (PAF), persistent (PEAF) and long standing (LSAF) and the patients in each type of AF were divided into two groups: asymptomatic and symptomatic. The primary endpoint was recurrent supraventricular tachyarrhythmias lasting for more than 30 seconds during follow-up 4 years after CA. The secondary endpoint was a composite of cardiovascular, cerebral, and gastrointestinal events during follow-up 4 years after CA. The incidence of complications related to CA between asymptomatic and symptomatic patients was also evaluated. Kaplan–Meier analysis was employed to estimate the primary and secondary endpoints. The statistical differences in primary and secondary endpoints between asymptomatic and symptomatic patients were evaluated using a log–rank test. The impact of symptom due to AF on the primary and secondary endpoint was evaluated using a Cox hazard analysis. The difference in incidence of complications between asymptomatic and symptomatic patients was evaluated using a chi–square test. Results In this study population, PAF was the most frequent at 64.4%, followed by PEAF (22.7%) and LSAF (13.0%). There were some significant differences in the baseline characteristics between asymptomatic and symptomatic patients in each type of AF. The proportion of male was significantly higher in asymptomatic patients than symptomatic patients in PAF (81.2% versus 67.2%, p&lt;0.001) and PEAF (86.4% versus 74.3%, p&lt;0.001). Left atrial diameter was larger in asymptomatic patients than symptomatic patients only in PAF (40±6mm versus 38±6mm, p&lt;0.001). In all types of AF, there was no significant difference in primary endpoint between asymptomatic and symptomatic patients as follows: 37.5% versus 40.6% (p=0.6) in PAF, 45.2% versus 55.1% (p=0.09) in PEAF and 59.3% versus 63.6% (p=1.0) in LSAF. There was also no significant difference in secondary endpoint between asymptomatic and symptomatic patients: 7.1% versus 6.8% (p=0.7) in PAF, 5.4% versus 8.7% (p=0.3) in PEAF and 4.4% versus 5.1% (p=0.5) in LSAF. In a Cox hazard analysis, the symptom did not affect both of the primary and secondary endpoints in each type of AF. In regard to the incidence of complications related to CA, there was no significant difference between asymptomatic and symptomatic patients in each type of AF. Conclusion CA of AF for asymptomatic patients can be safe and can lead to equivalent outcomes as well as symptomatic patients. Funding Acknowledgement Type of funding source: None

Clinical factors affecting the late resistance to gefitinib in patients with non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7191-7191
Author(s):  
Y. Segawa ◽  
K. Hotta ◽  
S. Umemura ◽  
Y. Fujiwara ◽  
T. Shinkai ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Proportional Hazard ◽  
Clinical Factors ◽  
Free Survival ◽  
Factors Affecting ◽  
Cox Proportional Hazard

7191 Background: The mechanism of late resistance of NSCLC to gefitinib is unclear. In this study, we assessed clinical factors affecting the late resistance in patients with NSCLC. Methods: Between 2000 and 2004, 197 consecutive patients with NSCLC underwent treatment with gefitinib in our institutions. Of those, 56 patients who had received a prior chemotherapy and continued treatment with gefitinib during at least 6 months were included in this study. The characteristics of these patients were as follows: median age, 62.5 years (range, 28 to 77 years); male/female, 22/34 patients; PS 0/1/2/3/4, 15/31/8/0/2 patients; and adeno/nonadenocarcinoma, 52/4 patients. Thirty-two patients never smoked and 24 were former or current smokers. Nineteen patients underwent surgical resection of NSCLC. Numbers of chemotherapy regimens were one in 31 patients, two in 18, three in 6, four in 1, respectively. Results: Of 56 patients, three achieved a CR and 39 attained a PR, with an overall response rate of 75% (95% CI, 69.2 to 80.8%). The remaining 14 patients had a long SD. At a median follow-up time of 21.6 months (range, 7.7 to 59.7 months), median time to progression was 19.5 months, with progression-free survival rates of 68.5% at 1-year, 33.6% at 2-year, and 21.2% at 3-year, respectively. In a univariate analysis regarding progression-free survival, presences of metastasis to brain (p = 0.008), bone (p = 0.025), liver (p = 0.046), and adrenal (p = 0.008), decreased levels of hemoglobin (p = 0.021) and albumin (p = 0.017), and use of multiple chemotherapy regimens prior to treatment with gefitinib (p = 0.026) were significant factors. In a multivariate analysis using Cox proportional hazard model, presence of brain metastasis was a significant factor clinically affecting the late resistance to gefitinib (hazard ratio, 2.14; 95% CI, 1.10 to 4.17, p = 0.025). In addition, decreased hemoglobin level (p = 0.074) and prior multiple chemotherapy regimens (p = 0.069) were tended to be significant. Conclusions: In patients undergoing treatment with gefitinib, presence of brain metastasis was an important factor indicative of the emergence of late resistance in this study. It is needed to confirm this finding in a large cohort of patients with NSCLC. No significant financial relationships to disclose.

Metformin use in diabetic patients with multiple myeloma (MM): A SEER-Medicare study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18127-e18127
Author(s):  
Shivaprasad Manjappa ◽  
Mark A Fiala ◽  
Ravi Vij ◽  
Keith Stockerl-Goldstein ◽  
Mark A. Schroeder ◽  
...  
Keyword(s):  
Female Gender ◽  
Diabetic Patients ◽  
Proportional Hazard ◽  
Part D ◽  
Cox Proportional Hazard ◽  
Comorbidity Index ◽  
Medicare Database ◽  
Insulin Use ◽  
The Impact

e18127 Background: Metformin, an oral hypoglycemic agent, has been linked to favorable outcomes among patients (pts) with cancer (Coyle et al. Ann Oncol 2016). Wu et al. demonstrated better overall survival (OS) with metformin use in pts with mm and Diabetes Mellitus (DM) (Br J Cancer 2014). They also found that patient with steroid-induced DM [SID] had worse outcomes than pts with pre-existing DM [PDM]. However, Keller et al. did not find these associations in a study of VA mm pts (Blood 2015 126:4502). We evaluated the impact of DM and metformin use on outcomes of pts with mm in the SEER-Medicare database. Methods: We used SEER-Medicare claims from 2007-2013 for pts with newly diagnosed MM. DM was identified using ICD-9 codes, antidiabetic medications by Medicare part D prescription claims. Multivariate analysis was performed by Cox proportional hazard modelling to evaluate (1) Association of DM type (PDM or SID) with mm outcomes and (2) Impact of metformin on outcomes of pts with mm and DM. Covariates included age, gender, transplant, CKD (chronic kidney disease), CCI (Charlson Comorbidity Index), and use of other antidiabetic medications. Potential smoldering mm cases in the dataset were controlled for using a pre-established algorithm (Fakhri, et al,Blood 2016 128:2348) Results: Out of 4708 mm pts, 45% had DM. Among the pts with DM, 28% were on metformin. Out of the 2112 pts with DM, 20% had SID. Median follow up was 26 months. We found no association between PDM (aHR 1.04, 95% CI 0.96-1.12) or SID (aHR 1.03, 0.91-1.17) with OS when compared to non-diabetic pts. Metformin use, female gender, transplant and CCI < 5 were significantly associated with improved OS. Metformin use was associated with an 18% decrease in mortality (aHR 0.82, 0.72-0.93, p = 0.002); controlling for CKD did not impact the association (aHR 0.83 (0.73- 0.94, p = 0.005). Other antidiabetic medications including insulin were not associated with OS. Conclusions: DM (PDM or SID) and insulin use were not associated with poorer outcomes. Metformin use was associated with improved OS among pts with mm and DM in the SEER-Medicare database. The impact of metformin on outcomes in mm pts should be further investigated in prospective clinical trials.

scholarly journals P0779THE POPULATION ATTRIBUTABLE FRACTION OF HYPERURICEMIA FOR ALL-CAUSE AND CARDIOVASCULAR MORTALITY: A NATIONWIDE COMMUNITY-BASED STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tomomi Tanaka ◽  
Tomomi Tanaka ◽  
Masahiro Miyata ◽  
Kazunobu Ichikawa ◽  
Tsuneo Konta ◽  
...  
Keyword(s):  
Cardiovascular Mortality ◽  
Large Scale ◽  
Hazard Analysis ◽  
Population Attributable Fraction ◽  
Attributable Fraction ◽  
Proportional Hazard ◽  
Community Based ◽  
Cox Proportional Hazard ◽  
Hazard Ratios

Abstract Background and Aims Hyperuricemia is often observed in subjects with chronic kidney disease and is associated with all-cause and cardiovascular mortality. In this study, we evaluated the effect size of hyperuricemia for all-cause and cardiovascular mortality in a community-based population, using the index of population attributable fraction (PAF). Method This large-scale cohort study used the nationwide database of 500,511 health check-up participants (215,728 men, 284,783 women, average age 62 years) and calculated the PAF of hyperuricemia (serum uric acid &gt;7 mg/dL) for all-cause and cardiovascular deaths during the 7-year follow-up period. Results The frequency of hyperuricemia at baseline was 9.7% in total subjects (men: 22.0%; women: 2.6%). During the follow-up period, 5,578 deaths (1.1%) were noted (men: 3,749 [1.7%], women: 1,829 [0.6%]), including 1,104 cardiovascular deaths (0.2%) (men: 762 [0.4%], women: 342 [0.1%]). In the Cox proportional hazard analysis adjusted for confounding factors including age, gender, body mass index, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia and eGFR, hyperuricemia was an independent risk factor for all-cause and cardiovascular mortality, (adjusted hazard ratios [95% confidence interval]; 1.39 [1.27-1.53] for all-cause mortality, and 1.76 [1.47-2.11] for cardiovascular mortality). The adjusted PAF of hyperuricemia for all-cause and cardiovascular deaths were 3.1% and 4.7% (approximately 1 in 32 all-cause deaths, and 1 in 21 cardiovascular deaths), respectively. In subgroup analyses, the association between hyperuricemia and death was stronger in men and smokers. The adjusted PAF for all-cause and cardiovascular deaths was 5.5% and 8.6% (approximately 1 in 18 all-cause deaths, 1 in 12 cardiovascular deaths) in men, and 6.2% and 8.2% (approximately 1 in 16 all-cause deaths, 1 in 12 cardiovascular deaths) in smokers, respectively. Conclusion This study showed that a substantial number of all-cause and cardiovascular deaths, was statistically attributed to hyperuricemia in the community-based population, especially men and smokers.

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