A Comparative Study of Surgery versus Radiation Therapy on the Risk of Cardiovascular Disease Mortality in Patients with Early Stage Non-Small Cell Lung Cancer

The correlations between body mass index (BMI) and risk of all-cause and cardiovascular disease (CVD) mortality in patients with type 2 diabetes mellitus (T2DM) are still controversial. To explore the correlation between BMI and the risk of all-cause and CVD mortality in patients with T2DM. The data sources China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed, Web of Science, Embase, and The Cochrane Library were searched up until May 25, 2024. After adjusting for confounding factors, the original study on the association between BMI and all-cause and CVD mortality in patients with T2DM was analyzed. Number of all-cause and CVD mortality events, BMI, and basic characteristics were extracted. Twenty-eight papers with a total of 728 321 participants were finally included. Compared to normal-weight patients with T2DM, the risk of all-cause (HR = 1.61; 95% CI [1.51, 1.72]; P = .000) and CVD (HR = 1.31; 95% CI [1.10, 1.54]; P = .002) mortality were increased in underweight patients; however, they were reduced (HR = 0.85; 95% CI [0.81, 0.89]; P = .000) and (HR = 0.86; 95% CI [0.78, 0.96]; P = .007), respectively in patients with overweight. Also, there were significant reductions in the risk of all-cause (HR = 0.85; 95% CI [0.78, 0.92]; P = .000) and CVD (HR = 0.81; 95% CI [0.74, 0.89]; P = .000] mortality in patients with mild obesity. The difference in the risk of all-cause mortality (HR = 0.98; 95% CI [0.80, 1.21]; P = .881) in patients with moderate obesity was not statistically significant. We found that there were correlations between BMI and the risk of all-cause and CVD mortality in patients with T2DM. The obesity paradox remains.

Background Current guidelines recommend that adults with chronic health conditions should engage in regular physical activity (PA), and avoid inactivity. Yet, the exact role of PA trajectories in the mortality risk of patients with coronary heart disease (CHD) remains unclear. Purpose We aimed to perform a systematic review and meta-analysis on the association of longitudinal trajectories of PA with all-cause and cardiovascular disease (CVD) mortality in patients with CHD. Methods We performed a systematic review and meta-analysis based on PRISMA statement. Six electronic databases were searched for cohort studies that analysed the association of PA trajectories (inactive over time, active over time, increased activity over time, and decreased activity over time) with the risk of all-cause and CVD mortality in patients with CHD. Study quality was evaluated by the Newcastle Ottawa scale. We used the inverse variance weighted method to combine summary measures using random-effects models to minimize the effect of between-study heterogeneity. The study is registered in PROSPERO. Results We meta-analyzed nine longitudinal cohorts involving 33,576 patients (25010 acute CHD, 8566 chronic CHD, mean age 62.5 years, 34% women, median follow-up duration 7.2 years), according to four PA trajectories. All studies assessed PA through validated questionnaires. The definitions of activity and inactivity at baseline and follow-ups were in agreement with current PA guidelines. Trajectories were calculated based on comparison of activity status at baseline and follow-up. All the studies defined increased activity over time as moving from the inactive to the active category, and decreased activity over time as moving from the active to the inactive category. Compared to patients remaining inactive over time, the lowest risk of all-cause and CVD mortality was observed in patients remaining active over time (HR [95% CI]: 0.50 [0.39–0.63] and 0.48 [0.35–0.68], respectively), followed by patients who increased their PA over time (HR [95% CI]:0.55 [0.44–0.7] and 0.63 [0.51–0.78], respectively), and patients who decreased activity over time (HR [95% CI]: 0.80 [0.64–0.99] and 0.91 [0.67–1.24], respectively). These results were consistent both in the acute and chronic CHD settings. The overall risk of bias was low, and no evidence of publication bias was observed. Multiple sensitivity analyses provided consistent results. Conclusions In patients with CHD, the risk of all-cause and CVD mortality is progressively reduced from being inactive over time, to decreased activity over time, to increased activity over time, to being active over time. These findings highlight the benefits of adopting a more physically active lifestyle in patients with chronic and acute CHD, independent of previous PA levels. Future studies should clarify the complex interactions between motivations and disease severity as potential drivers for PA trajectories Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): University of Bern

Cardiovascular disease (CVD) mortality in schizophrenia is more frequent than in the general population. Whether second-generation antipsychotics (SGAs) increase risk of CVD morbidity and mortality has yet to be determined. We conducted a retrospective cohort study using an administrative database to identify patients with DSM-III- or DSM-IV-diagnosed schizophrenia, treated in Maryland, who started clozapine treatment (n = 1,084) or were never treated with clozapine (initiated on risperidone; n = 602) between 1994 and 2000. Deaths between 1994 and 2004 were identified by the Social Security Death Index, and death records were obtained. During the 6- to 10-year follow-up period, there were 136 deaths, of which 43 were attributed to CVD. Cardiovascular disease mortality in patients aged younger than 55 years at medication start was approximately 1.1% (clozapine, 1.1%; risperidone, 1.0%) in both groups at 5 years and 2.7% (clozapine) and 2.8% (risperidone) at 10 years (chi(2)(1) = 0.12, P = .73). Patients who started treatment at ages >or= 55 years had CVD mortality of 8.5% (clozapine) and 3.6% (risperidone) at 5 years and 16.0% (clozapine) and 5.7% (risperidone) at 10 years (chi(2)(1) = 2.13, P = .144). In a Cox regression model, patients aged >or= 55 years were at greater risk of mortality than younger patients (hazard ratio = 4.6, P < .001); whites were at greater risk than nonwhites (HR = 2.1, P = .046); however, SGA treatment (HR = 1.2; 95% CI, 0.6-2.4; P = .61) and sex (HR = 0.9, P = .69) were not statistically significant predictors of CVD, nor was there a significant age x clozapine interaction (chi(2)(1) = 1.52, P = .22). Age-, race-, and gender-adjusted standardized mortality ratios were significantly elevated (clozapine, 4.70; 95% CI, 3.19-6.67; risperidone, 2.88; 95% CI, 1.38-5.30) compared to year 2000 rates for the Maryland general population but did not differ by antipsychotic group (chi(2)(1) = 1.42, P = .23). The risk of CVD mortality in schizophrenia does not differ between clozapine and risperidone in adults despite known differences in risk profiles for weight gain and metabolic side effects. However, we cannot rule out an increased risk of CVD mortality among those starting treatment at ages 55 years or older.

ObjectivesType 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD) may exacerbate atherosclerosis through mechanisms such as chronic inflammation, oxidative stress, and lipid redistribution. This study aims to investigate the relationship between atherogenic index of plasma (AIP) and cardiovascular disease (CVD) mortality in patients with T2DM and DKD.MethodsCOX regression models and restricted cubic spline (RCS) curves were utilized to analyze the survival outcomes and non-linear associations among patients with T2DM and DKD. Threshold effects were observed in both global and inflection point models, confirming the predictive value of AIP for participants. Subgroup analysis further investigated the interaction of other variables within the AIP index on T2DM and patients with DKD with CVD mortality.ResultsA total of 5,108 patients diagnosed with T2DM, along with 1,598 patients suffering from DKD, were included in this study. In patients with DKD, the AIP index has a “U”-shaped association with CVD mortality. The hazard ratio (HR) and 95% confidence interval of the third quartile of CVD mortality in patients with DKD is Model3: 0.76 (0.61–0.96) (P < 0.023). The inflection point of the threshold effect analysis is 0.14. When AIP is less than 0.14, the effect size and 95% confidence interval of CVD mortality risk in patients with DKD is 0.62 (0.40–0.96) (P < 0.033). When AIP is greater than or equal to 0.14, the effect size and 95% confidence interval of CVD mortality risk in patients with DKD is 1.68 (1.15–2.45) (P < 0.008).ConclusionsThe relationship between AIP and CVD mortality in patients with DKD exhibits a “U” shaped curve, with a turning point value of 0.14. When AIP is below 0.14, the risk significantly decreases (HR = 0.62); conversely, when AIP is equal to or exceeds 0.14, the risk markedly increases (HR = 1.68).Supplementary InformationThe online version contains supplementary material available at 10.1186/s12872-025-05234-1.

To explore the association between Metabolic Score for Insulin Resistance (METS-IR) and the risk of cardiovascular disease (CVD) death in patients with rheumatoid arthritis (RA). This retrospective cohort study extracted data on 1,218 RA patients from the National Health and Nutrition Examination Survey. The weighted univariate and multivariate Cox regression model was established to explore the association between METS-IR and CVD mortality. Subgroup analysis was performed in terms of age, gender, body mass index, diabetes, and CVD. Hazard ratios (HRs) and 95% confidence levels (CIs) were presented. Increased METS-IR was associated with a significantly higher risk of CVD mortality (HR=4.59, 95%CI: 1.98-10.67), and METS-IR>2.48 was associated with higher odds of CVD mortality compared with METS-IR ≤ 2.25 (HR=3.57, 95%CI: 2.04-6.24). METS-IR was positively associated with the risk of CVD mortality (HR=3.83, 95%CI: 1.62-9.08), and METS-IR>2.48 was associated with a significantly higher risk of CVD mortality in contrast to METS-IR ≤ 2.25 (HR=3.38, 95%CI: 1.87-6.09). Increased METS-IR was associated with a significantly higher risk of CVD mortality in RA patients. Clinicians could consider incorporating the METS-IR score into routine assessment of the prognosis of RA patients.

Accumulating evidence shows that NAFLD might play a role in the etiology and progression of CVD, but little is known on the association of NAFLD and CVD mortality in patients with a history of a myocardial infarction (MI). Therefore, we studied the relationship of Fatty Liver Index (FLI), as indicator for non-alcoholic fatty liver disease (NAFLD), with 12-year risk of cardiovascular disease (CVD) and all-cause mortality in post-MI patients. We included 4165 Dutch patients from the Alpha Omega Cohort aged 60-80 years who had an MI ≤10 years prior to study enrolment. NAFLD was defined as FLI ≥60. Patients were followed for cause-specific mortality from enrolment (2002-2006) through December 2018. Hazard ratios for CVD and all-cause mortality were obtained by multivariable Cox regression using FLI <30 (indicating absence of NAFLD) as the reference. Baseline FLI as a continuous measure was studied with mortality using restricted cubic splines analyses. The median (IQR) FLI was 68 (48-84). Sixty percent of the patients had FLI ≥60, who were more likely to be male and more often had diabetes, high blood pressure, and high serum cholesterol levels. During 12 years of follow-up, 2042 deaths occurred of which 846 from CVD. Patients with NAFLD were at increased risk of CVD mortality (HR: 1.55 [1.19, 2.03]) and all-cause mortality (HR: 1.21 [1.03; 1.41]) compared to patients without NAFLD. Results remained consistent after excluding patients with obesity and diabetes. To conclude, the adverse association of FLI with CVD mortality was stronger in female than in male patients with conventional cut-off points. FLI ≥60, indicating NAFLD, was a predictor for CVD and all-cause mortality in post-MI patients, independent of other cardiometabolic risk factors. However, cut-off points might differ between male and female patients for predicting CVD mortality.

Atherogenic index predicts all-cause and cardiovascular mortality in incident peritoneal dialysis patients

Background: Prediabetes has become a global health issue, and currently, the relationship between vitamin levels and mortality in prediabetes remains unclear. This study aims to investigate the association between the levels of eleven vitamins and all-cause and cardiovascular disease (CVD) mortality in prediabetes patients. Methods: This cross-sectional study included 14 634 prediabetes patients from 10 cycles of the National Health and Nutrition Examination Survey between 1999 and 2018. Mortality and underlying causes of death were determined by linking records from the National Death Index until December 31, 2019. Multivariable Cox proportional hazards regression models were established to assess hazard ratios and 95% confidence intervals for all-cause, CVD, cancer, and other mortalities. Restricted cubic splines were used to visualize non-linear associations between various vitamins and mortality risk. Results: During the follow-up period, 2316/14 634 prediabetes patients died (12.55%), with 722 deaths (3.68%) attributed to CVD. After multivariable adjustment, vitamin B1, niacin, folate, vitamin C, vitamin E, and vitamin K levels exhibited non-linear associations with all-cause mortality (all p < 0.05). Vitamin B1, niacin, and vitamin E levels showed non-linear associations with CVD mortality (p < 0.05). Vitamin B6 exhibited a linear negative association with all-cause, CVD, and other mortalities (p > 0.05). However, vitamins A and B2 levels were not significantly associated with mortality rates (all p > 0.05). Consistent results were observed in the subgroup analyses after complete adjustment for variables. Conclusions: Higher levels of dietary vitamins B1, B6, niacin, folate, vitamin C, vitamin E, and vitamin K were significantly associated with lower risk of all-cause mortality and CVD mortality in patients with prediabetes. There was no association between vitamin A and B2 levels and all-cause and CVD mortality among individuals with prediabetes. These findings suggest the importance of correcting vitamin deficiencies to prevent mortality in prediabetes patients.

Objective: To investigate the effect of pre-dialysis blood pressure (Pre-BP) on all-cause and cardiovascular disease (CVD) mortality in patients on maintenance hemodialysis (MHD). Methods: This single-center, retrospective cohort study enrolled patients undergoing first-time hemodialysis between January 1, 2007, and June 30, 2021, from the dialysis registry of the First Affiliated Hospital, Zhejiang University School of Medicine. General information and laboratory parameters were collected. Pre-dialysis systolic blood pressure (Pre-SBP) and pre-dialysis diastolic blood pressure (Pre-DBP) were calculated and averaged at 4-6 months after dialysis. The mean Pre-SBP and Pre-DBP values were used as continuous variables, and restricted cubic spline (RCS) curves were used to assess the relationship between Pre-BP and mortality risk. Patients were subsequently divided into six groups for Pre-DBP and six groups for Pre-SBP combined with Pre-DBP. Survival analyses were performed using the Kaplan-Meier method. All-cause and CVD mortality were compared between groups using the log-rank test. Multivariate Cox regression models were used to analyze the associations between Pre-BP and all-cause and CVD mortality. Results: A total of 1 213 patients were enrolled. By the end of follow-up, 175 patients (14.4%) had died, of whom 62 (35.4%) died from CVD. Kaplan-Meier survival curves showed that the Pre-DBP<65 mmHg group (1 mmHg=0.133 kPa) had a significantly lower cumulative survival rate (χ²=90.52, P<0.001) and a significantly higher CVD mortality rate (χ²=35.54, P<0.001) than the other groups. The combined Pre-SBP and Pre-DBP analysis showed that the Pre-SBP≥150 mmHg and Pre-DBP<80 mmHg groups had a significantly lower cumulative survival rate (χ²=45.58, P<0.001) and a significantly higher CVD mortality rate (χ²=30.13, P<0.001) than the other groups. Multivariate Cox regression model analysis showed that compared with other groups, the risk of MHD all-cause mortality was increased in the Pre-DBP<65 mmHg group and the Pre-SBP≥150 mmHg and Pre-DBP<80 mmHg group [HR (95%CI)=1.927 (1.195-3.109), 3.298 (1.567-6.939), both P<0.05]. Conclusion: In patients undergoing MHD, Pre-DBP<65 mmHg or Pre-SBP≥150 mmHg and Pre-DBP<80 mmHg were independent risk factors for all-cause mortality, with a low cumulative survival rate and a high risk of CVD mortality.

Stroke represents the primary cause of death and persistent disability globally, leading to around 5.5 million annual patient fatalities. The objective was to explore the relationship of dietary fiber with all-cause and cardiovascular disease (CVD) mortality risk in patients with stroke. We extracted stroke patients' data from the National Health and Nutrition Examination Survey (NHANES) database. All-cause and CVD mortality were outcomes. Dietary fiber consists of non-digestible forms of carbohydrates, usually polysaccharides that originate from plant-based foods. Covariates including demographic data, vital signs, comorbidities, laboratory parameters, and medication use were screened using the weighted multivariate Cox regression models with backward elimination. Weighted univariate and multivariate Cox regression models were performed to explore the relationship between dietary fiber intake and all-cause/CVD mortality, with hazard ratios (HRs) and 95% confidence intervals (CIs). The association was further investigated in different subgroups. A total of 1,578 patients with stroke were included, of whom 688 (43.6%) died. Total fiber and vegetable fiber intake were analyzed as categorical variables, and the lowest intake was considered reference groups. High intake of total fiber (HR, 0.73; 95% CI, 0.57-0.94) and high intake of vegetable fiber (HR, 0.63; 95% CI, 0.48-0.82) were related to lower all-cause mortality risk in individuals with stroke. Similar findings were also observed between higher total fiber (HR, 0.56; 95% CI, 0.37-0.85) and vegetable fiber intake (HR, 0.57; 95% CI, 0.36-0.89) with decreased CVD mortality risk. The relationship between higher total fiber intake and lower all-cause mortality risk was discovered in individuals aged ≥ 60 yrs, smoking, non-CVD, and chronic kidney disease (CKD). High total fiber, or vegetable fiber consumption was linked to lower CVD mortality risk in stroke individuals aged ≥ 60 yrs, females, body mass index ≥ 30 kg/m2, non-smoking, and CKD. Dietary fiber intake and vegetable fiber intake may benefit the prognosis of patients with stroke. Increasing dietary fiber consumption, especially vegetable fiber intake, potentially benefits the prognosis of stroke patients.

Oxidative balance score (OBS) is a composite measures that assess the balance between pro-oxidant and antioxidant factors in an individual’s diet and lifestyle, with higher scores indicating greater antioxidant exposure. Despite its potential significance, there is a limited body of research exploring the relationship between OBS and all-cause and cardiovascular disease (CVD) mortality specifically in younger patients with diabetes. We aimed to investigate the possible relationship between OBS and all-cause and CVD mortality in younger patients with diabetes. Data for this study were obtained from the 2003–2018 NHANES. This study enrolled 3501 participants. The endpoints were all-cause and CVD mortality, determined by the National Death Index (NDI). OBS, which consists of 16 dietary factors and 4 lifestyle factors, is categorized into pro-oxidants and antioxidants. The OBS was categorized into four quartiles (Q1-Q4). We used multivariable Cox proportional hazards regression models to examine the association between continuous and quartile measures of OBS, lifestyle OBS (lifestyle antioxidants such as physical activity, etc., and lifestyle pro-oxidants such as alcohol, smoking, etc.), and dietary OBS (dietary antioxidants such as fiber, β-carotene, riboflavin, etc., and dietary pro-oxidants, such as total fat, etc.) with all-cause and CVD mortality. Additionally, we explored restricted cubic spline (RCS) analysis and also performed subgroup analyses and interaction tests. The occurrence of 409 all-cause deaths (11.7%) and 108 CVD-related deaths (3.1%) was recorded during the follow-up period. Our results found that OBS, lifestyle OBS, and dietary OBS were negatively associated with patients’ all-cause and CVD mortality. The RCS analysis further validated the association of a linear negative correlation between OBS and all-cause and CVD mortality. The results of our subgroup analyses revealed that the negative association between OBS and CVD mortality may be influenced by alcohol use. In conclusion, results from a nationally representative study of younger American patients with diabetes suggest a negative association between OBS, lifestyle OBS, and dietary OBS and all-cause and CVD mortality. Antioxidant-rich diets and lifestyle improvements are essential for reducing all-cause and CVD mortality in patients.

Hypertension and proteinuria are major risk factors for cardiovascular disease (CVD) mortality in patients with type 2 diabetes. Blood pressure (BP) targets have been progressively lowered in these patients to prevent or delay the progression of nephropathy. However, no long-term population-based studies have been reported on the interaction between BP and proteinuria with respect to total and CVD mortality in patients with type 2 diabetes. We prospectively followed 881 middle-aged type 2 diabetic patients, free of CVD events at baseline, for up to 18 years. Participants were categorized into four groups according to baseline systolic BP (<130, 130-139, 140-159 and ≥160 mmHg) and further stratified by proteinuria (≤150 or >150 mg L(-1)). Cox proportional hazards model was used to estimate the joint association between systolic BP and proteinuria and the risk of mortality. During follow-up, 607 patients died including 395 because of CVD. After adjustment for confounding factors, total and CVD mortality were significantly higher in patients with proteinuria and systolic BP <130 mmHg compared with those with systolic BP between 130 and 160 mmHg. The prognosis was similar in patients with systolic BP <130 mmHg or ≥160 mmHg. Among patients without proteinuria, systolic BP <130 mmHg was associated with a nonsignificant reduction in mortality. Type 2 diabetic patients with proteinuria and with systolic BP <130 mmHg may have an increased risk of CVD mortality. The presence of proteinuria should be taken into account when defining the target systolic BP level for the prevention of fatal CVD events in patients with type 2 diabetes.

Introduction: Elevated BP is associated with increased risk of cardiovascular mortality. However, there is ongoing debate whether intensive BP lowering may paradoxically increase the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). This study was undertaken to understand the association of BP with risk of CVD mortality in patients with T2DM. Method: This was a cohort study on 83,721 patients with T2DM age 40 years or older using data from a multi-institutional diabetes registry in Singapore from 2013 to 2019. The relationships between BP and CVD mortality were analyzed using Cox multivariable regression model, adjusting for covariates including gender, use of anti-hypertensive medications and presence of co-existing CVD. Results: Overall, the mean age was 65.3 years with 50.6% women, 78.9% on antihypertensive medications, 21.3% with pre-existing CVD and 7.6 per 1000 person-years experienced the outcome over 7 years. Compared to SBP 120-129 mm Hg, the risk of CVD mortality was higher in SBP 140 mm Hg in patients with and without pre-existing CVD, the elderly and non-elderly. The hazard ratios (HR) were 1.27 (95% CI: 1.12-1.45), 1.87 (1.65-2.12), 1.49 (1.35-1.64) and 1.87 (1.55-2.25), respectively. Using DBP 70-79 mm Hg as reference, DBP &lt; 70 mm Hg was also associated with higher risk of CVD mortality in all patient groups, with corresponding HR 1.25 (1.12-1.39), 1.23 (1.11-1.36), 1.19 (1.10-1.29) and 1.54 (1.32-1.80), respectively. DBP 90 mm Hg was also associated with higher risk of CVD mortality in the elderly and those without pre-existing CVD. Conclusion: In patients with T2DM, higher SBP is associated with raised CVD mortality risk. Elevated DBP is independently associated with higher risk of CVD mortality albeit only in those without pre-existing CVD and the elderly. DBP &lt; 70 mm Hg is also associated with risk of CVD outcome although reverse causality cannot be ruled out.

Testicular germ-cell tumors (GCTs) represent one of the few solid tumors in which the majority of patients with metastatic disease are cured. In 2015, it is estimated that there will be 8,430 new occurrences and only 380 deaths as a result of testicular cancer. Treatment for testicular GCTs involves radical orchiectomy in almost all patients, regardless of the extent of disease. Subsequent treatment options, which depend on disease stage, include active surveillance, retroperitoneal lymph node dissection (RPLND), and cytotoxic chemotherapy. Radiation therapy is also an option in patients diagnosed with pure seminoma. With the implementation and refinement of cisplatin-based combination chemotherapy in the late 1970s and 1980s, approximately 80% of all patients with metastatic GCTs now are cured. Therefore, understanding the acute and long-term effects associated with treatment for a largely curable disease is important to optimize the care of this patient population. In the article accompanying this editorial, using the SEER database, Fung et al compared the cardiovascular disease (CVD) mortality risk in 15,006 patients with nonseminomatous germ-cell tumors (NSGCTs) who either received chemotherapy as part of their initial treatment plan (n 6,909) or underwent surgery alone (n 8,097) with the CVD mortality risk in the general population. Compared with the general population, there was an increased risk in CVD mortality in patients who were treated with chemotherapy; however, there was no difference in CVD mortality in the surgery-alone group. In total, 54 cardiovascular deaths occurred in the chemotherapy group, and 50 occurred in the surgery-only group. Of interest, the statistically significant increase in CVD mortality in the chemotherapy group compared with the general population was limited to the first year after the diagnosis of testicular NSGCT. In the first year after diagnosis, 11 patients who received chemotherapy for the treatment of testicular NSGCT, versus two patients in the surgery-only group, had a cardiovascular cause of death. Several population-based, observational studies have shown an increased long-term risk of developing CVD in testicular GCT survivors. The most likely explanation for the increased incidence of CVD seen in this patient population is the early development of atherosclerotic disease, possibly secondary to metabolic syndrome. Willemse et al demonstrated a 1.9-fold increased risk of developing metabolic syndrome in testicular GCT survivors and a 2.3-fold higher risk in the subgroup that received chemotherapy compared with healthy men as controls. The mechanism for the development of metabolic syndrome in long-term survivors is not completely understood but may be associated, in part, with hypogonadism that results from cytotoxic chemotherapy. Conversely, Fung et al hypothesize that their novel finding of early CVD mortality may at least partially occur through the direct toxic effect of cisplatin on the vascular system and the resultant endothelial dysfunction. SEER is a large, population-based cancer database that provides extensive information on demographics, tumor characteristics, and initial treatment modalities. The SEER registries also collect and report data on vital status and cause of death, which allow for the study of cancer incidence, survival, and trends in care over time. However, it is important to be aware of some pitfalls when analyses are conducted with the SEER database. First, analyses from SEER are limited by the potential inherent confounders and bias associated with any retrospective analysis. In addition, the heterogeneity and lack of granularity in the SEER-coded causes of death may make the true etiology less clear. In the study by Fung et al, the SEER-coded diseases of heart account for six of the 11 deaths in the chemotherapy group in the first year after testicular NSGCT diagnosis, which suggests an arterial thrombotic event as the cause of death. However, this SEER category also includes the International Classification of Diseases 9th and 10th revisions codes for acute pulmonary embolism, a venous thromboembolic event (VTE). There is abundant evidence that cisplatin increases the risk of VTE in a multitude of malignancies. In testicular GCTs, the estimated thromboembolic (arterial and venous) rate has ranged from 8.4% to 18% in patients who received cisplatin-based chemotherapy. Greater than 80% of the events were VTE in these studies. It is also established that VTE leads to increased mortality in patients with cancer. Because there is a known predominance of VTE associated with cisplatin, the inclusion of pulmonary embolism in the analysis may have contributed significantly to the CVD mortality seen in the chemotherapy group in the study by Fung et al. In addition to the aforementioned six deaths as a result of diseases of heart, the remaining five deaths in the first year resulted from cerebrovascular diseases. This SEER-coded category also is heterogeneous, because it is not possible to discern whether the deaths as a JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 28 OCTOBER 1 2015

Remnant cholesterol as a risk factor for all-cause and cardiovascular mortality in incident peritoneal dialysis patients