Long-term Medical Outcomes of Living Kidney Donors

Historically, to minimize risks, living kidney donors have been highly selected and healthy. Operative risks are well-defined, yet concern remains about long-term risks. In the general population, even a mild reduction in glomerular filtration rate (GFR) is associated with cardiovascular disease, chronic kidney disease, and end-stage kidney disease (ESKD). However, reduction in GFR in the general population is due to kidney or systemic disease. Retrospective studies comparing donors with matched general population controls have found no increased donor risk. Prospective studies comparing donors with controls (maximum follow-up, 9 years) have reported that donor GFR is stable or increases slightly, whereas GFR decreases in controls. However, these same studies identified metabolic and vascular donor abnormalities. There are a few retrospective studies comparing donors with controls. Each has limitations in selection of the control group, statistical analyses, and/or length of follow-up. One such study reported increased donor mortality; 2 reported a small increase in absolute risk of ESKD. Risk factors for donor ESKD are similar to those in the general population. Postdonation pregnancies are also associated with increased risk of hypertension and preeclampsia. There is a critical need for long-term follow-up studies comparing donors with controls from the same era, geographic area, and socioeconomic status who are healthy, with normal renal function on the date matching the date of donation, and are matched on demographic characteristics with the donors. These data are needed to optimize donor candidate counseling and informed consent.     

Echocardiography-Based Cardiac Structure Parameters for the Long-term Risk of End-Stage Kidney Disease in Black Individuals: The Atherosclerosis Risk in Communities Study

ObjectiveTo assess whether echocardiographic parameters of left ventricular (LV) structure and function relate to the long-term risk of incident end-stage kidney disease (ESKD).Patients and MethodsWe conducted a prospective cohort study analyzing 2137 Black participants from the Jackson site of the Atherosclerosis Risk in Communities Study from January 1, 1993, through July 31, 2017. Echocardiographic parameters of LV structure and function were obtained from 1993 to 1995. The primary outcome incident ESKD was identified through the linkage to the United States Renal Data System. Cox proportional hazards models were used to estimate the hazard ratios (HRs) according to each echocardiographic parameter.ResultsThere were 117 incident ESKD cases during a median follow-up of 22.2 (interquartile range, 15.0-23.3) years. Multivariable Cox models revealed that a higher LV mass index was significantly associated with the risk of ESKD (HR, 2.38; 95% CI, 1.21 to 4.68 for highest vs lowest quartile, P = 0.012). The HRs were significant and even higher for LV posterior wall thickness, with slightly higher HRs when their measures in end-systole (HR for highest vs lowest quartile, 4.38; 95% CI, 1.94 to 9.92, P < 0.001) vs end-diastole (HR, 3.50; 95% CI, 1.53 to 8.01, P = 0.003) were used. The associations were not significant for LV function parameters.ConclusionIn Black individuals residing in the community, echocardiographic parameters of LV structure, including LV wall thickness, were robustly associated with the risk of subsequently incident ESKD. These results have potential implications for novel prevention and management strategies for persons with abnormal LV structure.     

Adherence to a Healthy Sleep Pattern and Risk of Chronic Kidney Disease: The UK Biobank Study

ObjectiveTo examine the association of a healthy sleep pattern, characterized by sleep of 7 to 8 h/d, morning person, no insomnia, no frequent snoring, and no daytime sleepiness, with the risk of chronic kidney disease (CKD).MethodsWe included 392,218 European adults, aged 38 to 73 years, who were free of CKD at recruitment between March 13, 2006, and October 1, 2010, from the UK Biobank study. Data on sleep behaviors were collected through questionnaires at recruitment. Cox proportional hazards regression models were used to assess the relations between the healthy sleep score and risk of CKD.ResultsWe identified 18,842 incident CKD cases after a mean follow-up of 11.1 (SD 2.2) years. The healthy sleep score was inversely associated with the risk of CKD in a dose-dependent manner (P for trend, <.001). Compared with the participants with a poor sleep pattern (score of 0-1), the multivariate adjusted hazard ratio of CKD was 0.77 (95% CI, 0.71 to 0.84) for those with the healthiest sleep pattern (score of 5). In addition, we found that the inverse association was stronger in individuals without history of hypertension compared with individuals with hypertension at baseline (P for interaction, .003) and in those 60 years of age or younger compared with their older counterparts (P for interaction, <.001).ConclusionOur data suggest that adherence to an overall healthy sleep pattern is associated with a lower risk of CKD, especially for individuals without history of hypertension and those who are younger.     

Left Atrial Strain Is the Best Predictor of Adverse Cardiovascular Outcomes in Patients with Chronic Kidney Disease

Patients with stage 3 and stage 4 CKD demonstrate alterations in LV GLS, LVMI, E/e′, LAVI, and LASr but had normal LVEF. Each of these parameters was evaluated using reported normal values as a cutoff (normal indicated as green) in the figure. Left atrial reservoir strain was the strongest predictor of death and MACE and the only echocardiographic parameter that predicted adverse events.

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Urinary Sodium-to-Potassium Ratio and Incident Chronic Kidney Disease: Results From the Korean Genome and Epidemiology Study

ObjectiveTo evaluate the association of sodium-potassium intake balance on kidney function.Patients and MethodsData from the Korean Genome and Epidemiology Study were used. The participants were enrolled between June 1, 2001, and January 31, 2003, and were followed-up until December 31, 2016. The 24-hour excretion levels of sodium and potassium were calculated using the Kawasaki formula with spot urinary potassium and sodium measurements. Participants were categorized into tertiles according to the estimated 24-hour urinary sodium-to-potassium (Na/K) ratio. The primary outcome was incident chronic kidney disease (CKD), defined as an estimated glomerular filtration rate of <60 mL/min per 1.73 m² in two or more consecutive measurements during the follow-up period.ResultsThis study included 4088 participants with normal kidney function. The mean age was 52.4±8.9 years, and 1747 (42.7%) were men. The median estimated 24-hour urinary sodium excretion level, potassium excretion level, and Na/K ratio (inter quartile range) were 4.9 (4.1-5.8) g/d, 2.1 (1.8-2.5) g/d, and 2.3 (1.9-2.7) g/d, respectively. During 37,950 person-years of follow-up (median, 11.5 years), 532 participants developed CKD, and the corresponding incidence rate was 14.0 (95% CI, 12.9-15.3) per 1000 person-years. Multivariable Cox hazard analysis revealed that the risk of incident CKD was significantly lower in the lowest tertile than in the highest tertile (HR, 0.78; 95% CI, 0.63-0.97). However, no significant association was found with incident CKD risk when urinary excretion levels of sodium or potassium were evaluated individually.ConclusionA low urinary Na/K ratio may relate with lower CKD development risk in adults with preserved kidney function.     

Adherence to Chronic Kidney Disease Screening Guidelines Among Patients With Type 2 Diabetes in a US Administrative Claims Database

ObjectiveTo examine the screening rates for kidney damage and function among patients with type 2 diabetes (T2D) and chronic kidney disease stage at diabetes diagnosis using a US administrative claims database.Patients and MethodsThis cohort study used a claims database enriched with laboratory results data. Patients with T2D (defined as 1 inpatient or 2 outpatient claims for diabetes), aged 18 years or older, and with at least 1 year of follow-up enrollment were identified. Patients with type 1 diabetes, kidney disease, or other related conditions at baseline were excluded. We estimated screening rates using laboratory orders for serum creatinine and estimated glomerular filtration rate (eGFR) measurement and urine albumin to creatinine ratio (UACR). Chronic kidney disease severity was reported using the Kidney Disease: Improving Global Outcomes classification based on laboratory results.ResultsA total of 1,881,447 patients with T2D were eligible for analysis. Mean ± SD age was 63.1±13.1 years; 947,150 patients (50.3%) were male. Serum creatinine tests were ordered within 14 days of the index date among 290,722 patients of 622,915 (46.7%) patients with newly-recognized T2D. Overall, 1,595,964 patients (84.8%) had at least one serum creatinine test ordered during the 1-year follow-up period. Fewer patients received a UACR test during follow-up (814,897 [43.3%]). Less than half of all patients with T2D received a laboratory test order for both serum creatinine and urine albumin measurements during the follow-up period.ConclusionPhysicians treating patients with diabetes are selectively adhering to chronic kidney disease screening guidelines, as indicated by high rates of eGFR testing, but less frequent UACR testing. Despite recommendations to monitor both eGFR and UACR, less than half of patients were screened for albuminuria during the 1-year follow-up.     

Revascularization in Patients With Non-ST Elevation Myocardial Infarction and Advanced Chronic Kidney Disease

ObjectiveTo investigate the impact of revascularization on long-term survival and renal outcome in non–ST-elevation myocardial infarction (NSTEMI) patients with severe chronic kidney disease (CKD).Patients and MethodsThis study includes NSTEMI patients with an estimated glomerular filtration rate <30 mL/min per 1.73 m², including those on chronic hemodialysis who were identified from the multicenter Chang Gung Research Database from January 1, 2007, to December 31, 2017. Inverse probability of treatment weighting was used to generate comparable groups. The survival and the risk of progression to chronic hemodialysis between those receiving revascularization, either percutaneous coronary intervention or coronary artery bypass graft, and those receiving medical therapy during index hospitalization were compared.ResultsA total of 2821 NSTEMI patients with severe CKD, including 1141 patients on chronic hemodialysis, were identified. Of these, 1149 patients received revascularization and 1672 received medical therapies. The differences in demographics, comorbidities, and presentations between groups were balanced after inverse probability of treatment weighting. After a mean follow-up of 1.82 years, revascularization was associated with a lower risk of all-cause mortality (adjusted HR, 0.61; 95% CI, 0.54-0.70). For non–dialysis-dependent patients who had survival to discharge, revascularization had a higher risk of progression to chronic hemodialysis (adjusted HR, 1.83; 95% CI, 1.49-2.26) after a mean follow-up of 2.3 years.ConclusionRevascularization was associated with a lower risk of all-cause mortality in NSTEMI patients with severe CKD. For non–dialysis-dependent patients who survived to discharge, revascularization was associated with a higher risk of progression to chronic hemodialysis.     

Reducing the Risk of Mortality in Chronic Obstructive Pulmonary Disease With Pharmacotherapy: A Narrative Review

In 2020, chronic obstructive pulmonary disease (COPD) was the fifth leading cause of death in the United States excluding COVID-19, and its mortality burden has been rising since the 1980s. Smoking cessation, long-term oxygen therapy, noninvasive ventilation, and lung volume reduction surgery have had a beneficial effect on mortality; however, until recently, the effects of pharmacologic therapies on all-cause mortality have been unclear. Inhaled pharmacologic treatments for patients with COPD include combinations of long-acting muscarinic receptor antagonists (LAMAs), long-acting-β_2-agonists (LABAs), and inhaled corticosteroids (ICS). The recent IMPACT and ETHOS clinical trials reported mortality benefits with ICS/LAMA/LABA triple therapy compared with LAMA/LABA dual therapy. In IMPACT, fluticasone furoate/umeclidinium/vilanterol therapy significantly reduced the risk of on-/off-treatment all-cause mortality vs umeclidinium/vilanterol (hazard ratio, 0.72; 95% CI, 0.53 to 0.99; P=.042). The ETHOS trial found a reduction in the risk of on-/off-treatment all-cause mortality in patients treated with budesonide/glycopyrrolate/formoterol vs glycopyrrolate/formoterol (hazard ratio, 0.51 [0.33 to 0.80]; nominal P=.0035). Both trials included populations of patients with symptomatic COPD at high risk of future exacerbations, and a post hoc analysis of the final retrieved vital status data suggested that the observed mortality benefits are conferred by the ICS component. In conclusion, triple therapy reduces the risk of mortality in patients with symptomatic COPD characterized by moderate or severe airflow obstruction and a recent history of moderate or severe exacerbations. This benefit is likely to be driven by reductions in exacerbations. Future research efforts should focus on improving the long-term prognosis of patients living with COPD.     

Role of Physical Activity in Lowering Risk of End-Stage Renal Disease

ObjectiveTo investigate the association between the amount and intensity of leisure-time physical activity (LTPA) and the risk of end-stage renal disease (ESRD).MethodsThe study examined a cohort of 543,667 participants aged 20 years and older who participated in a health screening program from January 1, 1996, through December 31, 2017. We identified 2520 individuals undergoing dialysis or who had a kidney transplant by linking participants’ encrypted personal identification with the registry for ESRD with a median follow-up of 13 years. We classified participants into 5 categories measured by metabolic equivalent of tasks. Within each category, we analyzed the effect of moderate- and vigorous-intensity LTPA in reducing risk of ESRD. We used a Cox proportional hazards model to calculate hazard ratios (HRs).ResultsWe observed a dose-response relationship between LTPA and the risk of ESRD. The fully active group had a 12% lower hazard of ESRD compared with the no reported LTPA group (HR, 0.88; 95% CI, 0.80 to 0.98) adjusting for covariates including baseline estimated glomerular filtration rate and proteinuria. Within the same category of LTPA, vigorous-intensity exercise carried a 35% lower HR for ESRD compared with moderate-intensity exercise (HR, 0.65; 95% CI, 0.52 to 0.81). The effect was observed stronger among men, younger participants, and participants with diabetes or hyperlipidemia.ConclusionSustained LTPA (≥ 150 minutes per week), particularly with vigorous intensity, significantly lowered the ESRD risk, even among individuals with comorbidities such as diabetes or hyperlipidemia. This finding suggested that patients with no reported LTPA with cardiovascular risks should engage in more LTPA to lower their risk of ESRD.     

Diabetic Kidney Disease Back in Focus: Management Field Guide for Health Care Professionals in the 21st Century

Chronic kidney disease due to diabetes, or diabetic kidney disease (DKD), is a worldwide leading cause of chronic kidney disease and kidney failure and an increasingly important global public health issue. It is associated with poor quality of life, high burden of chronic diseases, and increased risk of premature death. Until recently, people with DKD had limited therapeutic options. Treatments have focused largely on glycemic and blood pressure control and renin-angiotensin system blockade, leaving patients with significant residual risk for progression of DKD. The availability of newer classes of glucose-lowering agents, namely, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, has changed the therapeutic landscape for these patients. These therapies have offered unprecedented opportunities to reduce the risk for progression of kidney disease and the risk of death that have led to recent updates to clinical guidelines. As such, the American Diabetes Association, the Kidney Disease: Improving Global Outcomes, and the European Association for the Study of Diabetes now recommend the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists for patients with DKD to provide both kidney and cardiovascular protective benefits. This review highlights the importance of early detection of DKD and summarizes the latest recommendations in the clinical guidelines on management of patients with DKD with hope of facilitating their uptake into everyday clinical practice. An integrated approach to patient care with a multidisciplinary focus can help achieve the necessary shift in clinical care of patients with DKD.     

Efficacy of Prolonged Antibiotic Therapy for Renal Cyst Infections in Polycystic Kidney Disease

ObjectiveTo determine the impact of antibiotic therapy (ATBT) on outcomes of renal cyst infection (CyI) in patients with polycystic kidney disease.Patients and MethodsWe undertook a single-center retrospective study of CyI in autosomal dominant polycystic kidney disease (January 1, 2000, through December 31, 2018). Cyst infections were classified as definite (microbiologically proven), probable (radiologic signs), or possible (clinical or biologic signs only). We studied the determinants of ATBT failure (persistence of infection beyond 72 hours of microbiologically adequate initial ATBT, with requirement for ATBT change, cyst drainage, or nephrectomy) and recurrences (>14 days after the end of ATBT).ResultsAmong 90 patients, 139 CyIs (11 definite, 74 probable, 54 possible) were compiled. Cultures were positive in 106 of 139 (76%) episodes, with Escherichia coli found in 89 of 106 (84%). Treatment failures and recurrences within 1 year of follow-up were more frequent in definite/probable CyI (20/85 [34%] and 16/85 [19%]) than in possible CyI (2/54 [4%] and 4/54 [7%]; P<.01 and P=.08, respectively). Male sex (odds ratio [OR], 7.79; 95% CI, 1.72 to 46.68; P<.01), peak C-reactive protein level above 250 mg/L (OR, 7.29; 95% CI, 1.78 to 35.74; P<.01; to convert C-reactive protein values to nmol/L, multiply by 9.524), and cyst wall thickening (OR, 7.70; 95% CI, 1.77 to 43.47; P=.01) but not the modalities of initial ATBT were independently associated with higher risk of failure. In a Cox proportional hazards model, kidney transplant recipients exhibited higher risk of recurrence (hazard ratio, 3.76; 95% CI, 1.06 to 13.37; P=.04), whereas a total duration of ATBT of 28 days or longer was protective (hazard ratio, 0.02; 95% CI, 0.00 to 0.16; P<.001), with an inverse correlation between duration and recurrence (81% for treatment <21 days, 47% for 21 to 27 days, 2% for ≥28 days; P<.0001).ConclusionInitial first-line ATBT had no significant effect on renal CyI treatment failure. Treatment duration of 28 days and longer reduced recurrences.     

Nonlinguistic Cognitive Factors Predict Treatment-Induced Recovery in Chronic Poststroke Aphasia

ObjectiveTo determine if pretreatment nonlinguistic cognition predicted language treatment outcomes and if so, which specific nonlinguistic cognitive subskills predicted naming therapy outcomes.DesignRetrospective.SettingResearch clinic.ParticipantsStudy 1 included data from 67 persons with aphasia who underwent language treatment and a pretreatment cognitive-linguistic assessment battery (N=67). Study 2 included data from 27 study 1 participants who completed additional pretreatment nonlinguistic cognitive assessments.Interventions120-minute sessions of sentence comprehension (n=26) or naming treatment (n=41) 2 times per week for up to 10-12 weeks.Main Outcome MeasuresProportion of potential maximal gain (PMG) (assessed immediately after treatment [10-12wk]; formula=mean posttreatment score–mean pretreatment score/total number of trained items–mean pretreatment score) and proportion of potential maximal gain maintained (PMGM) (assessed 12wk after posttreatment [22-24wk]; formula=mean maintenance score–mean pretreatment score/total number of trained items–mean pretreatment score) as outcome variables; and pretreatment assessment scores as predictor variables.ResultsIn study 1, 37% of participants demonstrated nonlinguistic cognitive deficits. Principal component analyses reduced assessment data to 2 components: linguistic and nonlinguistic cognition. Backward elimination regression revealed that higher linguistic and nonlinguistic cognitive function significantly predicted higher PMG after language therapy. In study 2, principal component analysis of only the nonlinguistic cognitive measures identified 3 components: executive function, verbal short-term memory, and visual short-term memory. Controlling for pretreatment apraxia of speech and auditory comprehension deficits, regression analyses revealed that higher executive function and visual short-term memory significantly predicted higher PMG and PMGM after naming therapy.ConclusionsPretreatment nonlinguistic cognitive function significantly influenced language treatment outcomes and maintenance of therapy gains.     

Dietary Risk Factors for Incident and Recurrent Symptomatic Kidney Stones

ObjectiveTo compare dietary factors between incident symptomatic stone formers and controls, and among the incident stone formers, to determine whether dietary factors were predictive of symptomatic recurrence.Patients and MethodsWe prospectively recruited 411 local incident symptomatic kidney stone formers (medical record validated) and 384 controls who were seen at Mayo Clinic in Minnesota or Florida between January 1, 2009, and August 31, 2018. Dietary factors were based on a Viocare, Inc, food frequency questionnaire administered during a baseline in-person study visit. Logistic regression compared dietary risk factors between incident symptomatic stone formers and controls. Incident stone formers were followed up for validated symptomatic recurrence in the medical record. Cox proportional hazards models estimated risk of symptomatic recurrence with dietary factors. Analyses adjusted for fluid intake, energy intake, and nondietary risk factors.ResultsIn fully adjusted analyses, lower dietary calcium, potassium, caffeine, phytate, and fluid intake were all associated with a higher odds of an incident symptomatic kidney stone. Among incident stone formers, 73 experienced symptomatic recurrence during a median 4.1 years of follow-up. Adjusting for body mass index, fluid intake, and energy intake, lower dietary calcium and lower potassium intake were predictive of symptomatic kidney stone recurrence. With further adjustment for nondietary risk factors, lower dietary calcium intake remained a predictor of recurrence, but lower potassium intake only remained a predictor of recurrence among those not taking thiazide diuretics or calcium supplements.ConclusionEnriching diets in stone formers with foods high in calcium and potassium may help prevent recurrent symptomatic kidney stones.     

Real-World Experience of Angiotensin Receptor–Neprilysin Inhibition in Reduced Ejection Fraction Heart Failure Patients With Advanced Kidney Disease

ObjectiveTo investigate the effectiveness and safety of angiotensin receptor-neprilysin inhibitors (ARNIs) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min per 1.73 m²), which have been excluded from the landmark trials.Patients and MethodsThis study examined 3281 patients pooled from two multicenter HFrEF cohorts, and 661 patients with baseline eGFR less than 30 mL/min per 1.73 m² were further analyzed (the Taiwan Society of Cardiology – Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry: May 1, 2013 to October 31, 2014, and the Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study: March 1, 2017, to December 31, 2018). Propensity score matching was performed to adjust for confounders. At 1-year follow-up, all-cause mortality, total heart failure hospitalizations, renal function, and left ventricular ejection fraction (LVEF) were used as the endpoints.ResultsAfter propensity score matching, 510 patients (age, 69.8±13.9 years; male, 61.0%; mean LVEF, 29.8±7.3%; mean eGFR, 19.8±9.0 mL/min per 1.73 m²) were included in the final analysis, including 278 patients receiving ARNI treatment (ARNI group) and 232 patients not on ARNI treatment (non-ARNI group). Baseline characteristics were comparable between the two groups. At 1 year, eGFR and LVEF measurements were significantly higher in the ARNI group than in the non-ARNI group (25.0±17.1 mL/min per 1.73 m² vs 21.4±17.5 mL/min per 1.73 m²; P=.04; and 40.1±12.9% vs. 33.1±10.8%, P<.001, respectively). The ARNI group had significantly lower risks of 1-year all-cause mortality (19.4 vs 30.9 per 100-person year; P=.02), and total HF rehospitalizations (70.0 vs 110.4 per 100-person year; P=.01) than non-ARNI users.ConclusionOur results show the effectiveness of ARNIs in HFrEF patients with advanced chronic kidney disease in a real-world setting.     

Early Detection of Pancreatic Cancer in Patients With Chronic Liver Disease Under Hepatocellular Carcinoma Surveillance

ObjectiveTo evaluate whether patients with hepatitis B virus (HBV)– and hepatitis C virus (HCV)–related chronic liver disease were diagnosed as having pancreatic cancer (PC) at an early stage during abdominal imaging surveillance for hepatocellular carcinoma (HCC).Patients and MethodsWe retrospectively examined 447 patients with PC diagnosed at Ehime University Hospital and affiliated centers (2011-2013). Data were collected regarding HBV and HCV status, likelihood of PC diagnosis, and Union for International Cancer Control (UICC) stage. Intergroup comparisons were performed using the χ² test.ResultsThe UICC stage distribution in the HCC surveillance group (n=16) was stage 0 (n=2, 12.5%), stage IA (n=3, 18.8%), stage IB (n=2, 12.5%), stage IIA (n=2, 12.5%), stage IIB (n=2, 12.5%), stage III (n=1, 6.3%), and stage IV (n=4, 25%). The UICC stage distribution in the nonsurveillance group (n=431) was stage 0 (n=4, 0.9%), stage IA (n=28, 6.5%), stage IB (n=27, 6.3%), stage IIA (n=86, 20.0%), stage IIB (n=48, 11.1%), stage III (n=56, 13.0%), and stage IV (n=182, 42.2%). The HCC surveillance group had significantly more patients with stage 0 disease than with stages IA through IV (P=.02). Similar results were observed when including stages IA (P=.007) and IB (P=.004) as early stages but not stage IIA (P=.10). A dilated pancreatic duct led to a PC diagnosis in all 6 patients with stage 0 disease.ConclusionPatients with HBV- and HCV-related chronic liver disease had an early PC diagnosis during HCC surveillance. Careful evaluation of the pancreas is warranted during HCC surveillance.     

Long-term Cardiovascular Risk in Astronauts: Comparing NASA Mission Astronauts With a Healthy Cohort From the Cooper Center Longitudinal Study

ObjectiveTo determine the long-term cardiovascular disease risk of astronauts with spaceflight exposure compared with a well-matched cohort.MethodsNational Aeronautics and Space Administration (NASA) astronauts are selected into their profession based upon education, unique skills, and health and are exposed to cardiovascular disease risk factors during spaceflight. The Cooper Center Longitudinal Study (CCLS) is a generally healthy cohort from a preventive medicine clinic in Dallas, Texas. Using a matched cohort design, astronauts who were selected beginning April 1, 1959, (and each subsequent selection class through 2009) and exposed to spaceflight were matched to CCLS participants who met astronaut selection criteria; 1514 CCLS participants matched to 303 astronauts in a 5-to-1 ratio on sex, date of birth, and age. The outcome of cardiovascular mortality through December 31, 2016, was determined by death certificate or National Death Index.ResultsThere were 11 deaths caused by cardiovascular disease (CVD) among astronauts and 46 among CCLS participants. There was no evidence of increased mortality risk in astronauts (hazard ratio [HR]=1.10; 95% confidence interval [CI], 0.50 to 2.45) with adjustment for baseline cardiovascular covariates. However, the secondary outcome of CVD events showed an increased adjusted risk in astronauts (HR=2.41; 95% CI, 1.26 to 4.63).ConclusionNo increased risk of CVD mortality was observed in astronauts with spaceflight exposure compared with a well-matched cohort, but there was evidence of increased total CVD events. Given that the duration of spaceflight will increase, particularly on missions to Mars, continued surveillance and mitigation of CVD risk is needed to ensure the safety of those who venture into space.