Introduction: Smoking is a major risk factor for atherosclerosis, but its impact is heterogeneous across different vascular beds (e.g., stronger association with peripheral artery disease than coronary disease). However, whether the association of cigarette smoking with vascular calcification is (dis)similar across vascular beds is uncertain. Methods: In 1,961 ARIC participants without a history of coronary heart disease at visit 7 (2018-19), we quantified the associations of pack-years of smoking and years since cessation with coronary artery calcium (CAC) and extra-coronary calcification (ECC) using multivariable logistic regression models. High CAC and ECC (aortic valve, aortic valve ring, mitral valve, ascending aorta, and descending aorta calcification) were defined as Agatston score >75th percentile and were analyzed separately as dependent variables. Results: Pack-years of smoking demonstrated an independent and robust dose-response relationship with CAC, ascending and descending aorta calcification, and aortic valve ring calcification (Table). The association was particularly evident for descending aorta calcification (e.g., adjusted odds ratio [aOR] 3.57 [95%CI 2.46-5.19] for ≥40 pack-years). The results were similar for the duration since smoking cessation, with the most prolonged risk seen for the descending aorta (i.e., even ≥30 years of smoking cessation had OR of 1.34 [1.03-1.47]). Aortic valve and mitral valve calcification demonstrated modest associations with smoking. Conclusions: Cigarette smoking showed a robust association with coronary and extra-coronary calcification, and its association was particularly strong with descending aorta calcification. Our findings further emphasize the harm of smoking on broad ranges of vascular beds and simultaneously highlight unique pathophysiologic mechanisms across different vascular beds and cardiac valves.

Title: Cigarette smoking and risk of hospitalization with acute kidney injury: The Atherosclerosis Risk in Communities (ARIC) Study Background: Smoking has been associated with progression of chronic kidney disease. However, its association with the development of acute kidney injury (AKI) has not been prospectively assessed in the community. AKI poses significant morbidities and healthcare costs, thus understanding modifiable risk factors of AKI is crucial. Methods: Among 14,587 participants (mean age 54 [standard deviation: 6] years, 55% females and 25.4% Blacks) from the Atherosclerosis Risk in Communities Study, we quantified the association of smoking status with incident hospitalization with AKI (AKI diagnosis on discharge records in any diagnostic position) through 2019 using Cox models. Sensitivity analyses included censoring interim CVD events during follow-up and restricting to AKI as the primary diagnosis. Results: Over a median follow-up of 26.3 years, 2,986 participants had incident hospitalization with AKI (incidence rate per 1,000 person-years: 8.8; 95% CI: 8.4-9.1). In multivariable Cox models, current smokers had a >2-fold higher risk of AKI compared with never smokers (HR: 2.25; 95% CI: 2.04-2.48) (Table). There was a dose-response relationship between smoking pack-years at baseline and risk of AKI (e.g., HRs 1.34 [1.21, 1.50] with 10-25 pack-years, 1.78 [1.59, 1.99] with 25-40 pack-years, and 2.03 [1.80-2.29] with ≥40 pack-years vs. never smokers). These associations were consistent with similar HRs in the two sensitivity analyses censoring interim cardiovascular diseases and analyzing AKI as the primary cause of hospitalization (Table). Conclusions: In a community-based cohort, smoking was associated with the risk of incident hospitalization with AKI, which was independent of potential confounders and robust in a few sensitivity analyses. These results suggest the importance of smoking cessation to reduce the risk of AKI.

ObjectiveTo inform guidance for cancer detection in patients with idiopathic inflammatory myopathy (IIM), we evaluated the diagnostic yield of computed tomography (CT) imaging for cancer screening/surveillance within distinct IIM subtypes and myositis‐specific autoantibody strata.MethodsWe conducted a single‐center, retrospective cohort study in IIM patients. Overall diagnostic yield (number of cancers diagnosed/number of tests performed), percentage of false positives (number of biopsies performed not leading to cancer diagnosis/number of tests performed), and test characteristics were determined on CT of the chest and abdomen/pelvis.ResultsWithin the first 3 years since IIM symptom onset, a total of 9 of 1,011 (0.9%) chest CT scans and 12 of 657 (1.8%) abdomen/pelvis CT scans detected cancer. Diagnostic yields for both CT of the chest and CT of the abdomen/pelvis were highest in dermatomyositis, specifically anti–transcription intermediary factor 1γ (2.9% and 2.4% for CT of the chest and abdomen/pelvis, respectively). The highest percentage of false positives was in patients with antisynthetase syndrome (ASyS) (4.4%) and immune‐mediated necrotizing myopathy (4.4%) on CT of the chest, and ASyS (3.8%) on CT of the abdomen/pelvis. Patients ages <40 years old at IIM onset had both low diagnostic yields (0% and 0.5%) and high false‐positive rates (1.9% and 4.4%) for CT of the chest and abdomen/pelvis, respectively.ConclusionIn a tertiary referral cohort of IIM patients, CT imaging has a wide range of diagnostic yield and frequency of false positives for contemporaneous cancer. These findings suggest that cancer detection strategies targeted according to IIM subtype, autoantibody positivity, and age may maximize cancer detection while minimizing the harms and costs of over‐screening.

Introduction: Noncommunicable diseases (e.g. type 2 diabetes, hypertension, cardiovascular disease) are the leading cause of death globally and among adults in Ethiopia. Suboptimal diet (with high intake of sugar, salt, and saturated fat) is a major risk factor for such diseases and the consumption of processed foods rich in these nutrients is rising globally. Mandatory nutrition information on packaged foods, potentially with warning labels, can guide consumers and create healthier food environments. However, such information is lacking in many countries, including Ethiopia. Hypothesis: We assessed the hypothesis that the display of nutrition information (including sugar, sodium, and saturated fat) would be low on packaged foods and beverages in Ethiopia. Methods: A database of packaged foods was created in 2021 from an assessment across 18 markets within Addis Ababa, Ethiopia. The analysis included 1388 products in four major food categories (cereals; snack foods; sweets; and beverages). Results: In total, 880 (63%) products displayed nutrient content information. This was most common among cereals (73%), and least common in snack food (43%) (Table 1). For specific nutrients, the display of sodium/salt (38%) was similar to sugar (35%) and saturated fat (34%). This discrepancy was highest in the beverages category. Conclusion: Nutrition labeling was incomplete in four major packaged food categories in Ethiopia. Fewer than half of snack foods displayed any nutrient content information, and while nearly three-fourths of cereals had some label, data on all three nutrients (sugar, sodium, and saturated fat) was missing on more than half of these products. Mandatory warning labels will allow consumers to assess the nutrient content of packaged foods and may encourage reformulation by industry to meet consumer demand and avoid placement of warning labels on their products.

Introduction: Femur fracture can have devastating consequences in older patients. Lower extremity peripheral artery disease (PAD) reduces physical function, which can in turn increase the risk of falls. However, less is known regarding the association of PAD with incident femur fracture in older adults. Hypothesis: PAD is associated with a higher risk of incident femur fracture independent of potential confounders. Methods: We included 5,276 participants from ARIC Visit 5 (2011-2013) (mean age 76 [standard deviation: 5] years, 57% women and 22% self-identified Black race). Femur fractures were defined as an outpatient encounter or hospitalization with ICD-9 codes: 820-821 or ICD-10 codes: S72. We quantified the association of PAD status at baseline, based on ankle-brachial index (ABI) ≤0.9 or clinical history of PAD, with incident femur fracture using multivariable Cox regression and follow-up until 2019. Results: There were 224 incident femur fractures over a median follow-up of 7.2 [IQI 5.6-7.8] years. The incidence rate of femur fracture was almost 2-times higher in participants with PAD compared to those without a history of PAD and ABI 1.11-1.20 (reference group) (10.5 [7.5-14.8] vs. 5.5 [4.3-6.9] per 1,000 person-years). This association persisted after accounting for demographic (hazards ratio [HR]: 1.86 [95% CI 1.23-2.84] in Model 1) and other confounders (HR 1.59 [1.04-2.46] in Model 2) (Table). When we excluded participants with a clinical history of PAD, low ABI (≤0.9) remained significantly associated with incident femur fracture compared to the reference group (HR 1.94 [1.18-3.19]). Our findings were consistent in demographic and clinical subgroups (e.g., by sex and diabetes status). Conclusions: In community-dwelling older adults, PAD, even when not clinically diagnosed, was associated with an increased risk of femur fracture. Clinicians and patients should be aware of this complication of PAD and consider preventive measures to avoid falls (e.g., exercise counseling, and making home safer).

ObjectiveThis study investigates cancer risk in idiopathic inflammatory myopathy (IIM) relative to the general population.MethodsWe conducted a single‐center, retrospective cohort study of IIM patients and malignancy. Myositis‐specific and ‐associated autoantibodies were determined by Euroimmun line blot, enzyme‐linked immunosorbent assay, and immunoprecipitation. We calculated standardized prevalence ratios (SPRs) and adjusted for calendar year, age, sex, race, and ethnicity by comparing observed cancers in IIM patients versus expected cancers in the general population using the Surveillance, Epidemiology, and End Results registry.ResultsOf 1,172 IIM patients, 203 (17%) patients with a cancer history were studied. Over a median follow‐up of 5.2 years, the observed number of IIM patients diagnosed with cancer was increased 1.43‐fold (SPR 1.43 [95% confidence interval (95% CI) 1.15–1.77]; P = 0.002). Within 3 years of IIM symptom onset, an increased SPR was observed for anti–transcription intermediary factor 1γ (anti‐TIF1γ)–positive patients for ovarian and breast cancer (ovarian SPR 18.39 [95% CI 5.01–47.08], P < 0.001; breast SPR 3.84 [95% CI 1.99–6.71], P < 0.001). As expected, anti‐TIF1γ positivity was associated with a significantly elevated SPR; however, only 55% (36 of 66) of all cancers within 3 years of dermatomyositis onset were observed in anti‐TIF1γ–positive patients. Other myositis‐specific autoantibodies, including anti–Mi‐2, anti–small ubiquitin‐like modifier activating enzyme (SAE), and anti‐nuclear matrix protein 2 (NXP‐2), accounted for 26% (17 of 66) of cancers diagnosed within 3 years of dermatomyositis onset. No cancer association, positive or negative, was observed for patients with antisynthetase, anti–melanoma differentiation–associated protein 5 (anti–MDA‐5), or anti–hydroxymethylglutaryl‐coenzyme A reductase (anti‐HMGCR) antibodies.ConclusionIn a tertiary referral center population, anti‐TIF1γ was most strongly associated with breast and ovarian cancer. Patients with antisynthetase, anti–MDA‐5, or anti‐HMGCR antibodies had the same cancer risk as the general population.image

BACKGROUND Growth differentiation factor 15 (GDF-15) is a stress-responsive biomarker associated with several types of cardiovascular diseases. However, conflicting results have been reported regarding its association with incident atrial fibrillation (AF) in the general population. METHODS In 10 234 White and Black Atherosclerosis Risk in Communities (ARIC) Study participants (mean age 60 years, 20.5% Blacks) free of AF at baseline (1993 to 1995), we quantified the association of GDF-15 with incident AF using Cox regression models. GDF-15 concentration was measured by an aptamer-based proteomic method. AF was defined as AF diagnosis by electrocardiogram at subsequent ARIC visits or AF diagnosis in hospitalization records or death certificates. Harrell's c-statistic and categorical net reclassification improvement were computed for risk discrimination and reclassification. RESULTS There were 2217 cases of incident AF over a median follow-up of 20.6 years (incidence rate 12.3 cases/1000 person-years). After adjusting for potential confounders, GDF-15 was independently associated with incident AF, with a hazard ratio (HR) of 1.42 (95% CI, 1.24-1.62) for the top vs bottom quartile. The result remained consistent (HR 1.23 [95% CI, 1.07-1.41]) even after further adjusting for 2 cardiac biomarkers, cardiac troponin T and natriuretic peptide. The results were largely consistent across demographic subgroups. The addition of GDF-15 modestly improved the c-statistic by 0.003 (95% CI, 0.001-0.006) beyond known risk factors of AF. CONCLUSIONS In this community-based biracial cohort, higher concentrations of GDF-15 were independently associated with incident AF, supporting its potential value as a clinical marker of AF risk.

Introduction: Growth differentiation factor 15 (GDF-15) is a marker of oxidative stress and inflammation and has been associated with several cardiovascular disease (CVD) phenotypes. However, conflicting results have been reported regarding the association of GDF-15 with incident atrial fibrillation (AF) in the general population. Hypotheses: Higher GDF-15 level is associated with increased risk of incident AF independent of potential confounders. Methods: In 10,101 White and Black ARIC participants (mean age 60 years and 20.9% Blacks) free of AF at baseline (1993-95), we quantified the association of GDF-15 and incident AF using three Cox proportional hazards models. GDF-15 was measured by SOMA scan assay. AF was defined by hospitalizations with AF diagnosis or death certificates (ICD-9 codes: 427.31-427.32; ICD-10 codes: I48.x) or AF diagnosis by ECG at subsequent ARIC visits. Results: There were 2165 cases of incident AF over a median follow-up of 20.7 years (incidence rate 12.1 cases/1,000 person-years). After adjusting for demographic characteristics and cardiovascular risk factors, log GDF-15 was significantly associated with incident AF (hazard ratio 1.42 (1.25-1.63) for top vs. bottom quartile) (Model 1 in Table ). The result was robust even further adjusting for history of other CVD phenotypes and cardiac markers (Models 2 and 3 in Table ). In Model 3, quartiles of high-sensitive cardiac troponin T (hs-cTnT) did not demonstrate significant associations with incident AF. Conclusions: In community-based population, elevated GDF-15 level was independently and robustly associated with incident AF (even more strongly than troponin). These results suggest the involvement of GDF-15 in the development of AF and the potential of GDF-15 as a risk marker to identify individuals at high risk of AF.

Background: Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 (COVID-19) is uncertain, in part, because of potential confounding by age and sex. Methods: We performed a systematic review of studies that explored pre-existing CVD and its traditional risk factors as risk factors of severe COVID-19 (defined as death, acute respiratory distress syndrome, mechanical ventilation, or intensive care unit admission). We searched PubMed and Embase for papers in English with original data (≥10 cases of severe COVID-19). Using random-effects models, we pooled relative risk (RR) estimates and conducted meta-regression analyses. Results: Of the 661 publications identified in our search, 25 papers met our inclusion criteria, with 76,638 COVID-19 patients including 11,766 severe cases. Older age was consistently associated with severe COVID-19 in all eight eligible studies, with RR >~5 in >60-65 vs. <50 years. Three studies showed no change in the RR of age after adjusting for covariate(s). In univariate analyses, factors robustly associated with severe COVID-19 were male sex (10 studies; pooled RR=1.73, [95%CI 1.50-2.01]), hypertension (8 studies; 2.87 [2.09-3.93]), diabetes (9 studies; 3.20 [2.26-4.53]), and CVD (10 studies; 4.97 [3.76-6.58]). RR for male sex was likely to be independent of age. For the other three factors, meta-regression analyses suggested confounding by age. Only four studies reported multivariable analysis, but most of them showed adjusted RR ~2 for hypertension, diabetes, and CVD. No study explored renin-angiotensin system inhibitors as a risk factor for severe COVID-19. Conclusions: Despite the potential for confounding, these results suggest that hypertension, diabetes, and CVD are independently associated with severe COVID-19 and, together with age and male sex, can be used to inform objective decisions on COVID-19 testing, clinical management, and workforce planning.

Thrombocytosis has been identified as an unfavorable prognostic factor in several types of cancer. This study aimed to evaluate the prognostic value of pretreatment platelet count in association with the TNM staging system and therapeutic regimens in patients with nasopharyngeal carcinoma (NPC).

The aim of the present study was to investigate the prognostic value of different pretreatment platelet (PLT) counts on the treatment outcome in nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone. A total of 1,501 NPC patients, including 412 receiving CCRT and 1,089 receiving RT, were enrolled in the present study. The PLT count cut-off points for the CCRT and RT groups were 150 and 300x10(9)/l, respectively, and the PLT counts were categorized it into three groups: Low (PLT-150x109/1), moderate (150x10(9)/l300x10(9)/l). To identify independent predictors of overall survival (OS), the Cox proportional hazards model was used to determine local-regional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates in the CCRT and RT patients. Furthermore, univariate and multivariate analysis indicated that compared with a moderate PLT count, a low PLT count was an independent unfavorable prognostic factor for OS rate in CCRT patients [hazard ratio (HR), 2.024; 95% confidence interval (CI), 1.165-3.516], and a high PLT count was an independent unfavorable prognostic factor for OS and DMFS rates in CCRT (OS: HR, 1.742; 95% CI, 1.090-2.786; DFMS: HR, 2.110; 95%CI, 1.084-4.108) and RT (OS: HR, 1.740; 95%CI, 1.283-2.362; DMFS: HR, 2.819; 95% CI, 1.766-4.497) patients. Compared with a low PLT count, a high PLT count was significantly and independently associated with a poor DMFS rate in the RT patients (P=0.025; HR, 2.454; 95% CI, 1.121-5.372). Therefore, the present study indicates that low and high PLT counts may be useful indicators of survival and distant metastasis in NPC patients who have undergone radiation treatment.