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The relation between cardiorespiratory fitness (CRF) and prostate cancer is not well established. The objective of this study was to determine whether CRF is associated with prostate cancer screening, incidence, or mortality.The Henry Ford Exercise Testing Project is a retrospective cohort study of men aged 40 to 70 years without cancer who underwent physician-referred exercise stress testing from 1995 to 2009. CRF was quantified in metabolic equivalents of task (METs) (6 [reference], 6-9, 10-11, and ≥12 METs), estimated from the peak workload achieved during a symptom-limited, maximal exercise stress test. Prostate-specific antigen (PSA) testing, incident prostate cancer, and all-cause mortality were analyzed with multivariable adjusted Poisson regression and Cox proportional hazard models.In total, 22,827 men were included, of whom 739 developed prostate cancer, with a median follow-up of 7.5 years. Men who had high fitness (≥12 METs) had an 28% higher risk of PSA screening (95% CI, 1.2-1.3) compared with those who had low fitness (6 METs. After adjusting for PSA screening, fitness was associated with higher prostate cancer incidence (men aged55 years, P = .02; men aged55 years, P ≤ .01), but not with advanced prostate cancer. Among the men who were diagnosed with prostate cancer, high fitness was associated with a 60% lower risk of all-cause mortality (95% CI, 0.2-0.9).Although men with high fitness are more likely to undergo PSA screening, this does not fully account for the increased incidence of prostate cancer seen among these individuals. However, men with high fitness have a lower risk of death after a prostate cancer diagnosis, suggesting that the cancers identified may be low-risk with little impact on long-term outcomes.

Objectives This study compared risk discrimination for the prediction of coronary heart disease (CHD) and cardiovascular disease (CVD) deaths for the Pooled Cohort Equations (PCE), the MESA (Multi-Ethnic Study of Atherosclerosis) Risk Score (with and without coronary artery calcium [CAC]), and of simple addition of CAC to the PCE. Background The PCE predict 10-year risk of atherosclerotic CVD events, and the MESA Risk Score predicts risk of CHD. Their comparative performance for the prediction of fatal events is poorly understood. Methods We evaluated 53,487 patients ages 45 to 79 years from the CAC Consortium, a retrospective cohort study of asymptomatic individuals referred for clinical CAC scoring. Risk discrimination was measured using C-statistics. Results Mean age was 57 years, 35% were women, and 39% had CAC of 0. There were 421 CHD and 775 CVD deaths over a mean 12-year follow-up. In the overall study population, discrimination with the MESA Risk Score with CAC and the PCE was almost identical for both outcomes (C-statistics: 0.80 and 0.79 for CHD death, 0.77 and 0.78 for CVD death, respectively). Addition of CAC to the PCE improved risk discrimination, yielding the largest C-statistics. The MESA Risk Score with CAC and the PCE plus CAC showed the best discrimination among the 45% of patients with 5% to 20% estimated risk. Secondary analyses by estimated CVD risk strata showed modestly improved risk discrimination with CAC also among low- and high-estimated risk groups. Conclusions Our findings support the current guideline recommendation to use, among available risk scores, the PCE for initial risk assessment and to use CAC for further risk assessment in a broad borderline and intermediate risk group. Also, in select individuals at low or high estimated risk, CAC modestly improved discrimination. Studies in unselected populations will lead to further understanding of the potential value of tools combining risk scores and CAC for optimal risk assessment.

An Expert Panel of the National Lipid Association reviewed the evidence related to the use of coronary artery calcium (CAC) scoring in clinical practice for adults seen for primary prevention of atherosclerotic cardiovascular disease. Recommendations for optimal use of this test in adults of various races/ethnicities, ages and multiple domains of primary prevention, including those with a 10-year ASCVD risk

Objectives The purpose of this study was to identify predictors of healthy arterial aging (long-term coronary artery calcification [CAC] of 0) among individuals with metabolic syndrome (Me...

Introduction The prevalence of e-cigarette use among lesbian, gay, bisexual, and transgender (LGBT) individuals and its association with risk behaviors was studied. Methods Using data from the Behavioral Risk Factor Surveillance System (BRFSS) survey, self-reported sexual orientation, e-cigarette use, cigarettes, marijuana, smokeless tobacco, and high-risk behavior (using non-prescribed drugs, treatment for sexually transmitted disease, or receiving monetary or drug compensation in exchange for sex in the previous year) were assessed. Multivariable-adjusted logistic regression models were used to study the association between LGBT and risk behaviors. Results The prevalence of e-cigarette use among LGBT adults was 13%, nearly twice that of heterosexual adults. LGBT adults were more likely [Odds Ratio (95% Confidence Interval)] to report current use of e-cigarettes 1.84 (1.64, 2.06), cigarettes 1.61 (1.49, 1.73), marijuana 2.37 (1.99, 2.82), and high-risk behavior 3.69 (3.40, 4.01) compared to heterosexual adults. Results for smokeless tobacco were not significant. Conclusion There are disparities in e-cigarette and other risk behaviors among LGBT adults, which may increase risk of adverse health effects in this vulnerable population.

The prognostic value of traditional atherosclerotic cardiovascular disease (ASCVD) risk factors may decrease with age. We sought to determine whether the association between traditional ASCVD risk factors and incident coronary artery calcium (CAC) differs for younger versus older persons. We included 5,108 participants with baseline CAC = 0. Repeat CAC scoring occurred over 3 to 11 years of follow-up. Multivariable Cox proportional hazards regression assessed the association between traditional risk factors and incident CAC in young (32 to 45 years), middle-aged (46 to 64 years), and older adults (65 to 84 years). A total of 61% of the participants were women and 37% were Black. The proportion with incident CAC ranged from 22% among young adults, 34% for middle-aged adults, and 45% for older adults. In young adults, traditional risk factors were significantly associated with incident CAC except for diastolic blood pressure and high-density lipoprotein (HDL) cholesterol, whereas only total cholesterol/HDL cholesterol ≥3.5 (p = 0.04) was significantly associated with incident CAC in older persons. Non-HDL cholesterol (p = 0.02) was more strongly associated with incident CAC in young (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09 to 1.31) and middle aged (HR 1.14, 95% CI 1.07 to 1.23) compared to older adults (HR 1.11, 95% CI 0.99 to 1.23). When added to demographics, traditional risk factors provided a greater C-statistic improvement for incident CAC prediction in young (0.752, +0.070, p0.001) versus middle-aged (0.645, +0.054, p0.001) and older adults (0.597,+0.025, p = 0.08). In conclusion, traditional risk factors more strongly predict incident CAC in young compared to older adults, underlining the importance of primordial prevention through middle age while identifying the challenges of ASCVD risk assessment in older persons.

A core principle of the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Chest Pain Guideline is the importance of preventive therapies among patients with nonobstructive or obstructive coronary artery disease (CAD). Accordingly, this editorial provides unique insights that emphasize the role of preventive cardiology throughout the new guideline. For the first time, CAD was defined to also include nonobstructive plaque. This definition was based on the fact that individuals who have nonobstructive plaque are at an increased risk of atherosclerotic events compared with those who do not. Herein, we highlight guideline recommendations related to the diagnosis and management of nonobstructive CAD. We also highlight recommendations which emphasize the importance of preventive therapies. Adoption of these recommendations have the potential to lead to enhanced preventive therapies and improve patient outcomes.

Stagnating COVID-19 vaccination rates and vaccine hesitancy remain a threat to public health. Improved strategies for real-time tracking and estimation of population-level behavior regarding vaccinations are needed. The aim of this study was to evaluate whether online search trends for COIVD-19 and influenza mirror vaccination rates. State-level weekly fraction of online searches for top vaccination-related search terms and CDC vaccination data were obtained from June 1, 2020, to May 31, 2021. Next, trends in online search and vaccination data for COVID-19 and influenza were analyzed for visual and quantitative correlation patterns using Spearman’s rank correlation analysis. Online searches in the US for COVID-19 vaccinations increased 2.71-fold (95% CI: 1.98-3.45) in the 4 weeks after the FDA emergency authorization compared to the precedent 4 weeks. In March-April 2021, US online searches reached a plateau that was followed by a decline of 83.3% (95% CI: 31.2%-135.3%) until May 31, 2021. The timing of peaks in online searches varied across US states. Online searches were strongly correlated with vaccination rates (r=0.71, 95% CI: 0.45 - 0.87), preceding actual reported vaccination rates in 44 of 51 states. Online search trends preceded vaccination trends by a median of 3.0 weeks (95% CI: 2.0-4.0 weeks) across all states. For influenza vaccination searches, seasonal peaks in September-October between 2016-2020 were noted. Influenza search trends highly correlated with the timing of actual vaccinations for the 2019-2020 (r=0.82, 95% CI: 0.64 – 0.93) and 2020-2021 season (r=0.91, 95% CI: 0.78 – 0.97). Search trends and real-world vaccination rates are highly correlated. Temporal alignment and correlation levels were higher for influenza vaccinations; however, only online searches for COVID-19 vaccination preceded vaccination trends. These findings indicate that US online search data can potentially guide public health efforts, including policy changes and identifying geographical areas to expand vaccination campaigns.

Aims The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) trial demonstrated that icosapent ethyl lowered the risk of atherosclerotic cardiovascular disease (ASCVD) among patients with elevated triglycerides. However, how to appropriately implement its use in clinical practice is not well-defined. We aimed to determine whether plaque burden as assessed by coronary artery calcium (CAC) could stratify ASCVD risk among patients eligible for icosapent ethyl. Methods and results Among 23 759 patients who underwent computed tomography angiography (CTA) in the Western Denmark Heart Registry, we identified eligibility for the REDUCE-IT trial. A total of 2146 participants (9%) met enrolment criteria for REDUCE-IT. During a median of 4.3 years of follow-up, 146 ASCVD events occurred. Overall, there was a stepwise increase in ASCVD event rates per 1000 person-years with increasing CAC (CAC = 0: 10.5, CAC 1-299: 18.7, CAC ≥300: 49.8). REDUCE-IT-eligible patients with CAC ≥300 had a multivariable-adjusted hazard ratio of 3.1 compared with CAC = 0 (95% confidence interval: 1.9–4.9). Coronary artery calcium differentiated risk similarly in patients with and without obstructive coronary artery disease (CAD). Overall, the 5-year estimated number needed to treat to prevent one event with icosapent ethyl was 45 and ranged from 87 in those with CAC = 0 to 17 in those with CAC ≥300. Some patients with non-obstructive CAD had lower estimated number needed to treat than patients with obstructive CAD when their plaque burden was higher. Conclusion Atherosclerotic plaque burden as assessed by CAC can identify REDUCE-IT-eligible patients who are expected to derive most, and least, absolute benefit from treatment with icosapent ethyl regardless of obstructive versus non-obstructive CAD status.

Aims This study explored the association of coronary artery calcium (CAC) with incident cancer subtypes in the Multi-Ethnic Study of Atherosclerosis (MESA). CAC is an established predictor of cardiovascular disease (CVD), with emerging data also supporting independent predictive value for cancer. The association of CAC with risk for individual cancer subtypes is unknown. Methods and results We included 6271 MESA participants, aged 45–84 and without known CVD or self-reported history of cancer. There were 777 incident cancer cases during mean follow-up of 12.9 ± 3.1 years. Lung and colorectal cancer (186 cases) were grouped based on their strong overlap with CVD risk profile; prostate (men) and ovarian, uterine, and breast cancer (women) were considered as sex-specific cancers (in total 250 cases). Incidence rates and Fine and Gray competing risks models were used to assess relative risk of cancer-specific outcomes stratified by CAC groups or Log(CAC+1). The mean age was 61.7 ± 10.2 years, 52.7% were women, and 36.5% were White. Overall, all-cause cancer incidence increased with CAC scores, with rates per 1000 person-years of 13.1 [95% confidence interval (CI): 11.7–14.7] for CAC = 0 and 35.8 (95% CI: 30.2–42.4) for CAC ≥400. Compared with CAC = 0, hazards for those with CAC ≥400 were increased for lung and colorectal cancer in men [subdistribution hazard ratio (SHR): 2.2 (95% CI: 1.1–4.7)] and women [SHR: 2.2 (95% CI: 1.0–4.6)], but not significantly for sex-specific cancers across sexes. Conclusion CAC scores were associated with cancer risk in both sexes; however, this was stronger for lung and colorectal when compared with sex-specific cancers. Our data support potential synergistic use of CAC scores in the identification of both CVD and lung and colorectal cancer risk.

The prevalence of aortic valve calcification (AVC) increases with age. However, the sex-and race-specific burden of AVC and associated cardiovascular risk factors among adults ≥75 years are not well studied.We calculated the sex-and race-specific burden of AVC among 2283 older Black and White adults (mean age:80.5 [SD:4.3] years) without overt coronary heart disease from the Atherosclerosis Risk in Communities Study who underwent non-contrast cardiac-gated CT-imaging at visit 7 (2018-2019). Using Poisson regression with robust variance, we calculated the adjusted prevalence ratios (aPR) of the association of AVC with cardiovascular risk factors.The overall AVC prevalence was 44.8%, with White males having the highest prevalence at 58.2%. The prevalence was similar for Black males (40.5%), White females (38.9%), and Black females (36.8%). AVC prevalence increased significantly with age among all race-sex groups. The probability of any AVC at age 80 years was 55.4%, 40.0%, 37.3%, and 36.2% for White males, Black males, White females, and Black females, respectively. Among persons with prevalent AVC, White males had the highest median AVC score (100.9 Agatston Units [AU]), followed by Black males (68.5AU), White females (52.3AU), and Black females (46.5AU). After adjusting for cardiovascular risk factors, Black males (aPR:0.53; 95%CI:0.33-0.83), White females (aPR:0.68; 95%CI:0.61-0.77), and Black females (aPR:0.49; 95%CI:0.31-0.77) had lower AVC prevalence compared to White males. In addition, systolic blood pressure, non-HDL-cholesterol, and lipoprotein (a) were independently associated with AVC, with no significant race/sex interactions.AVC, although highly prevalent, was not universally present in this cohort of older adults. White males had ∼50-60% higher prevalence than other race-sex groups. Moreover, cardiovascular risk factors measured in older age showed significant association with AVC.

Background: Coronary artery calcium (CAC) is one of the most potent predictors of cardiovascular disease (CVD). Also, thoracic extra-coronary calcification (ECC) (e.g., aortic valve calcification) has provided additional prognostic information beyond CAC. However, data on CAC and ECC as predictors of CVD outcomes are limited in individuals aged ≥75 years and rarely report near-term prognosis despite its importance in the 75-and-older population given life expectancy. Methods: In 1,672 ARIC participants (age 75-94 years) without history of clinical coronary heart disease (CHD) at visit 7 (2018-2019), we assessed the associations of CAC and ECC with CVD (including CHD, stroke, and heart failure) over a median follow-up of 1.1 (IQI 0.7-1.5) years (46 CVD total cases), using adjusted Cox models. CAC and ECC were modeled categorically (Agatston scores 0-99 [reference], 100-299, and 300+) and continuously (log[Agatston score+1]). Results: Higher scores of CAC and calcium in the aortic valve (only when modeled continuously) and ascending aorta were significantly associated with elevated risk of CVD (e.g., adjusted hazard ratio [HR]: 2.79 [95% CI 1.21, 6.44] for CAC 300+ and 5.90 [2.42, 14.39] for ascending aorta calcium 300+ vs. 0-99.) ( Table ). We confirmed consistent results after excluding participants with prevalent stroke, and the association of aortic valve calcium 300+ with CVD became statistically significant (HR 2.31 [95% CI 1.02, 5.24]. When each CVD outcome was analyzed separately, significant associations with CHD and heart failure were shown in CAC (only when modeled continuously) and ascending aorta calcium (e.g., 4.98 [95% CI 1.10, 22.58] for CHD and 6.88 [2.14, 22.04] in ascending aorta calcium 300+). Conclusions: Coronary artery, ascending aorta, and aortic valve calcifications were positively associated with 1-year risk of CVD in 75+ year old. Our results support the prognostic value of CAC and ECC even in very old adults and suggest distinct prognostic implications of different vascular beds.

Background: Personalized cardiovascular disease (CVD) preventive therapy for older adults is important and emphasized in current clinical guidelines. Older adults often have multiple chronic conditions, are at higher risk for medication side effects, and may have different preferences when weighing multiple health outcomes. However, little is known about preferences for outcomes related to CVD preventive therapies in older adults. Methods: In May 2021, using an online panel, we surveyed US older adults (age 65-84 years) on outcome preferences related to statin (benefit-related outcomes: heart attack and stroke; side effect-related outcomes: diabetes, abnormal liver test, and muscle pain) or aspirin (benefit-related outcomes: heart attack and stroke; side effects: brain bleed, bowel bleed, and stomach ulcer). We used best-worst scaling, a novel stated-preference research method, to quantify relative outcome priorities. A standardized score was calculated for each outcome to indicate the strength of preference, ranging from -1.0 (least worrisome) to +1.0 (most worrisome). Results: 304 participants (median age 75, 45% male) completed the statin survey and 303 participants (median age 74, 46% male) completed the aspirin survey. In both surveys, stroke and heart attack, the two benefit outcomes from CVD prevention, were considered significantly more worrisome than outcomes related to side effects of the preventive therapies ( Table ). The general trend was similar for those age 65-74 vs. 75-84, although those age 75-84 tended to worry more about stroke than heart attack. Conclusions: Older adults considered the outcomes related to the benefits of CVD preventive therapies more important than outcomes related to the therapies’ side effects. These results suggest that older adults tend to prioritize the benefits of CVD preventive therapies over their side effects. Integrating individualized patient preferences with risk prediction to guide personalized shared decision-making is an important next step.

Objectives: To evaluate the association between inflammatory bowel disease (IBD) and atherosclerotic cardiovascular disease (ASCVD) and whether this association is modified by age or sex. Methods: We conducted a cross-sectional analysis using data from the 2015–2016 National Health Interview Survey (NHIS). The exposure of interest was self-reported IBD. The outcome of interest was prevalent ASCVD, which included a history of angina, myocardial infarction or stroke. We used survey-specific descriptive statistics to obtain weighted national estimates for IBD and ASCVD prevalence. Logistic regression models were used to assess the association between IBD and ASCVD, progressively adjusting for demographics and traditional risk factors. Effect modification by age and sex was evaluated. Results: Among participants with IBD, the age-adjusted prevalence of ASCVD was 12.0% compared to 6.9% among those without IBD (p

Aim The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower ( Methods and results Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD −1.56; RR 0.94 (0.89–1.00)], cardiovascular mortality [ARD −1.49; RR 0.90 (0.81–1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy. Conclusion This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.

Type 2 diabetes prevention requires the accurate identification of those at high risk. Beyond the association of fasting serum triacylglycerols with diabetes, triacylglycerol-enriched remnant lipoproteins (TRLs) more accurately reflect pathophysiological changes that underlie progression to diabetes, such as hepatic insulin resistance, pancreatic steatosis and systemic inflammation. We hypothesised that TRL-related factors could improve risk prediction for incident diabetes. We included individuals from the Brazilian Longitudinal Study of Adult Health cohort. We trained a logistic regression model for the risk of incident diabetes in 80% of the cohort using tenfold cross-validation, and tested the model in the remaining 20% of the cohort (test set). Variables included medical history and traits of the metabolic syndrome, followed by TRL-related measurements (plasma concentration, TRL particle diameter, cholesterol and triacylglycerol content). TRL features were measured using NMR spectroscopy. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Among 4463 at-risk individuals, there were 366 new cases of diabetes after a mean (±SD) of 3.7 (±0.63) years of follow-up. We derived an 18-variable model with a global AUROC of 0.846 (95% CI: 0.829, 0.869). Overall TRL-related markers were not associated with diabetes. However, TRL particle diameter increased the AUROC, particularly in individuals with HbA1c

Coronary heart disease is a chronic, systemic disease with a wide range of associated symptoms, clinical outcomes, and health care expenditure. Adverse events from coronary heart disease can be mitigated or avoided with lifestyle and risk factor modifications, and medical therapy. These measures are effective in slowing the progression of atherosclerotic disease and in reducing the risk of thrombosis in the setting of plaque disruptions. With increasing effectiveness of prevention and medical therapy, the role of coronary artery revascularization has decreased and is largely confined to subgroups of patients with unacceptable angina, severe left ventricular systolic dysfunction, or high-risk coronary anatomy. There is a compelling need to allocate resources appropriately to improve prevention. Herein, we review the scientific evidence in support of medical therapy and revascularization for the management of patients with stable coronary heart disease and discuss implications for the evaluation of patients with stable angina and public policy.

Background and aims There are limited data on serial coronary artery calcium (CAC) assessments outside North American and European populations. We sought to investigate risk factors for CAC incidence and progression in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods We included individuals with no prior cardiovascular disease and two CAC measurements in ELSA-Brasil. Incident CAC was defined as a baseline CAC of 0 followed by CAC >0 on the second study. CAC progression was defined according to multiple published criteria. We performed logistic and linear regression to identify risk factors for CAC incidence and progression. We also examined risk factor effect modification by baseline CAC (0 vs. >0). Results A total of 2707 individuals were included (57% women, age 48.6 ± 7.7 years). Participants self-identified as white (55%), brown (24%), black (16%), Asian (4%) and Indigenous (1%). The mean period between CAC assessments was 5.1 ± 0.9 years. CAC incidence occurred in 282 (13.3%) of 2127 individuals with baseline CAC of 0. CAC progression occurred in 319 (55%) of 580 participants with baseline CAC >0. Risk factors for CAC incidence included older age, male sex, white race, hypertension, diabetes, higher BMI, smoking, lower HDL-C, higher LDL-C and triglycerides, and metabolic syndrome. Older age and elevated LDL-C were associated with CAC incidence, but not progression. Risk factors consistently associated with CAC progression were hypertension, diabetes, hypertriglyceridemia, and metabolic syndrome. On interaction testing, these four risk factors were more strongly associated with CAC progression as compared to CAC incidence. Conclusions CAC incidence was associated with multiple traditional risk factors, whereas the only risk factors associated with progression of CAC were hypertension, diabetes, hypertriglyceridemia, and metabolic syndrome.

Background Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear. Objectives The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF. Methods The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio. Results Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p, Central Illustration

The 2017 American blood pressure (BP) guidelines recommended a personalized risk-based approach to treatment in stage 1 hypertension. We sought to establish the utility of coronary artery or thoracic aortic calcium (CAC or TAC) as additional risk modifiers in this setting. We included 1859 Multiethnic Study of Atherosclerosis participants with stage 1 hypertension. We compared adjusted HR for the composite outcome of incident atherosclerotic cardiovascular disease or heart failure across predefined categories of either CAC or TAC (0, 1 to 100, or >100) in: (1) the full sample; (2) 4 high-risk subgroups recommended for pharmacotherapy to a BP goal 100. CAC >100 was independently associated with a higher relative risk of events compared with CAC = 0 (e.g., adjusted HR [9.5 (1.8 to 18.7)] in the low-risk subgroup). NNT10 for CAC = 0 were 3 to 5 times higher than those for CAC >100 in all analyses. TAC was not a reliable risk modifier in our study. In conclusion, CAC, but not TAC, can further guide risk-based allocation of treatment in stage 1 hypertension and should be considered as a risk modifier in future guidelines.

Background Most previous research has studied the association of hypertension with cardiovascular disease (CVD) and all-cause mortality by focusing on the transition from the initial state to a single outcome. We investigated the impact of hypertension, defined according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) (new) and the Seventh Report of the Joint National Committee (JNC7) (old), on CVD death and all-cause mortality considering non-fatal CVD as an intermediate event between two CVD-free and mortality states. Methods A total of 3002 Iranian population (47.4% men), aged ≥50 years were followed from 1999 to 2014. Two multi-state semi-Markov models with three transitions were defined for CVD death and all-cause mortality as two outcomes. The multivariable Cox model was used to estimate the effect of hypertension on transition hazards. The mean of 15-year life expectancy of participants in each transition was estimated using the restricted mean survival time. Results The ACC/AHA guideline increased the prevalence of hypertension from 43.3 to 68.6%. Among CVD-free individuals, hypertension was significantly associated with increased risk of non-fatal CVD [Hazard Ratio, 1.52 (1.28–1.81) and 1.48 (1.21–1.80)], CVD death [2.96 (2.06–4.25) and 1.98 (1.30–3.04)] and all-cause mortality [1.64 (1.32–2.05) and 1.31 (1.01–1.69)] according the old and new guidelines, respectively. However, after incident non-fatal CVD, the association between hypertension and mortality events was not significant according to both definitions. Hypertensive participants experienced a first non-fatal CVD about 0.9 and 0.6 years earlier than normotensive population according to JNC7 and the 2017 ACC/AHA guidelines, respectively. Conclusion Hypertension, according to JNC7 and the ACC/AHA guidelines, significantly increased the risk of mortality events among CVD-free population although the risk was attenuated using ACC/AHA guideline. Hypertension also decreased the number of years lived without CVD and early onset of CVD, and consequently, an increase in the time spent with these diseases. After non-fatal CVD, hypertension had no significant impact on mortality risk according to both guidelines.

Objective To study the association between cardiorespiratory fitness (CRF) and incident stroke types. Patients and Methods We studied a retrospective cohort of patients referred for treadmill stress testing in the Henry Ford Health System (Henry Ford ExercIse Testing Project) without history of stroke. CRF was expressed by metabolic equivalents of task (METs). Using appropriate International Classification of Diseases, Ninth Revision codes, incident stroke was ascertained through linkage with administrative claims files and classified as ischemic, hemorrhagic, and subarachnoid hemorrhage (SAH). Multivariable-adjusted Cox proportional hazards models examined the association between CRF and incident stroke. Results Among 67,550 patients, mean ± SD age was 54±13 years, 46% (n=31,089) were women, and 64% (n=43,274) were white. After a median follow-up of 5.4 (interquartile range 2.7-8.5) years, a total of 7512 incident strokes occurred (6320 ischemic, 2481 hemorrhagic, and 275 SAH). Overall, there was a graded lower incidence of stroke with higher MET categories. Patients with METs of 12 or more had lower risk of overall stroke [0.42 (95% CI, 0.36-0.49)], ischemic stroke [0.69 (95% CI, 0.58-0.82)], and hemorrhagic stroke [0.71 (95% CI, 0.52-0.95)]. Conclusion In a large ethnically diverse cohort of patients referred for treadmill stress testing, CRF is inversely associated with risk for ischemic and hemorrhagic stroke.

Context The worldwide rise in the prevalence of cardiometabolic disease, and the introduction of therapeutic options for treating metabolic disease that also lower cardiovascular risk, calls for a restructuring of how we care for patients with cardiometabolic disease. We propose establishment of a new medicine subspecialty, Cardiometabolic Medicine. Evidence Acquisition This summary is based on a synthesis of published original and review articles identified through PubMed, professional society guidelines, and the authors’ knowledge of the fields of metabolism, diabetes, and cardiology. Evidence Synthesis The growing prevalence of cardiometabolic disease will continue to be perhaps the greatest challenge in the United States and throughout the world. We have entered an era where a large set of clinical tools are available that help prevent and treat cardiometabolic disease; however, our old models of clinical training and siloed care are barriers to rapid uptake and efficient healthcare delivery and are in need of change. Conclusions Establishing the field of Cardiometabolic Medicine would be a small step in the right direction towards providing the best possible comprehensive care for those with complex cardiometabolic disease.

Objectives This study sought to evaluate the association and burden of coronary artery calcium (CAC) with long-term, cause-specific mortality across the spectrum of baseline risk. Background Although CAC is a known predictor of short-term, all-cause mortality, data on long-term and cause-specific mortality are inadequate. Methods The CAC Consortium cohort is a multicenter cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC testing. The following risk factors (RFs) were considered: 1) current cigarette smoking; 2) dyslipidemia; 3) diabetes mellitus; 4) hypertension; and 5) family history of CHD. Results During the 12.5-years median follow-up, 3,158 (4.7%) deaths occurred; 32% were cardiovascular disease (CVD) deaths. Participants with CAC scores ≥400 had a significantly increased risk for CHD and CVD mortality (hazard ratio [HR]: 5.44; 95% confidence interval [CI]: 3.88 to 7.62; and HR: 4.15; 95% CI: 3.29 to 5.22, respectively) compared with CAC of 0. Participants with ≥3 RFs had a smaller increased risk for CHD and CVD mortality (HR: 2.09; 95% CI: 1.52 to 2.85; and HR: 1.84; 95% CI: 1.46 to 2.31, respectively) compared with those without RFs. Across RF strata, CAC added prognostic information. For example, participants without RFs but with CAC ≥400 had significantly higher all-cause, non-CVD, CVD, and CHD mortality rates compared with participants with ≥3 RFs and CAC of 0. Conclusions Across the spectrum of RF burden, a higher CAC score was strongly associated with long-term, all-cause mortality and a greater proportion of deaths due to CVD and CHD. Absence of CAC identified people with a low risk over 12 years of follow-up, with most deaths being non-CVD in nature, regardless of RF burden.

Background The purpose of this study is to determine if a new score calculated with coronary artery calcium (CAC) density and volume is associated with total coronary artery plaque burden and composition on coronary CT angiography (CCTA) compared to the Agatston score (AS). Methods We identified 347 men enrolled in the Multicenter AIDS cohort study who underwent contrast and non-contrast CCTs, and had CAC>0. CAC densities (mean Hounsfield Units [HU]) per plaque) and volumes on non-contrast CCT were measured. A Density-Volume Calcium score was calculated by multiplying the plaque volume by a factor based on the mean HU of the plaque (4, 3, 2 and 1 for 130–199, 200–299, 300–399, and ≥400HU). Total Density-Volume Calcium score was determined by the sum of these individual scores. The semi-quantitative partially calcified and total plaque scores (PCPS and TPS) on CCTA were calculated. The associations between Density-Volume Calcium score, PCPS and TPS were examined. Results Overall, 2879 CAC plaques were assessed. Multivariable linear regression models demonstrated a stronger association between the log Density-Volume Calcium score and both the PCPS (β 0.99, 95%CI 0.80–1.19) and TPS (β 2.15, 95%CI 1.88–2.42) compared to the log of AS (PCPS: β 0.77, 95%CI 0.61–0.94; TPS: β 1.70, 95%CI 1.48–1.94). Similar results were observed for numbers of PC or TP segments. Conclusion The new CAC score weighted towards lower density demonstrated improved correlation with semi-quantitative PC and TP burden on CCTA compared to the traditional AS, which suggests it has utility as an alternative measure of atherosclerotic burden.

The 2018 and 2019 guidelines from the American College of Cardiology and American Heart Association reflect the complexity of individualized cholesterol management. The documents address more detailed risk assessment, newer nonstatin cholesterol-lowering drugs, special attention to patient subgroups, and consideration of the value of therapy, all with the aim of creating personalized treatment plans for each patient. Overall, the guidelines recommend shared decision-making to meet the individual needs of each patient.

Although high coronary artery calcium (CAC) scores predict high risk, absence of CAC has been shown to be a powerful negative risk marker for the development of coronary heart disease (CHD) ([1][1]). Accordingly, the 2018 American College of Cardiology/American Heart Association/Multisociety

Introduction The association between e-cigarette use and chronic bronchitis, emphysema, and chronic obstructive pulmonary disease has not been studied thoroughly, particularly in populations defined by concomitant combustible smoking status. Methods Using pooled 2016 and 2017 data from the Behavioral Risk Factor Surveillance System, investigators studied 705,159 participants with complete self-reported information on e-cigarette use, combustible cigarette use, key covariates, and chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. Current e-cigarette use was the main exposure, with current use further classified as daily or occasional use. The main outcome was defined as reported ever having a diagnosis of chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. For all the analyses, multivariable adjusted logistic regression was used, with the study population stratified by combustible cigarette use status (never, former, or current). All the analyses were conducted in 2019. Results Of 705,159 participants, 25,175 (3.6%) were current e-cigarette users, 64,792 (9.2%) current combustible cigarette smokers, 207,905 (29.5%) former combustible cigarette smokers, 432,462 (61.3%) never combustible cigarette smokers, and 14,036 (2.0%) dual users of e-cigarettes and combustible cigarettes. A total of 53,702 (7.6%) participants self-reported chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. Among never combustible cigarette smokers, current e-cigarette use was associated with 75% higher odds of chronic bronchitis, emphysema, or chronic obstructive pulmonary disease compared with never e-cigarette users (OR=1.75, 95% CI=1.25, 2.45), with daily users of e-cigarettes having the highest odds (OR=2.64, 95% CI=1.43, 4.89). Similar associations between e-cigarette use and chronic bronchitis, emphysema, or chronic obstructive pulmonary disease were noted among both former and current combustible cigarette smokers. Conclusions The results suggest possible e-cigarette–related pulmonary toxicity across all the categories of combustible cigarette smoking status, including those who had never smoked combustible cigarettes.

The prognostic utility of coronary artery calcium (CAC) for individuals taking statins is unclear. We hypothesized that CAC remains associated with atherosclerotic cardiovascular disease (ASCVD) events in individuals using statins at baseline or among those started on statin at follow-up. The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of 6,814 participants who were enrolled between 2000 and 2002 and were free of clinical ASCVD at baseline. Four follow-up visits were conducted in 2002 to 2004, 2004 to 2006, 2005 to 2007, and 2010 to 2012. CAC was assessed at baseline and follow-up using either an electron-beam CT scanner or a multidetector CT system. Statin use at baseline and follow up was self-reported. Among 6,811 participants with complete information on statin use, mean age was 62 (SD = 10) years, 53% were women, 38% white, 12% Chinese-American, 28% African American, and 22% Hispanic. In multivariable analyses, CAC >0 was associated with a significantly higher risk of ASCVD events regardless of baseline or incident statin use. For example, hazard ratios (95% confidence interval) for the association between CAC >0 and ASCVD were 2.46 (1.41, 4.28) for baseline statin users, 2.08 (1.68, 2.57) for baseline-statin nonusers, and 2.21 (1.56, 3.15) for those started on a statin at follow-up. In conclusion, current statin use does not weaken the prognostic utility of CAC. CAC is associated with incident ASCVD regardless of baseline or incident statin use.

OBJECTIVE To determine the effect of fitness on the association between BMI and mortality among patients with diabetes. RESEARCH DESIGN AND METHODS We identified 8,528 patients with diabetes (self-report, medication use, or electronic medical record diagnosis) from the Henry Ford Exercise Testing Project (FIT Project). Patients with a BMI RESULTS Patients had a mean age of 58 ± 11 years (49% women) with 1,319 deaths over a mean follow-up of 10.0 ± 4.1 years. Overall, obese patients had a 30% lower mortality hazard (P < 0.001) compared with normal-weight patients. In adjusted spline modeling, higher BMI as a continuous variable was predominantly associated with a lower mortality risk in the lowest fitness group and among patients with moderate fitness and BMI ≥30 kg/m2. Compared with the lowest fitness group, patients with higher fitness had an ∼50% (6–9.9 METs) and 70% (≥10 METs) lower mortality hazard regardless of BMI (P < 0.001). CONCLUSIONS Among patients with diabetes, the obesity paradox was less pronounced for patients with the highest fitness level, and these patients also had the lowest risk of mortality.

Background Serum gamma-glutamyl transferase (GGT) is a marker of oxidative stress, associated with increased cardiovascular (CV) risk. The impact of smoking on oxidative stress may be aggravated in individuals with non-alcoholic fatty liver disease (NAFLD). We aimed to ascertain the association of smoking on GGT levels in the presence or absence of NAFLD. Methods We evaluated 6,354 healthy subjects (43 ± 10 years, 79% males) without clinical cardiovascular disease (CVD) undergoing an employer-sponsored physical between December 2008 and December 2010. NAFLD was diagnosed by ultrasound and participants were categorized as current or non-smokers by self report. A multivariate linear regression of the cross-sectional association between smoking and GGT was conducted based on NAFLD status. Results The prevalence of NAFLD was 36% (n = 2,299) and 564 (9%) were current smokers. Smokers had significantly higher GGT levels in the presence of NAFLD (P < 0.001). After multivariable adjustment, current smoking was associated with 4.65 IU/L higher GGT level, P < 0.001, compared to non-smokers. When stratified by NAFLD, the magnitude of this association was higher in subjects with NAFLD (β-coefficient: 11.12; 95% confidence interval (CI): 5.76 - 16.48; P < 0.001); however, no such relationship was observed in those without NAFLD (β: -0.02; 95% CI: -3.59, 3.56; P = 0.992). Overall the interaction of NAFLD and smoking with GGT levels as markers of oxidative stress was statistically significant. Conclusions Smoking is independently associated with significantly increased oxidative stress as measured by GGT level. This association demonstrates effect modification by NAFLD status, suggesting that smoking may intensify CV risk in individuals with NAFLD.

Individuals with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are considered high-risk and current guidelines recommend initiating high-intensity statin therapy in this group. We sought to examine the predictive ability of zero CAC in this high-risk group.Multi-Ethnic Study of Atherosclerosis participants without clinical cardiovascular disease and baseline LDL-C ≥190 mg/dL were identified. Cardiovascular risk factors were compared between those with CAC = 0 and CAC0. Multivariable Poisson regression was used to identify predictors of CAC = 0. Association of CAC = 0 with incident cardiovascular events over a median follow-up of 13.2 years was examined using multivariable-adjusted Cox regression.246 individuals (mean age = 63 ± 9.4 years; 42% male; 31% white; 37% CAC = 0) with LDL-C ≥190 mg/dL were identified (mean LDL-C = 215 ± 27 mg/dL). Age65 years (RR = 2.17, 95%CI = 1.49-3.23), female sex (RR = 2.10, 95%CI = 1.42-3.10), and no diabetes (RR = 2.22, 95%CI = 1.18-4.17) were associated with CAC = 0. Individuals with CAC = 0 had a lower risk for future cardiovascular events (incidence rate per 1000 person-years = 4.7; 10-year risk = 3.7%; risk/year = 0.4%) than those with CAC0 (incidence rate per 1000 person-years = 26.4; 10-year risk = 20%; risk/year = 2.0%), adjusted HR 0.25 (95%CI = 0.10-0.66).Among persons with LDL-C ≥190 mg/dL, younger age, female sex, and the absence of diabetes were associated with CAC = 0. CAC = 0 was associated with a low risk of cardiovascular events, suggesting the utility of CAC assessment for stratifying risk in this high-risk group.

BACKGROUND:The Coronary Artery Calcium Data and Reporting System (CAC-DRS), which takes into account the Agatston score category (A) and the number of calcified vessels (N) has not yet been validated in terms of its prognostic significance. METHODS:We included 54,678 patients from the CAC Consortium, a large retrospective clinical cohort of asymptomatic individuals free of baseline cardiovascular disease (CVD). CAC-DRS groups were derived from routine, cardiac-gated CAC scans. Cox proportional hazards regression models, adjusted for traditional CVD risk factors, were used to assess the association between CAC-DRS groups and CHD, CVD, and all-cause mortality. CAC-DRS was then compared to CAC score groups and regional CAC distribution using area under the curve (AUC) analysis. RESULTS:The study population had a mean age of 54.2 ± 10.7, 34.4% female, and mean ASCVD score 7.3% ± 9.0. Over a mean follow-up of 12 ± 4 years, a total of 2,469 deaths (including 398 CHD deaths and 762 CVD deaths) were recorded. There was a graded risk for CHD, CVD and all-cause mortality with increasing CAC-DRS groups ranging from an all-cause mortality rate of 1.2 per 1,000 person-years for A0 to 15.4 per 1,000 person-years for A3/N4. In multivariable-adjusted models, those with CAC-DRS A3/N4 had significantly higher risk for CHD mortality (HR 5.9 (95% CI 3.6-9.9), CVD mortality (HR4.0 (95% CI 2.8-5.7), and all-cause mortality a (HR 2.5 (95% CI 2.1-3.0) compared to CAC-DRS A0. CAC-DRS had higher AUC than CAC score groups (0.762 vs 0.754, P

Importance: Atherosclerosis burden and coronary artery calcium (CAC) are associated with the risk for atherosclerotic cardiovascular disease (ASCVD) events, with absence of plaque and CAC indicating low risk. Whether this is true in patients with elevated levels of low-density lipoprotein cholesterol (LDL-C) is not known. Specifically, a high prevalence of noncalcified plaque might signal high risk.Objective: To determine the prevalence of noncalcified and calcified plaque in symptomatic adults and assess its association with cardiovascular events across the LDL-C spectrum.Design, Setting, and Participants: This cohort study included symptomatic patients undergoing coronary computed tomographic angiography from January 1, 2008, to December 31, 2017, from the seminational Western Denmark Heart Registry. Follow-up was completed on July 6, 2018. Data were analyzed from April 2 to December 2, 2021.Exposures: Prevalence of calcified and noncalcified plaque according to LDL-C strata of less than 77, 77 to 112, 113 to 154, 155 to 189, and at least 190 mg/dL. Severity of coronary artery disease was categorized using CAC scores of 0, 1 to 99, and ≥100, where higher numbers indicate greater CAC burden.Main Outcomes and Measures: Atherosclerotic cardiovascular disease events (myocardial infarction and stroke) and death.Results: A total of 23 143 patients with a median age of 58 (IQR, 50-65) years (12 857 [55.6%] women) were included in the analysis. During median follow-up of 4.2 (IQR, 2.3-6.1) years, 1029 ASCVD and death events occurred. Across all LDL-C strata, absence of CAC was a prevalent finding (ranging from 438 of 948 [46.2%] in patients with LDL-C levels of at least 190 mg/dL to 4370 of 7964 [54.9%] in patients with LDL-C levels of 77-112 mg/dL) and associated with no detectable plaque in most patients, ranging from 338 of 438 (77.2%) in those with LDL-C levels of at least 190 mg/dL to 1067 of 1204 (88.6%) in those with LDL-C levels of less than 77 mg/dL. In all LDL-C groups, absence of CAC was associated with low rates of ASCVD and death (6.3 [95% CI, 5.6-7.0] per 1000 person-years), with increasing rates in patients with CAC scores of 1 to 99 (11.1 [95% CI, 10.0-12.5] per 1000 person-years) and CAC scores of at least 100 (21.9 [95% CI, 19.9-24.4] per 1000 person-years). Among those with CAC scores of 0, the event rate per 1000 person-years was 6.3 (95% CI, 5.6-7.0) in the overall population compared with 6.9 (95% CI, 4.0-11.9) in those with LDL-C levels of at least 190 mg/dL. Across all LDL-C strata, rates were similar and low in those with CAC scores of 0, regardless of whether they had no plaque or purely noncalcified plaque.Conclusions and Relevance: The findings of this cohort study suggest that in symptomatic patients with severely elevated LDL-C levels of at least 190 mg/dL who are universally considered to be at high risk by guidelines, absence of calcified and noncalcified plaque on coronary computed tomographic angiography was associated with low risk for ASCVD events. These results further suggest that atherosclerosis burden, including CAC, can be used to individualize treatment intensity in patients with severely elevated LDL-C levels.

High-dose eicosapentaenoic acid (EPA) therapy was beneficial in high-risk patients without clinical cardiovascular disease (CVD). Whether higher plasma levels of EPA and docosahexaenoic acid (DHA) have similar benefits in those without subclinical CVD is unclear. We aim to evaluate the interplay between plasma omega-3 fatty acids and coronary artery calcium (CAC) in relation to CVD events.We examined 6568 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with plasma EPA and DHA levels and CAC measured at baseline. The primary outcome was incident CVD events (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Hazard ratios for the primary outcome were adjusted for potential confounder using Cox regression.Mean ± SD age was 62.1 ± 10.2 years and 52.9% were females. The median follow-up time was 15.6 years. Higher logIn an ethnically diverse population free of clinical CVD, higher plasma omega-3 fatty acid levels were associated with fewer long-term CVD events. The absolute decrease in CVD events with higher omega-3 fatty acid levels was more apparent at higher CAC scores.

Background: Cardiac structure and function are important in determining ischemic stroke (IS) etiology, but whether there is an association with cognition post IS is unknown. Methods: IS patients admitted to Johns Hopkins Hospital (2017-2019) underwent transthoracic echocardiography. IS was classified (TOAST) by a masked reviewer. Parasternal short axis left atrial (LA) diameter was evaluated as a continuous variable with a spline at 4cm (normal ≤4cm versus enlarged >4cm); left ventricle ejection fraction (LVEF) was evaluated as a nonlinear continuous variable with two spline knots at 40% and 65%. Cognition was assessed by telephone using the Six Item Screener (SIS), which tests orientation (day, month, year) and recall (grass, paper, shoe) and was dichotomized into low (0-3, worse score) and high (4-6, better score), and conservatively imputing low category scores for non-answerers. Multivariable logistic regression determined the association of SIS category with LA or LVEF, each, adjusted for covariates. Results: Participants (N=119) were on average 60 (18-89) years, 60% male, and 59% Black. Mean LA diameter was 3.9cm ( SD =0.8) and mean LVEF 61.4% ( SD =10.5). For LA diameter ≤4cm, each 1cm increase was associated with 5.93 greater odds (95% CI=1.49-23.65) of scoring in the high SIS category, while for LA diameter >4cm each 1cm increase was associated with lower odds (OR=0.88, 95% CI=0.39-1.99) of scoring in the high SIS category (Figure 1). Decreased (OR=0.91, 95% CI=0.74-1.11), normal (OR=0.98, 95% CI=0.91-1.06) or hyperdynamic LVEF (OR=1.02, 95% CI=0.90-1.14) showed no relationship with SIS category. Conclusions: In this study, a 1cm change in LA diameter was significantly associated with a higher score on a telephone cognition screening test, if patients had a LA diameter within normal range, but without the same association with SIS if the LA diameter was >4cm. We cautiously suggest that LA function may be associated with cognition post-stroke.

RATIONALE: Electronic cigarette (e-cigarette) use is highly prevalent among young adults. However, longitudinal data assessing the association between e-cigarette use and respiratory symptoms are lacking. OBJECTIVES: To determine whether e-cigarette use is associated with the development of respiratory symptoms in young adults. METHODS: Data are derived from the PATH (Population Assessment of Tobacco and Health) study waves 2 (2014–2015), 3 (2015–2016), 4 (2016–2018), and 5 (2018–2019). Young adults aged 18–24 years at baseline with no prevalent respiratory disease or symptoms were included in the analyses. Binary logistic regression models with a generalized estimating equation were used to estimate time-varying and time-lagged associations of e-cigarette use during waves 2–4, with respiratory symptom development approximately 12 months later at waves 3–5. MEASUREMENTS AND MAIN RESULTS: The per-wave prevalence of former and current e-cigarette use was 15.2% and 5.6%, respectively. Former e-cigarette use was associated with higher odds of developing any respiratory symptom (adjusted odds ratio [aOR], 1.20; 95% confidence interval [CI], 1.04–1.39) and wheezing in the chest (aOR, 1.41; 95% CI, 1.08–1.83) in multivariable adjusted models. Current e-cigarette use was associated with higher odds for any respiratory symptom (aOR, 1.32; 95% CI, 1.06–1.65) and wheezing in the chest (aOR, 1.51; 95% CI, 1.06–2.14). Associations persisted among participants who never smoked combustible cigarettes. CONCLUSIONS: In this nationally representative cohort of young adults, former and current e-cigarette use was associated with higher odds of developing wheezing-related respiratory symptoms, after accounting for cigarette smoking and other combustible tobacco product use.