Risk Factors and Emergency Department Outcomes in Methamphetamine-Associated Cardiomyopathy: A Case-Control Study.

BACKGROUND: Methamphetamine-associated cardiomyopathy (MACM) is a known complication of methamphetamine use; however, risk factors and outcomes of patients with MACM are not well understood. STUDY OBJECTIVES: This study aims to identify risk factors, emergency department (ED) interventions, and outcomes for MACM. METHODS: This case-control study was conducted between 2012 and 2020 at two academic EDs. ED patients ≥18 years with an index visit that included documented methamphetamine use were included. Patients with documented MACM during follow-up (3 months-3 years) were considered cases (MACM). A control group comprised of patients with documented methamphetamine use but no known MACM was matched at a 2:1 ratio. Logistic regression was used to model risk factors for MACM. RESULTS: A total of 9833 patients with methamphetamine use were identified. From this, 160 MACM patients were matched to 322 controls. The mean age was 48.4 years, and 143 patients (29.7%) were female. MACM patients were more likely to be admitted on their index visit (45.6% vs. 34.8%, p = 0.021). Significant variables associated with MACM included: admission at the index visit (odds ratio [OR] 1.51), diabetes (OR 3.02), kidney disease (OR 5.47), and pulmonary disease (OR 2.39). MACM patients had more ED visits in the follow-up period (10.1 vs. 7, p = 0.009) and were admitted at a higher rate across all visits (32.5% vs. 15.4%, p = 0.009). Additionally, MACM patients had significantly longer hospital stays than controls (mean 18 additional days, p = 0.009). CONCLUSION: Patients who developed MACM had traditional risk factors for heart failure and experienced significantly more ED visits, more hospitalizations, and longer hospital stays than matched controls.

Associations of urinary isoprostanes with measures of subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background: Urinary isoprostanes are markers of systemic oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC), thoracic aortic calcium (TAC) and carotid plaque are measure subclinical atherosclerosis and prognosticate ASCVD risk. We examined the associations between urinary isoprostane levels and measures of plaque prevalence, burden, incidence and progression across three vascular beds in a cohort from the Multi-Ethnic Study of Atherosclerosis. Methods: Urinary levels of 8-isoprostane and 2,3-dinor-8-F2-isoprostane were measured in 1089 participants (mean ± SD 62 ± 8 years, 48% women) at baseline. Participants underwent computed tomography for CAC and TAC, and duplex ultrasound for carotid plaque. TAC and CAC were reassessed at 2.4 and 10 years, respectively. Regression models were adjusted for CVD risk factors. Results: In adjusted models, there were no significant associations between isoprostane levels with CAC prevalence or progression. Highest versus lowest tertile of 8-isoprostane was associated with 28% lower prevalence of descending TAC at baseline [prevalence ratio (PR) 0.72 95% CI (0.56, 0.94)], while 1-SD higher 2,3-dinor-8-F2-isoprostane was associated with 96% higher incident ascending TAC at follow-up [Relative Risk 1.96 (1.24, 3.09)]. Highest versus lowest tertile of isoprostane measures were associated with 22% higher prevalence of carotid plaque [(PR 1.22 (1.04, 1.45)] and 14% difference [3,26] in greater extent of carotid plaque at baseline. Conclusions: Higher urinary isoprostanes were inconsistently associated with some measures of subclinical atherosclerosis by imaging. This suggests a limited role of urinary isoprostane levels as a prognostic marker for the development of ASCVD. Trial registration: The MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.

Inter-arm systolic blood pressure difference: non-persistence and association with incident cardiovascular disease in the Multi-ethnic Study of Atherosclerosis.

We investigated inter-arm systolic blood pressure (sIAD) difference, reproducibility, and incident cardiovascular disease (CVD). We hypothesized that higher sIAD values have low prevalence and nonpersistence over years, but that CVD risk is higher starting from the time of first high absolute sIAD. In Multi-Ethnic Study of Atherosclerosis participants (n = 6725, 53% female, 45-84 years old), Doppler systolic blood pressure (SBP) measurements were made in both arms (10-minute interval) thrice over 9.5 years. Proportional hazards for CVD (coronary heart disease, heart failure, stroke, peripheral arterial disease (PAD)) over 16.4 years were tested according to time-varying absolute inter-arm difference with covariates: (1) age, gender, race, and clinic; (2) model 1 plus height, heart rate, BP, antihypertensives, BMI, smoking status, lipids, lipid lowering medication, and diabetes. High sIAD was not persistent across exams. Maximum absolute sIAD ≥ 15 mmHg was found at least once in 815 persons. Maximum absolute sIAD had a graded relationship with incident stroke or PAD: 6.2% events; model 2 hazard ratio per 10 mmHg 1.34 (95% CI, 1.15-1.56) and this risk was approximately doubled for maximum absolute sIAD ≥ 15 mmHg vs 0-4 mmHg. Total CVD risk (18.4% events) was increased only for maximum absolute sIAD ≥25 mmHg. Associations with incident CVD did not differ for higher SBP in left vs right arm. A higher maximum absolute sIAD at any exam was associated with greater risk for stroke and PAD especially for values ≥ 15 mmHg, and ≥25 mmHg for other CVD. Measuring SBP between arms may help identify individuals at risk for CVD.

Coronary artery calcium incidence and changes using direct plaque measurements: The MASALA study.

BACKGROUND AND AIMS: We aimed to identify predictors of change in direct measures of coronary artery calcium (CAC) volume and density in South Asian participants. METHODS: We used data from participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with prevalent CAC and direct measures of CAC by serial computed tomography (CT) exams (2010-2013, 2016-2018). We examined the distribution of incident CAC volume and peak density, as well as progression and identified risk factors for progression of change in volume and density in multivariable models. RESULTS: The study cohort consisted of 102 participants with incident CAC and 285 with CAC progression. CAC volume and density were highest, and incident CAC was most common in the left anterior descending artery (LAD). The greatest progression in volume was in the right coronary artery and the greatest change in density was in the left main. In linear regression models for CAC progression adjusted for baseline density, volume, risk factors, smoking (ß +190.1, p = 0.02), baseline volume (ß +0.24 per mm3, p < 0.01), and scan interval (ß +0.15 per day, p = 0.01) were associated with change in total volume whereas Lp(a) (ß +0.81 per mg/dL, p = 0.03), exercise (ß +0.19 per 10 MET-min/week, p = 0.01), and baseline volume (ß +0.15 per mm3, p < 0.01) and density (ß -0.55 per unit, p < 0.01) were associated with change in total density. CONCLUSIONS: In this South Asian cohort, smoking was associated with CAC volume progression, while Lp(a) and exercise were associated with progression of peak CAC density.

Systolic dysfunction in patients with methamphetamine use and heart failure with preserved ejection fraction.

BACKGROUND: We aimed to evaluate for occult systolic dysfunction and the effect of methamphetamine cessation among patients with methamphetamine use (MU) and heart failure with preserved ejection fraction (HFpEF). METHODS: A retrospective cohort of patients with HFpEF with serial echocardiograms was stratified by MU and evaluated using myocardial strain analysis on echocardiograms at baseline and 1 year to measure global longitudinal strain (GLS). Contemporaneous controls with an ICD diagnosis of HF within 3 days of an MU case were chosen. RESULTS: Patients with MU (n = 31) were younger (49 ± 10 vs 59 ± 16 years, p < 0.01) and more frequently male (55% vs 26%, p = 0.04) than controls (n = 23). There was no baseline difference in ejection fraction (EF) (median 66% [IQR 58,71%] vs 62% [56,69%], p = 0.33) or GLS (-13.0% [-16.3,-10.9%] vs -14.8% [-16.0,-11.3%], p = 0.40). At one-year follow-up, MU cessation (n = 15) was associated with improvement in GLS (absolute change -4.4% [-6.5,-1.7%], p < 0.01), while no absolute change was observed with continued MU (n = 16) (0.74% [-1.2,2.8%], p = 0.22) or controls without MU (-0.6% [-2.1,2.8%], p = 0.78). Of those with abnormal baseline GLS, normalization was observed in 46% with MU cessation, none with continued MU, and 5% of controls (p < 0.001). Among MU patients, improvement in GLS was associated with decreased HF admissions per year [HR 0.74 per 1% change in GLS, 95% CI 0.55,0.98, p = 0.04]. CONCLUSIONS: Patients with MU and HFpEF may have occult systolic dysfunction as demonstrated by abnormal GLS, and MU cessation at 1 year is associated with improvement in GLS and a reduction in risk of HF admissions.

Associations of endogenous sex hormone levels with the prevalence and progression of valvular and thoracic aortic calcification in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Sex hormones (SH) may contribute to sex differences in cardiovascular disease (CVD). High free testosterone (T) and low sex hormone binding globulin (SHBG) have been associated with progression of coronary artery calcification in women. We now examined the association of SH with extra-coronary calcification (ECC) prevalence and progression among MESA participants. METHODS: We studied 2,737 postmenopausal women and 3,130 men free of clinical CVD with baseline SH levels. ECC measurements [ascending and descending thoracic aortic calcification (ATAC, DTAC), mitral annular calcification (MAC), aortic valve calcification (AVC)] were obtained by computed tomography at baseline and after 2.4 ± 0.9 years. We used multivariable Poisson regression to evaluate associations with ECC prevalence and incidence (Agatston scores >0) and linear mixed effects models for ECC progression, per 1-SD increment in log(SH) in women and men separately. RESULTS: The mean age was 65 ± 9 and 62 ± 10 years for women and men, respectively. In women, greater free T and lower SHBG were associated with MAC incidence in a demographic-adjusted model only. In men, lower free T was associated with MAC prevalence, DTAC incidence and progression, while greater SHBG was associated with MAC prevalence and DTAC progression after further adjusting for CVD risk factors. CONCLUSIONS: In this diverse cohort free of CVD, we found some associations of SH with ECC measures. In particular, free T was inversely associated with prevalent MAC and DTAC progression in men independent of CVD risk factors. SH may influence vascular calcification, but further work is needed to understand clinical implications of these findings.

Methamphetamine-Associated Heart Failure Hospitalizations Across the United States: Geographic and Social Disparities.

Background Although methamphetamine abuse is associated with the development of heart failure (HF), nationwide data on methamphetamine-associated HF (MethHF) hospitalizations are limited. This study evaluates nationwide HF hospitalizations associated with substance abuse to better understand MethHF prevalence trends and the clinical characteristics of those patients. Methods and Results This cross-sectional period-prevalence study used hospital discharge data from the National Inpatient Sample to identify adult primary HF hospitalizations with a secondary diagnosis of abuse of methamphetamines, cocaine, or alcohol in the United States from 2002 to 2014. All 2014 MethHF admissions were separated by regional census division to evaluate geographical distribution. Demographics, payer information, and clinical characteristics of MethHF hospitalizations were compared with all other HF hospitalizations. Total nationwide MethHF hospitalizations increased from 547 in 2002 to 6625 in 2014 with a predominance on the West Coast. Methamphetamine abuse was slightly more common among primary HF hospitalizations compared with all-cause hospitalizations (7.4 versus 6.4 per 1000; Cohen h=0.012; P<0.001). Among HF hospitalizations, patients with MethHF were younger (mean age, 48.9 versus 72.4 years; Cohen d=1.93; P<0.001), more likely to be on Medicaid (59.4% versus 8.8%; Cohen h=1.16; P<0.001) or uninsured (12.0% versus 2.6%; Cohen h=0.36; P<0.001), and more likely to present to urban hospitals (43.8% versus 28.3%; Cohen h=0.32; P<0.001) than patients with non-methamphetamine associated HF. Patients with MethHF had higher rates of psychiatric comorbidities and were more likely to leave the hospital against medical advice. Conclusions MethHF hospitalizations have significantly increased in the United States, particularly on the West Coast. Coordinated public health policies and systems of care are needed to address this rising epidemic.

Clinical and echocardiographic outcomes in heart failure associated with methamphetamine use and cessation.

OBJECTIVE: Methamphetamine use is associated with systolic dysfunction, pulmonary arterial hypertension and may also be associated with diastolic dysfunction. The impact of methamphetamine cessation on methamphetamine-associated heart failure (MethHF) remains poorly characterised. We aimed to longitudinally characterise methamphetamine-associated heart failure patients with reduced (METHrEF) and preserved (METHpEF) left ventricular ejection fraction (EF), and evaluate the relationship between methamphetamine cessation and clinical outcomes. METHODS: We performed a retrospective cohort study, and reviewed medical records of patients with METHrEF, METHpEF and heart failure controls without methamphetamine use. Echocardiographic variables were recorded for up to 12 months, with clinical follow-up extending to 24 months. RESULTS: Among METHrEF patients (n=28, mean age 51±9 years, 82.1% male), cessation was associated with improvement in EF (+10.6±13.1%, p=0.009) and fewer heart failure admissions per year compared with continued use (median 0.0, IQR 0.0-1.0 vs median 2.0, IQR 1.0-3.0, p=0.039). METHpEF patients (n=28, mean age 50±8 years, 60.7% male) had higher baseline right ventricular systolic pressure (median 53.44, IQR 43.70-84.00 vs median 36.64, IQR 29.44-45.95, p=0.011), and lower lateral E/E' ratio (8.1±3.6 vs 11.2±4., p<0.01) compared with controls (n=32). Significant improvements in echocardiographic parameters and clinical outcomes were not observed following cessation in this group. CONCLUSIONS: METHrEF patients who cease methamphetamine use have significant improvement in left ventricular systolic function and fewer heart failure admissions, suggesting that METHrEF may be reversible. Echocardiographic parameters suggest that some patients with METHpEF may have pulmonary hypertension in the absence of overt signs of left ventricular diastolic dysfunction, but additional study is needed to characterise this patient cohort.

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Left Ventricular Thrombus.

BACKGROUND: Use of direct oral anticoagulants (DOACs) for the treatment of left ventricular (LV) thrombus has gained considerable interest. OBJECTIVE: We aimed to evaluate if DOACs are effective in the treatment of LV thrombus compared with warfarin. METHODS: We evaluated the medical records of patients diagnosed with a new LV thrombus at a tertiary medical center. The primary outcome was the composite of thrombus persistence, stroke, or systemic embolism. We adjusted for potential confounders using multiple logistic regression. The safety outcome was the composite of hemorrhagic stroke or bleeding requiring blood transfusion. RESULTS: A total of 129 patients were treated with warfarin and 22, with a DOAC. In unadjusted analysis, 54.3% of patients treated with warfarin met criteria for the efficacy outcome as compared with 40.9% of patients treated with a DOAC (P = 0.25). In adjusted analysis, no difference between groups was observed (odds ratio = 0.39; 95% CI = 0.14-1.06; P = 0.07 for DOAC vs warfarin). In all, 3.9% of patients treated with warfarin met safety criteria as compared with 4.5% of patients treated with a DOAC. A total of 8 patients in the warfarin group had a stroke or systemic embolism as compared with 0 patients in the DOAC group (P = 0.37). CONCLUSION AND RELEVANCE: Our data suggest that DOACs may be reasonable alternatives for treatment of LV thrombus. When added to the totality of available studies, this study demonstrates that the effectiveness of DOACs in LV thrombus remains uncertain. Randomized clinical trials are needed.

Progression of valvular calcification and risk of incident stroke: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Prevalent valvular calcification (VC) is associated with stroke but little is known about associations of VC progression with stroke. METHODS: Progression (interval increase >0 Agatston units/year) of aortic valvular calcification (AVC) and mitral annular calcification (MAC) was assessed by two cardiac CTs over a median of 2.4 years. We determined the risk of adjudicated total and ischemic stroke using Cox regression adjusted for cardiovascular disease (CVD) risk factors. RESULTS: We studied 5,539 MESA participants free of baseline CVD and atrial fibrillation. Baseline mean ± SD age was 62 ± 10 years; 53% were women; 83% had no progression of VC; 15%, progression at one site (AVC or MAC), and 3%, progression at both sites. Over a median of 12 years, 211 total and 167 ischemic strokes occurred. The number of sites with VC progression (range 0-2) was not associated with total and ischemic stroke (all p > 0.05). We found MAC progression to be associated with increased risk of total stroke [adjusted hazard ratio (95% CI) 1.59 (1.11, 2.28)] and ischemic stroke [1.64 (1.10, 2.45)]. Results remained significant after further adjustment for baseline coronary artery calcification. After excluding participants with interim atrial fibrillation and coronary heart disease, findings were no longer statistically significant in fully-adjusted models. There was no interaction by age, sex, or race/ethnicity. There was no association with AVC progression and stroke. CONCLUSIONS: Progression of MAC but not AVC over 2.4 years is associated with increased risk of total and ischemic stroke.

Associations of recreational and non-recreational physical activity with coronary artery calcium density vs. volume and cardiovascular disease events: the Multi-Ethnic Study of Atherosclerosis.

AIMS: The benefits of physical activity (PA) on cardiovascular disease (CVD) are well known. However, studies suggest PA is associated with coronary artery calcium (CAC), a subclinical marker of CVD. In this study, we evaluated the associations of self-reported recreational and non-recreational PA with CAC composition and incident CVD events. Prior studies suggest high CAC density may be protective for CVD events. METHODS AND RESULTS: We evaluated 3393 participants of the Multi-Ethnic Study of Atherosclerosis with prevalent CAC. After adjusting for demographics, the highest quintile of recreational PA was associated with 0.07 (95% confidence interval 0.01-0.13) units greater CAC density but was not associated with CAC volume. In contrast, the highest quintile of non-recreational PA was associated with 0.08 (0.02-0.14) units lower CAC density and a trend toward 0.13 (-0.01 to 0.27) log-units higher CAC volume. There were 520 CVD events over a 13.7-year median follow-up. Recreational PA was associated with lower CVD risk (hazard ratio 0.88, 0.79-0.98, per standard deviation), with an effect size that was not changed with adjustment for CAC composition or across levels of prevalent CAC. CONCLUSION: Recreational PA may be associated with a higher density but not a higher volume of CAC. Non-recreational PA may be associated with lower CAC density, suggesting these forms of PA may not have equivalent associations with this subclinical marker of CVD. While PA may affect the composition of CAC, the associations of PA with CVD risk appear to be independent of CAC.

The Impact of Substance Abuse on Heart Failure Hospitalizations.

BACKGROUND: The burden of substance abuse among patients with heart failure and its association with subsequent emergency department visits and hospital admissions are poorly characterized. METHODS: We evaluated the medical records of patients with a diagnosis of heart failure treated at the University of California-San Diego from 2005 to 2016. We identified substance abuse via diagnosis codes or urine drug screens. We used Poisson regression to evaluate the incidence rate ratios (IRR) of substance abuse for emergency department visits or hospitalizations with a primary diagnosis of heart failure, adjusted for age, sex, race, medical insurance status, and medical diagnoses. RESULTS: We identified 11,268 patients with heart failure and 15,909 hospital encounters for heart failure over 49,712 person-years of follow-up. Substance abuse was diagnosed in 15.2% of patients. Disorders such as methamphetamine abuse (prevalence 5.2%, IRR 1.96, 95% confidence interval [CI] 1.85-2.07), opioid use and abuse (8.2%, IRR 1.54, 95% CI 1.47-1.61), and alcohol abuse (4.5%, IRR 1.51, 95% CI 1.42-1.60) were associated with a greater number of hospital encounters for heart failure, with associations that were comparable to diagnoses such as atrial fibrillation (37%, IRR 1.78, 95% CI 1.73-1.84), ischemic heart disease (24%, IRR 1.67, 95% CI 1.62-1.73), and chronic kidney disease (26%, IRR 1.57, 95% CI 1.51-1.62). CONCLUSIONS: Although less prevalent than common medical comorbidities in patients with heart failure, substance-abuse disorders are significant sources of morbidity that are independently associated with emergency department visits and hospitalizations for heart failure. Greater recognition and treatment of substance abuse may improve outcomes among patients with heart failure.

Clinical Characteristics and Outcomes of Patients With Heart Failure and Methamphetamine Abuse.

BACKGROUND: Despite a global epidemic of methamphetamine abuse, methamphetamine-associated heart failure (MethHF) remains poorly understood. We sought to evaluate characteristics and outcomes for patients with MethHF. METHODS: We reviewed the electronic health records of the University of California, San Diego, from 2005 to 2016. We compared characteristics and outcomes between 896 patients with MethHF and 20,576 patients with heart failure (HF) identified using diagnosis codes, urine toxicology, and natriuretic peptides. RESULTS: Compared with HF, patients with MethHF were younger (50±10 vs 67±16 years), predominantly male (72% vs 54%), and had more psychiatric and substance use comorbidities, including mood/anxiety disorders (29% vs 16%) and opioid use (44% vs 7%). MethHF had a higher 5-year HF readmission rate (64±4% vs 45±1%; hazard ratio [HR] 1.53, P < .001) and a lower 10-year total mortality rate (25±3% vs 28±1%; HR 0.85, P = .09). Predictors of poor outcomes included mood/anxiety disorders (HF readmission HR 1.41, P = .04) and opioid abuse (mortality HR 1.52, P = .04). CONCLUSIONS: Patients with MethHF are frequently encumbered by psychiatric and substance abuse comorbidities, and carry a substantial risk of HF readmission and mortality. Comprehensive efforts are needed to stem this emerging epidemic.

Characteristics and Outcomes of Methamphetamine Abuse Among Veterans With Heart Failure.

Methamphetamine is one of the most commonly abused illicit substances worldwide. Chronic methamphetamine abuse (MA) is associated with the development of a dilated cardiomyopathy. MA in patients with heart failure (MethHF) is increasingly reported yet poorly characterized. This was a retrospective cohort study of veterans treated at the VA Medical Center in San Diego between 2005 and 2015 with a diagnosis of HF and a history of MA. The incidence of MA each year was calculated, and clinical characteristics and outcomes of veterans with HF with and without MA were compared. Among 9,491 veterans with HF, 429 were identified as having a history of MA. Between 2006 and 2015, the incidence of MA in veterans with HF doubled from 3.44% to 6.70%. Of the 429 identified, 106 veterans had a hospitalization for HF and they were compared with veterans with HF without evidence of MA (HF). Compared with veterans with HF, veterans with MethHF were significantly younger (60.7 ± 7.3 vs 71.6 ± 11.6 years, p <0.001), with more frequent co-morbid post-traumatic stress disorder (16.8% vs 4.4%, p = 0.006), depression (28.7% vs 11.0%, p = 0.002), homelessness (27.9% vs 8.9%, p = 0.001), and unemployment (55.8% vs 30.0%, p <0.001). Despite their younger age, veterans with MethHF had high rates of HF readmission or emergency room visit (49% vs 38% in MethHF vs HF, p = 0.34) and mortality at 6 months (27% vs 38% in MethHF vs HF, p = 0.10) compared with HF. In conclusion, MA in veterans with HF is on the rise. Certain demographic and clinical characteristics of veterans with MethHF may contribute to their poor outcomes.

Hypertension in Hispanics/Latinos: Epidemiology and Considerations for Management.

ABSTRAC: PURPOSE OF REVIEW: Hispanic/Latino Americans are among the fastest growing ethnic populations in the United States (US). Hypertension, in particular uncontrolled hypertension, is a significant source of cardiovascular morbidity and mortality in this population. In this review, we outline the epidemiology of hypertension and certain considerations in the management of hypertension in this heterogeneous population. RECENT FINDINGS: Substantial variation in hypertension prevalence and control exists among different ethnic subgroups of Hispanics. More specifically, and in the community, outcomes for hypertension management are less favorable, suggesting that suboptimal hypertension control may be the result of social factors. In this regard, community-based interventions have shown promise in addressing these shortfalls. Nonetheless, significant barriers to effective hypertension care exist in the Hispanic community, including the increasing prevalence of comorbidities that impact hypertension such as obesity. Pharmacologic therapies for hypertension have been highly effective in Hispanic subjects participating in clinical trials. Notably, studies that disaggregate Hispanics by their ancestral origin may provide greater insight into the sources of ethnic disparities. Culturally tailored interventions may improve hypertension management and outcomes in Hispanic populations. Additional population and clinical trials in Hispanic patients of different ancestral heritages are needed.

The novel inflammatory marker GlycA and the prevalence and progression of valvular and thoracic aortic calcification: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: GlycA is a novel composite biomarker of systemic inflammation reflecting posttranslational glycosylation of acute phase reactants. GlycA has been associated with coronary artery calcium, cardiovascular disease (CVD) events and mortality. Vascular calcifications outside of the coronary arteries are risk markers of CVD and mortality. Whether GlycA is linked to extra-coronary calcifications (ECC) is not well established. METHODS: We studied 6462 MESA participants free of clinical CVD who had plasma GlycA measured at baseline. ECCs [calcification in aortic valve (AVC), mitral annulus (MAC), ascending and descending thoracic aorta (ATAC, DTAC)] were ascertained at baseline and follow-up visit (median 2.3-yrs later) by cardiac CT. Poisson regression models with robust variance estimation assessed associations of GlycA with prevalent and incident ECC. Linear mixed models assessed the cross-sectional and 2-year change in ECC. Models were adjusted for demographic and lifestyle factors. RESULTS: In cross-sectional analysis, GlycA (per SD increment) was positively associated with prevalent AVC, ATAC and DTAC with adjusted prevalence ratios (95% CI) of 1.08 (1.01-1.14), 1.18 (1.03-1.34) and 1.10 (1.06-1.14), respectively. There was also a significant association between GlycA and baseline extent of both ATAC and DTAC. Longitudinally, GlycA was positively associated with incident MAC and DTAC, with adjusted incidence ratios of 1.18 (1.03-1.37) and 1.17 (1.07-1.28), respectively. GlycA was also associated with 2-year change in MAC and DTAC extent. CONCLUSIONS: In this diverse cohort free from clinical CVD, we found GlycA was positively associated with prevalent and incident ECC measures, in particular for progression of MAC and DTAC.

Outcomes following implantable cardioverter-defibrillator generator replacement in patients with recovered left ventricular systolic function: The National Cardiovascular Data Registry.

BACKGROUND: Some patients with heart failure (HF) experience recovery of left ventricular (LV) systolic function by the end of their implantable cardioverter-defibrillator (ICD) generator battery life. Outcomes following generator replacement in this setting are poorly understood. OBJECTIVE: We sought to describe outcomes following ICD generator replacement associated with recovery of LV systolic function. METHODS: We evaluated 26,197 Medicare beneficiaries enrolled in the American College of Cardiology's National Cardiovascular Data Registry ICD Registry who underwent primary prevention ICD generator replacement between 2006 and 2009, stratified by LV ejection fraction (LVEF): reduced (LVEF ≤35%), partially recovered (LVEF >35% and ≤50%), and recovered (LVEF >50%). RESULTS: At the time of generator replacement, 1915 (7.3%) patients had recovered LVEF and 4576 (17.5%) had partially recovered LVEF. Periprocedural events were rare (<1%) in all patients. In patients with reduced LVEF, the incidence of HF readmission and mortality at 3 years was 27.5% and 32.7%, respectively. In comparison, the rates of HF readmission and mortality were lower for patients with partially recovered LVEF (readmission: 15.9%; hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.61-0.72; mortality: 23.0%; HR 0.82; 95% CI 0.76-0.87) and those with recovered LVEF (readmission: 12.2%; HR 0.55; 95% CI 0.48-0.63; mortality: 18.2%; HR 0.72; 95% CI 0.64-0.80). CONCLUSION: Patients with partially recovered and recovered LVEF have lower risks of mid-term adverse outcomes than do those with reduced LVEF following ICD generator replacement. Approximately 3 in 4 patients continue to have reduced LVEF at the time of generator replacement and are at high risk of HF readmission and mortality. These data highlight the prognostic associations of LVEF in patients undergoing generator replacement as well as the clinical encounter for generator replacement as an opportunity to identify those at increased risk of adverse outcomes.

Thoracic Aorta Calcification and Noncardiovascular Disease-Related Mortality.

Objective- Arterial calcification is highly correlated with underlying atherosclerosis. Arterial calcification of the thoracic aorta is evident in many older individuals at high susceptibility to aging-related diseases and non-cardiovascular disease (CVD)-related mortality. In this study, we evaluated the association of thoracic aorta calcification (TAC) with non-CVD morbidity and mortality. Approach and Results- We analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis, a prospective cohort study of subclinical atherosclerosis, in which participants underwent cardiac computed tomography at baseline and were followed longitudinally for incident CVD events and non-CVD events. Using modified proportional hazards models accounting for the competing risk of CVD death and controlling for demographics, CVD risk factors, coronary artery calcium, and CVD events, we evaluated whether TAC was independently associated with non-CVD morbidity and mortality. Among 6765 participants (mean age, 62 years), 704 non-CVD deaths occurred for a median follow-up of 12.2 years. Compared with no TAC, the highest tertile of TAC volume was associated with a higher risk of non-CVD mortality (hazard ratio, 1.56; 95% confidence interval, 1.23-1.97), as well as several non-CVD diagnoses, including hip fracture (2.14; 1.03-4.46), chronic obstructive pulmonary disease (2.06; 1.29-3.29), and pneumonia (1.79; 1.30-2.45), with magnitudes of association that were larger than for those of coronary artery calcium. Conclusions- TAC is associated with non-CVD morbidity and non-CVD mortality, potentially through a pathway that is unrelated to atherosclerosis. TAC may be a general marker of biological aging and an indicator of increased risk of non-CVD and death.