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Objective: To apply the practical parsimonious modeling method of the Intermountain Mortality Risk Score in a primary care environment to predict chronic disease (ChrD) onset., Patients and Methods: Primary care patients free of ChrD (women: n=98,711; men: n=45,543) were evaluated to develop (70% [n=95,882] of patients) and validate (the other 30% [n=48,372]) the sex-specific Intermountain Chronic Disease Risk Score (ICHRON) if seen initially between January 1, 2003, and December 31, 2005. The sex-specific ICHRON was composed of comprehensive metabolic profile and complete blood count components and age. The primary outcome was the first diagnosis of coronary artery disease, myocardial infarction, heart failure, atrial fibrillation, stroke, diabetes, renal failure, chronic obstructive pulmonary disease, peripheral vascular disease, or dementia within 3 years of baseline., Results: At 3 years, 9.0% of men (mean age, 44±16 years) and 6.6% of women (mean age, 42±16 years) received a diagnosis of ChrD. In the derivation population, C-statistics were 0.783 (95% CI, 0.774-0.791) for men and 0.774 (95% CI, 0.767-0.781) for women. In the validation population, C-statistics were 0.774 (95% CI, 0.762-0.786) for men and 0.762 (95% CI, 0.752-0.772) for women. Evaluation of 10-year outcomes for ICHRON and analysis of its association with each outcome individually at 3 years revealed similar predictive ability., Conclusion: An augmented intelligence clinical decision tool for primary care, ICHRON, is developed using common laboratory parameters, which provides good discrimination of ChrD risk at 3 and 10 years., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Conflicting data exist regarding the impact of reversible pulmonary hypertension (PHTN) on post-transplant (Tx) outcomes. In this study we sought to determine the influence of reversible PHTN on outcomes after Tx., Methods: We retrospectively reviewed the records of adult patients who underwent heart Tx from 1993 to 2002. Patients were grouped depending on their measured pulmonary vascular resistance (PVR). Group 1 patients had a pre-Tx pulmonary vascular resistance (PVR) of < 3 Wood units (WU). Patients with reversible PHTN, defined as pre-Tx PVR > or = 3 WU and reversing to < 3 WU either with sub-lingual or intravenous vasodilatory agents, were divided into two groups based on their PVR before the reversibility test (PVR: Group 2, 3 to 4.5 WU; Group 3, > 4.5 WU)., Results: Records for 222 adult heart recipients were reviewed (Group 1, n = 171; Group 2, n = 35; Group 3, n = 16). Baseline clinical characteristics (age, gender, heart failure etiology, history of diabetes, ischemic time, donor age and gender) were similar in the three groups and the average follow-up was 58 months. One-month and 1-year mortality (Groups 1, 2 and 3: 2%, 0% and 13%; and 8%, 0% and 13%, respectively) did not differ significantly between groups. Actuarial mortality was assessed using Cox regression analysis, adjusted for age and gender, and no increased risk of death was demonstrated for patients with reversible PHTN (for Group 2: multivariate hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.17 to 1.32, p = 0.15; for Group 3: HR 0.98, CI 0.34 to 2.84, p = 0.97). No differences were observed between the three groups for various post-Tx events, such as hospital stay, ICU stay, extubation time, transfusions, acute allograft dysfunction, acute hepatic dysfunction, acute and chronic renal dysfunction, infections, neurologic complications, gastrointestinal complications and coronary allograft vasculopathy., Conclusions: Reversible pulmonary hypertension is associated with similarly good post-transplant survival outcomes and morbidity, regardless of severity.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being administered on an unprecedented scale. Assessing the risks of side effects is needed to aid clinicians in early detection and treatment. This study examined the risk of inflammatory heart disease, including pericarditis and myocarditis, after SARS-CoV-2 vaccination. Methods Intermountain Healthcare patients with inflammatory heart disease from December 15, 2020 to June 15, 2021, and with or without preceding SARS-CoV-2 vaccinations, were studied. Relative rates of inflammatory heart disease were examined for vaccinated patients compared to unvaccinated patients. Results Of 67 patients identified with inflammatory heart disease, 21 (31.3%) had a SARS-Cov-2 vaccination within the previous 60 days. Overall, 914 611 Intermountain Healthcare patients received a SARS-CoV-2 vaccine, resulting in an inflammatory heart disease rate of 2.30 per 100 000 vaccinated patients. The relative risk of inflammatory heart disease for the vaccinated patients compared to the unvaccinated patients was 2.05 times higher rate within the 30-day window (P  = .01) and had a trend toward increase in the 60-day window (relative rate = 1.63; P  = .07). All vaccinated patients with inflammatory heart disease were treated successfully with 1 death related to a pre-existing condition. Conclusions Although rare, the rate of inflammatory heart disease was greater in a SARS-CoV-2-vaccinated population than the unvaccinated population. This risk is eclipsed by the risk of contracting coronavirus disease 2019 and its associated, commonly severe outcomes. Nevertheless, clinicians and patients should be informed of this risk to facilitate earlier recognition and treatment. [ABSTRACT FROM AUTHOR]

Background: Coronary heart disease, including its clinical manifestation, myocardial infarction (MI), is a common, complex disease with a substantive genetic component. State-of-the-art genetic epidemiology evaluates thousands of single nucleotide polymorphisms (SNPs) in association with disease cases and controls. In an independent but demographically similar population, this study tested 6 SNPs that were previously reported to be associated with MI. Methods: Patients hospitalized for an acute MI (n = 413) at an early age (men <55 years, women <65 years) were compared with age-discordant (men ≥65 years, women ≥70 years) control patients (n = 792) who had no MI history and no hospitalization for MI at index angiography or during longitudinal follow-up. Six SNPs were genotyped in the genes palladin, ROS1, TAS2R50, OR13G1, and ZNF627. Results: Findings were not different from the null hypothesis, with ZNF627 (AG vs. GG: odds ratio [OR] 1.47, P = .16; AA vs. GG: OR 1.20, P = .50) and both ROS1 SNPs (GG vs AA: OR 0.72, P = .21; CC vs GG: OR 0.74, P = .24) showing potentially interesting ORs but nonsignificant probabilities. After full adjustment for all SNPs and covariables, only the ZNF627 heterozygote genotype had OR >1.5 (P = .14). Comparison of MI cases with controls without obstructive coronary artery disease and analyses stratified by sex provided similar findings. Conclusions: Six SNPs previously reported to be associated with MI were not validated, suggesting that further investigation is needed to verify the applicability of those SNPs to cardiovascular medicine. These findings emphasize the high potential for false-positive results even in staged genome-wide association studies and further emphasize the need for continued refinement of cardiovascular genetic methodologies for clinical application. [Copyright &y& Elsevier]

Abstract: Background: Heart failure (HF) patients may require cardiac assist device implantation prior to transplantation (Tx) because of either acute cardiogenic shock (ACS), with no prior history of HF, or for progression of pump failure in the setting of chronic HF. Aims: To investigate whether patients implanted with a cardiac assist device for ACS, have similar post-Tx outcomes as those who underwent cardiac assist device implantation because of progressive chronic HF. Methods and results: We compared post-Tx outcomes of consecutive patients bridged due to ACS (Acute Group) with the outcomes of patients bridged due to deterioration of chronic HF (Chronic Group). Seventy-three patients had a cardiac assist device implanted and underwent subsequent cardiac Tx. Thirty-five patients (48%) had a cardiac assist device implanted due to ACS, most often caused by massive acute myocardial infarction, and 38 patients (52%) because of progressive chronic HF. Despite greater compromise at the time of implantation, the Acute Group recovered satisfactorily and underwent Tx with similar post-Tx survival rates as the Chronic Group patients [1-year survival: 88.6% vs 86.8%, p =0.80, actuarial survival (mean follow-up 4.2 years): 80.0% vs 81.6%, p =0.86)]. Furthermore, no significant differences were observed between the 2 groups in various post-Tx events. Conclusion: Patients with ACS who underwent emergency cardiac assist device implantation as bridge to Tx had similar post-Tx outcomes as their more chronically ill counterparts who underwent device implantation on a non-urgent basis. [Copyright &y& Elsevier]

Objective: Allosensitization of left ventricular assist device recipients has been associated with perioperative transfusion of cellular blood products. The relative sensitizing contribution of leukofiltered cellular blood products, however, remains unclear. We investigated the pattern of sensitization in left ventricular assist device recipients in relation to cellular blood product transfusions received. Methods: Seventy-one consecutive nonsensitized recipients of the HeartMate left ventricular assist device (Thoratec Corporation, Pleasanton, Calif) as a bridge to transplantation were reviewed. Panel-reactive HLA antibody levels at consecutive times after device implantation were correlated with perioperative cellular blood product transfusions. Results: Fifty-four patients received leukofiltered cellular blood products (transfused), whereas 17 patients received only fresh-frozen plasma (nontransfused). Among nontransfused patients, 58.8% (10/17) became sensitized during mechanical support, versus 35.2% of transfused patients (19/54, P = .15). There was a trend toward more sensitization during the 12 weeks after device placement in nontransfused patients. Kaplan–Meier analysis revealed significantly more sensitization in nontransfused patients than in transfused patients, despite equal rates of transplantation (P = .05). A dose-response analysis revealed significant trends toward less sensitization and lower peak panel-reactive antibody level with more cellular blood product transfusions (P = .04). Multivariate Cox regression revealed only increasing transfusions to be associated with a reduced risk of sensitization (hazard ratio 0.18, P = .01). Conclusions: Sensitization becomes more prevalent with increasing length of support. Avoidance of perioperative leukocyte-filtered cellular blood product transfusions does not decrease the incidence or degree of HLA sensitization. Conversely, cellular blood product transfusions may be associated with lessened alloimmunization and may mitigate the sensitization seen in recipients of the HeartMate left ventricular assist device as a bridge to transplantation. [Copyright &y& Elsevier]

Objectives: The objective of this study was to identify associations of the cholesteryl ester transfer protein (CETP) gene with coronary artery disease (CAD) with tagging (t) single nucleotide polymorphisms (SNPs) chosen to optimally account for intra-genic variation. Background: The CETP gene plays a critical role in lipoprotein metabolism, but the common and well-studied TaqIB variant is inconsistently predictive of CAD. Methods: From a deoxyribonucleic acid bank of 10,020 individuals, nondiabetic nonsmoking patients (n = 4,811) with angiographically defined, clinically significant CAD (≥70% stenosis) or normal coronaries were genotyped for 11 CETP tSNPs. Myocardial infarction (MI) and lipid levels were evaluated as secondary end points. Results: Analysis of single tSNPs, corrected for multiple comparisons (p < 0.00485), identified allele +1086A to be associated with CAD (p = 0.0034). Suggestive allelic and significant genotypic associations were found for −631AA (odds ratio [OR] = 3.95, p = 0.004 vs. CC) and +2389GA (OR = 1.21, p = 0.003 vs. GG). Haplotype analysis by linkage disequilibrium (LD) group revealed a CAD association for LD group B (p = 0.0025 across T+1086A, C+878T, C+408T) and near significance for LD group A (p = 0.013 across C-631A, MspI, G+2389A). A weak protective trend for TaqIB was eliminated by adjustment for other tSNPs, and haplotype analyses suggested that TaqIB was simply a marker for other tSNPs or haplotypes. No tSNP or haplotype associations with MI were found. Conclusions: Multiple, less common SNPs and haplotype variants underlie CETP-related CAD risk, for which the common TaqIB variant is simply a poor marker. The occurrence of risk-related variants on separate haplotypes suggests genetic-risk complexity and allelic heterogeneity. (Database Registry of the Intermountain Heart Collaborative Study; http://clinicaltrials.gov/ct/show/NCT00406185?order=1; NCT00406185). [Copyright &y& Elsevier]

C-reactive protein (CRP) has been associated with atherosclerotic complications, and we hypothesized that CRP levels might also predict death in non-ischemic patients with left ventricular dysfunction. Two hundred and three patients with non-ischemic left ventricular dysfunction undergoing cardiac catheterization were included and were followed for 2.4 ± 1.4 years to determine the incidence of fatal events. Death occurred in 15% of patients with low CRP (1st and 2nd tertiles) and 30% of patients with high CRP (3rd tertile). After adjustment for 11 covariates, high CRP (p = 0.037, hazard ratio = 2.0) significantly and independently predicted mortality. Even in the absence of coronary artery disease, patients with left ventricular dysfunction are at increased risk of mortality based on their baseline CRP concentrations. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine the predictive ability of total white blood cell (WBC) count and its subtypes for risk of death or myocardial infarction (MI). Background: An elevated WBC count has been associated with cardiovascular risk, but which leukocyte subtypes carry this risk is uncertain. Methods: Consecutive patients without acute MI who were assessed angiographically for coronary artery disease (CAD) and were followed up long-term were studied. The predictive ability for death/MI of quartile (Q) 4 versus Q1 total WBC, neutrophil (N), lymphocyte (L), and monocyte (M) counts and N/L ratio were assessed using Cox regressions. Results: A total of 3,227 patients was studied. Mean age was 63 years; 63% of patients were male, and 65% had CAD. In multivariable modeling entering standard risk factors, presentation, and CAD severity, the total WBC (hazard ratio [HR] 1.4, p = 0.01) and M (HR 1.3, p &#60; 0.02) were weaker and N (HR 1.8, p &#60; 0.001), L (HR 0.51, p &#60; 0.001), and N/L ratio (HR 2.2, p &#60; 0.001) were independent predictors of death/MI. When WBC variables were entered together, N/L ratio and M were retained as independent predictors. Risk associations persisted in analyses restricted to CAD patients or including acute MI patients. Conclusions: Total WBC count is confirmed to be an independent predictor of death/MI in patients with or at high risk for CAD, but greater predictive ability is provided by high N (Q4 >6.6 × 103/μl) or low L counts. The greatest risk prediction is given by the N/L ratio, with Q4 versus Q1 (>4.71 versus &#60;1.96) increasing the hazard 2.2-fold. These findings have important implications for CAD risk assessment. [Copyright &y& Elsevier]

Objectives: Septic cardiomyopathy develops frequently in patients with sepsis and likely increases short-term mortality. However, whether septic cardiomyopathy is associated with long-term outcomes after sepsis is unknown. We investigated whether septic patients with septic cardiomyopathy have worse long-term outcomes than septic patients without septic cardiomyopathy.Design: Retrospective cohort study.Setting: Adult ICU.Patients: Adult ICU patients with sepsis.Interventions: None.Measurements and Main Results: Left ventricular global longitudinal systolic strain was our primary measure of septic cardiomyopathy. We employed a suite of multivariable survival analyses to explore linear and nonlinear associations between left ventricular global longitudinal systolic strain and major adverse cardiovascular events, which included death, stroke, and myocardial infarction. Our primary outcome was major adverse cardiovascular event through 24 months after ICU discharge. Among 290 study patients, median left ventricular global longitudinal systolic strain was -16.8% (interquartile range, -20.4% to -12.6%), and 38.3% of patients (n = 111) experienced a major adverse cardiovascular event within 24 months after discharge. On our primary, linear analysis, there was a trend (p = 0.08) toward association between left ventricular global longitudinal systolic strain and major adverse cardiovascular event (odds ratio, 1.03; CI, < 1 to 1.07). On our nonlinear analysis, the association was highly significant (p < 0.001) with both high and low left ventricular global longitudinal systolic strain associated with major adverse cardiovascular event among patients with pre-existing cardiac disease. This association was pronounced among patients who were younger (age < 65 yr) and had Charlson Comorbidity Index greater than 5.Conclusions: Among patients with sepsis and pre-existing cardiac disease who survived to ICU discharge, left ventricular global longitudinal systolic strain demonstrated a U-shaped association with cardiovascular outcomes through 24 months. The relationship was especially strong among younger patients with more comorbidities. These observations are likely of use to design of future trials. [ABSTRACT FROM AUTHOR]

Although increased cholesterol levels predict mortality in patients with coronary artery disease, it is unclear whether hypercholesterolemia is associated with adverse survival in patients with heart failure. A cohort of subjects derived from the Intermountain Heart Collaborative Study Registry (1993 to 2003) who had ejection fractions ≤40% or clinical diagnoses of heart failure and long-term follow-up for death were studied (n = 1,646). Total cholesterol (TC) was divided into quartiles: quartile 1, <141.3 mg/dl; quartile 2, 141.3 to 167.9 mg/dl; quartile 3, 168.0 to 201.0 mg/dl; and quartile 4, >201.0 mg/dl. Multivariate Cox regression models were used to evaluate the associations of cholesterol, statin therapy, and C-reactive protein to mortality. The mean age was 65.5 years; 65% of the subjects were men and 65% had coronary artery disease. Although 53% were using statins, statin use was not different across TC quartiles. Average time to death was 2.4 years (maximum 10). Mortality for quartile 4 versus quartile 1 was not different (hazard ratio [HR] 1.12, p = 0.52); mortality was reduced for quartile 3 versus quartile 1 (HR 0.66, p = 0.027) and tended to be reduced for quartile 2 versus quartile 1 (HR 0.77, p = 0.14). Subanalysis of patients not using statins (n = 737, death = 20.2%) found no association between TC and survival (for quartile 3 vs quartile 1, HR 0.97, p = 0.89), but for patients using statins (n=848, death = 16.3%), the effect was even greater for quartile 3 versus quartile 1 (HR 0.40, p = 0.002) than in the overall population. Nonsurvivors had higher levels of C-reactive protein than survivors. In conclusion, elevated TC appears to be associated with improved survival. The effect was stronger in patients receiving statin therapy, but the cause of this differential effect is uncertain. [Copyright &y& Elsevier]

Inflammation has been implicated in the pathogenesis of cardiovascular diseases. C-reactive protein (CRP), a marker of systemic inflammation, predicts the risk of coronary events and stroke. Atrial fibrillation (AF) is associated with atrial structural changes that may have an inflammatory basis. We tested the hypothesis that CRP is a risk factor for AF. Subjects were those included in the database registry of the Intermountain Heart Collaborative Study from 1994 to 2001. Patients who had ≥1 electrocardiogram that demonstrated AF formed the disease group (n = 347), and those who had neither electrocardiographic nor clinical evidence for AF comprised the control group (n = 2,449). Logistic regression assessed the quartile (Q) of CRP and 13 other clinical and angiographic predictors of AF. Average age was 63 ± 12 years, 33% were women, and 61% had advanced coronary artery disease. Patients who had AF were older (by 7 years) and more frequently had a history of heart failure than did controls (41% vs 9%). CRP was higher in patients who had AF than in controls (p &#60;0.001). Q-CRP was a univariable predictor of AF (odds ratio 1.39/Q, 95% confidence interval 1.25 to 1.55, p &#60;0.001). Adjusting for age and heart failure decreased the predictive value of Q-CRP to 1.20/Q (95% confidence 1.07 to 1.34, p = 0.002), whereas further adjustment for 11 other variables had little additional effect (odds ratio 1.19/Q, 95% confidence interval 1.06 to 1.33, p = 0.003). Thus, high levels of CRP independently predicted an increased risk of AF among a large, prospectively studied patient cohort that was assessed angiographically. Increased CRP is a new risk marker for AF propensity, and testing therapies that target inflammation should be considered. [Copyright &y& Elsevier]

To determine whether sex and age affect serum C-reactive protein level and its prognostic value in patients with coronary artery disease.In a consecutive series of 2254 patients with angiographically defined coronary artery disease, baseline C-reactive protein and predictive value for incident death or nonfatal myocardial infarction by sex and age (<55 and ≥55 years) were compared. C-reactive protein levels were measured by fluorescence polarization immunoassay with use of a medium-sensitivity method. Patients were followed for a mean (±SD) of 3.1 ± 2.2 years. Comparisons used ln-transformed C-reactive protein and linear and time-to-event regression analyses, adjusting for confounders.Overall, women had higher geometric mean C-reactive protein levels than did men (1.47 vs. 1.30 mg/dL, P <0.001), even after adjustment for age, hyperlipidemia, diabetes, prior myocardial infarction, body mass index, and heart failure (P = 0.002). High C-reactive protein levels were associated with increased mortality or myocardial infarction among men (adjusted hazard ratio [HR] = 1.9; 95% confidence interval [CI]: 1.5 to 2.3) but not among women (HR = 1.0; 95% CI: 0.69 to 1.4). Among patients aged <55 years, C-reactive protein level was similarly predictive in men and women (HR = 2.2 vs. 2.7), whereas in patients ≥55 years of age, it remained predictive for men (HR = 1.8; 95% CI: 1.5 to 2.3) but not women (HR = 0.93; 95% CI: 0.63 to 1.4).We found that the prognostic value of C-reactive protein in coronary artery disease patients varied by sex and age. This sex-age interaction may have important implications for C-reactive protein–based secondary risk assessment and requires further investigation. [Copyright &y& Elsevier]

: BackgroundIn 1998, the Food and Drug Administration mandated the fortification of food products with folic acid. The effect of this rule on mortality associated with homocysteine levels in patients with coronary artery disease is unknown.: MethodsWe studied 2481 consecutive patients with coronary artery disease who underwent coronary angiography between 1994 and 1999, and who had baseline homocysteine measurements and at least 2 years of follow-up. Patients were divided into prefortification (1994 to 1997, n = 1595) and postfortification (1998 to 1999, n = 886) groups, as well as classified based on baseline homocysteine levels (normal to low, intermediate, and high). Homocysteine levels were measured by fluorescence polarization immunoassay. Mortality was determined by telephone survey or from a national Social Security database or hospital records.: ResultsAfter implementation of the fortification rule, median homocysteine levels declined from 13.8 to 12.3 μmol/L (P <0.001), and the proportion of patients with high homocysteine levels (>15 μmol/L) decreased from 41% (n = 650) to 28% (n = 249) (P <0.001). Overall, homocysteine was a modest risk factor for mortality (adjusted relative risk [RR] = 1.03 per μmol/L; 95% confidence interval [CI]: 1.01 to 1.05; P = 0.006). There was no significant interaction between fortification status and homocysteine category with mortality (P for interaction = 0.85). Two-year mortality was reduced minimally (7.8% [n = 124] to 7.2% [n = 64]; RR = 0.93; 95% CI: 0.68 to 1.27; P = 0.63; adjusted RR = 0.97; 95% CI: 0.68 to 1.40), but was consistent with the expectation of a modest reduction in homocysteine levels.: ConclusionHomocysteine is an independent, graded risk factor for mortality. Homocysteine levels decreased modestly after the fortification of food with folic acid, but the effects on mortality were minor and likely attributable to other factors, indicating the need for more aggressive measures to reduce homocysteine-associated cardiovascular risk. [Copyright &y& Elsevier]

High-sensitivity C-reactive protein (CRP), proposed as a new coronary risk marker, may reflect either an acute phase reaction or the level of chronic inflammation. Thus, CRP may be less predictive of long-term outcomes when measured after acute myocardial infarction (AMI) than after unstable angina pectoris (UAP) or stable angina pectoris (SAP). A total of 1,360 patients with severe coronary artery disease (≥1 stenosis ≥70%) had CRP levels obtained at angiography. Presenting diagnoses were SAP (n = 599), UAP (n = 442), or AMI (n = 319). During follow-up (mean 2.8 years), death or nonfatal AMI (D/AMI) occurred in 19.5%, 16.1%, and 17.2% (p = NS) with SAP, UAP, and AMI, respectively. Corresponding median CRP levels were 1.31, 1.27, and 2.50 mg/dl (p <0.001). For the overall cohort, increasing age, low ejection fraction, revascularization, and elevated CRP were the strongest of 6 independent predictors for D/AMI. Among those presenting with SAP, CRP levels above the first tertile were associated with an adjusted hazard ratio of 1.8 (95% confidence interval [CI] 1.2 to 2.8, p <0.009) for D/AMI. After UAP, the hazard ratio was 2.7 (95% CI 1.4 to 5.0, p <0.002). However, when measured during hospitalization for AMI, CRP was not predictive of long-term outcome (hazard ratio 1.0 [95 % CI 0.5 to 1.7] p = 0.86). In conclusion, predischarge CRP levels are higher after AMI than after UAP or SAP. However, whereas CRP is strongly predictive of long-term D/AMI for patients presenting with SAP or UAP, it is not predictive shortly after AMI, suggesting that measurements should be delayed until the acute phase reaction is over and levels have returned to baseline. [Copyright &y& Elsevier]