Kimberly D. Brunisholz

Randomized cross-over trial of short-term water-only fasting: Metabolic and cardiovascular consequences

BACKGROUND AND AIMS Routine, periodic fasting is associated with a lower prevalence of coronary artery disease (CAD). Animal studies show that fasting may increase longevity and alter biological parameters related to longevity. We evaluated whether fasting initiates acute changes in biomarker expression in humans that may impact short- and long-term health. METHODS AND RESULTS Apparently-healthy volunteers (N = 30) without a recent history of fasting were enrolled in a randomized cross-over trial. A one-day water-only fast was the intervention and changes in biomarkers were the study endpoints. Bonferroni correction required p ≤ 0.00167 for significance (p < 0.05 was a trend that was only suggestively significant). The one-day fasting intervention acutely increased human growth hormone (p = 1.1 × 10⁻⁴), hemoglobin (p = 4.8 × 10⁻⁷), red blood cell count (p = 2.5 × 10⁻⁶), hematocrit (p = 3.0 × 10⁻⁶), total cholesterol (p = 5.8 × 10⁻⁵), and high-density lipoprotein cholesterol (p = 0.0015), and decreased triglycerides (p = 1.3 × 10⁻⁴), bicarbonate (p = 3.9 × 10⁻⁴), and weight (p = 1.0 × 10⁻⁷), compared to a day of usual eating. For those randomized to fast the first day (n = 16), most factors including human growth hormone and cholesterol returned to baseline after the full 48 h, with the exception of weight (p = 2.5 × 10⁻⁴) and (suggestively significant) triglycerides (p = 0.028). CONCLUSION Fasting induced acute changes in biomarkers of metabolic, cardiovascular, and general health. The long-term consequences of these short-term changes are unknown but repeated episodes of periodic short-term fasting should be evaluated as a preventive treatment with the potential to reduce metabolic disease risk. Clinical trial registration (ClinicalTrials.gov): NCT01059760 (Expression of Longevity Genes in Response to Extended Fasting [The Fasting and Expression of Longevity Genes during Food abstinence {FEELGOOD} Trial]).

Interleukin receptor family member ST2 concentrations in patients following heart transplantation

Abstract Objective: To evaluate soluble (s) ST2 as a biomarker of rejection, allograft vasculopathy and mortality after orthotopic heart transplantation (OHT). Methods: sST2 concentrations were measured in 241 patients following OHT. Results: Elevated sST2 was associated with cellular rejection (CR) ≥1R, with highest rates of CR in the 4th sST2 quartile (p = 0.003). No significant association between sST2 and antibody-mediated rejection or allograft vasculopathy was found. sST2 ≥30 ng/mL independently predicted death over 7-year follow-up (HR = 2.01; 95% CI 1.15–3.51; p = 0.01). Conclusion: Concentrations of sST2 are associated with the presence of CR and predict long-term mortality following OHT.

Repeated measurement of the intermountain risk score enhances prognostication for mortality.

Background The Intermountain Risk Score (IMRS), composed of the complete blood count (CBC) and basic metabolic profile (BMP), predicts mortality and morbidity in medical and general populations. Whether longitudinal repeated measurement of IMRS is useful for prognostication is an important question for its clinical applicability. Methods Females (N = 5,698) and males (N = 5,437) with CBC and BMP panels measured 6 months to 2.0 years apart (mean 1.0 year) had baseline and follow-up IMRS computed. Survival analysis during 4.0±2.5 years (maximum 10 years) evaluated mortality (females: n = 1,255 deaths; males: n = 1,164 deaths) and incident major events (myocardial infarction, heart failure [HF], and stroke). Results Both baseline and follow-up IMRS (categorized as high-risk vs. low-risk) were independently associated with mortality (all p<0.001) in bivariable models. For females, follow-up IMRS had hazard ratio (HR) = 5.23 (95% confidence interval [CI] = 4.11, 6.64) and baseline IMRS had HR = 3.66 (CI = 2.94, 4.55). Among males, follow-up IMRS had HR = 4.28 (CI = 3.51, 5.22) and baseline IMRS had HR = 2.32 (CI = 1.91, 2.82). IMRS components such as RDW, measured at both time points, also predicted mortality. Baseline and follow-up IMRS strongly predicted incident HF in both genders. Conclusions Repeated measurement of IMRS at baseline and at about one year of follow-up were independently prognostic for mortality and incident HF among initially hospitalized patients. RDW and other CBC and BMP values were also predictive of outcomes. Further research should evaluate the utility of IMRS as a tool for clinical risk adjustment.

The intermountain risk score predicts incremental age-specific long-term survival and life expectancy

The Intermountain Risk Score (IMRS) encapsulates the mortality risk information from all components of the complete blood count (CBC) and basic metabolic profile (BMP), along with age. To individualize the IMRS more clearly, this study evaluated whether IMRS weightings for 1-year mortality predict age-specific survival over more than a decade of follow-up. Sex-specific 1-year IMRS values were calculated for general medical patients with CBC and BMP laboratory tests drawn during 1999-2005. The population was divided randomly 60% (N = 71,921, examination sample) and 40% (N = 47,458, validation sample). Age-specific risk thresholds were established, and both survival and life expectancy were compared across low-, moderate-, and high-risk IMRS categories. During 7.3 ± 1.8 years of follow-up (range, 4.5-11.1 years), the average IMRS of decedents was higher than censored in all age/sex strata (all P < 0.001). For examination and validation samples, every age stratum had incrementally lower survival for higher risk IMRS, with hazard ratios of 2.5-8.5 (P < 0.001). Life expectancies were also significantly shorter for higher risk IMRS (all P < 0.001): For example, among 50-59 year-olds, life expectancy was 7.5, 6.8, and 5.9 years for women with low-, moderate-, and high-risk IMRS (with mortality in 5.7%, 16.3%, and 37.0% of patients, respectively). In Men, life expectancy was 7.3, 6.8, and 5.4 for low-, moderate-, and high-risk IMRS (with patients having 7.3%, 19.5%, and 40.0% mortality), respectively. IMRS significantly stratified survival and life expectancy within age-defined subgroups during more than a decade of follow-up. IMRS may be used to stratify age-specific risk of mortality in research, clinical/preventive, and quality improvement applications. A web calculator is located at http://intermountainhealthcare.org/IMRS.

The association of antidepressant and statin use with death and incident cardiovascular disease varies by depression severity

Abstract Depression has been reported to be associated with a greater risk of death and cardiovascular disease (CVD); however, the impact of antidepressants (ADM) on CVD risk remains controversial. Statin use is known to decrease CVD risk. Whether the use of these medications together affects CVD risk has not been studied. Patients (N = 26,828) completing the patient health questionnaire (PHQ-9), ≥40 years of age, without prior CVD, and no prior ADM use were studied. Depressive severity was categorized as none-mild (PHQ-9 score ≤14, n = 21,517) and moderate-severe (PHQ-9 score ≥15, n = 5311). Cox hazard regression was used to evaluate the association of no ADM/no statin use (n = 23,104 [86.1%]), ADM/no statin use (n = 877 [3.3%]), no ADM/statin use (n = 2627 [9.8%]), and ADM/statin use (n = 220 [.8%]) with major adverse cardiovascular events (MACE: death, CAD, stroke). Patients averaged 56 ± 12 years; 61% female. There were 1182 (4.4%) 3 year MACE events. The association of ADM and statin use with MACE varied by depressive symptom severity, with statin therapy associated with a decreased risk in the none-mild group (HR = .78, p = .007) and ADM in the moderate-high group (HR = 0.58, p = 0.02). Concomitant use of ADMs and statins did not appear to provide additive benefit.

THE ASSOCIATION OF ANTIDEPRESSANT AND STATIN USE TO FUTURE DEATH AND INCIDENT CARDIOVASCULAR DISEASE VARIES BY DEPRESSION SEVERITY

Depression has been reported to be associated with a greater risk of death and cardiovascular disease (CVD); however, the impact of antidepressants (ADM) on CVD risk remains controversial. Statin use is known to decrease CVD risk. Whether the use of these medications together affects CVD risk

IMRS-HF: A CLINICAL DECISION TOOL FOR PREDICTING 30-DAY HOSPITAL READMISSION AMONG HEART FAILURE PATIENTS

Innovative strategies and tools for stratification of 30-day readmission (30dR) risk are needed due to penalties legislated in the Affordable Care Act (ACA). The Intermountain Risk Score (IMRS) is a sex-specific tool derived to predict mortality using the complete blood count (CBC), basic metabolic

CAN EFFECTIVE TREATMENT OF DEPRESSION REDUCE FUTURE CARDIOVASCULAR RISK

Depression is known to be a risk factor for adverse cardiovascular (CV) outcomes. However, how changes in depressive symptom severity affect CV risk is not clear. Pts (N=7550) who completed two patient health questionnaire (PHQ)-9 surveys >90 days apart and were >40 yrs of age were studied. Pts