Aims
Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. The newly proposed HFA‐PEFF algorithm entails a stepwise approach. Step 1, typically performed in the ambulatory ...setting, establishes a pre‐test likelihood. The second step calculates a score based on echocardiography and natriuretic peptides. The aim of this study is to validate the diagnostic value and establish the clinical impact of the second step of the HFA‐PEFF score.
Methods and results
The second step of the HFA‐PEFF score was evaluated in two independent, prospective cohorts, i.e. the Maastricht cohort (228 HFpEF patients and 42 controls) and the Northwestern Chicago cohort (459 HFpEF patients). In Maastricht, the HFA‐PEFF score categorizes 11 (4%) of the total cohort with suspected HFpEF in the low‐likelihood (0–1 points) and 161 (60%) in the high‐likelihood category (5–6 points). A high HFA‐PEFF score can rule in HFpEF with high specificity (93%) and positive predictive value (98%). A low score can rule out HFpEF with a sensitivity of 99% and a negative predictive value of 73%. The diagnostic accuracy of the score is 0.90 (0.84–0.96), by the area under the curve of the receiver operating characteristic curve. However, 98 (36%) are classified in the intermediate‐likelihood category, where additional testing is advised. The distribution of the score shows a similar pattern in the Northwestern (Chicago) and Maastricht HFpEF patients (53% vs. 65% high, 43% vs. 34% intermediate, 4.8% vs. 1.3% low).
Conclusion
This study validates and characterizes the HFA‐PEFF score in two independent, well phenotyped cohorts. We demonstrate that the HFA‐PEFF score is helpful in clinical practice for the diagnosis of HFpEF.
AMPK and SIRT1: a long-standing partnership? Ruderman, Neil B; Xu, X Julia; Nelson, Lauren ...
American journal of physiology: endocrinology and metabolism,
04/2010, Letnik:
298, Številka:
4
Journal Article
Recenzirano
Odprti dostop
AMP-activated protein kinase (AMPK) and the histone/protein deacetylase SIRT1 are fuel-sensing molecules that have coexisted in cells throughout evolution. When a cell's energy state is diminished, ...AMPK activation restores energy balance by stimulating catabolic processes that generate ATP and downregulating anabolic processes that consume ATP but are not acutely needed for survival. SIRT1 in turn is best known historically for producing genetic changes that mediate the increase in longevity caused by calorie restriction. Although the two molecules have been studied intensively for many years, only recently has it become apparent that they have similar effects on diverse processes such as cellular fuel metabolism, inflammation, and mitochondrial function. In this review we will examine the evidence that these similarities occur because AMPK and SIRT1 both regulate each other and share many common target molecules. In addition, we will discuss the clinical relevance of these interactions and in particular the possibility that their dysregulation predisposes to disorders such as type 2 diabetes and atherosclerotic cardiovascular disease and is a target for their therapy.
We examined purging for weight control, diet pill use, and obesity across sexual orientation identity and ethnicity groups.
Anonymous survey data were analyzed from 24 591 high school students of ...diverse ethnicities in the federal Youth Risk Behavioral Surveillance System Survey in 2005 and 2007. Self-reported data were gathered on gender, ethnicity, sexual orientation identity, height, weight, and purging and diet pill use in the past 30 days. We used multivariable logistic regression to estimate odds of purging, diet pill use, and obesity associated with sexual orientation identity in gender-stratified models and examined for the presence of interactions between ethnicity and sexual orientation.
Lesbian, gay, and bisexual (LGB) identity was associated with substantially elevated odds of purging and diet pill use in both girls and boys (odds ratios OR range = 1.9-6.8). Bisexual girls and boys were also at elevated odds of obesity compared to same-gender heterosexuals (OR = 2.3 and 2.1, respectively).
Interventions to reduce eating disorders and obesity that are appropriate for LGB youths of diverse ethnicities are urgently needed.
This work evaluated the psychometric properties of the single-item Opioid Craving Visual Analog Scale (OC-VAS) for opioid use disorder (OUD).
Psychometric evaluation of the OC-VAS (range: 0–100 mm) ...was supported by Subjective Opiate Withdrawal Scale (SOWS) item 16 and total score, Clinical Opiate Withdrawal Scale (COWS) scores, and the 36-Item Short-Form Health Survey, using data from phase 3 study (NCT02357901; N = 487) participants who received randomized treatment and completed the OC-VAS at screening. Descriptive properties, test-retest reliability, construct validity, known-groups validity, and responsiveness were assessed. Interpretation of meaningful change and predictive validity were also explored.
Descriptive properties for the OC-VAS at screening did not provide evidence of problematic floor/ceiling effects or missingness. The test-retest reliability was established by weekly intraclass correlations >0.70. At the screening and end of the study, the strong positive correlations between OC-VAS and SOWS Total/Item 16 score and the significant OC-VAS differences among COWS severity groups supported construct validity and known-groups (discriminating ability) validity, respectively. The associations between the changes in OC-VAS and in supporting measures/opioid use from screening to the end of the study demonstrated responsiveness and the ability to detect change in clinical status. During the induction and randomization treatment periods, significant relationships were identified between OC-VAS score and subsequent opioid use.
This psychometric evaluation of the OC-VAS performed on a large OUD patient population provides evidence to support its use to measure the severity of opioid craving and its ability to predict opioid use.
•Psychometric results support OC-VAS as a patient-reported measure of opioid craving.•OC-VAS test-retest reliability interclass correlation coefficients were > 0.70.•OC-VAS adequately discriminated across severity categories of the COWS total score.•OC-VAS demonstrated the ability to detect change as defined by SOWS and COWS scores.•The predictive validity of OC-VAS was more sensitive than SOWS Item 16.
Objectives: The Atopic Dermatitis Control Tool (ADCT) was designed to evaluate patient-perceived AD control and facilitate patient-physician discussion on long-term disease control.
Methods: The ...study was performed in adult patients with AD. Development of the ADCT followed US Food and Drug Administration (FDA) guidelines on patient-reported outcome measures (PROMs). Qualitative research, including targeted literature review, interviews with clinical experts, and combined concept elicitation/cognitive debriefing with patients with AD, was conducted to provide a list of comprehensive concepts capturing AD control per physician and patient perspectives. Quantitative methods assessed psychometric properties of the instrument and defined the threshold for AD control.
Results: The resulting pilot six-item ADCT, reflecting key concepts related to AD control, had 7-day recall and assessed symptoms and impacts on patients' everyday lives by severity and/or frequency. The ADCT showed good content validity (well understood by adult patients with AD), and quick completion time (<2 min). Psychometric analysis indicated no floor/ceiling effects for response distributions, particularly strong (r ≥ 0.80) inter-item correlations for the six ADCT items, robust construct validity (r > 0.50), and item-level discriminating ability (p < .03); this supported the derivation of a total score based on responses to all items. ADCT total score showed evidence of strong internal consistency reliability (Cronbach's alpha >0.80). A score ≥7 points was identified as an optimum threshold to identify patients whose AD is "not in control."
Conclusions: No single validated instrument has been available to holistically evaluate patient-perceived AD control. The newly developed ADCT displays good-to-excellent content validity, construct validity, internal consistency, reliability, and discriminating ability.
ABSTRACT
Aim
Epicardial adipose tissue (EAT) may play a role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). We investigated associations of EAT with proteomics, ...coronary flow reserve (CFR), cardiac structure and function, and quality of life (QoL) in the prospective multinational PROMIS‐HFpEF cohort.
Methods and results
Epicardial adipose tissue was measured by echocardiography in 182 patients and defined as increased if ≥9 mm. Proteins were measured using high‐throughput proximity extension assays. Microvascular dysfunction was evaluated with Doppler‐based CFR, cardiac structural and functional indices with echocardiography and QoL by Kansas City Cardiomyopathy Questionnaire (KCCQ). Patients with increased EAT (n = 54; 30%) had higher body mass index (32 28–40 vs. 27 23–30 kg/m2; p < 0.001), lower N‐terminal pro‐B‐type natriuretic peptide (466 193–1133 vs. 1120 494–1990 pg/ml; p < 0.001), smaller indexed left ventricular (LV) end‐diastolic and left atrial (LA) volumes and tendency to lower KCCQ score. Non‐indexed LV/LA volumes did not differ between groups. When adjusted for body mass index, EAT remained associated with LV septal wall thickness (coefficient 1.02, 95% confidence interval CI 1.00–1.04; p = 0.018) and mitral E wave deceleration time (coefficient 1.03, 95% CI 1.01–1.05; p = 0.005). Increased EAT was associated with proteomic markers of adipose biology and inflammation, insulin resistance, endothelial dysfunction, and dyslipidaemia but not significantly with CFR.
Conclusion
Increased EAT was associated with cardiac structural alterations and proteins expressing adiposity, inflammation, lower insulin sensitivity and endothelial dysfunction related to HFpEF pathology, probably driven by general obesity. Potential local mechanical or paracrine effects mediated by EAT remain to be elucidated.
We examined in HepG2 cells whether glucose-induced changes in AMP-activated protein kinase (AMPK) activity could be mediated by SIRT1, an NAD
+-dependent histone/protein deacetylase that has been ...linked to the increase in longevity caused by caloric restriction. Incubation with 25 vs. 5
mM glucose for 6
h concurrently diminished the phosphorylation of AMPK (Thr 172) and ACC (Ser 79), increased lactate release, and decreased the abundance and activity of SIRT1. In contrast, incubation with pyruvate (0.1 and 1
mM) for 2
h increased AMPK phosphorylation and SIRT1 abundance and activity. The putative SIRT1 activators resveratrol and quercetin also increased AMPK phosphorylation. None of the tested compounds (low or high glucose, pyruvate, and resveratrol) significantly altered the AMP/ATP ratio. Collectively, these findings raise the possibility that glucose-induced changes in AMPK are linked to alterations in SIRT1 abundance and activity and possibly cellular redox state.
Normalization of echocardiographic chamber measurements for body surface area may result in misclassification of individuals with obesity or sarcopenia. Normalization for alternative measures of body ...size may be preferable, but there remains a dearth of information on their normative values and association with cardiovascular function metrics.
A total of 3032 individuals underwent comprehensive 2-dimensional echocardiography at Exam 6 in MESA (Multi-Ethnic Study of Atherosclerosis). In the subgroup of 608 individuals free of cardiopulmonary disease (69.5±7.0 years, 46% male, 48% White, 17% Chinese, 15% Black, 21% Hispanic), normative values were derived for left and right cardiac chamber measurements across a variety of ratiometric (body surface area, body mass index, height) and allometric (height
, height
) scaling parameters. Normative upper and lower reference values were provided for each scaling parameter stratified across age groups, sex, and race or ethnicity. Among scaling parameters, body surface area and height were associated with the least variability across race and ethnicity categories and height
was associated with the least variability across sex categories.
In this diverse cohort of community-dwelling older adults, we provide normative values for common echocardiographic parameters across a variety of indexation methods.
Aims
Little information is available on sex differences in coronary microvascular dysfunction (CMD) in heart failure with preserved ejection fraction (HFpEF). We investigated sex‐specific proteomic ...profiles associated with CMD in patients with HFpEF.
Methods and results
Using the prospective multinational PROMIS‐HFpEF study (Prevalence of Microvascular Dysfunction in HFpEF; n = 182; 54.6% women), we compared clinical and biomarker correlates of CMD (defined as coronary flow reserve CFR <2.5) between men and women with HFpEF. We used lasso penalized regression to analyse 242 biomarkers from high‐throughput proximity extension assays, adjusting for age, body mass index, creatinine, smoking and study site. The prevalence of CMD was similarly high in men and women with HFpEF (77% vs. 70%; p = 0.27). Proteomic correlates of CFR differed by sex, with 10 versus 16 non‐overlapping biomarkers independently associated with CFR in men versus women, respectively. In men, proteomic correlates of CFR included chemokine ligand 20, brain natriuretic peptide, proteinase 3, transglutaminase 2, pregnancy‐associated plasma protein A and tumour necrosis factor receptor superfamily member 14. Among women, the strongest proteomic correlates with CFR were insulin‐like growth factor‐binding protein 1, phage shock protein D, CUB domain‐containing protein 1, prostasin, decorin, FMS‐like tyrosine kinase 3, ligand growth differentiation factor 15, spondin‐1, delta/notch‐like epidermal growth factor‐related receptor and tumour necrosis factor receptor superfamily member 13B. Pathway analyses suggested that CMD was related to the inflammation‐mediated chemokine and cytokine signalling pathway among men with HFpEF, and the P13‐kinase and transforming growth factor‐beta signalling pathway among women with HFpEF.
Conclusion
While the prevalence of CMD among men and women with HFpEF is similar, the drivers of microvascular dysfunction may differ by sex. The current inflammatory paradigm of CMD in HFpEF potentially predominates in men, while derangement in ventricular remodelling and fibrosis may play a more important role in women.
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