Trends in prevalence of comorbidities in heart failure clinical trials

Khan, Muhammad Shahzeb; Tahhan, Ayman Samman; Vaduganathan, Muthiah; Greene, Stephen J.; Alrohaibani, Alaaeddin; Anker, Stefan D.; Vardeny, Orly; Fonarow, Gregg C.; Butler, Javed

doi:10.1002/ejhf.1818

Cited by 94 publications

(93 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The reported prevalence of comorbidities varied with HF severity (5). As shown in Figure 1, we summarized the prevalence of major comorbidities according to the different organs and systems involved, such as hypertension (65%), atrial fibrillation (45%), chronic obstructive pulmonary disease (COPD)/asthma(40%), iron deficiency (30%), diabetes (40%), chronic kidney diseases (CKD) (25%), obesity (45%) (6,7), ischaemic heart disease (50%), hyperlipidaemia (55%) (8), depression (40%) (9)(10)(11), sleep apnea (40%) (12), sarcopenia (40%) (13) and liver dysfunction (10%) (14). The high prevalence of multi morbidity is associated with poor prognosis and heavy heath burdens, and therapy for multi morbidity in HF is still a challenge (15).…”

Section: Introductionmentioning

confidence: 99%

Metabolism and Chronic Inflammation: The Links Between Chronic Heart Failure and Comorbidities

Zhao

Wang

2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Heart failure (HF) patients often suffer from multiple comorbidities, such as diabetes, atrial fibrillation, depression, chronic obstructive pulmonary disease, and chronic kidney disease. The coexistance of comorbidities usually leads to multi morbidity and poor prognosis. Treatments for HF patients with multi morbidity are still an unmet clinical need, and finding an effective therapy strategy is of great value. HF can lead to comorbidity, and in return, comorbidity may promote the progression of HF, creating a vicious cycle. This reciprocal correlation indicates there may be some common causes and biological mechanisms. Metabolism remodeling and chronic inflammation play a vital role in the pathophysiological processes of HF and comorbidities, indicating metabolism and inflammation may be the links between HF and comorbidities. In this review, we comprehensively discuss the major underlying mechanisms and therapeutic implications for comorbidities of HF. We first summarize the potential role of metabolism and inflammation in HF. Then, we give an overview of the linkage between common comorbidities and HF, from the perspective of epidemiological evidence to the underlying metabolism and inflammation mechanisms. Moreover, with the help of bioinformatics, we summarize the shared risk factors, signal pathways, and therapeutic targets between HF and comorbidities. Metabolic syndrome, aging, deleterious lifestyles (sedentary behavior, poor dietary patterns, smoking, etc.), and other risk factors common to HF and comorbidities are all associated with common mechanisms. Impaired mitochondrial biogenesis, autophagy, insulin resistance, and oxidative stress, are among the major mechanisms of both HF and comorbidities. Gene enrichment analysis showed the PI3K/AKT pathway may probably play a central role in multi morbidity. Additionally, drug targets common to HF and several common comorbidities were found by network analysis. Such analysis has already been instrumental in drug repurposing to treat HF and comorbidity. And the result suggests sodium-glucose transporter-2 (SGLT-2) inhibitors, IL-1β inhibitors, and metformin may be promising drugs for repurposing to treat multi morbidity. We propose that targeting the metabolic and inflammatory pathways that are common to HF and comorbidities may provide a promising therapeutic strategy.

show abstract

Section: Introductionmentioning

confidence: 99%

Metabolism and Chronic Inflammation: The Links Between Chronic Heart Failure and Comorbidities

Zhao

Wang

2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…However, patients included in randomized clinical trials (RCTs) usually differ from those that physicians manage every day in clinical practice; they are usually younger, more stable, have fewer comorbidities, higher adherence rates to therapy, and attend more follow-up visits than real-world patients 17,18 . In a recent systematic review of 118 trials published between 2001 and 2016, Khan et al found that 72% excluded patients with ≥ 1 comorbid condition among dementia, anaemia, diabetes mellitus, severe or uncontrolled hypertension, chronic kidney www.nature.com/scientificreports/ disease (CKD), atrial fibrillation, chronic liver disease, stroke, cancer, and COPD 19 . CKD was the most common exclusion criterion (47% of trials).…”

Section: Discussionmentioning

confidence: 99%

Mortality trends in an ambulatory multidisciplinary heart failure unit from 2001 to 2018

Spitaleri

Lupón

Domingo

et al. 2021

Sci Rep

View full text Add to dashboard Cite

To assess mortality trends at 1 and 3 years from 2001 to 2018 in a real-life cohort of HF outpatients from different etiologies with depressed and preserved LVEF. A total of 2368 consecutive patients with HF (mean age 66.4 ± 12.9 years, 71% men, 15.4% with preserved LVEF) admitted to a HF clinic from August 2001 to September 2018 were included in the study. Patients were divided into five quintiles (Q) according to the period of admission. Trends for all-cause and cardiovascular mortality from Q1 to Q5 were assessed by linear regression. Patients with LVEF < 50% had a progressive decrease in the rates of all-cause and cardiovascular death at 1 year (12.1% in Q1 to 6.5% in Q5, p = 0.003; and 8.4% in Q1 to 3.8% in Q5, p = 0.007, respectively) and 3 years (30.5% in Q1 to 17.0% in Q5, p = 0.003; and 23.9% in Q1 to 9.8% in Q5, p = 0.003, respectively). These trends remained significant after adjusting for clinical characteristics and risk. No significant trend in mortality was observed in patients with LVEF ≥ 50%. In a cohort of real-life ambulatory patients with HF, mortality progressively declined in patients with LVEF < 50%, but the same trend was not observed in patients with preserved LVEF.

show abstract

“…The inclusion and exclusion criteria in our study have been very strict; therefore the resulting analyzed population is aligned with the current definitions of HFpEF [ 1 , 26 , 27 ]. In support of our selection criteria, a recent review concerning heart failure clinical trials concludes that only 27% of the HFpEF trials report patient-specific comorbidities, and unfortunately, most studies exclude a number of patients because of their comorbidities [ 28 ]. However, patients with DM, anemia, CKD, pulmonary disease were not excluded from our study, thus allowing a more realistic overview of this heterogeneous population.…”

Section: Discussionmentioning

confidence: 99%

“…This is especially important since Khan et al underline the need to also include a multi-morbid population in the HFpEF trials to create a broader image, closer to real-life cases. These combined pathologies bear the potential to induce acute presentations and heart failure decompensation [ 28 ]. In agreement with their publication we have observed in our study a moderate, although statistically significant, correlation between the number of comorbidities and HFR.…”

Section: Discussionmentioning

confidence: 99%

The E/e’ Ratio—Role in Risk Stratification of Acute Heart Failure with Preserved Ejection Fraction

et al. 2021

View full text Add to dashboard Cite

Background and Objectives: Heart failure with preserved ejection fraction (HFpEF) remains a worldwide management problem. Although there is a general effort for characterizing this population, few studies have assessed the predictive value of the echocardiographic E/e’ ratio in patients with acute HFpEF. The aim of the study was to identify groups with different prognosis in patients hospitalized with a first acute episode of HFpEF. Materials and Methods: The primary endpoint of the study was heart failure readmissions (HFR) at 6 months, while the secondary outcome was six-month mortality. We consecutively enrolled 91 patients hospitalized for the first time with acute HFpEF. We examined the E/e’ ratio as an independent predictor for HFR using univariate regression. Results: We identified and validated the E/e’ ratio as an independent predictor for HFR. An E/e’ ratio threshold value of 13.80 was calculated [(area under the receiver operating characteristic curve (AUROC) = 0.693, sensitivity = 78.60%, specificity = 55%, p < 0.004)] and validated as an inflection point for an increased number of HFR. Thus, we divided the study cohort into two groups: group 1 with an E/e’ ratio < 13.80 (n = 39) and group 2 with an E/e’ ratio > 13.80 (n = 49). Compared to group 1, group 2 had an increased number of HFR (p = 0.003) and a shorter time to first HFR (p = 0.002). However, this parameter did not influence all-cause mortality within six months (p = 0.84). Conclusions: The dimensionless E/e’ ratio is a useful discriminator between patients with acute HFpEF. An E/e’ value over 13.80 represents a simple, yet effective instrument for assessing the HFR risk. However, all-cause mortality at six months is not influenced by the E/e’ ratio.

show abstract

Trends in prevalence of comorbidities in heart failure clinical trials

Cited by 94 publications

References 37 publications

Metabolism and Chronic Inflammation: The Links Between Chronic Heart Failure and Comorbidities

Metabolism and Chronic Inflammation: The Links Between Chronic Heart Failure and Comorbidities

Mortality trends in an ambulatory multidisciplinary heart failure unit from 2001 to 2018

The E/e’ Ratio—Role in Risk Stratification of Acute Heart Failure with Preserved Ejection Fraction

Contact Info

Product

Resources

About