Epidemiology of heart failure Groenewegen, Amy; Rutten, Frans H.; Mosterd, Arend ...
European journal of heart failure,
August 2020, Volume:
22, Issue:
8
Journal Article
Peer reviewed
Open access
The heart failure syndrome has first been described as an emerging epidemic about 25 years ago. Today, because of a growing and ageing population, the total number of heart failure patients still ...continues to rise. However, the case mix of heart failure seems to be evolving. Incidence has stabilized and may even be decreasing in some populations, but alarming opposite trends have been observed in the relatively young, possibly related to an increase in obesity. In addition, a clear transition towards heart failure with a preserved ejection fraction has occurred. Although this transition is partially artificial, due to improved recognition of heart failure as a disorder affecting the entire left ventricular ejection fraction spectrum, links can be made with the growing burden of obesity‐related diseases and with the ageing of the population. Similarly, evidence suggests that the number of patients with heart failure may be on the rise in low‐income countries struggling under the double burden of communicable diseases and conditions associated with a Western‐type lifestyle. These findings, together with the observation that the mortality rate of heart failure is declining less rapidly than previously, indicate we have not reached the end of the epidemic yet. In this review, the evolving epidemiology of heart failure is put into perspective, to discern major trends and project future directions.
Higher levels of physical activity are associated with a lower risk of cardiovascular events. Nevertheless, there is debate on the dose-response relationship of exercise and cardiovascular disease ...outcomes and whether high volumes of exercise may accelerate coronary atherosclerosis. We aimed to determine the relationship between lifelong exercise volumes and coronary atherosclerosis.
Middle-aged men engaged in competitive or recreational leisure sports underwent a noncontrast and contrast-enhanced computed tomography scan to assess coronary artery calcification (CAC) and plaque characteristics. Participants reported lifelong exercise history patterns. Exercise volumes were multiplied by metabolic equivalent of task (MET) scores to calculate MET-minutes per week. Participants' activity was categorized as <1000, 1000 to 2000, or >2000 MET-min/wk.
A total of 284 men (age, 55±7 years) were included. CAC was present in 150 of 284 participants (53%) with a median CAC score of 35.8 (interquartile range, 9.3-145.8). Athletes with a lifelong exercise volume >2000 MET-min/wk (n=75) had a significantly higher CAC score (9.4 interquartile range, 0-60.9 versus 0 interquartile range, 0-43.5;
=0.02) and prevalence of CAC (68%; adjusted odds ratio OR
=3.2; 95% confidence interval CI, 1.6-6.6) and plaque (77%; OR
=3.3; 95% CI, 1.6-7.1) compared with <1000 MET-min/wk (n=88; 43% and 56%, respectively). Very vigorous intensity exercise (≥9 MET) was associated with CAC (OR
=1.47; 95% CI, 1.14-1.91) and plaque (OR
=1.56; 95% CI, 1.17-2.08). Among participants with CAC>0, there was no difference in CAC score (
=0.20), area (
=0.21), density (
=0.25), and regions of interest (
=0.20) across exercise volume groups. Among participants with plaque, the most active group (>2000 MET-min/wk) had a lower prevalence of mixed plaques (48% versus 69%; OR
=0.35; 95% CI, 0.15-0.85) and more often had only calcified plaques (38% versus 16%; OR
=3.57; 95% CI, 1.28-9.97) compared with the least active group (<1000 MET-min/wk).
Participants in the >2000 MET-min/wk group had a higher prevalence of CAC and atherosclerotic plaques. The most active group, however, had a more benign composition of plaques, with fewer mixed plaques and more often only calcified plaques. These observations may explain the increased longevity typical of endurance athletes despite the presence of more coronary atherosclerotic plaque in the most active participants.
Plasma osteoprotegerin (OPG) and vascular smooth muscle cell (VSMC) derived extracellular vesicles (EVs) are important regulators in the process of vascular calcification (VC). In population studies, ...high levels of OPG are associated with events. In animal studies, however, high OPG levels result in reduction of VC. VSMC-derived EVs are assumed to be responsible for OPG transport and VC but this role has not been studied. For this, we investigated the association between OPG in plasma and circulating EVs with coronary artery calcium (CAC) as surrogate for VC in symptomatic patients. We retrospectively assessed 742 patients undergoing myocardial perfusion imaging (MPI). CAC scores were determined on the MPI-CT images using a previously developed automated algorithm. Levels of OPG were quantified in plasma and two EV-subpopulations (LDL and TEX), using an electrochemiluminescence immunoassay. Circulating levels of OPG were independently associated with CAC scores in plasma; OR 1.39 (95% CI 1.17-1.65), and both EV populations; EV-LDL; OR 1.51 (95% CI 1.27-1.80) and EV-TEX; OR 1.21 (95% CI 1.02-1.42). High levels of OPG in plasma were independently associated with CAC scores in this symptomatic patient cohort. High levels of EV-derived OPG showed the same positive association with CAC scores, suggesting that EV-derived OPG mirrors the same pathophysiological process as plasma OPG.
The 2017 Dutch Physical Activity Guidelines Weggemans, Rianne M; Backx, Frank J G; Borghouts, Lars ...
The international journal of behavioral nutrition and physical activity,
06/2018, Volume:
15, Issue:
1
Journal Article
Peer reviewed
Open access
The objective of this study was to derive evidence-based physical activity guidelines for the general Dutch population.
Two systematic reviews were conducted of English language meta-analyses in ...PubMed summarizing separately randomized controlled trials and prospective cohort studies on the relation between physical activity and sedentary behaviour on the one hand and the risk of all-cause mortality and incidence of 15 major chronic diseases and conditions on the other hand. Other outcome measures were risk factors for cardiovascular disease and type 2 diabetes, physical functioning, and fitness. On the basis of these reviews, an expert committee derived physical activity guidelines. In deriving the guidelines, the committee first selected only experimental and observational prospective findings with a strong level of evidence and then integrated both lines of evidence.
The evidence found for beneficial effects on a large number of the outcome measures was sufficiently strong to draw up guidelines to increase physical activity and reduce sedentary behaviour, respectively. At the same time, the current evidence did not provide a sufficient basis for quantifying how much physical activity is minimally needed to achieve beneficial health effects, or at what amount sedentary behaviour becomes detrimental. A general tenet was that at every level of current activity, further increases in physical activity provide additional health benefits, with relatively larger effects among those who are currently not active or active only at light intensity. Three specific guidelines on (1) moderate- and vigorous-intensity physical activity, (2) bone- and muscle-strengthening activities, and (3) sedentary behaviour were formulated separately for adults and children.
There is an unabated need for evidence-based physical activity guidelines that can guide public health policies. Research in which physical activity is measured both objectively (quantity) and subjectively (type and quality) is needed to provide better estimates of the type and actual amount of physical activity required for health.
Abstract Background Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild ...symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure. Objectives The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum. Methods This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorize patients. The authors determined whether risk, on the basis of these scores, modified the treatment effect of LCZ696. Results The complete MAGGIC risk score was available for 8,375 of the 8,399 patients in PARADIGM-HF. The median MAGGIC score was 20 (IQR: 16 to 24). An increase of 1 point was associated with a 6% increased risk for the primary endpoint (p < 0.001) and a 7% increased risk for cardiovascular death (p < 0.001). The benefit of LCZ696 over enalapril for the primary endpoint was similar across the spectrum of risk (p = 0.159). Treating 100 patients for 2 years with LCZ696 instead of enalapril led to 7 fewer patients in the highest quintile of risk experiencing primary outcomes, compared with 3 in the lowest quintile. Analyses using the EMPHASIS-HF risk score gave similar findings. Conclusions Although most PARADIGM-HF patients had mild symptoms, many were at high risk for adverse outcomes and obtained a large absolute benefit from LCZ696, compared with enalapril, over a relatively short treatment period. LCZ696’s benefit was consistent across the spectrum of risk. (PARADIGM-HF trial Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure; NCT01035255 )
Inflammation plays a pivotal role in atherothrombosis. Colchicine is an anti-inflammatory drug that may attenuate this process. Cardiovascular protective effects of anti-inflammatory drugs, however, ...seem to be limited to patients with a biochemical response. We therefore investigated whether short-term exposure to colchicine reduced inflammatory markers and whether additional laboratory changes occur in patients with chronic coronary artery disease. In 138 consecutive patients with chronic coronary artery disease and a high sensitivity C-reactive Protein (hs-CRP) greater than or equal to 2 mg/L, inflammatory markers, lipids, haematologic parameters and renal function were measured at baseline and after 30 days exposure to colchicine 0.5mg once daily. Hs-CRP decreased from baseline 4.40 mg/L (interquartile range IQR 2.83-6.99 mg/L) to 2.33 mg/L (IQR 1.41-4.17, median of the differences -1.66 mg/L, 95% confidence interval CI -2.17 - -1.22 mg/L, p-value <0.01), corresponding to a median change from baseline of -40%. Interleukin-6 decreased from 2.51 ng/L (IQR 1.59-4.32 ng/L) to 2.22 ng/L (median of the differences -0.36 ng/L, 95%CI -0.70 - -0.01 ng/L, p-value 0.04), corresponding to a median change from baseline of -16%. No clinically relevant changes in lipid fractions were observed. Both leukocyte and thrombocyte count decreased (median change from baseline -7% and -4% respectively). Estimated glomerular filtration rate decreased with a mean change from baseline of -2%. In patients with chronic coronary artery disease and elevated hs-CRP, one-month exposure to colchicine 0.5 mg once daily was associated with a reduction of inflammatory markers. A small effect was seen on white blood cell count and platelet count, as well as a small decrease in estimated glomerular filtration rate.
Previous studies investigating the role of circulating microRNAs in acute coronary syndrome (ACS) were based on small patient numbers, performed no comparison with established markers of cardiac ...injury and did not have appropriate controls. We determined the potential diagnostic value of circulating microRNAs as novel early biomarkers in 332 suspected ACS patients on presentation to the emergency department (ED) in a prospective single‐centre study including cardiac miRNAs (miR‐1, ‐208a and ‐499), miR‐21 and miR‐146a. Levels of all miRs studied were significantly increased in 106 patients diagnosed with ACS, even in patients with initially negative high‐sensitive (hs) troponin or symptom onset <3 h. MiR‐1, miR‐499 and miR‐21 significantly increased the diagnostic value in all suspected ACS patients when added to hs‐troponin T (AUC 0.90). These three miRs were strong predictors of ACS independent of clinical co‐variates including patient history and cardiovascular risk factors. Interestingly, the combination of these three miRs resulted in a significantly higher AUC of 0.94 than hs‐troponin T (0.89). Circulating microRNAs hold great potential as novel early biomarkers for the management of suspected ACS patients.
Despite the use of high-sensitive cardiac troponin there remains a group of high-sensitive cardiac troponin negative patients with unstable angina with a non-neglectable risk for future adverse ...cardiovascular events, emphasising the need for additional risk stratification. Plasma extracellular vesicles are small bilayer membrane vesicles known for their potential role as biomarker source. Their role in unstable angina remains unexplored. We investigate if extracellular vesicle proteins are associated with unstable angina in patients with chest pain and low high-sensitive cardiac troponin. The MINERVA study included patients presenting with acute chest pain but no acute coronary syndrome. We performed an exploratory retrospective case-control analysis among 269 patients. Cases were defined as patients with low high-sensitive cardiac troponin and proven ischemia. Patients without ischemia were selected as controls. Blood samples were fractionated to analyse the EV proteins in three plasma-subfractions: TEX, HDL and LDL. Protein levels were quantified using electrochemiluminescence immunoassay. Lower levels of (adjusted) EV cystatin c in the TEX subfraction were associated with having unstable angina (OR 0.93 95% CI 0.88-0.99). In patients with acute chest pain but low high-sensitive cardiac troponin, lower levels of plasma extracellular vesicle cystatin c are associated with having unstable angina. This finding is hypothesis generating only considering the small sample size and needs to be confirmed in larger cohort studies, but still identifies extracellular vesicle proteins as source for additional risk stratification.
Abstract Background Elderly heart failure (HF) patients frequently have multiple comorbidities. The prognostic impact of combined comorbidities is poorly quantified in these patients. We assessed the ...impact of comorbidities on 3-year mortality in geriatric outpatients with newly diagnosed HF. Methods and Results Of 93 geriatric outpatients with HF (mean age 82.7 years, 36.6% men), 52 patients (55.9%) died within 3 years after HF was diagnosed. Comorbidity was measured with the Charlson Comorbidity Index (CCI). Age- and gender-adjusted hazard ratio (HR) for 3-year mortality was 1.6 (95% confidence interval CI 0.9–3.2) for patients with 3–4 CCI points and 3.2 (95% CI 1.5–6.8) for those with >4 CCI points, compared with 1–2 CCI points. After adjustment for age, gender, left ventricular ejection fraction (LVEF), and N-terminal pro–B-type natriuretic peptide, CCI remained predictive of death (CCI 3–4: HR 1.5 (95% CI 0.7–2.9); CCI >4: HR 4.0 (95% CI 1.9–8.8)). In addition to age and gender, the c-statistics for CCI and LVEF were similar (0.63 95% CI 0.55–0.70 and 0.64 95% CI 0.56–0.72, respectively). Conclusions The majority of geriatric outpatients with new HF die within 3 years. Comorbidity, summarized in the CCI, is the strongest independent predictor of mortality.
Objectives The purpose of this trial was to study the effect of a high bolus dose (HBD) of tirofiban on clinical outcome in patients undergoing primary percutaneous coronary intervention for ...ST-segment elevation myocardial infarction (STEMI). Background The On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2) placebo-controlled, double-blind, randomized trial showed that early administration of HBD tirofiban in the ambulance improves ST-segment resolution in patients with STEMI undergoing primary percutaneous coronary intervention. The effect of early tirofiban treatment on clinical outcome is unclear. Methods The On-TIME 2 trial consisted of 2 phases: an open-label phase, followed by a double-blind, placebo-controlled phase. STEMI patients were randomized to either HBD tirofiban or no tirofiban (phase 1) or placebo (phase 2) in addition to aspirin, heparin, and high-dose clopidogrel. The protocol pre-specified a pooled analysis of the 2 study phases to assess the incidence of major adverse cardiac events at the 30-day follow-up and on total mortality at the 1-year follow-up. Results During a 3-year period, 1,398 patients were randomized, 414 in phase 1 and 984 in phase 2. Major adverse cardiac events at 30 days were significantly reduced (5.8% vs. 8.6%, p = 0.043). There was a strong trend toward a decrease in mortality (2.2% vs. 4.1%, p = 0.051) in patients who were randomized to tirofiban pre-treatment, which was maintained during the 1-year follow-up (3.7% vs. 5.8%, p = 0.08). No clinically relevant difference in bleeding was observed. Conclusions Early, pre-hospital initiation of HBD tirofiban, in addition to high-dose clopidogrel, improves the clinical outcome after primary percutaneous coronary intervention in patients with STEMI. (Ongoing 2b/3a inhibition In Myocardial infarction Evaluation; ISRCTN06195297 )
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