Long-term cardiovascular complications following sepsis: is senescence the missing link?

AbstractAmong the long-term consequences of sepsis (also termed “post-sepsis syndrome”) the increased risk of unexplained cardiovascular complications, such as myocardial infarction, acute heart failure or stroke, is one of the emerging specific health concerns. The vascular accelerated ageing also named premature senescence is a potential mechanism contributing to atherothrombosis, consequently leading to cardiovascular events. Indeed, vascular senescence-associated major adverse cardiovascular events (MACE) are a potential feature in sepsis survivors and of the elderly at cardiovascular risk. In these patients, accelerated vascular senescence could be one of the potential facilitating mechanisms. This review will focus on premature senescence in sepsis regardless of age. It will highlight and refine the potential relationships between sepsis and accelerated vascular senescence. In particular, key cellular mechanisms contributing to cardiovascular events in post-sepsis syndrome will be highlighted, and potential therapeutic strategies to reduce the cardiovascular risk will be further discussed.

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Underlying cardiovascular risk and major adverse cardiovascular events after acute respiratory infection: a population-based cohort study of over 4.2 million individuals in England, 2008-2018

10.1101/2021.03.18.21253890 ◽

2021 ◽

Author(s):

Jennifer Davidson ◽

Amitava Banerjee ◽

Liam Smeeth ◽

Helen I McDonald ◽

Daniel J Grint ◽

...

Keyword(s):

Cohort Study ◽

Cardiovascular Risk ◽

Cardiovascular Events ◽

Respiratory Infections ◽

Cardiovascular Complications ◽

Major Adverse Cardiovascular Events ◽

Mortality Data ◽

Clinical Practice Research Datalink ◽

Increased Risk ◽

One Year

Background While acute respiratory infections (ARIs) can lead to cardiovascular complications, the effect of underlying cardiovascular risk profile on ARI incidence and cardiovascular complications in those without established cardiovascular disease (CVD) is unknown. Whether to consider individuals at raised cardiovascular risk a priority group for vaccination against respiratory infections therefore remains unclear. Methods We conducted a cohort study in individuals aged 40-64 years without established CVD or a chronic health condition eligible for influenza vaccination, using Clinical Practice Research Datalink GOLD and Aurum data from 01/09/2008-31/08/2018 linked to Hospital Episode Statistics Admitted Patient Care and Office for National Statistics mortality data from England. We classified cardiovascular risk based on diagnosed hypertension and overall predicted cardiovascular risk estimated using QRISK2 score (≥10% compared with <10%). Using multivariable Poisson regression models, we obtained incidence rate ratios (IRR) for ARI. Among individuals who had an ARI, we then used multivariable Cox regression to obtain hazard ratios (HR) for the risk of major adverse cardiovascular events (MACE) within one year of infection. Findings 4,212,930 individuals were included; 12.5% had hypertension and 14.4% had a QRISK2 score ≥10%. After adjusting for confounders, patients with hypertension (IRR 1.04, 95% CI 1.03-1.05) or QRISK2 score ≥10% (IRR 1.39, 1.37-1.40) had a higher incidence of ARI. Of the 442,408 individuals with an ARI, 4,196 had a MACE within one year of infection. After adjustment, hypertension (HR 1.98, 1.83-2.15) and QRISK2 score ≥10% (HR 3.65, 3.42-3.89) were associated with substantial increased risk of a MACE after infection. Interpretation People without diagnosed CVD but who have raised cardiovascular risk, measured by diagnosed hypertension or, in particular, overall predicted cardiovascular risk, have increased incidence of both ARI and cardiovascular complications following an ARI.

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Cardiovascular complications according to severity of renal artery stenosis based on Doppler ultrasound

Archives of Medical Science ◽

10.5114/aoms/132002 ◽

2021 ◽

Author(s):

Łukasz Artyszuk ◽

Bartosz Symonides ◽

Zbigniew Gaciong ◽

Cezary Szmigielski

Keyword(s):

Cardiovascular Risk ◽

Renal Artery ◽

Renal Artery Stenosis ◽

Doppler Ultrasound ◽

Cardiovascular Events ◽

Cardiovascular Complications ◽

Artery Stenosis ◽

Control Group ◽

Percutaneous Coronary Angioplasty ◽

Increased Risk

IntroductionThe interactions between atherosclerotic renal artery stenosis, independently of severity, and cardiovascular risk, and mortality, are complex and have not been fully researched. The aim of this study was the assessment of the risk of cardiovascular events and mortality in patients with haemodynamically non-significant (NS-RAS) and significant renal artery stenosis (S-RAS) diagnosed with ultrasonography.Material and methodsThe study group consisted of all consecutive patients (n = 2059) who underwent Doppler ultrasound of the renal arteries during a 4-year period. The patients were divided, according to the renal aortic ratio (RAR), into the following groups: S-RAS (RAR ≥ 3.5), NS-RAS (1 < RAR < 3.5), and normal RAR (control group; RAR ≤ 1). The risk of cardiovascular events and death was estimated using Cox’s proportional hazard model, including severity of RAS, age, and gender, based on the data from the National Health Fund on causes of hospitalization, deaths, and statistics on percutaneous coronary angioplasty procedures.ResultsSignificant renal artery stenosis was found in 112 patients (5.4%), NS-RAS in 313 patients (15.2%), and 1634 patients (79.4%) were qualified to the control group. The NS-RAS group had an increased risk of stroke (7.0% vs. 3.0%, HR = 1.77, p = 0.032); S-RAS patients were at increased risk of heart failure (16.1% vs. 5.2%, HR = 2.19, p = 0.002) and death (19.6% vs. 4.3%, HR = 3.08, p < 0.001).ConclusionsThe presence of haemodynamically non-significant renal artery stenosis is an indicator of systemic atherosclerotic changes in vital organs and an important cardiovascular risk factor for stroke.

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Low total cholesterol is associated with increased major adverse cardiovascular events in men aged ≥70 years not taking statins

Heart ◽

10.1136/heartjnl-2019-315449 ◽

2019 ◽

Vol 106 (9) ◽

pp. 698-705 ◽

Cited By ~ 2

Author(s):

Sonali Rukshana Gnanenthiran ◽

Austin C C Ng ◽

Robert Cumming ◽

David B Brieger ◽

David Le Couteur ◽

...

Keyword(s):

Total Cholesterol ◽

Statin Therapy ◽

Cardiovascular Events ◽

Community Dwelling ◽

Major Adverse Cardiovascular Events ◽

Study Cohort ◽

Increased Risk ◽

Comorbidity Burden ◽

Statin Use

ObjectiveLow levels of total cholesterol (TC) are associated with adverse outcomes in older populations. Whether this phenomenon is independent of statin use is unknown. We investigated the association between low TC levels and long-term major adverse cardiovascular events (MACE) in a prospective study of men aged ≥70 years without ischaemic heart disease (IHD) and whether this was influenced by statin use.MethodsThe CHAMP (Concord Health and Ageing in Men Project) cohort is a prospective cohort study of community-dwelling men aged ≥70 years. The relationship between TC and long-term MACE was analysed using Cox-regression modelling adjusted for comorbidities and stratified by statin use.ResultsThe study cohort comprised 1289 men (mean (±SD) age, 77.0±5.5 years; mean follow-up, 6.4±2.7 years). Decreasing TC level was associated with increased comorbidity burden, frailty and MACE (linear trend p<0.001). In men not on statin therapy (n=731), each 1 mmol/L decrease in TC was associated with increased MACE (HR 1.27, 95% CI 1.10 to 1.45, p=0.001) and mortality (HR 1.22, 95% CI 1.03 to 1.44, p=0.02) adjusted for comorbidities. In contrast, low TC in men on statins (n=558) was not associated with MACE (HR 0.91, 95% CI 0.74 to 1.11) or mortality (HR 0.86, 95% CI 0.68 to 1.09).ConclusionLow TC is associated with increased risk of MACE in older men without IHD who are not taking statin therapy but not in those on statins.

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Prognostic value of ST2 for MACEs and all-cause mortality in patients with coronary artery disease during a long-term follow up

10.21203/rs.3.rs-63605/v1 ◽

2020 ◽

Author(s):

Man Li ◽

Lei Duan ◽

Yulun Cai ◽

Benchuan Hao ◽

Jianqiao Chen ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Events ◽

Prognostic Value ◽

Cox Regression ◽

Major Adverse Cardiovascular Events ◽

Kaplan Meier ◽

Increased Risk ◽

Artery Disease

Abstract Background: Suppression of tumorigenesis-2 is implicated in the myocardial overload and it was long been recognized as an inflammation marker related to heart failure and acute coronary syndromes, but the data on prognostic value of suppression of tumorigenesis-2 on patients with coronary artery disease remains limited. The study ought to investigate the prognostic value of suppression of tumorigenesis-2 in patients with established coronary artery disease.Methods: In this prospective cohort study, a total of 3641 consecutive patients were included. The primary end point was major adverse cardiovascular events. Kaplan-Meier survival estimates indicated that the patients with higher levels of ST2 (ST2> 19 ng/ml) had a significantly increased risk of MACEs (log-rank p＜0.001) and all-cause death (log-rank p＜0.001). The secondary end point was all-cause death. The association between suppression of tumorigenesis-2 and outcomes was investigated using multivariable COX regression.Results: During a median follow up of 6.4 years, there were 775 patients had the occurrence of major adverse cardiovascular events and 275 patients died. Kaplan-Meier survival estimates indicated that the patients with higher levels of ST2 (ST2> 19 ng/ml) had a significantly increased risk of MACEs (log-rank p＜0.001) and all-cause death (log-rank p＜0.001). Multiple COX regression models showed that higher level of suppression of tumorigenesis-2 was an independent predictor in developing major adverse cardiovascular events (HR=1.36, 95% CI 1.17-1.56, p＜0.001) and all-cause death (HR=2.01, 95%CI 1.56-2.59, p＜0.001). The addition of suppression of tumorigenesis-2 to established risk factors significantly improved risk prediction of the composite outcome of major adverse cardiovascular events and all-cause death (c-statistic, net reclassification index, and integrated discrimination improvement, all p＜0.05).Conclusions: Higher level of suppression of tumorigenesis-2 is significantly associated with long-term all-cause death and major adverse cardiovascular events. Suppression of tumorigenesis-2 may provide incremental prognostic value beyond traditional risk factors.

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0719 The Association of Sleep Apnea and Cardiorespiratory Fitness with Long-Term Major Cardiovascular Events

SLEEP ◽

10.1093/sleep/zsaa056.715 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A273-A274

Author(s):

M Barillas-Lara ◽

J Medina-Inojosa ◽

B Kolla ◽

J R Smith ◽

A R Bonikowske ◽

...

Keyword(s):

Coronary Artery ◽

Cardiorespiratory Fitness ◽

Cardiovascular Events ◽

Bypass Graft ◽

Peak Oxygen Consumption ◽

Systemic Hypertension ◽

Major Adverse Cardiovascular Events ◽

Apnea Hypopnea Index ◽

Increased Risk

Abstract Introduction Sleep disordered breathing (SDB) is associated with adverse cardiovascular outcomes and decreased cardiorespiratory fitness (CRF). The risk of long-term major adverse cardiovascular events (MACE) when SDB and decreased CRF co-occur has not been determined. Methods We included consecutive patients that underwent a symptom-limited cardiopulmonary exercise test followed by first-time diagnostic polysomnography within 6 months. Patients were stratified based on the presence of moderate-severe SDB (apnea/hypopnea index ≥15/hour) and decreased CRF defined as <70% predicted peak oxygen consumption (VO2). MACE was a composite outcome of myocardial infarction (MI), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), stroke/transient ischemic attack (TIA) and death. Cox-proportional hazard models adjusting for factors known to influence CRF and MACE were constructed. Results Of 498 included patients (60±13 years, 28.1% female), 175 (35%) had MACE (MI=17, PCI=14, CABG=13, stroke=20, TIA=12, deaths=99) at a median follow-up of 8.7 years (interquartile range=6.5-10.3 years). After adjusting for age, sex, beta-blockers, systemic hypertension, diabetes mellitus, coronary artery disease, cardiac arrhythmia, chronic obstructive pulmonary disease, smoking and positive airway pressure (PAP) usage, decreased CRF alone (HR=1.91, 95%CI=1.15-3.18, p=0.012), but not SDB alone (HR=1.26, 95%CI=0.75-2.13, p=0.389) was associated with increased risk of MACE. Those with SDB and decreased CRF had increased risk of MACE compared to patients with decreased CRF alone (HR=1.85, 95%CI=1.21-2.84, p<0.005) after accounting for these confounders; the risk was attenuated after additionally adjusting for adequate adherence to PAP (HR=1.85, 95%CI=0.99-3.05, p=0.05). Conclusion The incidence of MACE, including mortality, was high in this sample. Moderate-severe SDB with concurrent decreased CRF was associated with higher risk of MACE than decreased CRF alone. These results highlight the importance of including CRF in the risk assessment of patients with SDB, and conversely, that of screening for SDB in patients with low peak VO2. Support None.

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Preoperative Estimates of Glomerular Filtration Rate as Predictors of Outcome after Surgery

Anesthesiology ◽

10.1097/aln.0b013e318287b72c ◽

2013 ◽

Vol 118 (4) ◽

pp. 809-824 ◽

Cited By ~ 53

Author(s):

John F. Mooney ◽

Isuru Ranasinghe ◽

Clara K. Chow ◽

Vlado Perkovic ◽

Federica Barzi ◽

...

Keyword(s):

Acute Kidney Injury ◽

Glomerular Filtration Rate ◽

Cardiovascular Events ◽

Filtration Rate ◽

Kidney Injury ◽

Major Adverse Cardiovascular Events ◽

Increased Risk ◽

All Cause Mortality ◽

The Relationship

Abstract Background: Kidney dysfunction is a strong determinant of prognosis in many settings. Methods: A systematic review and meta-analysis was undertaken to explore the relationship between estimated glomerular filtration rate (eGFR) and adverse outcomes after surgery. Cohort studies reporting the relationship between eGFR and major outcomes, including all-cause mortality, major adverse cardiovascular events, and acute kidney injury after cardiac or noncardiac surgery, were included. Results: Forty-six studies were included, of which 44 focused exclusively on cardiac and vascular surgery. Within 30 days of surgery, eGFR less than 60 ml·min·1.73 m−2 was associated with a threefold increased risk of death (multivariable adjusted relative risk [RR] 2.98; 95% confidence interval [CI] 1.95–4.96) and acute kidney injury (adjusted RR 3.13; 95% CI 2.22–4.41). An eGFR less than 60 ml·min·1.73 m−2 was associated with an increased risk of all-cause mortality (adjusted RR 1.61; 95% CI 1.38–1.87) and major adverse cardiovascular events (adjusted RR 1.49; 95% CI 1.32–1.67) during long-term follow-up. There was a nonlinear association between eGFR and the risk of early mortality such that, compared with patients having an eGFR more than 90 ml·min·1.73 m−2 the pooled RR for death at 30 days in those with an eGFR between 30 and 60 ml·min·1.73 m−2 was 1.62 (95% CI 1.43–1.80), rising to 2.85 (95% CI 2.49–3.27) in patients with an eGFR less than 30 ml·min·1.73 m−2 and 3.75 (95% CI 3.44–4.08) in those with an eGFR less than 15 ml·min·1.73 m−2. Conclusion: There is a powerful relationship between eGFR, and both short- and long-term prognosis after, predominantly cardiac and vascular, surgery.

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Prediction of Cardiovascular Events by Type I Central Systolic Blood Pressure

Hypertension ◽

10.1161/hypertensionaha.120.16163 ◽

2020 ◽

Author(s):

Florence Lamarche ◽

Mohsen Agharazii ◽

François Madore ◽

Rémi Goupil

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Cardiovascular Events ◽

Administrative Databases ◽

Youden Index ◽

Major Adverse Cardiovascular Events ◽

Type I ◽

Increased Risk

Compared with brachial blood pressure (BP), central systolic BP (SBP) can provide a better indication of the hemodynamic strain inflicted on target organs, but it is unclear whether this translates into improved cardiovascular risk stratification. We aimed to assess which of central or brachial BP best predicts cardiovascular risk and to identify the central SBP threshold associated with increased risk of future cardiovascular events. This study included 13 461 participants of CARTaGENE with available central BP and follow-up data from administrative databases but without cardiovascular disease or antihypertensive medication. Central BP was estimated by radial artery tonometry, calibrated for brachial SBP and diastolic BP (type I), and a generalized transfer function (SphygmoCor). The outcome was major adverse cardiovascular events. Cox proportional-hazards models, differences in areas under the curves, net reclassification indices, and integrated discrimination indices were calculated. Youden index was used to identify SBP thresholds. Over a median follow-up of 8.75 years, 1327 major adverse cardiovascular events occurred. The differences in areas under the curves, net reclassification indices, and integrated discrimination indices were of 0.2% ([95% CI, 0.1–0.3] P <0.01), 0.11 ([95% CI, 0.03–0.20] P =0.01), and 0.0004 ([95% CI, −0.0001 to 0.0014] P =0.3), all likely not clinically significant. Central and brachial SBPs of 112 mm Hg (95% CI, 111.2–114.1) and 121 mm Hg (95% CI, 120.2–121.9) were identified as optimal BP thresholds. In conclusion, central BP measured with a type I device is statistically but likely not clinically superior to brachial BP in a general population without prior cardiovascular disease. Based on the risk of major adverse cardiovascular events, the optimal type I central SBP appears to be 112 mm Hg.

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