BACKGROUND: Inflammation is associated with adverse cardiovascular events. Data from recent trials suggest that colchicine reduces the risk of cardiovascular events. METHODS: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo. The results of the colchicine trial are reported here. The primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. C-reactive protein was measured at 3 months in a subgroup of patients, and safety was also assessed. RESULTS: A total of 7062 patients at 104 centers in 14 countries underwent randomization; at the time of analysis, the vital status was unknown for 45 patients (0.6%), and this information was most likely missing at random. A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P = 0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was -1.28 mg per liter (95% CI, -1.81 to -0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups. CONCLUSIONS: Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization). (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).

• MeSH
• C-reaktivní protein analýza   MeSH
• dvojitá slepá metoda MeSH
• infarkt myokardu * farmakoterapie   mortalita   MeSH
• Kaplanův-Meierův odhad MeSH
• kardiovaskulární nemoci mortalita   prevence a kontrola   epidemiologie   MeSH
• kolchicin * škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• senioři MeSH
• spironolakton terapeutické užití   škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• C-reaktivní protein MeSH
• kolchicin * MeSH
• spironolakton MeSH

BACKGROUND: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain. METHODS: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo. The results of the spironolactone trial are reported here. The two primary outcomes were a composite of death from cardiovascular causes or new or worsening heart failure, evaluated as the total number of events; and a composite of the first occurrence of myocardial infarction, stroke, new or worsening heart failure, or death from cardiovascular causes. Safety was also assessed. RESULTS: We enrolled 7062 patients at 104 centers in 14 countries; 3537 patients were assigned to receive spironolactone and 3525 to receive placebo. At the time of our analyses, the vital status was unknown for 45 patients (0.6%). For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group as compared with 220 events (2.1 per 100 patient-years) in the placebo group over a median follow-up period of 3 years (hazard ratio adjusted for competing risk of death from noncardiovascular causes, 0.91; 95% confidence interval [CI], 0.69 to 1.21; P = 0.51). With respect to the second primary outcome, an event occurred in 280 of 3537 patients (7.9%) in the spironolactone group and 294 of 3525 patients (8.3%) in the placebo group (hazard ratio adjusted for competing risk, 0.96; 95% CI, 0.81 to 1.13; P = 0.60). Serious adverse events were reported in 255 patients (7.2%) in the spironolactone group and 241 (6.8%) in the placebo group. CONCLUSIONS: Among patients with myocardial infarction, spironolactone did not reduce the incidence of death from cardiovascular causes or new or worsening heart failure or the incidence of a composite of death from cardiovascular causes, myocardial infarction, stroke, or new or worsening heart failure. (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).

• MeSH
• antagonisté mineralokortikoidních receptorů * terapeutické užití   škodlivé účinky   MeSH
• cévní mozková příhoda epidemiologie   prevence a kontrola   MeSH
• dvojitá slepá metoda MeSH
• infarkt myokardu * farmakoterapie   mortalita   terapie   komplikace   MeSH
• Kaplanův-Meierův odhad MeSH
• kardiovaskulární nemoci mortalita   prevence a kontrola   MeSH
• kolchicin terapeutické užití   škodlivé účinky   MeSH
• koronární angioplastika MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• spironolakton * terapeutické užití   škodlivé účinky   MeSH
• srdeční selhání prevence a kontrola   etiologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté mineralokortikoidních receptorů * MeSH
• kolchicin MeSH
• spironolakton * MeSH

BACKGROUND: Atherosclerotic cardiovascular diseases (ACVDs), a condition characterised by lipid accumulation in arterial walls, which is often exacerbated by chronic inflammation disorders, is the major cause of mortality and morbidity worldwide. Colchicine, with its first medicinal use in ancient Egypt, is an inexpensive drug with anti-inflammatory properties. However, its role in primary prevention of ACVDs in the general population remains unknown. OBJECTIVES: To assess the clinical benefits and harms of colchicine as primary prevention of cardiovascular outcomes in the general population. SEARCH METHODS: We searched the Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, Web of Science, and LILACS. We searched ClinicalTrials.gov and WHO ICTRP for ongoing and unpublished studies. We also scanned the reference lists of relevant included studies, reviews, meta-analyses, and health technology reports to identify additional studies. There were no limitations on language, date of publication, or study setting. The search results were updated on 31 May 2023. SELECTION CRITERIA: Randomised controlled trials (RCTs) in any setting, recruiting adults without pre-existing cardiovascular disease. We included trials that compared colchicine versus placebo, non-steroidal anti-inflammatory drugs, corticosteroids, immunomodulating drugs, or usual care. Our primary outcomes were all-cause mortality, non-fatal myocardial infarction, stroke, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors independently selected studies, extracted data, and performed risk of bias and GRADE assessments. MAIN RESULTS: We identified 15 RCTs (1721 participants randomised; 1412 participants analysed) with follow-up periods ranging from 4 to 728 weeks. The intervention was oral colchicine compared with placebo, immunomodulating drugs, or usual care or no treatment. Due to biases and imprecision, the evidence was very uncertain for all outcomes. All trials but one had a high risk of bias. Five out of seven meta-analyses included fewer than six trials (71.4%). The objectives of the review were to assess cardiovascular outcomes in the general population, but many of the included trials focused on liver disease. Colchicine compared to placebo Colchicine may reduce all-cause mortality compared to placebo in primary prevention, but the evidence is very uncertain (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.51 to 0.91; 6 studies, 463 participants; very low-certainty evidence; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 6 to 67). Colchicine may result in little to no difference in non-fatal myocardial infarction, but the evidence is very uncertain (RR 0.87, 95% CI 0.41 to 1.82; 1 study, 100 participants; very low-certainty evidence). Colchicine may not reduce the incidence of stroke, but the evidence is very uncertain (RR 2.43, 95% CI 0.67 to 8.86; 1 study, 100 participants; very low-certainty evidence). Regarding adverse events, colchicine may increase the incidence of diarrhoea (RR 3.99, 95% CI 1.44 to 11.06; 8 studies, 605 participants; very low-certainty evidence; number needed to treat for an additional harmful outcome (NNTH) 10, 95% CI 6 to 17), and may have little to no effect on neurological outcomes such as seizure or mental confusion (RR 0.72, 95% CI 0.31 to 1.66; 2 studies, 155 participants; very low-certainty evidence), but the evidence is very uncertain. The effect of colchicine on cardiovascular mortality is also very uncertain (RR 1.27, 95% CI 0.03 to 62.43; 2 studies, 160 participants; very low-certainty evidence). Colchicine may not reduce post-cardiac procedure atrial fibrillation, but the evidence is very uncertain (RR 0.74, 95% CI 0.25 to 2.19; 1 study, 100 participants). We found no trials reporting on pericardial effusion, peripheral artery disease, heart failure, or unstable angina. Colchicine compared to methotrexate (immunomodulating drug) Colchicine may result in little to no difference in all-cause mortality compared to methotrexate, but the evidence is very uncertain (RR 0.42, 95% CI 0.12 to 1.51; 1 study, 85 participants; very low-certainty evidence). We found no trials reporting other cardiovascular outcomes or adverse events for this comparison. Colchicine compared to usual care or no treatment The evidence is very uncertain about the effect of colchicine compared with usual care on all-cause mortality in primary prevention (RR 1.07, 95% CI 0.90 to 1.27; 2 studies, 729 participants; very low-certainty evidence). Regarding adverse events, colchicine may increase the incidence of diarrhoea compared to usual care, but the evidence is very uncertain (RR 3.32, 95% CI 1.56 to 7.03; 2 studies, 729 participants; very low-certainty evidence; NNTH 18, 95% CI 12 to 42). No trials reported other cardiovascular outcomes for this comparison. AUTHORS' CONCLUSIONS: This Cochrane review evaluated the clinical benefits and harms of using colchicine for the primary prevention of cardiovascular events in the general population. Comparisons were made against placebo, immunomodulating medications, or usual care or no treatment. However, the certainty of the evidence for the predefined outcomes was very low, highlighting the pressing need for high-quality, rigorous studies to ascertain colchicine's clinical impact definitively. We identified numerous biases and inaccuracies in the included studies, limiting their generalisability and precluding a conclusive determination of colchicine's efficacy in preventing cardiovascular events. The existing evidence regarding colchicine's potential cardiovascular benefits or harms for primary prevention is inconclusive owing to the limitations inherent in the current studies. More robust clinical trials are needed to bridge this evidence gap effectively.

• MeSH
• antiflogistika nesteroidní terapeutické užití   škodlivé účinky   MeSH
• antiflogistika terapeutické užití   škodlivé účinky   MeSH
• cévní mozková příhoda prevence a kontrola   mortalita   MeSH
• infarkt myokardu * prevence a kontrola   mortalita   epidemiologie   MeSH
• kardiovaskulární nemoci * prevence a kontrola   mortalita   MeSH
• kolchicin * terapeutické užití   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• příčina smrti MeSH
• primární prevence * metody   MeSH
• randomizované kontrolované studie jako téma * MeSH
• zkreslení výsledků (epidemiologie) MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• antiflogistika MeSH
• kolchicin * MeSH

Prognostic significance of the timing in the cardiac cycle of the first (TP1) and second (TP2) systolic peak of the central aortic pulse wave is ill-defined. Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of adverse health outcomes associated with TP1 and TP2, estimated by the SphygmoCor software, were assessed in the International Database of Central Arterial Properties for Risk Stratification (IDCARS) (n = 5529). Model refinement was assessed by the integrated discrimination (ID) and net reclassification (NR) improvement. Over 4.1 years (median), 201 participants died and 248 and 159 patients experienced cardiovascular or cardiac endpoints. Mean TP1 and TP2, standardized for cohort, sex, age, and heart rate, were 103 and 228 ms. Shorter TP1 and TP2 were associated with higher mortality and shorter TP1 with a higher risk of cardiovascular and cardiac endpoints (trend p ≤ 0.004). The HRs relating total mortality and cardiovascular endpoints to TP2 were 0.82 (95% confidence interval [CI]: 0.72-0.94) and 0.87 (0.77-0.98), respectively. The HR relating cardiac endpoints to TP1 was 0.81 (0.68-0.97). For total mortality and cardiovascular endpoints in relation to TP2, NRI was significant (p ≤ 0.010), but not for cardiac endpoints in relation to TP1. Integrated discrimination improvement (IDI) was not significant for any endpoint. The HRs relating total mortality to TP2 were smaller (p ≤ 0.026) in women than men (0.67 vs. 0.95) and in older (≥ 60 years) versus younger (< 60 years) participants (0.80 vs. 0.88). Our study adds to the evidence supporting risk stratification based on aortic pulse analysis by showing that TP2 and TP1 carry prognostic information.

• Klíčová slova
• cardiovascular risk, mortality, population science, pulse wave transit time, waveform analysis,
• MeSH
• analýza pulzové vlny * metody   MeSH
• aorta patofyziologie   MeSH
• hodnocení rizik metody   statistika a číselné údaje   MeSH
• hypertenze epidemiologie   mortalita   patofyziologie   MeSH
• kardiovaskulární nemoci * mortalita   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdeční frekvence fyziologie   MeSH
• systola fyziologie   MeSH
• tuhost cévní stěny fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

STUDY OBJECTIVES: Sleep-disordered breathing and diabetes mellitus (DM) are often concomitant; however, data on the impact of sleep-disordered breathing on mortality in the population with diabetes remain scarce. METHODS: The population from the Sleep Heart Health Study, a multicenter prospective observational study representing 5,780 patients with polysomnography and mortality data, including 453 patients with DM, was analyzed to assess the impact of sleep-disordered breathing variables and the presence of DM on all-cause, cardiovascular disease, and noncardiovascular disease associated mortality. Survival analysis and proportional hazard regression models were used to calculate the adjusted hazard ratios (aHRs) for mortality. RESULTS: Patients with DM and the average oxygen saturation > 91.4% had significantly lower all-cause (aHR 0.52, confidence interval [CI] 0.34-0.80) and cardiovascular disease mortality risk (aHR 0.44, CI 0.22-0.87) as compared with patients with oxygen saturation below this value. Apnea-hypopnea index > 31 (aHR 1.58, CI 1.10-2.28) and oxygen desaturation index > 13.3 (aHR 1.58, CI 1.10-2.25) were associated with increased all-cause mortality in participants with DM on treatment. Sleep efficiency and proportion of rapid eye movement sleep did not have any impact on mortality in patients with DM and thus differed significantly from individuals without DM, where increased all-cause mortality was observed in those with sleep efficiency < 81.4% (aHR 0.77, CI 0.68-0.87) or rapid eye movement sleep < 14.9% (aHR 0.78, CI 0.68-0.89). CONCLUSIONS: Patients with diabetes on treatment and moderate to severe sleep-disordered breathing experience increased all-cause mortality. Reduced average oxygen saturation predicted both all-cause and cardiovascular death in the population with diabetes. CITATION: Vichova T, Petras M, Waldauf P, Westlake K, Vimmerova-Lattova Z, Polak J. Sleep-disordered breathing increases mortality in patients with diabetes. J Clin Sleep Med. 2025;21(1):89-99.

• Klíčová slova
• cardiovascular disease, diabetes mellitus, mortality, oxygen saturation, sleep-disordered breathing,
• MeSH
• diabetes mellitus * mortalita   epidemiologie   MeSH
• kardiovaskulární nemoci mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polysomnografie * statistika a číselné údaje   MeSH
• prospektivní studie MeSH
• senioři MeSH
• syndromy spánkové apnoe * mortalita   komplikace   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

BACKGROUND: This study investigates the association between frailty and mortality in Eastern European populations, which remains largely unexplored compared with Western Europe. The aim is to assess the risk of all-cause and cardiovascular mortality associated with varying levels of frailty. METHODS: A prospective multicentre cohort study was conducted, involving random population samples from the Czech Republic, Poland and Lithuania. The baseline survey (2002-2005) included 26 746 individuals aged 45-69 years, with an average follow-up of 13 years. Frailty was measured using a Comprehensive Geriatric Assessment (CGA)-based Frailty Index (FI), calculating the number of deficits in each domain. Cox proportional regression models and inverse probability weighting (IPW) were employed to account for risk factor differences among the frailty groups: robust, prefrail, mild, moderate and severe. RESULTS: The study included 14 287 people, among whom 891 were frail, with a total of 2402 deaths.Compared with non-frail persons, those with mild (IPW HR 2.06, 95% CI 1.60 to 2.66) and severe (IPW HR 2.71, 95% CI 1.45 to 5.07) frailty had more than twofold elevated risk of all-cause mortality. For cardiovascular mortality, the corresponding HRs were (IPW HR 3.05, 95% CI 2.14 to 4.35) and (IPW HR 3.88, 95% CI 1.95 to 7.74). Men exhibited a higher mortality risk at all frailty levels only in unweighted analysis. Country-specific differences were not significant. CONCLUSIONS: A CGA-based FI is an independent predictor of all-cause and cardiovascular mortality, with even mild frailty increasing the risk. Implementing frailty assessments can improve health risk prediction in older adults from Eastern Europe.

• Klíčová slova
• AGING, COHORT STUDIES, MORTALITY,
• MeSH
• geriatrické hodnocení * MeSH
• kardiovaskulární nemoci * mortalita   MeSH
• křehkost * mortalita   MeSH
• křehký senior * statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• příčina smrti MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Litva epidemiologie   MeSH
• Polsko epidemiologie   MeSH
• východní Evropa epidemiologie   MeSH

BACKGROUND: Subtle, prognostically important ECG features may not be apparent to physicians. In the course of supervised machine learning, thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology. We aimed to investigate whether neural network-derived ECG features could be used to predict future cardiovascular disease and mortality and have phenotypic and genotypic associations. METHODS: We extracted 5120 neural network-derived ECG features from an artificial intelligence-enabled ECG model trained for 6 simple diagnoses and applied unsupervised machine learning to identify 3 phenogroups. Using the identified phenogroups, we externally validated our findings in 5 diverse cohorts from the United States, Brazil, and the United Kingdom. Data were collected between 2000 and 2023. RESULTS: In total, 1 808 584 patients were included in this study. In the derivation cohort, the 3 phenogroups had significantly different mortality profiles. After adjusting for known covariates, phenogroup B had a 20% increase in long-term mortality compared with phenogroup A (hazard ratio, 1.20 [95% CI, 1.17-1.23]; P<0.0001; phenogroup A mortality, 2.2%; phenogroup B mortality, 6.1%). In univariate analyses, we found phenogroup B had a significantly greater risk of mortality in all cohorts (log-rank P<0.01 in all 5 cohorts). Phenome-wide association study showed phenogroup B had a higher rate of future atrial fibrillation (odds ratio, 2.89; P<0.00001), ventricular tachycardia (odds ratio, 2.00; P<0.00001), ischemic heart disease (odds ratio, 1.44; P<0.00001), and cardiomyopathy (odds ratio, 2.04; P<0.00001). A single-trait genome-wide association study yielded 4 loci. SCN10A, SCN5A, and CAV1 have roles in cardiac conduction and arrhythmia. ARHGAP24 does not have a clear cardiac role and may be a novel target. CONCLUSIONS: Neural network-derived ECG features can be used to predict all-cause mortality and future cardiovascular diseases. We have identified biologically plausible and novel phenotypic and genotypic associations that describe mechanisms for the increased risk identified.

• Klíčová slova
• cardiovascular diseases, electrocardiography, neural networks, computer, supervised machine learning, unsupervised machine learning,
• MeSH
• časové faktory MeSH
• elektrokardiografie * MeSH
• fenotyp * MeSH
• hodnocení rizik MeSH
• kardiovaskulární nemoci diagnóza   mortalita   genetika   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neuronové sítě * MeSH
• prediktivní hodnota testů * MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdeční frekvence MeSH
• strojové učení bez učitele MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Spojené státy americké epidemiologie   MeSH

OBJECTIVE: To examine the associations between characteristics of daily rainfall (intensity, duration, and frequency) and all cause, cardiovascular, and respiratory mortality. DESIGN: Two stage time series analysis. SETTING: 645 locations across 34 countries or regions. POPULATION: Daily mortality data, comprising a total of 109 954 744 all cause, 31 164 161 cardiovascular, and 11 817 278 respiratory deaths from 1980 to 2020. MAIN OUTCOME MEASURE: Association between daily mortality and rainfall events with return periods (the expected average time between occurrences of an extreme event of a certain magnitude) of one year, two years, and five years, with a 14 day lag period. A continuous relative intensity index was used to generate intensity-response curves to estimate mortality risks at a global scale. RESULTS: During the study period, a total of 50 913 rainfall events with a one year return period, 8362 events with a two year return period, and 3301 events with a five year return period were identified. A day of extreme rainfall with a five year return period was significantly associated with increased daily all cause, cardiovascular, and respiratory mortality, with cumulative relative risks across 0-14 lag days of 1.08 (95% confidence interval 1.05 to 1.11), 1.05 (1.02 to 1.08), and 1.29 (1.19 to 1.39), respectively. Rainfall events with a two year return period were associated with respiratory mortality only, whereas no significant associations were found for events with a one year return period. Non-linear analysis revealed protective effects (relative risk <1) with moderate-heavy rainfall events, shifting to adverse effects (relative risk >1) with extreme intensities. Additionally, mortality risks from extreme rainfall events appeared to be modified by climate type, baseline variability in rainfall, and vegetation coverage, whereas the moderating effects of population density and income level were not significant. Locations with lower variability of baseline rainfall or scarce vegetation coverage showed higher risks. CONCLUSION: Daily rainfall intensity is associated with varying health effects, with extreme events linked to an increasing relative risk for all cause, cardiovascular, and respiratory mortality. The observed associations varied with local climate and urban infrastructure.

• MeSH
• časové faktory MeSH
• celosvětové zdraví statistika a číselné údaje   MeSH
• déšť * MeSH
• kardiovaskulární nemoci * mortalita   MeSH
• lidé MeSH
• mortalita trendy   MeSH
• nemoci dýchací soustavy * mortalita   MeSH
• příčina smrti trendy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Ambient air pollution, including particulate matter (such as PM10 and PM2·5) and nitrogen dioxide (NO2), has been linked to increases in mortality. Whether populations' vulnerability to these pollutants has changed over time is unclear, and studies on this topic do not include multicountry analysis. We evaluated whether changes in exposure to air pollutants were associated with changes in mortality effect estimates over time. METHODS: We extracted cause-specific mortality and air pollution data collected between 1995 and 2016 from the Multi-Country Multi-City (MCC) Collaborative Research Network database. We applied a two-stage approach to analyse the short-term effects of NO2, PM10, and PM2·5 on cause-specific mortality using city-specific time series regression analyses and multilevel random-effects meta-analysis. We assessed changes over time using a longitudinal meta-regression with time as a linear fixed term and explored potential sources of heterogeneity and two-pollutant models. FINDINGS: Over 21·6 million cardiovascular and 7·7 million respiratory deaths in 380 cities across 24 countries over the study period were included in the analysis. All three air pollutants showed decreasing concentrations over time. The pooled results suggested no significant temporal change in the effect estimates per unit exposure of PM10, PM2·5, or NO2 and mortality. However, the risk of cardiovascular mortality increased from 0·37% (95% CI -0·05 to 0·80) in 1998 to 0·85% (0·55 to 1·16) in 2012 with a 10 μg/m3 increase in PM2·5. Two-pollutant models generally showed similar results to single-pollutant models for PM fractions and indicated temporal differences for NO2. INTERPRETATION: Although air pollution levels decreased during the study period, the effect sizes per unit increase in air pollution concentration have not changed. This observation might be due to the composition, toxicity, and sources of air pollution, as well as other factors, such as socioeconomic determinants or changes in population distribution and susceptibility. FUNDING: None.

• MeSH
• kardiovaskulární nemoci * mortalita   MeSH
• látky znečišťující vzduch * škodlivé účinky   analýza   MeSH
• lidé MeSH
• nemoci dýchací soustavy * mortalita   chemicky indukované   MeSH
• oxid dusičitý * analýza   škodlivé účinky   MeSH
• pevné částice * analýza   škodlivé účinky   MeSH
• velkoměsta * MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• znečištění ovzduší * škodlivé účinky   analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• velkoměsta * MeSH
• Názvy látek
• látky znečišťující vzduch * MeSH
• oxid dusičitý * MeSH
• pevné částice * MeSH

BACKGROUND: Wildfire activity is an important source of tropospheric ozone (O3) pollution. However, no study to date has systematically examined the associations of wildfire-related O3 exposure with mortality globally. METHODS: We did a multicountry two-stage time series analysis. From the Multi-City Multi-Country (MCC) Collaborative Research Network, data on daily all-cause, cardiovascular, and respiratory deaths were obtained from 749 locations in 43 countries or areas, representing overlapping periods from Jan 1, 2000, to Dec 31, 2016. We estimated the daily concentration of wildfire-related O3 in study locations using a chemical transport model, and then calibrated and downscaled O3 estimates to a resolution of 0·25° × 0·25° (approximately 28 km2 at the equator). Using a random-effects meta-analysis, we examined the associations of short-term wildfire-related O3 exposure (lag period of 0-2 days) with daily mortality, first at the location level and then pooled at the country, regional, and global levels. Annual excess mortality fraction in each location attributable to wildfire-related O3 was calculated with pooled effect estimates and used to obtain excess mortality fractions at country, regional, and global levels. FINDINGS: Between 2000 and 2016, the highest maximum daily wildfire-related O3 concentrations (≥30 μg/m3) were observed in locations in South America, central America, and southeastern Asia, and the country of South Africa. Across all locations, an increase of 1 μg/m3 in the mean daily concentration of wildfire-related O3 during lag 0-2 days was associated with increases of 0·55% (95% CI 0·29 to 0·80) in daily all-cause mortality, 0·44% (-0·10 to 0·99) in daily cardiovascular mortality, and 0·82% (0·18 to 1·47) in daily respiratory mortality. The associations of daily mortality rates with wildfire-related O3 exposure showed substantial geographical heterogeneity at the country and regional levels. Across all locations, estimated annual excess mortality fractions of 0·58% (95% CI 0·31 to 0·85; 31 606 deaths [95% CI 17 038 to 46 027]) for all-cause mortality, 0·41% (-0·10 to 0·91; 5249 [-1244 to 11 620]) for cardiovascular mortality, and 0·86% (0·18 to 1·51; 4657 [999 to 8206]) for respiratory mortality were attributable to short-term exposure to wildfire-related O3. INTERPRETATION: In this study, we observed an increase in all-cause and respiratory mortality associated with short-term wildfire-related O3 exposure. Effective risk and smoke management strategies should be implemented to protect the public from the impacts of wildfires. FUNDING: Australian Research Council and the Australian National Health and Medical Research Council.

• MeSH
• celosvětové zdraví MeSH
• kardiovaskulární nemoci * mortalita   MeSH
• látky znečišťující vzduch * škodlivé účinky   analýza   MeSH
• lidé MeSH
• nemoci dýchací soustavy * mortalita   MeSH
• ozon * škodlivé účinky   analýza   MeSH
• požáry v divočině * MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• znečištění ovzduší škodlivé účinky   analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• látky znečišťující vzduch * MeSH
• ozon * MeSH