Peri-Alkylated Terrylenes and Ternaphthalenes Building-Blocks Towards Multi-Edge Nanographenes.

Since its first synthesis by Clar in 1948, terrylene - a fully connected ternaphthalene oligomer via naphthalene's peri-positions - has gained special focus within the rylene family, drawing interest for its unique chemical, structural, optoelectronic and single photon emission properties. In this study, we introduce a novel synthetic pathway that enhances the solubility of terrylene derivatives through complete peri-alkylation, while also facilitating extensions at the bay-positions. This approach not only broadens the scope of terrylene's chemical versatility but also opens new avenues for developing solution processable novel multi-edge nanographenes and tailoring electronic energy levels through topological edge structures. Our findings include a comprehensive structural and spectroscopic characterization along with transient absorption spectroscopy and photophysics of both the synthesized peri-alkylated terrylene and its phenylene-fused derivative.

Designing an ECG curriculum for residents: Evidence-based approaches to improving resident ECG interpretation skills.

Residents enter their training with variable comfort and competency in electrocardiogram (ECG) interpretation. Accurately interpreting an ECG is a fundamental skill in medicine and resident physicians would benefit from a longitudinal, dedicated ECG curriculum as part of their training to enhance interpretation skills and improve patient outcomes. Educators currently employ a wide array of methodologies to teach their trainees proper ECG interpretation skills, with no single modality established as the gold-standard for teaching this crucial skill. We present evidence-based guidance on how educators may develop and implement an effective ECG interpretation curriculum as part of residency training.

Implementation of a longitudinal, near-peer ECG didactic curriculum in an internal medicine residency program and impact on ECG interpretation skills.

BACKGROUND: To determine the impact of a longitudinal, near-peer, dedicated ECG didactic curriculum on internal medicine resident ability to accurately interpret ECGs. METHODS: This study employs a prospective cohort design. Internal medicine residents at University at Buffalo participated in monthly ECG didactic sessions over a 7-month period. Residents were invited to complete pre- and post-curriculum questionnaires. Responses were anonymous and participation voluntary. Data collected included basic demographics, career interest, exposure to clinical cardiology, and number of sessions attended. Residents were asked to interpret sixteen unique ECGs, divided evenly among eight common rhythms into both questionnaires. Pre- and post-curriculum cohorts were compared using t-tests and chi-square analyses. Associations between attendance, comfort level in interpretation, and number of correct interpretations were analyzed using Pearson correlations. Multivariate linear regression determined the strongest predictor of the number of correct ECG interpretations. RESULTS: The post-curriculum cohort correctly interpreted a significantly greater percentage of ECGs compared to pre-curriculum cohort (74.5% vs. 60.9%, p < .001). Didactic attendance was significantly associated with comfort level in interpreting ECGs (r = .328, p = .018) and trended towards an increased number of correct interpretations (r = .248, p = .077). Residents who attended three or more sessions demonstrated increased ECG interpretation skills compared to those who attended two or fewer sessions (80.0% vs. 71.1%, p = .048). Number of clinical cardiology rotations attended was significantly associated with correct interpretations (r = .310, p < .001) and was the strongest predictor of accurately interpreting ECGs (ß = 0.29, p = .037). CONCLUSIONS: Participation in a longitudinal, near-peer ECG didactic curriculum improved resident ability to interpret ECGs. A curriculum which contains both didactic sessions and clinical exposure may offer the greatest benefit in improving ECG interpretation skills.

Characterizing cutaneous leishmaniasis in a conflict-affected region: a study from North Waziristan, Pakistan.

Background/aim: Cutaneous leishmaniasis is an emerging tropical disease that remains a serious public health issue in Pakistan, particularly in North Waziristan. The current research was carried out to investigate the presence of cutaneous leishmaniasis in this region. Materials and methods: This prospective observational study was conducted from October 2018 to December 2020 at District Head Quarter Hospital Miranshah in North Waziristan with the collaboration of the Pathology Department of Gomal Medical College Dera Ismail Khan, Khyber Pakhtunkhwa. Needle aspirates were used for the microscopic Giemsa-stained slides. SPSS was used for data analysis. Results: Of the 5406 clinically-suspected cases, 2603(48.2%) were positive by microscopic examination. Of these 2603 patients, 1474 (57%) were male and 1129 (43%) were female. Most of the lesions were on the face, followed by upper and lower limbs. The 5-10-year age group had the highest percentage of 1167 (45%). A single lesion affected 96.6% of the patients, while 2.7% had double lesions and 0.7% had triple lesions. A high number of cutaneous leishmaniasis were seen from April to August, while the lowest number was seen November to December. Conclusion: This study provides extensive information in relation to the existence of cutaneous leishmaniasis in the North Waziristan district of Pakistan, as well as the detailed demographic features of those affected by the disease.

Outcomes in congenital and childhood complete atrioventricular block: A meta-analysis.

BACKGROUND: The long-term outcomes of patients with congenital and childhood complete atrioventricular block (CCAVB/CAVB) after pacemaker implantation are unclear. METHODS: We performed a meta-analysis of all the studies of CCAVB. A systematic search of PubMed and CENTRAL databases from January 1, 1967 to January 31, 2020 was performed. The quality of studies included was critically appraised using the Newcastle-Ottawa scale, and outcome data were analyzed using the restricted maximum likelihood function. RESULTS: Twenty-nine studies were eligible for analysis, with a total of 1553 patients. The all-cause-mortality was 5.7% (95% confidence interval [CI]: 2.5%-9.9%), while pacing-induced cardiomyopathy (PICM) was seen in 3.8% (95% CI: 1.2-7.2). Diagnosis at birth (effect size [ES] [95%CI]: -2.23 [-0.36 to -0.10]; p < .001), presence of congenital heart disease (ES [95%CI]: -0.67 [0.41-0.93]; p < .001), younger age at pacemaker implantation (ES [95%CI]: -0.01 [-0.02 to -0.001]; p = .02), and duration of pacing (ES [95%CI]: -0.03 [-0.05 to -0.003]; p = .03), were associated with an higher mortality on binominal logistic regression. None of the parameters were significant on multivariate analysis. CONCLUSION: Pooled proportional mortality in patients with CCAVB and CAVB is 5.7% with an infrequent incidence of PICM (3.8%) in the paced patients with AVB suggesting that pacing in these patients is an effective management strategy with a low incidence of long-term side effects. Registry and randomized data can throw additional light regarding the natural history and appropriate management strategy in these patients.

Impact of intracardiac echocardiography on readmission morbidity and mortality following atrial fibrillation ablation.

INTRODUCTION: The use of intracardiac echocardiography (ICE) is beneficial during the ablation of atrial fibrillation (AF). Evidence is conflicting regarding the clinical impact of using ICE on arrhythmia recurrence and mortality. METHODS: Patients undergoing catheter ablation of AF during 2010-2017 were identified using the International Classification of Diseases-9th and 10th Revision-Clinical Modification (ICD-9-CM and ICD-10-CM) from the Nationwide Readmissions Database. Propensity matching was used to generate a control group. Patient demographics, Charlson comorbidity indexes, time from discharge to readmission, and the reason of readmission were extracted. RESULTS: From 2010 to 2017, 51 129 patients were included in the analysis out of which ICE was used in 8005 (15.7%) patients. The in-hospital mortality at readmission was significantly higher in the patients without ICE use (2.9% vs. 1.7%, p = .02). The length of stay (LOS) at readmission was significantly higher in non-ICE arm (median [interquartile range, IQR]: 3 [2-6] vs. 2 [3-5] days, p < .0001) with similar healthcare-associated cost (HAC) in both the groups (median [IQR]: US$7507.3 [4057.8-15 474.2] vs. 7339.4 [4024.8-15 191.6], p = .43). Freedom from readmission was 12% higher (hazard ratio [HR] [95% confidence interval, CI]: 0.88 [0.83-0.94], p < .0001) with the use of ICE at 90-day follow-up, which was driven by 24% reduction in heart failure (HF) at follow-up (HR [95% CI]: 0.76 [0.60-0.96], p = .02). CONCLUSIONS: ICE use during AF ablation procedure reduces readmissions at 90 days by 12%, driven by a 24% decrease in HF-related admissions. The non-ICE arm showed a significantly higher LOS which offsets marginally higher HAC in the ICE arm.

Handgrip strength-A risk indicator for type 2 diabetes: Systematic review and meta-analysis of observational cohort studies.

AIMS: Evolving debate suggests that handgrip strength (HGS), a measure of muscular strength, might be associated with the risk of type 2 diabetes (T2D); however, the evidence is conflicting. Using a systematic review and meta-analysis of published observational cohort studies in general populations, we aimed to assess the association of HGS with the future risk of T2D. METHODS: Relevant studies were sought from inception until April 2020 in MEDLINE, Embase, Web of Science, and manual search of relevant articles. Transformed or extracted relative risks (RRs) with 95% confidence intervals (CIs) comparing the top vs bottom thirds of HGS levels were pooled using random effects meta-analysis. RESULTS: A total of 10 unique observational cohort studies comprising of 177 826 participants and >5167 T2D cases were eligible. The pooled multivariable RR (95% CI) for T2D comparing the top vs bottom thirds of HGS levels was 0.73 (0.63-0.84). This association was consistent across several relevant subgroups except for evidence of effect modification by sample size (P value for meta-regression <.001): evidence of an association in smaller studies (<250 events) 0.50 (0.40-0.63), with no significant association in bigger studies (≥250 events) 0.87 (0.73-1.05). There was no evidence of small study effects using formal tests such as funnel plots and Egger's regression symmetry test. CONCLUSION: Pooled analysis of observational cohort studies suggests that HGS may be a risk indicator for T2D in the general population. The role of utilizing HGS measurements in T2D prevention strategies warrants further investigation.

Percentage of Age-Predicted Cardiorespiratory Fitness Is Inversely Associated with Cardiovascular Disease Mortality: A Prospective Cohort Study.

INTRODUCTION: Percentage of age-predicted cardiorespiratory fitness (% age-predicted CRF) is a potentially useful cardiopulmonary exercise testing (CPX) parameter, but there are limited data on its prognostic relevance for adverse cardiovascular disease (CVD) outcomes. We aimed to assess the association of % age-predicted CRF with CVD mortality and the extent to which % age-predicted CRF measurements could improve the prediction of CVD mortality. METHODS: Peak oxygen uptake, used as the measure of CRF, was directly assessed in 2,276 men who underwent CPX. The age-predicted CRF estimated from a regression equation for age was transformed to % age-predicted CRF with the following formula: (achieved CRF/age-predicted CRF) × 100. Hazard ratios (HRs) (95% confidence intervals [CIs]) and measures of risk discrimination for CVD mortality were calculated. RESULTS: During a median follow-up of 28.5 years, 643 fatal CVDs were recorded. The relationship between % age-predicted CRF and CVD mortality was dose response in nature. In analysis adjusted for conventional risk factors, one standard deviation increase in % age-predicted CRF was associated with a reduced risk of CVD mortality (HR 0.61; 95% CI: 0.56-0.67), which was minimally attenuated on further adjustment for several other confounders (HR 0.71; 95% CI: 0.64-0.78). Addition of % age-predicted CRF to a CVD mortality risk prediction model containing established risk factors significantly improved risk discrimination and reclassification. CONCLUSION: Percentage of age-predicted CRF is inversely and independently associated with CVD mortality in a graded fashion and significantly improves the prediction and classification of the long-term risk for CVD mortality beyond established risk factors.

Radiologically defined acute hydrocephalus in aneurysmal subarachnoid haemorrhage.

BACKGROUND: Ventriculomegaly is common in aneurysmal subarachnoid haemorrhage (aSAH). An imaging measure to predict the need for cerebrospinal fluid (CSF) diversion may be useful. The bicaudate index (BCI) has been previously applied to aSAH. Our aim was to derive and test a threshold BCI above which CSF diversion may be required. METHODS: Review of prospective registry. The derivation group (2009-2015) included WFNS grade 1-2 aSAH patients who deteriorated clinically, had a repeat CT brain and underwent CSF diversion. BCI was measured on post-deterioration CTs and the lower limit of the 95% confidence interval (95%CI) was the hydrocephalus threshold. In a separate test group (2016), in WFNS ≥ 2 patients, we compared BCI on diagnostic CTs with CSF diversion within 24 hours. RESULTS: The derivation group (n = 62) received an external ventricular (n = 57, 92%) or lumbar drain (n = 5, 8%). Mean post-deterioration BCI was 0.19 (95%CI 0.17-0.22) for age ≤49 years, 0.22 (95%CI 0.20-0.23) for age 50-64 years and 0.24 (95%CI 0.22-0.27) for age ≥65 years. Hydrocephalus thresholds were therefore 0.17, 0.20 and 0.22, respectively. In the test group (n = 105), there was no significant difference in BCI on the diagnostic CT between good and poor grade patients aged ≤49 years (p = 0.31) and ≥65 years (p = 0.96). 30/66 WFNS ≥ 2 patients underwent CSF diversion, although only 15/30 (50%) exceeded BCI thresholds for hydrocephalus. CONCLUSION: A significant proportion of aSAH patients may undergo CSF diversion without objective evidence of hydrocephalus. Our threshold values require further testing but may provide an objective measure to aid clinical decision making in aSAH.

Haematological outcomes in progression of malaria: A cohort study from district Dera Ismail Khan, Pakistan.

Malaria is the second highest reported disease from public health sector which affects about 4 million people each year in Pakistan. The study sought to evaluate the haematological changes in malarial patients in order to find any relation of these changes with malarial pathogenesis. This cross sectional descriptive study was designed at the pathology department of Gomal Medical College, Dera Ismail Khan during March 2015 to February 2017. Blood samples were collected from 400 malaria microscopy positive in EDTA tubes for the analysis of haematological parameters like Total leucocyte count, Haemoglobin, Platelets, Mean Cell Volume, Mean Cell Haemoglobin and Mean Cell Haemoglobin Concentration. Out of the 400 cases of malaria, 366 (91.5%) were Plasmodium vivax, 24 (6.0%) were Plasmodium falciparum and 10 (2.5%) were co-infection of Plasmodium vivax and Plasmodium falciparum infection. Anaemia was seen in 148 (37%) of cases; thrombocytopenia was 316(79%) and 60 (15%) cases had leucopenia. This study shows that malarial patients exhibited important changes in haematological parameters like thrombocytopenia; anaemia and leucopenia are significant predictors of malaria infection. When used in combination with other clinical and microscopy methods, these parameters could improve the diagnosis and treatment of malaria.

Heart Failure Epidemiology in Patients With Diabetes Mellitus Without Coronary Heart Disease.

BACKGROUND: Epidemiology of patients with comorbid heart failure (HF) and diabetes mellitus (DM) without coronary heart disease (CHD) is not well described. METHODS AND RESULTS: We assessed HF incidence and outcomes in 2896 participants of the Health ABC Study (age 74.0 ± 3.0 years, 48.4% men, 41.1% black, 34.6% with DM) in relation to prio DM and CHD status. During a median follow-up of 11.4 years, 484 participants (16.7%) developed incident HF; 214 (44.2%) had DM of whom 71 (33.1%) had no prio CHD. Incident HF rate was 2.5% per 100 person-years in those with and 1.5% in those without DM (hazard ratio [HR] 1.66, 95% CI 1.39-1.99). In those with DM, incident HF rate was 4.6% in those with and 1.3% in those without CHD (HR 3.75, 95% CI 2.81-4.99). During a median follow-up of 2.1 years after HF onset, 329 (68.0%) of the participants died. Amongst those with DM, annual mortality was 22.6% in those with versus 25.9% without CHD (HR 0.86, 95% CI 0.61-1.22). All-cause hospitalizations after incident HF in DM patients were 55.0 per 100 person-years in those with and 33.3 in those without CHD (rate ratio [RR] 1.64, 95% CI 1.24-2.16); HF hospitalizations were 42.7 and 30.7 per 100-person years (RR 1.39, 95% CI 1.03-1.86) in those with and without CHD. Reduced ejection fraction was seen in 49.6% of HF patients with DM and CHD and in 34.7% of those without CHD (P = .08); mortality but not hospitalization risk tended to be lower in those with reduced compared with preserved ejection fraction regardless of CHD status. CONCLUSIONS: A sizeable proportion of HF in patients with DM develops in the absence of prior CHD; these patients are at risk for mortality similar to those with CHD. These data underscore the importance of modulating risk beyond atherosclerosis in patients with comorbid HF and DM.

Sauna bathing reduces the risk of venous thromboembolism: a prospective cohort study.

Emerging evidence suggests there is an inverse and independent association between sauna bathing and arterial thrombotic disease. However, the potential association between sauna bathing and venous thromboembolism (VTE) has not yet been investigated. We aimed to assess the prospective association between frequency of sauna bathing and the risk of VTE. Baseline sauna bathing habits were assessed in 2242 men aged 42-61 years without a history of VTE in the Kuopio Ischemic Heart Disease prospective cohort. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE. During a median follow-up of 24.9 years, 146 (6.5%) incident VTE events were recorded. In age-adjusted analyses, the HRs 95% (CIs) of VTE were 0.67 (0.47-0.96) and 0.95 (0.53-1.70) for participants who had 2-3 and ≥ 4 sauna sessions per week respectively compared with participants who had ≤ 1 sauna session per week. After further adjustment for several established risk factors including lifestyle factors, the corresponding HRs (95% CIs) were 0.67 (0.46-0.96) and 0.92 (0.51-1.68) respectively. Having sauna baths was associated with a reduced risk of VTE in a middle-aged male Caucasian population. Further studies in other populations and age groups are required to confirm these findings.

Application of Laplace-Adomian Decomposition Method for the Analytical Solution of Third-Order Dispersive Fractional Partial Differential Equations.

In the present article, we related the analytical solution of the fractional-order dispersive partial differential equations, using the Laplace-Adomian decomposition method. The Caputo operator is used to define the derivative of fractional-order. Laplace-Adomian decomposition method solutions for both fractional and integer orders are obtained in series form, showing higher convergence of the proposed method. Illustrative examples are considered to confirm the validity of the present method. The fractional order solutions that are convergent to integer order solutions are also investigated.

Analytical Solutions of Fractional-Order Diffusion Equations by Natural Transform Decomposition Method.

In the present article, fractional-order diffusion equations are solved using the Natural transform decomposition method. The series form solutions are obtained for fractional-order diffusion equations using the proposed method. Some numerical examples are presented to understand the procedure of the Natural transform decomposition method. The Natural transform decomposition method has shown the least volume of calculations and a high rate of convergence compared to other analytical techniques, the proposed method can also be easily applied to other non-linear problems. Therefore, the Natural transform decomposition method is considered to be one of the best analytical technique, to solve fractional-order linear and non-linear partial deferential equations, particularly fractional-order diffusion equation.

Analytical Solutions of Fractional-Order Heat and Wave Equations by the Natural Transform Decomposition Method.

In the present article, fractional-order heat and wave equations are solved by using the natural transform decomposition method. The series form solutions are obtained for fractional-order heat and wave equations, using the proposed method. Some numerical examples are presented to understand the procedure of natural transform decomposition method. The natural transform decomposition method procedure has shown that less volume of calculations and a high rate of convergence can be easily applied to other nonlinear problems. Therefore, the natural transform decomposition method is considered to be one of the best analytical techniques, in order to solve fractional-order linear and nonlinear Partial deferential equations, particularly fractional-order heat and wave equation.

Sauna bathing is associated with reduced cardiovascular mortality and improves risk prediction in men and women: a prospective cohort study.

BACKGROUND: Previous evidence indicates that sauna bathing is related to a reduced risk of fatal cardiovascular disease (CVD) events in men. The aim of this study was to investigate the relationship between sauna habits and CVD mortality in men and women, and whether adding information on sauna habits to conventional cardiovascular risk factors is associated with improvement in prediction of CVD mortality risk. METHODS: Sauna bathing habits were assessed at baseline in a sample of 1688 participants (mean age 63; range 53-74 years), of whom 51.4% were women. Multivariable-adjusted hazard ratios (HRs) were calculated to investigate the relationships of frequency and duration of sauna use with CVD mortality. RESULTS: A total of 181 fatal CVD events occurred during a median follow-up of 15.0 years (interquartile range, 14.1-15.9). The risk of CVD mortality decreased linearly with increasing sauna sessions per week with no threshold effect. In age- and sex-adjusted analysis, compared with participants who had one sauna bathing session per week, HRs (95% CIs) for CVD mortality were 0.71 (0.52 to 0.98) and 0.30 (0.14 to 0.64) for participants with two to three and four to seven sauna sessions per week, respectively. After adjustment for established CVD risk factors, potential confounders including physical activity, socioeconomic status, and incident coronary heart disease, the corresponding HRs (95% CIs) were 0.75 (0.52 to 1.08) and 0.23 (0.08 to 0.65), respectively. The duration of sauna use (minutes per week) was inversely associated with CVD mortality in a continuous manner. Addition of information on sauna bathing frequency to a CVD mortality risk prediction model containing established risk factors was associated with a C-index change (0.0091; P = 0.010), difference in - 2 log likelihood (P = 0.019), and categorical net reclassification improvement (4.14%; P = 0.004). CONCLUSIONS: Higher frequency and duration of sauna bathing are each strongly, inversely, and independently associated with fatal CVD events in middle-aged to elderly males and females. The frequency of sauna bathing improves the prediction of the long-term risk for CVD mortality.

Synthesis of Symmetric Bridged Bis-Pyrazolone Based Metal Complex Acid Dyes and their Applications on Leather.

Our present investigation aims at the synthesis and application of new, symmetric bridged bis-pyrazolone based acid dyes. The bis-pyrazolone compounds were accomplished from bis- hydrazine of 4,4'-Diaminostilbene-2,2'-disulfonic acid and ethyl acetoacetate. The bis-pyrazolones have been coupled with diazonium salts of o-hydroxyl aromatic amines which resulted in ligand dyes. The intermediate ligand dyes were treated with 3d transition metals to achieve the targeted metal complex acid dyes. The structures of investigated compounds were confirmed with the help of spectroscopic techniques. Dyes were applied on leather and their application parameters including their light fastness, wash fastness and rubbing fastness were determined. Graphical Abstract Symmetric brymmetric Bridged bis-Pyrazolone based Metal Complex Acid.

Short-term effects of Finnish sauna bathing on blood-based markers of cardiovascular function in non-naive sauna users.

Emerging evidence suggests that sauna bathing is associated with reduced risk of cardiovascular and all-cause mortality events. However, the biochemical pathways by which sauna bathing might confer its effects on cardiovascular function are not certain. We aimed to study the acute effects of Finnish sauna bathing on various blood-based cardiovascular biomarkers. The study included 102 non-naive sauna users (54% male) with mean age of 51.9 years, who had at least one cardiovascular risk factor. Participants underwent a 30-min single sauna session (mean temperature, 73 °C). Biochemical profiling was conducted before, immediately after sauna and 30-min post-sauna. Overall median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (n = 20 participants) was 46.0 ng/L before sauna exposure, which increased to 50.5 ng/l immediately after sauna (median change, + 12.00%; p < 0.001) and remained persistent at 30-min post-sauna (median change from pre-sauna to post-30-min sauna, + 13.93%; p < 0.001). The changes were more evident in males compared with females. There were no significant changes in overall levels of high sensitivity C-reactive protein, creatine kinase, high sensitivity troponin I, and creatine kinase-MBm. However, levels of creatine kinase increased in males (median change immediately after sauna, + 2.99%; p = 0.024). Levels of NT-proBNP increased after sauna exposure. The increase in levels of creatine kinase was more evident in males. Long-term interventional studies are warranted to evaluate if these biomarkers are involved in pathways underlying the associations of sauna bathing with cardiovascular outcomes.

Sensitive and Flexible Polymeric Strain Sensor for Accurate Human Motion Monitoring.

Flexible electronic devices offer the capability to integrate and adapt with human body. These devices are mountable on surfaces with various shapes, which allow us to attach them to clothes or directly onto the body. This paper suggests a facile fabrication strategy via electrospinning to develop a stretchable, and sensitive poly (vinylidene fluoride) nanofibrous strain sensor for human motion monitoring. A complete characterization on the single PVDF nano fiber has been performed. The charge generated by PVDF electrospun strain sensor changes was employed as a parameter to control the finger motion of the robotic arm. As a proof of concept, we developed a smart glove with five sensors integrated into it to detect the fingers motion and transfer it to a robotic hand. Our results shows that the proposed strain sensors are able to detect tiny motion of fingers and successfully run the robotic hand.

Cardiorespiratory fitness and nonfatalcardiovascular events: A population-based follow-up study.

BACKGROUND: To examine the prognostic value of cardiorespiratory fitness (CRF) with risk of first major nonfatal myocardial infarction (MI), stroke, and heart failure (HF) events. METHODS: Cardiorespiratory fitness, as measured by maximal oxygen uptake, was assessed at baseline in a prospective cohort of 2,089 men aged 42 to 61years. RESULTS: During a mean (SD) follow-up of 19.1(8.4) years, 522 nonfatal acute MI events, 198 acute all-cause nonfatal stroke events, and 221 nonfatal HF events were recorded. The hazard ratio per 1-metabolic-equivalent increase in CRF was 0.93 (95% CI 0.88-0.97) for nonfatal MI, 0.94 (95% CI0.87-1.01) for nonfatal stroke, and 0.84 (95% CI 0.78-0.91) for nonfatal HF events after adjustment for cardiovascular risk factors (age, systolic blood pressure, body mass index, history of cardiovascular disease, diabetes, smoking, alcohol use, serum creatinine, low-density lipoprotein levels, physical activity, and socioeconomic status). Further adjustment for left ventricular hypertrophy and resting heart rate did not attenuate these associations. Addition of CRF to conventional cardiovascular disease risk factors significantly improved both discrimination (C index) and category free net reclassification index (cf-NRI) for nonfatal MI (change in C index, 0.015 [95% CI 0.010-0.020] and change in cf-NRI 0.27, P<.01) and HF (change in C index 0.040 [95% CI 0.010-0.060] and change in cf-NRI 0.88, P<.01). CONCLUSION: In this Finnish population, there is a strong, inverse, and independent association between CRF and acute nonfatal MI and HF risk.