Search

Aims: The prediction of future trends in cardiovascular disease (CVD) mortality and their risk factors can assist policy-makers in healthcare planning. This study aims to project geospatial trends in CVDs and their underlying risk factors from 2025 to 2050., Methods and Results: Using historical data on mortality and disability-adjusted life years (DALYs) from the Global Burden of Disease (GBD) 2019 study, encompassing the period of 1990 to 2019, Poisson regression was performed to model mortality and DALYs associated with CVD and its associated risk factors from 2025 to 2050. Subgroup analysis was based on GBD super-regions. Between 2025 and 2050, a 90.0% increase in cardiovascular prevalence, 73.4% increase in crude mortality, and 54.7% increase in crude DALYs are projected, with an expected 35.6 million cardiovascular deaths in 2050 (from 20.5 million in 2025). However, age-standardized cardiovascular prevalence will be relatively constant (-3.6%), with decreasing age-standardized mortality (-30.5%) and age-standardized DALYs (-29.6%). In 2050, ischaemic heart disease will remain the leading cause of cardiovascular deaths (20 million deaths) while high systolic blood pressure will be the main cardiovascular risk factor driving mortality (18.9 million deaths). Central Europe, Eastern Europe, and Central Asia super-region is set to incur the highest age-standardized cardiovascular mortality rate in 2050 (305 deaths per 100 000 population)., Conclusion: In the coming decades, the relatively constant age-standardized prevalence of global CVD suggests that the net effect of summative preventative efforts will likely continue to be unchanged. The fall in age-standardized cardiovascular mortality reflects the improvement in medical care following diagnosis. However, future healthcare systems can expect a rapid rise in crude cardiovascular mortality, driven by the ageing global populace. The continued rise in CVD burden will largely be attributed to atherosclerotic diseases., Registration: Not applicable., Competing Interests: Conflict of interest: M.Y.C. receives speaker’s fees and research grants from Astra Zeneca, Abbott Technologies and Boston Scientific. M.Y.C receives salary support from a National Medical Research Council Clinician Scientist Award-Senior Category (MOH-000280-00). N.W.S.C. has received research grant support from NUHS Seed Fund, National University of Singapore Yong Loo Lin School of Medicine's Academic Fellowship Scheme, the NUHS Clinician Scientist Program, and National Medical Research Council Research Training Fellowship. J.L.J. is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Jana Care, Janssen, Novartis, Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. A.M.R. holds the New Zealand Heart Foundation Chair of cardiovascular Studies; and has received advisory board fees and/or grant support from Roche Diagnostics, Novo Nordisk, Abbott Laboratories, Thermo Fisher, Medtronic, Sphingotec, Novartis and Astra Zeneca. The remaining authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Conflict of interest: S.T. received research grants from Abbot Vascular Japan, Boston Scientific Japan, and Medtronic and received honoraria from Boston Scientific Japan. The author Shinya Goto discloses to receive personal from the Duke Clinical Research Institute as the member of the Steering Committee. Shinya Goto is an Associate Editor for Circulation and received quality fee from the American Heart Association. Shinichi Goto has nothing to disclose.

Measures of functional brain network segregation and integration vary with an individual's age, cognitive ability, and health status. Based on these relationships, these measures are frequently examined to study and quantify large-scale patterns of network organization in both basic and applied research settings. However, there is limited information on the stability and reliability of the network measures as applied to functional time-series; these measurement properties are critical to understand if the measures are to be used for individualized characterization of brain networks. We examine measurement reliability using several human datasets (Midnight Scan Club and Human Connectome Project [both Young Adult and Aging]). These datasets include participants with multiple scanning sessions, and collectively include individuals spanning a broad age range of the adult lifespan. The measurement and reliability of measures of resting-state network segregation and integration vary in relation to data quantity for a given participant's scan session; notably, both properties asymptote when estimated using adequate amounts of clean data. We demonstrate how this source of variability can systematically bias interpretation of differences and changes in brain network organization if appropriate safeguards are not included. These observations have important implications for cross-sectional, longitudinal, and interventional comparisons of functional brain network organization., (© The Author(s) 2024. Published by Oxford University Press.)

Aims: Artificial intelligence-driven small data platforms such as CURATE.AI hold potential for personalized hypertension care by assisting physicians in identifying personalized anti-hypertensive doses for titration. This trial aims to assess the feasibility of a larger randomized controlled trial (RCT), evaluating the efficacy of CURATE.AI-assisted dose titration intervention. We will also collect preliminary efficacy and safety data and explore stakeholder feedback in the early design process., Methods and Results: In this open-label, randomized, pilot feasibility trial, we aim to recruit 45 participants with primary hypertension. Participants will be randomized in 1:1:1 ratio into control (no intervention), home blood pressure monitoring (active control; HBPM), or CURATE.AI arms (intervention; HBPM and CURATE.AI-assisted dose titration). The home treatments include 1 month of two-drug anti-hypertensive regimens. Primary endpoints assess the logistical (e.g. dose adherence) and scientific (e.g. percentage of participants for which CURATE.AI profiles can be generated) feasibility, and define the progression criteria for the RCT in a 'traffic light system'. Secondary endpoints assess preliminary efficacy [e.g. mean change in office blood pressures (BPs)] and safety (e.g. hospitalization events) associated with each treatment protocol. Participants with both baseline and post-treatment BP measurements will form the intent-to-treat analysis. Following their involvement with the CURATE.AI intervention, feedback from CURATE.AI participants and healthcare providers will be collected via exit survey and interviews., Conclusion: Findings from this study will inform about potential refinements of the current treatment protocols before proceeding with a larger RCT, or potential expansion to collect additional information. Positive results may suggest the potential efficacy of CURATE.AI to improve BP control., Trial Registration Number: NCT05376683., Competing Interests: Conflict of interest: M.E. is an employee of Roche Diagnostics and a shareholder in F. Hoffmann-La Roche AG. A.T.L.T, S.-B.T., K.S.K., L.W.J.T., A.B., and D.H. are co-inventors of previously filed pending patents on AI-based therapy development. D.H. is a co-founder and shareholder of KYAN Therapeutics, which has licensed intellectual property pertaining to AI-based oncology drug development. All other authors have no conflict of interests to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Previous studies have shown that females with type 2 diabetes mellitus (T2DM) may have excess mortality risk compared to their male counterparts. An important next step to address the high global burden of T2DM and cardiovascular disease (CVD) is an umbrella review to summarize data on sex differences in cardiovascular outcomes for patients with T2DM and assess the strength of the evidence observed., Methods and Results: Medline and Embase were searched from inception till 7 August 2022 for systematic reviews and meta-analyses studying the effects of sex on cardiovascular outcomes in T2DM patients. Results from reviews were synthesized with a narrative synthesis, with a tabular presentation of findings and forest plots for reviews that performed a meta-analysis. 27 review articles evaluating sex differences in cardiovascular outcomes were included. Females with T2DM had a higher risk of developing coronary heart disease (CHD; RRR: 1.52, 95%CI: 1.32-1.76, P < 0.001), acute coronary syndrome (ACS; RRR: 1.38, 95%CI: 1.25-1.52, P < 0.001), heart failure (RRR: 1.09, 95%CI: 1.05-1.13, P < 0.001) than males. Females had a higher risk of all-cause mortality (RRR: 1.13, 95%CI: 1.07-1.19, P < 0.001), cardiac mortality (RRR: 1.49, 95%CI: 1.11-2.00, P = 0.009) and CHD mortality (RRR: 1.44, 95%CI: 1.20-1.73, P < 0.001) as compared to males., Conclusions: This umbrella review demonstrates that females with T2DM have a higher risk of cardiovascular outcomes than their male counterparts. Future research should address the basis of this heterogeneity and epidemiological factors for better quality of evidence, and identify actionable interventions that will narrow these sex disparities., Competing Interests: Conflicts of interest: Mark Y. Chan: Speaker’s fees and research grants Astra Zeneca, Abbott Technologies and Boston Scientific. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Randomized controlled trials (RCTs) of lipid-lowering therapy (LLT) in which the control groups received placebo without background LLT offer unique insights into the placebo and nocebo effects of lipid-lowering RCTs., Methods and Results: Embase and Medline were searched for hyperlipidaemia RCTs with placebo-controlled arms. Placebo arms with background LLT were excluded. A single arm meta-analysis of proportions was used to estimate major adverse cardiovascular events (MACE) and adverse events (AE). A meta-analysis of means was used to estimate the pooled mean differences of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoproteins (HDL) and triglycerides (TG).A total of 40 RCTs and 37 668 placebo-treated participants were included. The pooled mean changes for TC, LDL, HDL, and TG were -0.019 mmol/L, -0.028 mmol/L, 0.013 mmol/L, and 0.062 mmol/L respectively among placebo-treated participants, indicating a modest placebo effect. The pooled average nocebo effect among placebo-treated participants was 42.62% for all AEs and 3.38% for musculoskeletal-related AEs, 11.36% for gastrointestinal-related AEs, and 6.62% for headaches. Placebo-treated participants in secondary prevention RCTs had a far higher incidence of these nocebo effects than primary prevention RCTs: any AEs (OR 6.76, 95% CI: 5.56-8.24, P < 0.001), and gastrointestinal-related AE (OR 1.23, 95% CI: 1.00-1.51, P = 0.049). No differences in nocebo effects were found between the placebo arms of statin and non-statin trials., Conclusion: Our meta-analysis of placebo-treated participants in RCTs with no background LLT indicate a modest placebo effect but prominent nocebo effect of musculoskeletal, headache, and gastrointestinal symptoms that was greatest among secondary prevention RCTs. These findings may inform the design of future LLT RCTs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations., Methods and Results: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS., Conclusion: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Background: The global coronavirus disease 2019 pandemic has highlighted the importance of understanding the cardiovascular implications of coronavirus infections, with more severe disease in those with cardiovascular co-morbidities, and resulting cardiac manifestations such as myocardial injury, arrhythmias, and heart failure., Design: A systematic review of the current knowledge on the effects of coronavirus infection on the cardiovascular system in humans was performed and results were summarized., Methods: Databases such as MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science, ClinicalTrials.gov, Chinese Knowledge Resource Integrated Database and Chinese Clinical Trial Registry were searched on 20 March 2020., Results: In total, 135 studies were included, involving severe acute respiratory syndrome, Middle East respiratory syndrome, coronavirus disease 2019 and other coronaviruses. Most were case reports, case series and cohort studies of poor to fair quality. In post-mortem examinations of subjects who died from infection, around half had virus identified in heart tissues in severe acute respiratory syndrome, but none in Middle East respiratory syndrome and coronavirus disease 2019. Cardiac manifestations reported include tachycardia, bradycardia, arrhythmias, and myocardial injury, secondary to both systemic infection and treatment. Cardiac injury and arrhythmias are more prevalent in coronavirus disease 2019, and elevated cardiac markers are associated with intensive care unit admission and death. In severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019, comorbidities such as hypertension, diabetes mellitus, and heart disease are associated with intensive care unit admission, mechanical ventilation, and mortality. There were cases of misdiagnosis due to overlapping presentations of cardiovascular diseases and coronavirus infections, leading to hospital spread and delayed management of life-threatening conditions., Conclusion: This review highlighted the ways in which coronaviruses affect cardiovascular function and interacts with pre-existing cardiovascular diseases.

Adult aging is associated with differences in structure, function, and connectivity of brain areas. Age-based brain comparisons have typically rested on the assumption that brain areas exhibit a similar spatial organization across age; we evaluate this hypothesis directly. Area parcellation methods that identify locations where resting-state functional correlations (RSFC) exhibit abrupt transitions (boundary-mapping) are used to define cortical areas in cohorts of individuals sampled across a large range of the human adult lifespan (20-93 years). Most of the strongest areal boundaries are spatially consistent across age. Differences in parcellation boundaries are largely explained by differences in cortical thickness and anatomical alignment in older relative to younger adults. Despite the parcellation similarities, age-specific parcellations exhibit better internal validity relative to a young-adult parcellation applied to older adults' data, and age-specific parcels are better able to capture variability in task-evoked functional activity. Incorporating age-specific parcels as nodes in RSFC network analysis reveals that the spatial topography of the brain's large-scale system organization is comparable throughout aging, but confirms that the segregation of systems declines with increasing age. These observations demonstrate that many features of areal organization are consistent across adulthood, and reveal sources of age-related brain variation that contribute to the differences.

Background: There are conflicting data on whether changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) concentrations between time points (delta NT-proBNP and hs-CRP) are associated with a change in prognosis., Methods: We measured NT-proBNP and hs-CRP at 3 time points in 1665 patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). Cox proportional hazards was applied to the delta between temporal measurements to determine the continuous association with cardiovascular events. Effect estimates for delta NT-proBNP and hs-CRP are presented per 40% increase as the basic unit of temporal change., Results: Median NT-proBNP was 370.0 (25th, 75th percentiles, 130.0, 996.0), 340.0 (135.0, 875.0), and 267.0 (111.0, 684.0) ng/L; and median hs-CRP was 4.6 (1.7, 13.1), 1.9 (0.8, 4.5), and 1.8 (0.8, 4.4) mg/L at baseline, 30 days, and 6 months, respectively. The deltas between baseline and 6 months were the most prognostically informative. Every +40% increase of delta NT-proBNP (baseline to 6 months) was associated with a 14% greater risk of cardiovascular death (adjusted hazard ratio (HR) 1.14, 95% CI, 1.03-1.27) and with a 14% greater risk of all-cause death (adjusted HR 1.14, 95% CI, 1.04-1.26), while every +40% increase of delta hs-CRP (baseline to 6 months) was associated with a 9% greater risk of the composite end point (adjusted HR 1.09, 95% CI, 1.02-1.17) and a 10% greater risk of myocardial infarction (adjusted HR 1.10, 95%, CI 1.00-1.20)., Conclusions: Temporal changes in NT-proBNP and hs-CRP are quantitatively associated with future cardiovascular events, supporting their role in dynamic risk stratification of NSTEACS., Clinical Trial Registration: ClinicalTrials.gov identifier NCT00699998., (© 2017 American Association for Clinical Chemistry.)

Acute coronary syndrome (ACS) is the leading cause of morbidity and mortality. Accurate risk prediction in ACS patients is critically important for helping clinicians make therapeutic decisions, such as recommending a more aggressive intervention and intensive follow-up. However, risk stratification in ACS patients remains challenging, and the identification of novel predictors is necessary for improving the prognostic prediction in ACS patients. We employed metallomics and untargeted metabolomics approaches to discover new biomarkers from the plasma samples of 20 ACS patients and 20 non-ACS patients. We identified metabolic changes related to lysophosphatidylcholines, caffeine, glycolysis, tryptophan and sphingomyelin metabolism (p value <0.05) that were perturbed in the ACS patients. Moreover, circulating metal elements, including Mg, Ca, K, Zn, Ni, Ga and In (p value <0.05), were altered in the ACS patients versus the controls. These changes suggest possible changes in cell membrane permeability and rigidity in ACS patients.

Purpose of the Study: Recent evidence shows that engaging in learning new skills improves episodic memory in older adults. In this study, older adults who were computer novices were trained to use a tablet computer and associated software applications. We hypothesize that sustained engagement in this mentally challenging training would yield a dual benefit of improved cognition and enhancement of everyday function by introducing useful skills., Design and Methods: A total of 54 older adults (age 60-90) committed 15 hr/week for 3 months. Eighteen participants received extensive iPad training, learning a broad range of practical applications. The iPad group was compared with 2 separate controls: a Placebo group that engaged in passive tasks requiring little new learning; and a Social group that had regular social interaction, but no active skill acquisition. All participants completed the same cognitive battery pre- and post-engagement., Results: Compared with both controls, the iPad group showed greater improvements in episodic memory and processing speed but did not differ in mental control or visuospatial processing., Implications: iPad training improved cognition relative to engaging in social or nonchallenging activities. Mastering relevant technological devices have the added advantage of providing older adults with technological skills useful in facilitating everyday activities (e.g., banking). This work informs the selection of targeted activities for future interventions and community programs., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.)

The Association of Southeast Asian Nations aims to act as a single market and allow free movement of goods, services, and manpower. The purpose of this article is to present an overview of the current regulatory framework for health claims in Southeast Asia and to highlight the current barriers and opportunities in the regulatory frameworks in the Association of Southeast Asian Nations. To date, 5 countries in Southeast Asia, i.e., Indonesia, Malaysia, the Philippines, Singapore, and Thailand, have regulations and guidelines to permit the use of health claims on food products. There are inconsistencies in the regulations and the types of evidence required for health claim applications in these countries. A clear understanding of the regulatory frameworks in these countries may help to increase trade in this fast-growing region and to provide direction for the food industry and the regulatory community to develop and market food products with better nutritional quality tailored to the needs of Southeast Asian consumers., (© The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Aim: the purpose of this study was to investigate differences in long-term mortality following acute myocardial infarction (AMI) in patients from three major ethnicities of Asia., Methods and Results: We studied 15,151 patients hospitalized for AMI with a median follow-up of 7.3 years (maximum 12 years) in six publicly-funded hospitals in Singapore from 2000-2005. Overall and cause-specific cardiovascular (CV) mortality until 2012 were compared among three major ethnic groups that represent large parts of Asia: Chinese, Malay and Indian. Relative survival of all three ethnic groups was compared with a contemporaneous background reference population using the relative survival ratio (RSR) method. The median global registry of acute coronary events score was highest among Chinese, followed by Malay and Indians: 144 (25th percentile 119, 75th percentile 173), 138 (115, 167), and 131 (109, 160), respectively, p<0.0001; similarly, in-hospital mortality was highest among Chinese (9.8%) followed by Malay (7.6%) and Indian (6.4%) patients. In contrast, 12-year overall and cause-specific CV mortality was highest among Malay (46.2 and 32.0%) followed by Chinese (43.0 and 27.0%) and Indian (35.9 and 25.2%) patients, p<0.0001. The five-year RSR was lowest among Malay (RSR 0.69) followed by Chinese (RSR 0.73) and Indian (RSR 0.79) patients, compared with a background reference population (RSR 1.00)., Conclusions: We observed strong inter-Asian ethnic disparities in long-term mortality after AMI. Malay patients had the most discordant relationship between baseline risk and long-term mortality. Intensified interventions targeting Malay patients as a high-risk group are necessary to reduce disparities in long-term outcomes., (© The European Society of Cardiology 2014.)

Background: Most previous studies have reported superior results when blue dye and radiocolloids were used together for sentinel lymph node (SLN) biopsy in early breast cancer. Blue dye was reported to perform poorly when used alone, although more recent studies have found otherwise. This study reviewed the authors' practice of performing SLN biopsy with blue dye alone., Methods: This was a retrospective review of patients who underwent SLN biopsy using blue dye alone from 2001 to 2005, when SLN biopsy was performed selectively and always followed by axillary lymph node dissection (ALND), and from 2006 to 2010, when SLN biopsy was offered to all suitable patients and ALND done only when the SLN was not identified or positive for metastasis., Results: Between 2001 and 2005, 170 patients underwent SLN biopsy with blue dye alone. The overall SLN non-identification rate was 8·4 per cent. The overall false-negative rate was 34 per cent, but decreased with each subsequent year to 13 per cent in 2005. From 2006 to 2010, 610 patients underwent SLN biopsy with blue dye alone. The SLN was not identified in 12 patients (2·0 per cent) and no significant contributing factor was identified. A median of 2 (range 1-11) SLNs were identified. A non-SLN was found to be positive for metastasis in two patients with negative SLNs. Axillary nodal recurrence developed in one patient; none developed internal mammary nodal recurrence. Anaphylaxis occurred in one patient., Conclusion: Blue dye performed well as a single modality for SLN biopsy. Non-identification, axillary nodal recurrence and serious allergic reactions were uncommon., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Aim: Mutations in rrs [nucleotide (nt) 1401], gyrA gene (codons 90, 91 or 94), tlyA, ethA and thyA genes of Mycobacterium tuberculosis (MTB) were evaluated for their usefulness in predicting treatment outcome of kanamycin (KM), capreomycin (CPM), ofloxacin (OFX), ethionamide (ETH) and para-aminosalicylic acid (PAS)., Methods and Results: DNA sequence analyses of these genes were performed against 188 MTB isolates obtained from patients put on second-line anti-TB drugs (SLDs) with well-documented clinical history and treatment outcome. Mutations in rrs and gyrA have 100% positive predictive value (PPV) in predicting treatment failure for KM and OFX, while 88·9 and 80% were obtained, respectively, when tlyA and rrs mutations were considered in CPM. For ETH and PAS, the PPV of using ethA and thyA mutations to predict treatment failure was 82·5 and 89·3%, respectively., Conclusions: Our study demonstrated high specificities of gene mutations in predicting poor treatment outcome; however, further technical advancement is required to make the molecular detection of resistances to other SLDs feasible in clinical laboratories., Significance and Impact of the Study: This is the first study to correlate different polymorphisms of major SLD resistance gene markers with predicted treatment outcome, using an international set of well-documented clinical MTB strains., (© 2010 The Authors. Journal of Applied Microbiology © 2010 The Society for Applied Microbiology.)

Aims: Patients with chronic kidney disease (CKD) have high cardiovascular risk. Although stress imaging provides accurate risk estimation in this population, it is unknown if combinatorial cardiac imaging adds incremental value., Methods and Results: We performed transthoracic echocardiography and stress single photon emission computed tomography (SPECT) to assess their value in predicting late cardiovascular disease (CVD) mortality in 200 patients with creatinine clearance <60 mL/min without a history of coronary heart disease. During a median follow-up duration of 3.7 (3.5-4.0) years, there were 25 deaths because of CVD. Older age, abnormal SPECT, and increased indexed left atrial (LA) diameter were associated with CVD mortality on univariate analysis with P = 0.007, 0.01, and 0.004, respectively. In multivariable analysis, indexed LA diameter >24 mm/m(2) was independently predictive of CVD mortality [hazard ratio (HR) 2.75, confidence interval (CI) 1.14-6.59], but abnormal SPECT was not. Each mm/m(2) increase in indexed atrial diameter was associated with an HR 1.20 (95% CI 1.06-1.37)., Conclusions: In patients with CKD, the indexed LA diameter predicts CVD mortality independent of an abnormal SPECT result. Consideration should be given to this simple measurement as a prognostic tool in this population.

Aims: We sought to investigate the effect of adenosine pretreatment on the incidence of myonecrosis after non-urgent percutaneous coronary intervention (PCI)., Methods and Results: This was a prospective, randomized, open-label study. Patients who were scheduled for non-urgent PCI in de novo native coronary arteries were eligible. All patients were pretreated with aspirin and clopidogrel. Myonecrosis was measured by creatine kinase-myocardial band (CK-MB) elevation after PCI. A total of 62 patients were randomized into the adenosine (n = 31) or standard (n = 31) group. The adenosine group received 50 microg adenosine bolus before wiring of each lesion, whereas the standard group did not. Post-PCI myonecrosis occurred more frequently in the standard group (39 vs. 13%, OR 0.23, 95% CI 0.05-0.95, P = 0.020). After adjustment for drug-eluting stent implantation, multi-vessel stenting, and elevated baseline troponin, the OR was 0.19 (95% CI 0.05-0.72, P = 0.017). The median peak values of CK-MB in the adenosine and standard groups were 2 and 4 microg/L, respectively (P = 0.033). The adjusted difference was 1.95 microg/L (95% CI 0.13-3.77, P = 0.037). The incidences of myocardial infarction (>3 x CK-MB) were 6 and 16% in the adenosine and standard groups, respectively (OR 0.36; 95% CI 0.03-2.46, P = 0.229)., Conclusion: Pretreatment with 50 microg of adenosine decreases the incidence of myonecrosis after non-urgent PCI compared with that without pretreatment.

A case-control study was conducted on 1986 Hong Kong women to assess the risk of human papillomavirus (HPV) type 16 variants for cervical neoplasia. In total, 255 women were HPV-16 positive and were analyzed for E6 and E7 sequence variation. Two novel substitutions at E6 (T86I and Q116E) and 1 at E7 (R66W) were found. Most HPV-16 variants were of Asian (50.6%) or European (44.3%) lineage, and both lineages showed similar risk associations for high-grade and invasive cervical neoplasia. No increased risk was observed for the subclasses European variant and European 350G, which carry a higher risk for invasive cancer in some Western populations. The E7 N29S substitution, reported to have a higher risk in Korean women, was found equally distributed among normal and various degrees of neoplasia. The epidemiology and risk implication of HPV-16 variant infection in Hong Kong differ markedly from other parts of the world.

Human papillomavirus (HPV) type 58 has been found to be prevalent among Chinese patients with cervical cancer. This study examined the oncogenic risk of HPV58 variants in Hong Kong, a southern part of China. Altogether, 1924 women were studied: 42.8% with a normal cervix, 16.2% with cervical intraepithelial neoplasia (CIN) I, 12.7% with CIN II, 20.8% with CIN III, and 7.6% with invasive cervical cancer (ICC). The overall prevalence of HPV58 was 11.4% (220) and increased statistically significantly with the severity of neoplasia (P(trend)<.001, chi(2) test for trend). Among HPV58-positive women, the occurrence of E7 632C-->T (T20I) and E7 760G-->A (G63S) variants (T20I/G63S) showed a positive trend of association with the severity of neoplasia (P(trend)<.001, chi(2) test for trend). HPV58 variants carrying these two substitutions showed an odds ratio (OR) for ICC of 26.79 (95% confidence interval = 10.14 to 74.72), and this OR was 6.9-fold higher than the ORs of variants without these substitutions. Patients with CIN III or ICC who were also infected with T20I/G63S variants had a statistically significant younger age at diagnosis than those infected with other variants (median age = 37 years versus 48 years; P =.038, two-sided Mann-Whitney U test). Thus, HPV58 variants carrying E7 T20I/G63S substitutions may be associated with an increased risk for cervical cancer.

We studied retrospectively the territory-wide occurrence and trends of multidrug-resistant tuberculosis (MDR-TB) in Hong Kong over an 11-year period during which a short-course directly observed therapy ("DOTS-Plus") strategy has been in operation. The overall MDR rate was 2.1% (primary, 1.4% and acquired, 9.5%) and declined at 0.08% per year: smear-positive primary MDR cases declined at yearly rate of -0.065% (R2=.23), and smear-negative primary MDR cases increased at 0.035% yearly. With declining rates of smear positivity, sputum culture has become the mainstay of detection of MDR-TB. Although the overall notification rates showed the elderly (age >65 years) age group to be most affected, the occurrence of MDR-TB has been consistently highest in the 35-65 year age group (60.4% of MDR caseload). We demonstrated declining rates of sputum smear positivity of MDR-TB in a DOTS-plus environment and that a centralized laboratory database is essential in gathering epidemiological information for identifying particular risk groups and monitoring trends of MDR-TB in a community.

The conditions under which noscapine causes high levels of polyploidy in vitro in human lymphocytes were investigated to try to determine its mode of action and to assess whether it was likely to be a genotoxic hazard when used as an antitussive agent. Irrespective of duration of treatment or type of medium, there seemed to be a threshold for polyploidy induction between 15.0 and 30.0 micrograms/ml and a maximum between 100.0 and 150.0 micrograms/ml noscapine. High levels (10.0-20.0%) of noscapine-induced polyploidy were never found with 4 h treatments or with RPMI 1640 medium plus 15% (v/v) foetal calf serum; the use of Iscove's modified Dulbecco's medium and 24 h treatments were needed. The reasons for these observations seemed to be the faster cell division and greater sensitivity of cells grown in Iscove's medium. There was conflicting evidence about the mechanism of polyploidy induction by noscapine; either spindle damage or cell fusion remain as possibilities. The need for prolonged exposure and the precise nutritional requirements suggest that a short exposure, albeit at high concentration, in the upper gastro-intestinal tract is unlikely to be a hazard for humans. Furthermore, evidence of a threshold at approximately 20 micrograms/ml plus the virtual elimination of noscapine-induced polyploidy by microsomal metabolism (S9 mix) together with published metabolic data imply that the low-level systemic exposure after absorption may well not be hazardous. We conclude that the use of noscapine in cough mixtures does not pose a significant potential hazard for humans.