The global burden of metabolic disease: Data from 2000 to 2019.

Global estimates of prevalence, deaths, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 were examined for metabolic diseases (type 2 diabetes mellitus [T2DM], hypertension, and non-alcoholic fatty liver disease [NAFLD]). For metabolic risk factors (hyperlipidemia and obesity), estimates were limited to mortality and DALYs. From 2000 to 2019, prevalence rates increased for all metabolic diseases, with the greatest increase in high socio-demographic index (SDI) countries. Mortality rates decreased over time in hyperlipidemia, hypertension, and NAFLD, but not in T2DM and obesity. The highest mortality was found in the World Health Organization Eastern Mediterranean region, and low to low-middle SDI countries. The global prevalence of metabolic diseases has risen over the past two decades regardless of SDI. Urgent attention is needed to address the unchanging mortality rates attributed to metabolic disease and the entrenched sex-regional-socioeconomic disparities in mortality.

The global syndemic of metabolic diseases in the young adult population: A consortium of trends and projections from the Global Burden of Disease 2000-2019.

BACKGROUND: A significant proportion of premature deaths globally are related to metabolic diseases in young adults. We examined the global trends and mortality of metabolic diseases in individuals aged below 40 years using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. METHODS: From 2000 to 2019, global estimates of deaths and disability-adjusted life years (DALYs) were described for metabolic diseases (type 2 diabetes mellitus [T2DM], hyperlipidemia, hypertension, obesity, non-alcoholic fatty liver disease [NAFLD]). Subgroup analyses were performed based on sex, geographical regions and Socio-Demographic Index (SDI). Age-standardised death and DALYs were presented per 100,000 population with 95 % uncertainty intervals (UI). Projections of mortality and DALYs were estimated using regression models based on the GBD 2019 data and combining them with Institute for Health Metrics and Evaluation projection counts for years up to 2050. RESULTS: In 2019, the highest age-standardised death rates were observed in hypertension (133·88 [121·25-155·73]), followed by obesity (62·59 [39·92-89·13]), hyperlipidemia (56·51 [41·83-73·62]), T2DM (18·49 [17·18-19·66]) and NAFLD (2·09 [1·61-2·60]). Similarly, obesity (1932·54 [1276·61-2639·74]) had the highest age-standardised DALYs, followed by hypertension (2885·57 [2580·75-3201·05]), hyperlipidemia (1207·15 [975·07-1461·11]), T2DM (801·55 [670·58-954·43]) and NAFLD (53·33 [40·73-68·29]). Mortality rates decreased over time in hyperlipidemia (-0·6 %), hypertension (-0·47 %), NAFLD (-0·31 %) and T2DM (-0·20 %), but not in obesity (1·07 % increase). The highest metabolic-related mortality was observed in Eastern Mediterranean and low SDI countries. By 2050, obesity is projected to contribute to the largest number of deaths (102·8 % increase from 2019), followed by hypertension (61·4 % increase), hyperlipidemia (60·8 % increase), T2DM (158·6 % increase) and NAFLD (158·4 % increase), with males continuing to bear the greatest burden across all metabolic diseases. CONCLUSION: The growing burden of metabolic diseases, increasing obesity-related mortality trends, and the sex-regional-socioeconomic disparities evident in young adulthood, underlie the concerning growing global burden of metabolic diseases now and in future.

N-glycan profiles of acute myocardial infarction patients reveal potential biomarkers for diagnosis, severity assessment and treatment monitoring.

Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. Diagnostic challenges remain in this highly time-sensitive condition. Using capillary electrophoresis-laser-induced fluorescence, we analyzed the blood plasma N-glycan profile in a cohort study comprising 103 patients with AMI and 69 controls. Subsequently, the data generated was subjected to classification modeling to identify potential AMI biomarkers. An area under the Receiving Operating Characteristic curve (AUCROC) of 0.81 was obtained when discriminating AMI vs. non-MI patients. We postulate that the glycan profile involves a switch from a pro- to an anti-inflammatory state in the AMI pathophysiology. This was supported by significantly decreased levels in galactosylation, alongside increased levels in sialylation, afucosylation and GlcNAc bisection levels in the blood plasma of AMI patients. By substantiating the glycomics analysis with immunoglobulin G (IgG) protein measurements, robustness of the glycan-based classifiers was demonstrated. Changes in AMI-related IgG activities were also confirmed to be associated with alterations at the glycosylation level. Additionally, a glycan-biomarker panel derived from glycan features and current clinical biomarkers performed remarkably (AUCROC = 0.90, sensitivity = 0.579 at 5% false positive rate) when discriminating between patients with ST-segment elevation MI (n = 84) and non-ST-segment elevation MI (n = 19). Moreover, by applying the model trained using glycomics information, AMI and controls can still be discriminated at 1 and 6 months after baseline. Thus, glycomics biomarkers could potentially serve as a valuable complementary test to current diagnostic biomarkers. Additional research on their utility and associated biomechanisms via a large-scale study is recommended.

Cost-effectiveness analysis of biodegradable polymer versus durable polymer drug-eluting stents incorporating real-world evidence.

AIM: Compared with second-generation durable polymer drug-eluting stents (DP-DES), the cost-effectiveness of biodegradable polymer drug-eluting stents (BP-DES) remains unclear in the real-world setting. We assessed the cost-effectiveness of BP-DES in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). METHODS: We developed a decision-analytic model to compare the cost-effectiveness of BP-DES to DP-DES over 1 year and 5 years from healthcare payer perspective. Relative treatment effects during the first year post-PCI were obtained from a real-world population analysis while clinical event risks in the subsequent 4 years were derived from a meta-analysis of published studies. RESULTS: At 1 year, based on the clinical data analysis of 497 propensity-score matched pairs of patients, BP-DES were associated with an incremental cost-effectiveness ratio (ICER) of USD20 503 per quality-adjusted life-year (QALY) gained. At 5 years, BP-DES yielded an ICER of USD4062 per QALY gained. At the willingness-to-pay threshold of USD50 400 (one gross domestic product per capita in Singapore in 2015), BP-DES were cost-effective. Sensitivity analysis showed that the cost of stents had a significant impact on the cost-effectiveness of BP-DES. Threshold analysis demonstrated that if the cost difference between BP-DES and DP-DES exceeded USD493, BP-DES would not be cost-effective in patients with 1 year of follow-up. CONCLUSIONS: Biodegradable polymer drug-eluting stents were cost-effective compared with DP-DES in patients with coronary artery disease at 1 year and 5 years after PCI. It is worth noting that the cost of stents had a significant impact on the findings.

Cost-Effectiveness Analysis of Ticagrelor and Prasugrel for the Treatment of Acute Coronary Syndrome.

BACKGROUND: In the management of Asian patients with acute coronary syndrome (ACS), the comparative cost-effectiveness of ticagrelor and prasugrel, referenced to generic clopidogrel, is unknown. OBJECTIVE: To assess the cost-effectiveness of ticagrelor and prasugrel as compared with generic clopidogrel in patients with ACS in Singapore. METHODS: A Markov model simulating a typical cohort of 62-year-old patients with ACS was constructed from a patient's perspective over a lifetime horizon. Treatment effects and adverse events, including nonfatal myocardial infarction, major bleeding related to non-coronary artery bypass grafting, dyspnea, or death, were estimated from pivotal trials comparing clopidogrel with ticagrelor and prasugrel, respectively. Costs were estimated from a tertiary hospital with more than 1500 admissions for ACS per year. RESULTS: The incremental cost-effectiveness ratio (ICER) per life-year gained for ticagrelor was about three times more favorable than for prasugrel (Singapore dollar [SGD] 13,276 vs. SGD 38,809). The ICER per quality-adjusted life-year (QALY) for prasugrel and ticagrelor, however, was comparable at SGD 18,921 and SGD 18,647, respectively. Deterministic sensitivity analysis revealed that the ICER per QALY gained for prasugrel and ticagrelor was most sensitive to the hazard ratio of all-cause mortality and utility for dyspnea, respectively. Probabilistic sensitivity analysis demonstrated that compared with clopidogrel, the probabilities of prasugrel and ticagrelor being cost-effective are 87.1% and 88.3% based on the willingness-to-pay value of SGD 65,000 (one time the gross domestic product per capita in Singapore). CONCLUSIONS: Ticagrelor is more cost-effective than prasugrel in reducing all-cause mortality in patients with ACS. The cost-effectiveness of ticagrelor and prasugrel become similar, however, when accounting for the impact of dyspnea on QALY.

Immigrant status and disparities in health care delivery in patients with myocardial infarction.

BACKGROUND: We investigated the differences in socioeconomic status and quality health care between Singapore-born citizens and immigrants presenting with ST-segment elevation myocardial infarction (STEMI). METHODS: In a prospective study, patients admitted with STEMI were recruited for a questionnaire survey. The recruited patients were categorized based on their immigration status into Singapore-born citizens (SBC), foreign-born citizens (FBC), permanent residents (PR) and non-residents (NR). RESULTS: Among the 374 recruited patients, 286 (76.5%) patients were categorized as SBC, and the remaining 88 (23.5%) as immigrants. Further breakdown of the immigrants revealed that 33 were FBC (median duration of living in Singapore, 53 years), 22 were PR (18 years), and 33 were NR (11 years). Significant differences in socioeconomic status among SBC, FBC, PR and NR were detected. NR were in the lowest, while PR in the highest, socioeconomic class based on occupation (p=0.003), education level (p<0.001), and average monthly household income (p=0.020). There were no disparities in the proportion of patients treated with primary PCI (SBC 88%, FBC 82%, PR 91%, NR 79%, p=0.555). Median door-to-balloon times were similar among the four groups (56, 52, 60, 56min, p=0.614). Compared with SBC, PR was associated with longer symptom-to-balloon times (median difference 54.1 min; 95% CI 9.0 to 99.2). CONCLUSION: There were major differences in the socioeconomic status among SBC, FBC, PR and NR who presented with STEMI. Although there were no major disparities in access to high quality health care to these patients with different immigration status, symptom-to-balloon time differed substantially among the different migrant classes.

Prevalence, predictors, and impact of conservative medical management for patients with non-ST-segment elevation acute coronary syndromes who have angiographically documented significant coronary disease.

OBJECTIVES: We sought to characterize the utilization and impact of a conservative medical management strategy for patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) and significant coronary artery disease on early angiography. BACKGROUND: Practice guidelines recommend an early invasive management strategy for NSTE ACS, but revascularization procedures may not always be performed after early angiography, even when significant coronary artery disease is present. METHODS: We evaluated 8,225 intermediate- to high-risk NSTE ACS patients with at least 1 coronary lesion >50% stenosis on early angiography from the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) trial (2001 to 2003), comparing patients treated with conservative medical management with those who underwent in-hospital percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 7 days of randomization. RESULTS: A total of 2,633 patients (32%) were medically managed, 4,294 (52%) underwent PCI, and 1,298 (16%) underwent CABG. The strongest independent predictors of conservative medical management versus any intervention were prior CABG, lower body weight, lack of a reinfarction between randomization and catheterization, and 3-vessel disease. With conservative medical management, the cumulative risk of 1-year mortality after discharge increased rapidly during the first 90 days and thereafter remained higher at 7.7% compared with that seen in patients treated with PCI (3.6%) or CABG (6.2%). CONCLUSIONS: One-third of patients with NSTE ACS and significant coronary disease on early angiography were managed without in-hospital revascularization in the SYNERGY trial, and these patients had an increased risk of late mortality. These findings highlight the need for novel treatment approaches for NSTE ACS patients who are not candidates for revascularization. (SYNERGY trial; NCT00043784).