Cardiac and renal outcomes of direct oral anticoagulants in patients with atrial fibrillation.

BACKGROUND: Oral anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is the mainstay for stroke prevention in patients with non-valvular atrial fibrillation (AF). The DOACs might have a lower risk of declining renal function than warfarin. This study aimed to compare renal outcomes among rivaroxaban, edoxaban, dabigatran, and warfarin. METHOD: This cohort study identified 2203 adults with AF who started anticoagulation therapy between 1 July 2013 and 31 December 2020, in a clinical database at a single centre. Inverse probability of treatment weighting was adopted to balance baseline characteristics among four anticoagulants treatment groups. The primary outcome was a composite of cardiac and renal outcomes, involving a ≥30% decline in estimated glomerular filtration rate (eGFR), renal failure and cardiovascular death. RESULTS: After propensity score weighting, dabigatran was associated with significantly lower risks of a ≥30% decline in eGFR (hazard ratio [HR]: .69, 95% confidence interval [CI]: .497-.951, p = .0237), doubling of the serum creatinine level (HR: .49, 95% CI: .259-.927, p = .0282) and the cardiac and renal outcome composite (HR: .67, 95% CI: .485-.913, p = .0115) than warfarin. Rivaroxaban and edoxaban did not show significant protective effects on renal outcomes compared to warfarin. CONCLUSION: In this study, patients treated with dabigatran had significantly reduced risks of declining renal function and composite cardiac and renal events than those treated with warfarin. However, rivaroxaban and edoxaban were not associated with lower risks of any renal outcomes than warfarin. More studies are warranted to investigate and compare the impact of renal function between different DOACs in patients with AF.

Predictive Power of In-Hospital and Long-Term Mortality of the GRACE, TIMI, Revised CADILLAC and PAMI Score in NSTEMI Patients with Diabetes - Data from TSOC ACS-DM Registry.

BACKGROUND: Risk score is widely used in non-ST segment elevation myocardial infarction (NSTEMI) patients to predict the in-hospital outcome for immediate coronary angiography decision and care of unit selection. OBJECTIVES: This study compared the performances of the thrombolysis in myocardial infarction (TIMI), Global Registry of Acute Coronary Events (GRACE), Primary Angioplasty in Myocardial Infarction (PAMI), and Revised Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (Revised CADILLAC) risk scores in predicting in-hospital and long-term outcomes in diabetic NSTEMI patients. METHODS: A total of 750 diabetic NSTEMI patients from 27 hospitals were enrolled between January 2013 and December 2015 in the nationwide registry initiated by the Taiwan Society of Cardiology. Four score systems were calculated with receiver operator characteristic analysis used to compare outcome discrimination performance. RESULTS: No studied risk scores reached acceptable discrimination per area under curve (AUC) in the prediction of in-hospital outcome except for the revised CADILLAC score which reached acceptable discrimination in new-onset cardiogenic shock (AUC = 0.7191) and acute renal failure (AUC = 0.7283). In long-term outcomes, only the revised CADILLAC score reached acceptable discrimination of mortality prediction at 6, 12 and 24 months (AUC = 0.7261 at 6 months, 0.7319 at 12 months, and 0.7256 at 24 months). Subgroup analysis based on the revised CADILLAC score risk class showed a significant difference in adjusted mortality rate between low-risk group/intermediate-risk group and high-risk group. CONCLUSIONS: Only the revised CADILLAC score showed acceptable accuracy to predict the long-term mortality outcome among the scores studied.

In-Hospital Implementation of Evidence-Based Medications is Associated with Improved Survival in Diabetic Patients with Acute Coronary Syndrome - Data from TSOC ACS-DM Registry.

BACKGROUND: Patients with acute coronary syndrome (ACS) and diabetes mellitus (DM) receive less aggressive treatment and have worse outcomes in Taiwan. We sought to explore whether the current practices of prescribing guideline-directed medical therapy (GDMT) for ACS and clinical outcomes have improved over time. METHODS: A total of 1534 consecutive diabetic patients with ACS were enrolled between 2013 and 2015 from 27 hospitals in the nationwide registry initiated by the Taiwan Society of Cardiology (the TSOC ACS-DM Registry). Baseline and clinical demographics, treatment, and clinical outcomes were compared to those of 1000 ACS patients with DM recruited in the Taiwan ACS-full spectrum (ACS-FS) Registry, which was performed between 2008 and 2010. RESULTS: Compared to the DM patients in the Taiwan ACS-FS Registry, even though reperfusion therapy was carried out in significantly fewer patients, the primary percutaneous coronary intervention (PCI) rate for ST-segment elevation myocardial infarction (STEMI) and the prescription rates of GDMT for ACS including P2Y12 inhibitors, renin-angiotensin blockers, beta-blockers, and statins were significantly higher in those in the TSOC ACS-DM Registry. Moreover, significant reductions in 1-year mortality, recurrent nonfatal MI and stroke were observed compared to those of the DM patients in the Taiwan ACS-FS Registry. Multivariate analysis identified reperfusion therapy in combination with GDMT as a strong predictor of better 1-year outcomes [hazard ratio (95% confidence interval) = 0.54 (0.33-0.89)]. CONCLUSIONS: Marked improvements in performing primary PCI for STEMI and prescribing GDMT for ACS were observed over time in Taiwan. This was associated with improved 1-year event-free survival in the diabetic patients with ACS.

Frequency of Vascular Inflammation and Impact on Neointimal Proliferation of Drug Eluting Stents in Porcine Coronary Arteries.

BACKGROUND: We aimed to describe the frequency of vascular inflammatory reactions with second generation drug eluting stents (DES) compared to first generation DES, and analyze the impact on inflammation and neointimal proliferation in a porcine coronary model. METHODS: A total of 26 stents (7 multi-link VISION, 6 CYPHER, 6 TAXUS and 7 XIENCE V) were deployed in the coronary arteries of 10 domestic swine for 28 days, after which each stent was harvested and processed (divided into 8 or 9 segments) for histomorphometric analysis. RESULTS: A total of 202 histological segments [146 DES and 56 bare metal stents (BMS)] were included in this study. The mean neointimal thickness was significantly reduced in the DES group compared to the BMS group. The DES group had higher injury scores (DES = 0.99 ± 0.79 versus BMS = 0.67 ± 0.44, p < 0.004), inflammatory scores (DES = 2.09 ± 1.54 versus BMS = 0.64 ± 0.98, p < 0.001) and presence of para-strut granulomas (DES = 35% versus BMS = 2%, p < 0.001). In logistic regression analysis, the presence of para-strut granulomas correlated with an area of stenosis > 50% (RR: 6.11, 95% CI: 2.97 to 12.59, p = 0.001). In the DES group, the second generation stents had a lower neointimal area (XIENCE V: 1.64 ± 0.90 mm2) compared to the first generation stents (TAXUS: 2.36 ± 1.56 mm2, p = 0.005; CYPHER 2.78 ± 1.82 mm2, p = 0.001). The XIENCE V stents had lower inflammatory scores and lower frequency of para-strut granulomas compared to the first generation stents. CONCLUSIONS: Second generation DES had a lower incidence of vascular inflammatory reactions compared to first generation DES. This biological phenomenon appears to influence the patterns of neointimal formation.

Silent and Malignant Early Repolarization Syndrome Mimicking Hyper-Acute ST Elevation Myocardial Infarction.

A 55-year-old male with underlying type 2 diabetes mellitus and hypertension presented at our emergency department with ventricular fibrillation-related cardiac arrest. Hyper-acute ST elevation myocardial infarction was the preliminary diagnosis by 12-lead electrocardiography, which simultaneously showed J point ST elevation and tall T waves. However, the echocardiography showed concentric left ventricle hypertrophy and preserved left ventricular systolic function with no regional wall motion abnormalities, and coronary angiography did not show any critical coronary artery lesion. Malignant early repolarization syndrome was diagnosed, and an implantable cardioverter defibrillator was implanted. Early repolarization syndrome is associated with J point elevation, and more involved leads and an increased J point elevation amplitude can increase the risk of arrhythmogenicity. In summary, we report a case with asymptomatic type 3 early repolarization syndrome-induced idiopathic ventricular fibrillation mimicking hyper-acute ST elevation myocardial infarction.

Arterial Stiffness Index and Coronary Artery Plaques in Patients with Subclinical Coronary Atherosclerosis.

BACKGROUND: Arterial stiffness is a physiologic quantitative value used to measure arterial compliance. It is predictive of coronary atherosclerosis in patients with intermediate to high cardiovascular risk. However, a correlation between arterial stiffness and subclinical coronary atherosclerosis has yet to be established. Therefore, the purpose of this study was to evaluate arterial stiffness using an arterial stiffness index (ASI) and investigate its association with coronary artery plaque in patients with subclinical coronary atherosclerosis. METHODS: Our study enrolled 156 consecutive subjects who underwent health screening using a 64-slice cardiac computed tomography angiography (CCTA). Their arterial stiffness index was assessed noninvasively by CardioVision(®) MS-2000. The atheroma on the coronary vessel walls was analyzed. RESULTS: Of the 156 patients, 53 displayed at least one > 50% stenotic lesion over the coronary arteries in CCTA images. The patients with at least one > 50% coronary stenotic plaque were older and had higher systolic blood pressure and ASI values than patients without > 50% coronary stenotic plaque. After dividing the study population into 2 groups by those patients over and under 50 years of age, the ASI positively correlated with the presentation of at least one > 50% coronary stenotic plaque in patients aged ≥ 50 years (odds ratio = 1.02, 95% confidence interval: 1.00-1.04, p = 0.03). CONCLUSIONS: The ASI could play a role in risk stratification systems for coronary artery disease in patients with subclinical coronary atherosclerosis, and is a useful clinical marker for the correlation of early coronary plaque. KEY WORDS: Arterial stiffness; Arterial stiffness index; Atherosclerosis; Coronary artery plaque.

Adverse Cardiovascular Effects of COVID-19 Vaccination: A Systematic Review.

Several vaccines against coronavirus disease 2019 (COVID-19)-caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-have been developed since the COVID-19 pandemic began. Of these, 7 have been approved in the World Health Organization's Emergency Use Listing. However, these vaccines have been reported to have rare or serious adverse cardiovascular effects. This review presents updated information on the adverse cardiovascular effects of the approved COVID-19 vaccines-including inactivated vaccines, protein subunit vaccines, virus-like particles, nucleic acid vaccines, and viral vector vaccines-and the underlying mechanisms.

Combined Framingham Risk Score and Coronary Artery Calcium Score Predict Subclinical Coronary Plaque Assessed by Coronary Computed Tomography Angiogram in Asymptomatic Taiwanese Population.

BACKGROUND: We sought to determine the predictive value of the combined traditional Framingham risk score (FRS) and coronary artery calcium score (CACS) for subclinical coronary plaque detected by computed tomography coronary angiogram (CTCA) in asymptomatic subjects. METHOD: We evaluated 167 asymptomatic Taiwanese subjects (mean age, 57 ± 11.2 years), who underwent CTCA as part of a health evaluation. We examined the associations between FRS, CACS, serum biomarkers, and coronary plaque assessed by CTCA. RESULTS: Out of 167 subjects in the study, 95 had coronary artery atheroma. Of those possible predictors for coronary atherosclerosis, both FRS and CACS were independent predictors for the presence of coronary plaque [relative risk (RR): 1.29, 95% confidence interval (CI): 1.07-1.54, p = 0.006 and RR: 1.42, 95% CI: 1.16-1.75, p = 0.001, respectively]. Receiver operating characteristics curve analysis revealed that CACS and FRS were indicators of the presence of coronary plaque. The area under the curve for FRS and CACS was 0.729 and 0.889, respectively (p < 0.001). Furthermore, the area under the curve for combination of FRS and CACS was 0.936 (95% CI: 0.887-0.969, p < 0.001), and this combination provided a better diagnostic advantage than either FRS or CACS alone (p < 0.001 and p = 0.012 by C-statistic, respectively). CONCLUSIONS: In asymptomatic Taiwanese subjects with low to intermediate cardiovascular risk, both FRS and CACS were independently related to subclinical atherosclerosis. A combined FRS and CACS evaluation improved the efficacy of prediction for atherosclerotic plaque burden. KEY WORDS: Atherosclerosis; Computed coronary tomography angiogram; Coronary artery calcium score; Framingham risk score; Subclinical coronary plaque.

Effect of myopia on the progression of normal tension glaucoma.

PURPOSE: Identify risk factors of progression in treated normal-tension glaucoma (NTG) in highly myopic and non-highly myopic eyes. METHODS: This retrospective, observational case series study included 42 highly myopic glaucoma (HMG, <-6D) eyes and 39 non-highly myopic glaucoma (NHG,≧-6D) eyes. Glaucoma progression was determined by serial visual field data. Univariate and multivariate logistic regression method were used to detect associations between potential risk factors and glaucoma progression. RESULTS: Among 81 eyes from 81 normal-tension glaucoma patients (mean follow-up, 3.10 years), 20 of 42 eye (45.24%) in the HMG and 14 of 39 eyes (35.90%) in the NHG showed progression. The HMG group had larger optic disc tilt ratio (p = 0.007) and thinner inferior macular thickness (P = 0.03) than the NHG group. Changes in the linear regression values for MD for each group were as follows: -0.652 dB/year for the HMG and -0.717 dB/year for the NHG (P = 0.298). Basal pattern standard deviation (PSD) (OR: 1.55, p = 0.016) and post treatment IOP (OR = 1.54, p = 0.043) were risk factors for visual field progression in normal tension glaucoma patients. In subgroup analysis of HMG patients, PSD (OR: 2.77, p = 0.017) was a risk factor for visual field progression. CONCLUSION: Reduction IOP was postulated to be contributing in the prevention of visual field progression, especially in highly myopic NTG patients with large basal pattern standard deviation.

Comparing the effectiveness and safety of dual antiplatelet with ticagrelor or clopidogrel in elderly Asian patients with acute myocardial infraction.

Background: Current guidelines recommend potent P2Y12 inhibitors for patients after acute coronary syndrome. However, the data on the efficacy and safety of potent P2Y12 inhibitors in elderly Asian populations was limited. We aimed to investigate the major adverse cardiovascular events (MACE), bleeding events, and net adverse clinical events (NACE) with ticagrelor and clopidogrel in Taiwanese patients aged 65 and older after acute myocardial infarction (AMI). Methods: This retrospective population-based cohort study was conducted using data from the National Health Insurance Research Database. The AMI patients aged ≥65 years who underwent percutaneous coronary intervention (PCI) and survived after 1 month were included. The patients were separated into 2 cohorts depending on the type of dual antiplatelet therapy (DAPT) they received: ticagrelor plus aspirin (T + A) or clopidogrel plus aspirin (C + A). We used inverse probability of treatment weighting to balance the difference between these 2 study groups. The outcome included all-cause mortality, MACE (cardiovascular death, nonfatal ischemic stroke, and nonfatal myocardial infarction), intracerebral hemorrhage, major bleeding, and NACE which is composed of cardiovascular death, ischemic and hemorrhagic events. The follow-up period was up to 12 months. Results: From 2013 to 2017, a total of 14,715 patients who met the eligibility criteria were separated into 2 groups: 5,051 for T + A and 9,664 for C + A. Compared to patients with C + A, patients who received T + A had a lower risk of cardiovascular death and all-cause death, with an adjusted HR of 0.57 [95% confidence interval (CI), 0.38-0.85, p = 0.006] and 0.58 (95% CI 0.45-0.74, p < 0.001), respectively. No differences were found in MACE, intracranial and major bleeding between the 2 groups. In addition, the patients with T + A had a lower risk of NACE with an adjusted HR of 0.86 (95% CI 0.74-1.00, p = 0.045). Conclusion: Among elderly AMI patients receiving DAPT after successful PCI, ticagrelor was a more favorable P2Y12 inhibitor than clopidogrel because of lowering the risk of death and NACE without increasing the risk of severe bleeding. Ticagrelor is an effective and safe P2Y12 inhibitor in Asian elderly survivors after PCI.

Stress-induced cardiomyopathy caused by heat stroke.

Heat stroke is defined by central nervous system abnormalities and failure of proper maintenance of thermoregulation as a result of high core body temperature ensuing from exposure to high environmental temperatures or strenuous exercise. Common complications include acute respiratory distress syndrome, disseminated intravascular coagulation, acute renal injury, hepatic injury, and rhabdomyolysis. Myocardial injury may also occur during heat stroke, resulting in cardiac enzyme increase and ST-segment changes on the ECG. Such findings might behave as diagnostic pitfalls by mimicking the presentation of coronary artery occlusive myocardial infarction. A previous case report described a patient with heat stroke and ST-segment elevation, in which the definite cause of the ST-segment elevation was unclear; however, acute myocardial infarction caused by coronary artery disease was ruled out according to the clinical signs, serial ECG changes, and serum level of cardiac biomarkers. Stress-induced cardiomyopathy (Takotsubo cardiomyopathy) was suspected, but it could not be confirmed because of the lack of coronary angiography. We herein report a case of heat stroke presenting with ST-segment elevation and cardiogenic shock. Coronary angiography was performed and coronary artery occlusive myocardial infarction was ruled out because of the presence of patent coronary arteries. Left ventriculography showed midventricular and apical hypokinesis, and stress-induced cardiomyopathy was then determined to be the appropriate diagnosis. Heat stroke causes increase of serum catecholamine levels, in which oversecretion and abnormal responses to catecholamines are a possible cause of stress-induced cardiomyopathy. Catecholamines may therefore be the key in linking heat stroke and stress-induced cardiomyopathy.

The effect of de-escalation of P2Y12 receptor inhibitor therapy after acute myocardial infarction in patients undergoing percutaneous coronary intervention: A nationwide cohort study.

To examine the effect of de-escalation of P2Y12 inhibitor in dual antiplatelet therapy (DAPT) on major adverse cardiovascular events (MACE) and bleeding complications after acute myocardial infarction (AMI) in Taiwanese patients undergoing percutaneous coronary intervention (PCI). Patients who had received PCI during hospitalization for AMI (between 2013 and 2016) and were initially treated with aspirin and ticagrelor and without adverse events after 3 months of treatment were retrospectively evaluated. In total, 1,901 and 8,199 patients were identified as "de-escalated DAPT" (switched to aspirin and clopidogrel) and "unchanged DAPT" (continued on aspirin and ticagrelor) cohorts, respectively. With a mean follow-up of 8 months, the incidence rates (per 100 person-year) of death, AMI readmission and MACE were 2.89, 3.68, and 4.91 in the de-escalated cohort and 2.42, 3.28, and 4.72 in the unchanged cohort, respectively, based on an inverse probability of treatment weighted approach that adjusting for baseline characteristics of the patients. Multivariate Cox regression analyses showed the two groups had no significant differences in the hazard risk of death, AMI admission, and MACE. Additionally, there was no observed difference in the risk of bleeding, including major or clinically relevant non-major bleeding. The real-world data revealed that de-escalation of P2Y12 inhibitor in DAPT was not associated with a higher risk of death or AMI readmission in Taiwanese patients with AMI undergoing successful PCI.

Influenza Vaccination and the Risk of Ventricular Arrhythmias in Patients With Chronic Obstructive Pulmonary Disease: A Population-Based Longitudinal Study.

Backgrounds: Influenza vaccination could decrease the risk of major cardiac events in patients with chronic obstructive pulmonary disease (COPD). However, the effects of the vaccine on decreasing the risk of ventricular arrhythmia (VA) development in such patients remain unclear. Methods: We retrospectively analyzed the data of 18,658 patients with COPD (≥55 years old) from the National Health Insurance Research Database from January 1, 2001, to December 31, 2012. After a 1:1 propensity score matching by the year of diagnosis, we divided the patients into vaccinated and unvaccinated groups. Time-varying Cox proportional hazards regression was applied to assess the time to event hazards of influenza vaccination exposure. Results: The risk of VA occurrence was significantly lower in the vaccinated group during influenza season and all seasons [adjusted hazard ratio (aHR): 0.62, 95% CI: 0.41-0.95; aHR: 0.69, 95% CI: 0.44-1.08; and aHR: 0.65, 95% CI: 0.48-0.89, in the influenza season, non-influenza season, and all seasons, respectively]. Among patients with CHA2DS2-VASc scores (conditions and characteristics included congestive heart failure, hypertension, diabetes, stroke, vascular disease, age, and sex) of 2-3, receiving one time and two to three times of influenza vaccination were associated with lower risk of VA occurrence in all seasons (aHR: 0.28, 95% CI: 0.10-0.80; aHR: 0.27, 95% CI: 0.10-0.68, respectively). Among patients without stroke, peripheral vascular disease, and diabetes, a lower risk of VA occurrence after receiving one and two to three times vaccination was observed in all seasons. Among patients with a history of asthma and patients without a history of heart failure, ischemic heart disease, angina hypertension, or renal failure, a significantly lower risk of VA occurrence was observed after the first time of vaccination in all seasons. Conclusions: Influenza vaccination may be associated with lower risks of VA among patients with COPD aged 55-74. Further investigation is still needed to resolve this clinical question.

Comparison between ticagrelor versus clopidogrel in long term outcomes of Taiwanese diabetic subjects with acute coronary syndrome undergoing successful revascularization: From TSOC ACS-DM registry.

Although previous clinical trials demonstrated that ticagrelor could reduce cardiovascular events and mortality versus clopidogrel in patients with acute coronary syndrome (ACS), the real-world evidence of its clinical impacts on East Asian Diabetic population has rarely been investigated.Between November 2013 and June 2015, 1534 patients were recruited into the Acute Coronary Syndrome-Diabetes Mellitus Registry of the Taiwan Society of Cardiology (TSOC ACS-DM registry). After propensity score matching, a total of 730 patients undergoing successful revascularization and discharged on ticagrelor (N = 365) or clopidogrel (N = 365) were analyzed. The primary and secondary endpoints were all-cause mortality and re-hospitalization, respectively. The all-cause death associated with ticagrelor vs clopidogrel was 3.6% vs 7.4% (adjusted hazard ratio (HR) 0.34 [0.15-0.80]; P = .0138) at 24 months. The re-hospitalization rate at 24 months was 38.9% vs 39.2% (P = .3258).For diabetic patients with ACS, ticagrelor provided better survival benefit than clopidogrel without an increase of re-hospitalization in 24 months after successful percutaneous coronary intervention. This study in real-world circumstance provided valuable complementary data to externally validate platelet inhibition and patient outcomes (PLATO) finding especially in Asian diabetic population.

Comparison of the TIMI, GRACE, PAMI and CADILLAC risk scores for prediction of long-term cardiovascular outcomes in Taiwanese diabetic patients with ST-segment elevation myocardial infarction: From the registry of the Taiwan Society of Cardiology.

Acute coronary syndrome (ACS) patients with diabetes have significantly worse cardiovascular outcomes than those without diabetes. This study aimed to compare the performance of The Thrombolysis In Myocardial Infarction (TIMI), Global Registry of Acute Coronary Events (GRACE), Primary Angioplasty in Myocardial Infarction (PAMI), and Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) risk scores in predicting long-term cardiovascular outcomes in diabetic patients with ST-segment elevation myocardial infarction (STEMI). From the Acute Coronary Syndrome-Diabetes Mellitus Registry of the Taiwan Society of Cardiology, patients with STEMI were included. The TIMI, GRACE, PAMI, and CADILLAC risk scores were calculated. The discriminative potential of risk scores was analyzed using the area under the receiver-operating characteristics curve (AUC). In the 455 patients included, all four risk score systems demonstrated predictive accuracy for 6-, 12- and 24-month mortality with AUC values of 0.67-0.82. The CADILLAC score had the best discriminative accuracy, with an AUC of 0.8207 (p<0.0001), 0.8210 (p<0.0001), and 0.8192 (p<0.0001) for 6-, 12-, and 24-month mortality, respectively. It also had the best predictive value for bleeding and acute renal failure, with an AUC of 0.7919 (p<0.05) and 0.9764 (p<0.0001), respectively. Patients with CADILLAC risk scores >8 had poorer 2-year survival than those with lower scores (log-rank p<0.0001). In conclusion, the CADILLAC risk score is more effective than other risk scores in predicting 6-month, 1-year, and 2-year all-cause mortality in diabetic patients with STEMI. It also had the best predictive value for in-hospital bleeding and acute renal failure.

Incidence and risk of major heart diseases in middle-aged adults with moderate to severe vision impairment: a population-based cohort study.

BACKGROUND/AIM: To estimate the incidence and risk of major adverse cardiovascular events (MACEs), including heart failure and ischaemic heart disease, among middle-aged people with a visual disability (VD). METHODS: We used a national health insurance research database to conduct a population-based cohort study from 1 January 2000 to 31 December 2013. Patients with VD aged 35~65 years were recruited. For each VD patient, five age-matched, sex-matched and comorbidity-matched patients were randomly selected and recruited as controls. Control patients had no documented disability. RESULTS: This study recruited 978 patients with VD (mean age±SD, 55.1±7.8 years; 48.9% male) and 4677 controls. Compared with the same sex of the controls, women with VD had higher incidence of MACE 1 (7.9 vs 2.8/1000 person-years, p<0.001), MACE 2 (27.5 vs 16.9/1000 person-years, p<0.001), MACE 3 (3.7 vs 1.4/1000 person-years, p<0.005) and MACE 4 (4.5 vs 2.5/1000 person-years, p<0.05), and men with VD had higher incidence of MACE 1 (4.6 vs 2.0/1000 person-years, p<0.005). Compared with the controls, patients with VD had lower cumulative MACE 1~MACE 4-free probabilities and had an independently higher risk of MACE 1~MACE 4 during the 13-year study, yielding an adjusted hazard ratio range of 1.31~2.75. Those persons with VD who had diabetes and hypertension had greater risks of MACE 1~MACE 4. CONCLUSIONS: Middle-aged adults with VD were at risk of MACEs. A programme for MACE prevention is important for middle-aged people with VD. This is especially true for women and for those who also have diabetes and hypertension.