Five-Year Trends of Vascular Disease-Related Amputations in Romania: A Retrospective Database Study.

Background/Objectives: Lower extremity amputations (LEAs) are a burdensome complication of peripheral artery disease (PAD) and/or arterial embolism and thrombosis (AET). We assessed the trends in PAD- and/or AET-related LEAs in Romania. Methods: This retrospective study (2015-2019) analyzed data on minor and major LEAs in hospitalized patients recorded in the National School for Public Health, Management, and Health Education database. The absolute numbers and incidences of LEAs were analyzed by diagnosis type, year, age, sex, and amputation level. Results: Of 38,590 vascular disease-related amputations recorded nationwide, 36,162 were in PAD and 2428 in AET patients. The average LEA incidence in the general population was 34.73 (minimum: 31.96 in 2015; maximum: 36.57 in 2019). The average incidence of major amputations, amputations above the knee, hip amputations, amputations below the knee, and minor amputations was 16.21 (15.62 in 2015; 16.84 in 2018), 13.76 (13.33 in 2015; 14.28 in 2018), 0.29 (0.22 in 2017; 0.35 in 2019), 2.15 (2.00 in 2015; 2.28 in 2019), and 18.52 (16.34 in 2015; 20.12 in 2019), respectively. Yearly PAD- and/or AET-related amputations were significantly higher in men versus women. The overall number of LEAs increased with age, particularly in patients ≥ 70 years. The increase in the total number of amputations was mainly due to a constant rise in minor amputations for both groups, regardless of gender. Conclusions: PAD- and/or AET-related LEAs in Romania increased from 2015 to 2019, with men having a greater incidence than women. Raising awareness and effective management strategies are needed to prevent LEAs.

Genetic evidence for a causal link between gut microbiota and arterial embolism and thrombosis: a two-sample Mendelian randomization study.

Background: Previous research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study. Methods: Genetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Results: We identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08-2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42-0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25-3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P<0.05). Conclusion: Our systematic analyses provided evidence to support a potential causal relationship between several gut microbiota taxa and the risk of arterial embolism and thrombosis. More studies are required to show how the gut microbiota affects the development of arterial embolism and thrombosis.

Genetically predicted green tea intake and the risk of arterial embolism and thrombosis.

Background: In previous observational studies, green tea intake has been demonstrated to protect against arterial embolism and thrombosis. However, whether there is a causative connection between green tea intake and arterial embolism and thrombosis is currently unclear. Methods: A two-sample Mendelian randomization (MR) study has been designed to explore whether there is a causal association between green tea intake and arterial embolism and thrombosis by acquiring exposure and outcome data from previously published research. Data from the MRC-IEU (data on green tea intake, 64,949 participants) consortium and the FinnGen project (data on arterial embolism and thrombosis, 278 cases of arterial thrombosis and 92,349 control participants) has been utilized to determine the causal impact of green tea intake on arterial embolism and thrombosis. Results: We found that genetically predicted green tea intake was causally associated with a lower risk of arterial embolism and thrombosis (IVW odds ratio [OR] per SD decrease in green tea intake = 0.92 [95% confidence interval, 0.85-0.99]; p = 0.032). Moreover, the sensitivity analysis (both MR Egger regression and weighted median) yielded comparable estimates but with low precision. No directional pleiotropic effect between green tea intake and arterial embolism and thrombosis was observed in both funnel plots and MR-Egger intercepts. Conclusions: Our study provided causal evidence that genetically predicted green tea intake may be a protective factor against arterial embolism and thrombosis.

The Correlation between Lower Extremity Fracture and Subsequent Arterial Embolism and Thrombosis-A National Population Cohort Study.

The hazard of subsequent arterial embolism and thrombosis (SAET) in patients with lower leg fractures is not yet well demonstrated. The purpose of this study is to determine the correlation between lower leg fracture and SAET in Taiwan. A total of 134,844 patients with lower leg fractures (ICD-9-CM: 823) and chronological diagnosis as SAET (ICD-9-CM: 444.22) was matched (1:1) to the non-fracture cohort according to their propensity score (data coming from the National Health Insurance database between January 2000 to December 2012). Patients were matched by age, gender, and comorbidities. The incidence of SAET and correlation between SAET development and lower leg fracture was statistically analyzed, and subgroup analysis categorized by characteristics and comorbidities was conducted as well. The cumulative incidence of SAET was calculated by Kaplan-Meier analysis. Kaplan-Meier analysis plot showed that, by the end of the ten-year follow-up period, the cumulative incidence of SAET was significantly higher for the lower leg fracture cohort than for the non-fracture cohort (log-rank test: p < 0.001). The lower leg fracture, male, elder age (45-64-year-old; ≥65-year-old), hypertension, diabetes mellitus, and gout were significantly associated with lower extremity SAET risk compared with the matched group. There was an inseparable correlation between the lower leg fracture group and the risks of SAET; subgroup analysis by gender (male, female), age (age < 40 years, age 40-64 years, and age > 65 years) and comorbidities (hypertension, diabetes mellitus, and gout) show compatible results as well. Patients with lower leg fracture have a significantly increased risk of SAET since then two years after the fracture. The hazard of SAET was significantly higher in patients with lower leg fracture than in the non-fracture cohort, and the high incidence was found since then two years after fracture. Further studies are warranted.

Risks of thromboembolism associated with hormonal contraceptives related to body mass index and aging in Japanese women.

OBJECTIVE: The aim of this study is to estimate the risk of thromboembolism related to body mass index (BMI) and aging among users of hormonal contraceptives in Japan. METHODS: A case-control study of the risk of obesity and a descriptive study of the risk of age were conducted. We used the Pharmaceuticals and Medical Devices Agency database, and extracted thromboembolic events of combined oral contraceptive (COC) products. Control data were from the National Health and Nutrition Survey in Japan. Denominator of descriptive study was from IMS Health, JPM. RESULTS: A total of 306 thromboembolic events and 6423 controls were analyzed. The odds ratios (95% confidence interval) of the obesity groups (BMI ≥ 25) were 2.32 (1.71-3.15) for venous thromboembolism (VTE), 1.16 (0.62-2.18) for arterial embolism and thrombosis (ATE), and 1.83 (1.38-2.43) for overall thromboembolic events compared with the standard group (BMI of 18.5-24.9) as a reference. The estimated incidence rates of VTE, ATE and overall thromboembolic events per 10,000 person-years in users of therapeutic remedies for dysmenorrhea (35 µg ethinylestradiol combined with norethisterone, 20 µg ethinylestradiol combined with drospirenone and dienogest) among women aged 10-59 years from 2009 to 2013 were 2.38 (2.08-2.74), 0.63 (0.48-0.82), and 3.17 (2.81-3.57), respectively. This tendency was not seen for dienogest. CONCLUSIONS: The risk of VTE in the obesity group among COC users was more than 2 times higher than in the standard group. The incidence rates of VTE in Japanese users of all remedies for dysmenorrhea except dienogest were as high as in people in Western countries.

Thromboembolism as the adverse event of combined oral contraceptives in Japan.

BACKGROUND: The risk of thromboembolism associated with combined oral contraceptives (COCs) in Japanese women is not clear yet. The aim of this study is to estimate the current risk of thromboembolism among COC users in Japan. METHODS: We used the Pharmaceuticals and Medical Devices Agency (PMDA) database disclosed by PMDA from April 2004 to December 2013, and extracted thromboembolic events among adverse events from the adverse event information of COC products. RESULTS: Of the 581 thromboembolic events, venous thromboembolism (VTE) accounted for 394 events, arterial embolism and thrombosis (ATE) were 154, and thrombosis of unspecified sites was 33. In VTE, deep vein thrombosis and pulmonary embolism were the most frequent (78.4%), followed by cerebral vein thrombosis (11.4%). In ATE, cerebral infarction was the most frequent (76.0%) and approximately 6.9-fold higher than coronary heart diseases. The annual estimated incidence per 10,000 person-years of VTE, ATE and all thromboembolisms in current users of all COCs were 1.11 (95% confidence interval: 1.00-1.24), 0.37 (0.30-0.44), and 1.56 (1.42-1.71), respectively. The frequency of all thromboembolic events that developed within 90 days from the start of COCs was 45.5%, and that within 360 days was 81.2%. Sixteen deceased cases were suspected to be associated with thromboembolism, and the estimated mortality rate between 2009 and 2013 was 0.50 (0.30-0.84) per 100,000 person-years. CONCLUSIONS: Incidence rates of thromboembolism, particularly VTE, in Japanese current COC users became clear for the first time, being slightly lower than people in Western countries.