Associations of hormonal contraceptives and infertility medications on the risk of venous thromboembolism, ischemic stroke, and cardiovascular disease in women

2018 ◽  
Vol 67 (4) ◽  
pp. 729-735 ◽  
Author(s):  
Shu-qi Ge ◽  
Xin Tao ◽  
Li-si Cai ◽  
Xuan-ying Deng ◽  
Muh-fa Hwang ◽  
...  

The purpose of this study was to examine the relations of hormonal contraceptives and infertility drugs with the risk of venous thromboembolism (VTE), deep vein thrombosis (DVT), pulmonary embolism (PE), ischemic stroke, and cardiovascular disease. The Taiwan National Health Institute Research Database was searched for women who had taken hormonal contraceptives or infertility medications from 2000 to 2010. The two groups were age and index date matched with controls (1:4 ratios). Cox regression analysis was used to examine the risks of VTE, DTE, PE, ischemic stroke, and cardiovascular disease. A total of 32,067 women were included in the hormonal contraceptives group and 4710 in the infertility medications group (matched controls: 127,872 and 18,840, respectively). After adjustment for age, comorbidities, and other confounders, the contraceptives group had a higher risk of VTE (adjusted HR 1.14, 95% CI 1.004 to 1.30) and cardiovascular disease (adjusted HR 1.30, 95% CI 1.26 to 1.34), and lower risk of ischemic stroke (adjusted HR 0.90, 95% CI 0.86 to 0.95). The infertility medications group had a higher risk of VTE (adjusted HR 1.996, 95% CI 1.41 to 2.72) and DVT (adjusted HR 1.86, 95% CI 1.31 to 2.63), and lower risk of ischemic stroke (adjusted HR 0.82, 95% CI 0.68 to 0.99) and cardiovascular disease (adjusted HR 0.83, 95% CI 0.74 to 0.94). Hormonal contraceptives and infertility medications appear to lower the risk of ischemic stroke and increase the risk of VTE; however, their effect on the risk of other types of cardiovascular events varies.

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wen-Yi Huang ◽  
Chun-Wei Chang ◽  
Chiung-Mei Chen ◽  
Kuan-Hsing Chen ◽  
Chien-Hung Chang ◽  
...  

Abstract Background The incidence of cerebral stroke, including ischemic infarction and intracranial hemorrhage (ICH), increases in patients with nephrotic syndrome (NS). However, the clinical characteristics of patients with NS and stroke remain elusive. We aimed to investigate the clinical presentation and prognosis among patients with NS and ischemic stroke (IS) or ICH. Methods We conducted a population-based retrospective cohort study of patients with NS and acute stroke using the Chang Gung Research Database of Taiwan from January 1, 2001, to December 31, 2017. The participants were recruited from the 7 branches of Chang Gung Memorial Hospital. Results A total of 233 patients with IS and 57 patients with ICH were enrolled. The median age was 60 (52–70) years. The prevalence rates of hyperlipidemia, hyperuricemia, and smoking were higher in IS than in ICH. IS demonstrated lower white blood cell count (7.80 vs. 8.92 × 109/L) and high-sensitivity C-reactive protein level (33.42 vs. 144.10 nmol/L) and higher cholesterol (5.74 vs. 4.84 mmol/L), triglyceride (1.60 vs. 1.28 mmol/L), and albumin (24 vs. 18 g/L) levels compared with ICH. The dependent functional status and 30-day mortality were higher in ICH than in IS. The risk factors for 30-day mortality for patients with NS and stroke were coronary artery disease (CAD), ICH, and total anterior circulation syndrome. The multivariate Cox regression analysis revealed that CAD was positively associated with 30-day mortality in patients with IS (hazard ratio 24.58, 95 % CI 1.48 to 408.90). In patients with ICH, CAD and subarachnoid hemorrhage were positively associated with 30-day mortality (hazard ratio 5.49, 95 % CI 1.54 to 19.56; hazard ratio 6.32, 95 % CI 1.57 to 25.53, respectively). Conclusions ICH demonstrated a higher risk of dependence and 30-day mortality compared with IS in patients with NS. Intensive monitoring and treatment should be applied particularly in patients with NS and ICH.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Soojin Lee ◽  
Yeonhee Lee ◽  
Sehoon Park ◽  
Yaerim Kim ◽  
Kyungdo Han ◽  
...  

Abstract Background and Aims Cardiovascular disease is major cause of mortality among chronic kidney disease (CKD) patients, and it is fundamental to focus on reducing the potential risk factors. Regular physical activity is known to reduce the risk of cardiovascular disease in general population. However, whether the change of physical activity habits is beneficial for pre-dialysis CKD patients had not been examined thoroughly. Method We performed a nationwide population based cohort study using the database of Korean National Health Insurance System. Among adult patients who received national health screening program ≥2 times between 2012 and 2016, CKD patients were identified using the serum creatinine and dipstick albuminuria measurements. Those who previously underwent dialysis or diagnosed cardiovascular disease were excluded. The frequency and the intensity of the physical activity were obtained at least twice, from self-reported questionnaire during the health examination. The study groups were divided according to the status of physical activity habit alteration; active, quit exercise, start exercise, and inactive group. Then, the development of myocardial infarction (MI), stroke or death was assessed using the multivariate Cox regression analysis. Results During the median follow up of 3.18 years, 549,187 CKD patients were examined for adverse outcomes. Compared to those who remained inactive, the active group patients who consistently continued physical activity exhibited lower risk of MI (hazard ratio (HR); 0.76, 95% confidence interval (95% CI); 0.69-0.85), stroke (HR (95%CI) 0.69 (0.62-0.78)), and death (HR (95%CI) 0.62 (0.57-0.67)). Moreover, those who newly started physical activity also showed lower risk of adverse outcomes, compared to the inactive group (HR (95%CI) 0.83 (0.76-0.89)). Conclusion Continuation of physical activity in pre-dialysis CKD patients is beneficial to reduce the risk of cardiovascular disease development. Therefore, clinicians should encourage even mild intensity of physical activity to CKD patients.


Author(s):  
Raimo Jauhiainen ◽  
Jagadish Vangipurapu ◽  
Annamaria Laakso ◽  
Teemu Kuulasmaa ◽  
Johanna Kuusisto ◽  
...  

Abstract Background and aims To investigate the significance of nine amino acids as risk factors for incident cardiovascular disease events in 9,584 Finnish men. Materials and Methods A total of 9,584 men (age 57.4±7.0 years, body mass index 27.2±4.2 kg/m 2) from the METSIM study without cardiovascular disease and type 1 diabetes at baseline were included in this study. A total of 662 coronary artery disease (CAD) events, 394 ischemic stroke events, and 966 cardiovascular disease (CVD, CAD and stroke combined) events were recorded in a 12.3-year follow-up. Amino acids were measured using nuclear magnetic resonance platform. Results In Cox regression analysis phenylalanine and tyrosine were significantly associated with increased risk of CAD and CVD events, and phenylalanine with increased risk of ischemic stroke after the adjustment for confounding factors. Glutamine was significantly associated with decreased risk of stroke and CVD events and nominally with CAD events. Alanine was nominally associated with CAD events. Conclusion We identified alanine as a new amino acid associated with increased risk of CAD and glutamine as a new amino acid associated with decreased risk of ischemic stroke. We also confirmed that phenylalanine and tyrosine were associated with CAD, ischemic stroke, and CVD events.


2017 ◽  
Vol 23 (4) ◽  
pp. 319-328 ◽  
Author(s):  
Abrar Ahmad ◽  
Kristina Sundquist ◽  
Bengt Zöller ◽  
Peter J. Svensson ◽  
Jan Sundquist ◽  
...  

Thrombomodulin (THBD) serves as a cofactor for thrombin-mediated activation of anticoagulant protein C pathway. Genetic aberrations in THBD have been studied in arterial and venous thrombosis. However, genetic changes in THBD and their role in the risk assessment of recurrent venous thromboembolism (VTE) are not well understood. The aim of the present study was to identify the genetic aberrations in THBD and their association with the risk of VTE recurrence in a prospective population-based study. We sequenced the entire THBD gene, first in selected patients with VTE (n = 95) by Sanger sequencing and later validated those polymorphisms with minor allele frequency (MAF) ≥5% in the whole study population (n = 1465 with the follow-up period of 1998-2008) by Taqman polymerase chain reaction. In total, we identified 8 polymorphisms in THBD, and 3 polymorphisms with MAF ≥5% were further validated. No significant association between THBD polymorphisms and risk of VTE recurrence on univariate or multivariate Cox regression analysis was found (hazard ratio [HR] = 0.89, 95% confidence interval [CI] = 0.62-1.28, HR = 1.27, 95% CI = 0.88-1.85, and HR = 1.15, 95% CI = 0.80-1.66 for THBD rs1962, rs1042580, and rs3176123 polymorphisms, respectively), adjusted for family history, acquired risk factors for VTE, location of deep vein thrombosis, and risk of thrombophilia. Subanalysis of patients with unprovoked first VTE also showed no significant association of identified THBD polymorphisms with the risk of VTE recurrence. Our results show that aberrations in the THBD gene may not be useful for the assessment of VTE recurrence; however, further studies with large sample size are needed to confirm these findings.


TH Open ◽  
2017 ◽  
Vol 01 (01) ◽  
pp. e56-e65 ◽  
Author(s):  
C. Gibson ◽  
Alex Spyropoulos ◽  
Alexander Cohen ◽  
Russell Hull ◽  
Samuel Goldhaber ◽  
...  

Background The IMPROVE score is a validated venous thromboembolism (VTE) assessment tool to risk stratify hospitalized, medically ill patients based on clinical variables. It was hypothesized that addition of D-dimer measurement to derive a new IMPROVEDD score would improve identification of at risk of VTE. Methods The association of the IMPROVE score and D-dimer ≥ 2 × the upper limit of normal (ULN) with the risk of symptomatic deep vein thrombosis, nonfatal pulmonary embolism, or VTE-related death was evaluated in 7,441 hospitalized, medically ill patients randomized in the APEX trial. Based on the Cox regression analysis, the IMPROVEDD score was derived by adding two points to the IMPROVE score if the D-dimer was ≥ 2 × ULN. Results Baseline D-dimer was independently associated with symptomatic VTE through 77 days (adjusted HR: 2.22 [95% CI: 1.38–1.58], p = 0.001). Incorporation of D-dimer into the IMPROVE score improved VTE risk discrimination (ΔAUC: 0.06 [95% CI: 0.02–0.09], p = 0.0006) and reclassification (continuous NRI: 0.34 [95% CI: 0.17–0.51], p = 0.001; categorical NRI: 0.13 [95% CI: 0.03–0.23], p = 0.0159). Patients with an IMPROVEDD score of ≥2 had a greater VTE risk compared with those with an IMPROVEDD score of 0 to 1 (HR: 2.73 [95% CI: 1.52–4.90], p = 0.0007). Conclusion Incorporation of D-dimer into the IMPROVE VTE risk assessment model further improves risk stratification in hospitalized, medically ill patients who received thromboprophylaxis. An IMPROVEDD score of ≥2 identifies hospitalized, medically ill patients with a heightened risk for VTE through 77 days.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yu-Yen Chen ◽  
Yung-Feng Yen ◽  
Jun-Xian Lin ◽  
Shih-Chao Feng ◽  
Li-Chen Wei ◽  
...  

Purpose. To investigate whether the risk of subsequent stroke, ischemic stroke, hemorrhagic stroke, and all-cause mortality is increased among retinal vein occlusion (RVO) patients compared to non-RVO patients. Methods. From the entire population of the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2013, a total of 22919 subjects with RVO were enrolled in the RVO group, and 114595 propensity score (PS)-matched non-RVOs were enrolled in the comparison group. PS matching was based on age, gender, obesity, diabetes, hypertension, hyperlipidemia, coronary artery disease, atrial fibrillation, hyperviscosity syndrome, Charlson comorbidity index, glaucoma, and the use of antithrombotic drugs. A multivariate Cox regression analysis was used to estimate the adjusted hazard ratios (HRs) with a 95% confidence interval (CI) for each of the clinical outcomes, including stroke, ischemic stroke, hemorrhagic stroke, and all-cause mortality. Furthermore, we divided the RVO group into the branch retinal vein occlusion (BRVO) group and the central retinal vein occlusion (CRVO) group and separately compared their subsequent risks of the clinical outcomes with those of the comparison group. Results. After adjusting for PS, the RVO group had a significantly higher risk of stroke (adjusted HR = 1.36; 95% CI: 1.32–1.40), ischemic stroke (adjusted HR = 1.36; 95% CI: 1.32–1.40), and hemorrhagic stroke (adjusted HR = 1.34; 95% CI: 1.24–1.44). However, the all-cause mortality did not exhibit significant differences. Furthermore, both the BRVOs and CRVOs had a significantly higher risk of subsequent stroke, ischemic stroke, and hemorrhagic stroke than did the comparisons, whereas all-cause mortality was similar among the groups. Conclusions. People with RVO are at a significantly greater risk of developing stroke, ischemic stroke, and hemorrhagic stroke. However, RVO does not significantly increase the risk of all-cause mortality.


2020 ◽  
Vol 17 (3) ◽  
pp. 218-223
Author(s):  
Haichao Wang ◽  
Li Gong ◽  
Xiaomei Xia ◽  
Qiong Dong ◽  
Aiping Jin ◽  
...  

Background: Depression and anxiety after stroke are common conditions that are likely to be neglected. Abnormal red blood cell (RBC) indices may be associated with neuropsychiatric disorders. However, the association of RBC indices with post-stroke depression (PSD) and poststroke anxiety (PSA) has not been sufficiently investigated. Methods: We aimed to investigate the trajectory of post-stroke depression and anxiety in our follow- up stroke clinic at 1, 3, and 6 months, and the association of RBC indices with these. One hundred and sixty-two patients with a new diagnosis of ischemic stroke were followed up at 1, 3, and 6 months, and underwent Patient Health Questionnaire-9 (PHQ-9) and the general anxiety disorder 7-item (GAD-7) questionnaire for evaluation of depression and anxiety, respectively. First, we used Kaplan-Meier analysis to investigate the accumulated incidences of post-stroke depression and post-stroke anxiety. Next, to explore the association of RBC indices with psychiatric disorders after an ischemic stroke attack, we adjusted for demographic and vascular risk factors using multivariate Cox regression analysis. Results: Of the 162 patients with new-onset of ischemic stroke, we found the accumulated incidence rates of PSD (1.2%, 17.9%, and 35.8%) and PSA (1.2%, 13.6%, and 15.4%) at 1, 3, and 6 months, respectively. The incident PSD and PSA increased 3 months after a stroke attack. Multivariate Cox regression analysis indicated independent positive associations between PSD risk and higher mean corpuscular volume (MCV) (OR=1.42, 95% CI=1.16-1.76), older age (OR=2.63, 95% CI=1.16-5.93), and a negative relationship between male sex (OR=0.95, 95% CI=0.91-0.99) and PSA. Conclusion: The risks of PSD and PSA increased substantially 3 months beyond stroke onset. Of the RBC indices, higher MCV, showed an independent positive association with PSD.


2021 ◽  
pp. 1-9
Author(s):  
Ankur A. Dashputre ◽  
Keiichi Sumida ◽  
Fridtjof Thomas ◽  
Justin Gatwood ◽  
Oguz Akbilgic ◽  
...  

<b><i>Introduction:</i></b> Hypo- and hyperkalemia are associated with a higher risk of ischemic stroke. However, this association has not been examined in an advanced chronic kidney disease (CKD) population. <b><i>Methods:</i></b> From among 102,477 US veterans transitioning to dialysis between 2007 and 2015, 21,357 patients with 2 pre-dialysis outpatient estimated glomerular filtration rates &#x3c;30 mL/min/1.73 m<sup>2</sup> 90–365 days apart and at least 1 potassium (K) each in the baseline and follow-up period were identified. We separately examined the association of both baseline time-averaged K (chronic exposure) and time-updated K (acute exposure) treated as categorized (hypokalemia [K &#x3c;3.5 mEq/L] and hyperkalemia [K &#x3e;5.5 mEq/L] vs. referent [3.5–5.5 mEq/L]) and continuous exposure with time to the first ischemic stroke event prior to dialysis initiation using multivariable-adjusted Cox regression models. <b><i>Results:</i></b> A total of 2,638 (12.4%) ischemic stroke events (crude event rate 41.9 per 1,000 patient years; 95% confidence interval [CI] 40.4–43.6) over a median (Q<sub>1</sub>–Q<sub>3</sub>) follow-up time of 2.56 (1.59–3.89) years were observed. The baseline time-averaged K category of hypokalemia (adjusted hazard ratio [aHR], 95% CI: 1.35, 1.01–1.81) was marginally associated with a significantly higher risk of ischemic stroke. However, time-updated hyperkalemia was associated with a significantly lower risk of ischemic stroke (aHR, 95% CI: 0.82, 0.68–0.98). The exposure-outcome relationship remained consistent when using continuous K levels for both the exposures. <b><i>Discussion/Conclusion:</i></b> In patients with advanced CKD, hypokalemia (chronic exposure) was associated with a higher risk of ischemic stroke, whereas hyperkalemia (acute exposure) was associated with a lower risk of ischemic stroke. Further studies in this population are needed to explore the mechanisms underlying these associations.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chia-Yu Hsu ◽  
Chun-Yu Cheng ◽  
Jiann-Der Lee ◽  
Meng Lee ◽  
Bruce Ovbiagele

Abstract Objective We aim to compare the effect of long-term anti-seizure medication (ASM) monotherapy on the risk of death and new ischemic stroke in patients with post-stroke epilepsy (PSE). Patients and methods We identified all hospitalized patients (≥ 20 years) with a primary diagnosis of ischemic or hemorrhagic stroke from 2001 to 2012 using the National Health Insurance Research Database in Taiwan. The PSE cohort were defined as the stroke patients (1) who had no epilepsy and no ASMs use before the index stroke, and (2) who had epilepsy and ASMs use after 14 days from the stroke onset. The patients with PSE receiving ASM monotherapy were enrolled and were categorized into phenytoin, valproic acid, carbamazepine, and new ASM groups. We employed the Cox regression model to estimate the unadjusted and adjusted hazard ratios (HRs) with 95 % confidence intervals (CIs) of death and new ischemic stroke within 5 years across all groups, using the new ASM group as the reference. Results Of 6962 patients with PSE using ASM monotherapy, 3917 (56 %) were on phenytoin, 1623 (23 %) on valproic acid, 457 (7 %) on carbamazepine, and 965 (14 %) on new ASMs. After adjusting for confounders, compared with new ASM users, phenytoin users had a higher risk of death in 5 years (HR: 1.64; 95 % CI: 1.06–2.55). On the other hand, all ASM groups showed a similar risk of new ischemic stroke in 5 years. Conclusions Among patients with PSE on first-line monotherapy, compared to new ASMs, use of phenytoin was associated with a higher risk of death in 5 years.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Geng-He Chang ◽  
Fong-Fu Chou ◽  
Ming-Shao Tsai ◽  
Yao-Te Tsai ◽  
Ming-Yu Yang ◽  
...  

AbstractPatients with end-stage renal disease (ESRD) may demonstrate secondary hyperparathyroidism (SHPT), characterized by parathyroid hormone oversecretion in response to electrolyte imbalance (e.g., hypocalcemia and hyperphosphatemia). Moreover, this electrolyte imbalance may affect vocal cord muscle contraction and lead to voice change. Here, we explored the effects of SHPT on the voices of patients with ESRD. We used data of 147,026 patients with ESRD from the registry for catastrophic illness patients, a sub-database of Taiwan National Health Insurance Research Database. We divided these patients into 2 groups based on whether they had hyperparathyroidism (HPT) and compared vocal dysfunction (VD) incidence among them. We also prospectively included 60 ESRD patients with SHPT; 45 of them underwent parathyroidectomy. Preoperatively and postoperatively, voice analysis was used to investigate changes in vocal parameters. In the real-world database analysis, the presence of HPT significantly increased VD incidence in patients with ESRD (p = 0.003): Cox regression analysis results indicated that patients with ESRD had an approximately 1.6-fold increased VD risk (p = 0.003). In the clinical analysis, the “jitter” and “shimmer” factors improved significantly after operation, whereas the aerodynamic factors remained unchanged. In conclusion, SHPT was an independent risk factor for VD in patients with ESRD, mainly affecting their acoustic factors.


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