Association of COVID-19 with arterial and venous vascular diseases: a population-wide cohort study of 48 million adults in England and Wales

Importance: The long-term effects of COVID-19 on the incidence of vascular diseases are unclear. Objective: To quantify the association between time since diagnosis of COVID-19 and vascular disease, overall and by age, sex, ethnicity, and pre-existing disease. Design: Cohort study based on population-wide linked electronic health records, with follow up from January 1st to December 7th 2020. Setting and participants: Adults registered with an NHS general practice in England or Wales and alive on January 1st 2020. Exposures: Time since diagnosis of COVID-19 (categorised as 0-6 days, 1-2 weeks, 3-4, 5-8, 9-12, 13-26 and 27-49 weeks since diagnosis), with and without hospitalisation within 28 days of diagnosis. Main outcomes and measures: Primary outcomes were arterial thromboses (mainly acute myocardial infarction and ischaemic stroke) and venous thromboembolic events (VTE, mainly pulmonary embolism and lower limb deep vein thrombosis). We also studied other vascular events (transient ischaemic attack, haemorrhagic stroke, heart failure and angina). Hazard ratios were adjusted for demographic characteristics, previous disease diagnoses, comorbidities and medications. Results: Among 48 million adults, 130,930 were and 1,315,471 were not hospitalised within 28 days of COVID-19. In England, there were 259,742 first arterial thromboses and 60,066 first VTE during 41.6 million person-years follow-up. Adjusted hazard ratios (aHRs) for first arterial thrombosis compared with no COVID-19 declined rapidly from 21.7 (95% CI 21.0-22.4) to 3.87 (3.58-4.19) in weeks 1 and 2 after COVID-19, 2.80 (2.61-3.01) during weeks 3-4 then to 1.34 (1.21-1.48) during weeks 27-49. aHRs for first VTE declined from 33.2 (31.3-35.2) and 8.52 (7.59-9.58) in weeks 1 and 2 to 7.95 (7.28-8.68) and 4.26 (3.86-4.69) during weeks 3-4 and 5-8, then 2.20 (1.99-2.44) and 1.80 (1.50-2.17) during weeks 13-26 and 27-49 respectively. aHRs were higher, for longer after diagnosis, after hospitalised than non-hospitalised COVID-19. aHRs were also higher among people of Black and Asian than White ethnicity and among people without than with a previous event. Across the whole population estimated increases in risk of arterial thromboses and VTEs were 2.5% and 0.6% respectively 49 weeks after COVID-19, corresponding to 7,197 and 3,517 additional events respectively after 1.4 million COVID-19 diagnoses. Conclusions and Relevance: High rates of vascular disease early after COVID-19 diagnosis decline more rapidly for arterial thromboses than VTEs but rates remain elevated up to 49 weeks after COVID-19. These results support continued policies to avoid COVID-19 infection with effective COVID-19 vaccines and use of secondary preventive agents in high-risk patients.

Download Full-text

Differential cerebrovascular risks in glioblastoma and meningioma patients: a population-based matched cohort study in Wales (United Kingdom)

Neuro-Oncology ◽

10.1093/neuonc/noab195.028 ◽

2021 ◽

Vol 23 (Supplement_4) ◽

pp. iv12-iv12

Author(s):

Michael T C Poon ◽

Kai Jin ◽

Paul M Brennan ◽

Jonine Figueroa ◽

Cathie Sudlow

Keyword(s):

Cohort Study ◽

General Population ◽

Ischaemic Stroke ◽

Population Based ◽

Parametric Models ◽

Matched Cohort ◽

Matched Cohort Study ◽

Hazard Ratios ◽

History Of

Abstract Aims There is limited evidence on cerebrovascular risks in glioblastoma and meningioma patients. We aimed to compare cerebrovascular risks of these patients with the general population. Method We used population-based routine healthcare and administrative data linkage in this matched cohort study. Cases were adult glioblastoma and meningioma patients diagnosed in Wales 2000-2014 identified in the cancer registry. Controls from cancer-free general population were matched to cases (5:1 ratio) on age (±5 years), sex and GP practice. Factors included in multivariable models were age, sex, index of multiple deprivation, hypertension, diabetes, high cholesterol, history of cardiovascular disease, and medications for cardiovascular diseases. Outcomes were fatal and non-fatal haemorrhagic and ischaemic stroke. We used flexible parametric models adjusting for confounders to calculate the hazard ratios (HR). Results Final analytic population was 16,921 participants, of which 1,340 had glioblastoma and 1,498 had meningioma. The median follow-up time was 0.5 year for glioblastoma patients, 4.9 years for meningioma patients, and 6.6 years for controls. The number of haemorrhage and ischaemic stroke was 154 and 374 in the glioblastoma matched cohort, respectively, and 180 and 569 in the meningioma matched cohort, respectively. The adjusted HRs for haemorrhagic and ischaemic stroke were 3.74 (95%CI 1.87-6.57) and 5.62 (95%CI 2.56-10.42) in glioblastoma patients, respectively, and were 2.42 (95%CI 1.58-3.52) and 1.86 (95%CI 1.54-2.23) in meningioma patients compared with their controls. Conclusion Glioblastoma and meningioma patients had higher cerebrovascular risks; these risks were even higher for glioblastoma patients. Further assessment of these potentially modifiable risks may improve survivorship.

Download Full-text

Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study

BMJ ◽

10.1136/bmj.m3464 ◽

2020 ◽

pp. m3464 ◽

Cited By ~ 3

Author(s):

Yi-Xin Wang ◽

Mariel Arvizu ◽

Janet W Rich-Edwards ◽

Jennifer J Stuart ◽

JoAnn E Manson ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Cycle Length ◽

Premature Mortality ◽

Health Study ◽

Menstrual Cycles ◽

Hazard Ratios

AbstractObjectiveTo evaluate whether irregular or long menstrual cycles throughout the life course are associated with all cause and cause specific premature mortality (age <70 years).DesignProspective cohort study.SettingNurses’ Health Study II (1993-2017).Participants79 505 premenopausal women without a history of cardiovascular disease, cancer, or diabetes and who reported the usual length and regularity of their menstrual cycles at ages 14-17 years, 18-22 years, and 29-46 years.Main outcome measuresHazard ratios and 95% confidence intervals for all cause and cause specific premature mortality (death before age 70 years) were estimated from multivariable Cox proportional hazards models.ResultsDuring 24 years of follow-up, 1975 premature deaths were documented, including 894 from cancer and 172 from cardiovascular disease. Women who reported always having irregular menstrual cycles experienced higher mortality rates during follow-up than women who reported very regular cycles in the same age ranges. The crude mortality rate per 1000 person years of follow-up for women reporting very regular cycles and women reporting always irregular cycles were 1.05 and 1.23 for cycle characteristics at ages 14-17 years, 1.00 and 1.37 for cycle characteristics at ages 18-22 years, and 1.00 and 1.68 for cycle characteristics at ages 29-46 years. The corresponding multivariable adjusted hazard ratios for premature death during follow-up were 1.18 (95% confidence interval 1.02 to 1.37), 1.37 (1.09 to 1.73), and 1.39 (1.14 to 1.70), respectively. Similarly, women who reported that their usual cycle length was 40 days or more at ages 18-22 years and 29-46 years were more likely to die prematurely than women who reported a usual cycle length of 26-31 days in the same age ranges (1.34, 1.06 to 1.69; and 1.40, 1.17 to 1.68, respectively). These relations were strongest for deaths related to cardiovascular disease. The higher mortality associated with long and irregular menstrual cycles was slightly stronger among current smokers.ConclusionsIrregular and long menstrual cycles in adolescence and adulthood are associated with a greater risk of premature mortality (age <70 years). This relation is slightly stronger among women who smoke.

Download Full-text

Headache as a risk factor for dementia: A prospective population-based study

Cephalalgia ◽

10.1177/0333102413513181 ◽

2013 ◽

Vol 34 (5) ◽

pp. 327-335 ◽

Cited By ~ 22

Author(s):

Knut Hagen ◽

Eystein Stordal ◽

Mattias Linde ◽

Timothy J Steiner ◽

John-Anker Zwart ◽

...

Keyword(s):

Risk Factor ◽

Cohort Study ◽

Cox Regression ◽

Subsequent Development ◽

Population Based ◽

Health Study ◽

Cox Regression Analysis ◽

Hazard Ratios ◽

Increased Risk

Background Headache has not been established as a risk factor for dementia. The aim of this study was to determine whether any headache was associated with subsequent development of vascular dementia (VaD), Alzheimer’s disease (AD) or other types of dementia. Methods This prospective population-based cohort study used baseline data from the Nord-Trøndelag Health Study (HUNT 2) performed during 1995–1997 and, from the same Norwegian county, a register of cases diagnosed with dementia during 1997–2010. Participants aged ≥20 years who responded to headache questions in HUNT 2 were categorized (headache free; with any headache; with migraine; with nonmigrainous headache). Hazard ratios (HRs) for later inclusion in the dementia register were estimated using Cox regression analysis. Results Of 51,383 participants providing headache data in HUNT 2, 378 appeared in the dementia register during the follow-up period. Compared to those who were headache free, participants with any headache had increased risk of VaD ( n = 63) (multivariate-adjusted HR = 2.3, 95% CI 1.4–3.8, p = 0.002) and of mixed dementia (VaD and AD ( n = 52)) (adjusted HR = 2.0, 95% CI 1.1–3.5, p = 0.018). There was no association between any headache and later development of AD ( n = 180). Conclusion In this prospective population-based cohort study, any headache was a risk factor for development of VaD.

Download Full-text

Pre-eclampsia and risk of later kidney disease: nationwide cohort study

BMJ ◽

10.1136/bmj.l1516 ◽

2019 ◽

pp. l1516 ◽

Cited By ~ 22

Author(s):

Jonas H Kristensen ◽

Saima Basit ◽

Jan Wohlfahrt ◽

Mette Brimnes Damholt ◽

Heather A Boyd

Keyword(s):

Chronic Kidney Disease ◽

Cohort Study ◽

Kidney Disease ◽

Outcome Measure ◽

Cox Regression ◽

Hazard Ratio ◽

Hazard Ratios ◽

Gestational Age At Delivery ◽

History Of

ABSTRACTObjectiveTo investigate associations between pre-eclampsia and later risk of kidney disease.DesignNationwide register based cohort study.SettingDenmark.PopulationAll women with at least one pregnancy lasting at least 20 weeks between 1978 and 2015.Main outcome measureHazard ratios comparing rates of kidney disease between women with and without a history of pre-eclampsia, stratified by gestational age at delivery and estimated using Cox regression.ResultsThe cohort consisted of 1 072 330 women followed for 19 994 470 person years (average 18.6 years/woman). Compared with women with no previous pre-eclampsia, those with a history of pre-eclampsia were more likely to develop chronic renal conditions: hazard ratio 3.93 (95% confidence interval 2.90 to 5.33, for early preterm pre-eclampsia (delivery <34 weeks); 2.81 (2.13 to 3.71) for late preterm pre-eclampsia (delivery 34-36 weeks); 2.27 (2.02 to 2.55) for term pre-eclampsia (delivery ≥37 weeks). In particular, strong associations were observed for chronic kidney disease, hypertensive kidney disease, and glomerular/proteinuric disease. Adjustment for cardiovascular disease and hypertension only partially attenuated the observed associations. Stratifying the analyses on time since pregnancy showed that associations between pre-eclampsia and chronic kidney disease and glomerular/proteinuric disease were much stronger within five years of the latest pregnancy (hazard ratio 6.11 (3.84 to 9.72) and 4.77 (3.88 to 5.86), respectively) than five years or longer after the latest pregnancy (2.06 (1.69 to 2.50) and 1.50 (1.19 to 1.88). By contrast, associations between pre-eclampsia and acute renal conditions were modest.Conclusions Pre-eclampsia, particularly early preterm pre-eclampsia, was strongly associated with several chronic renal disorders later in life. More research is needed to determine which women are most likely to develop kidney disease after pre-eclampsia, what mechanisms underlie the association, and what clinical follow-up and interventions (and in what timeframe post-pregnancy) would be most appropriate and effective.

Download Full-text

Antiplatelet Agents In Diabetic Lower Extremity Vascular Disease. A Va Cooperative Study

Thrombosis and Haemostasis ◽

10.1055/s-0038-1652222 ◽

1981 ◽

Vol 46 (01) ◽

pp. 091-091

Author(s):

J Colwell

Keyword(s):

Lower Extremity ◽

Vascular Disease ◽

Collaborative Study ◽

Antiplatelet Agents ◽

Vascular Complication ◽

Smoking History ◽

Diabetic Patients ◽

Vascular Events ◽

Diabetic Vascular Disease

Peripheral vascular disease is a devastating complication of diabetes mellitus. Post-operative vascular death rates are 10% or more following amputation for gangrene in diabetic patients, and three year mortality approaches 30%. An additional 20-30% of patients require subsequent amputation for diabetic gangrene. In view of these statistics, and because of the postulated role of the blood platelet in diabetic vascular disease, a collaborative study on antiplatelet agents was begun in 10 VA medical centers in 1977. In a double-blinded study, aspirin (325 mg tid) plus dipyridamole (75 mg tid) or placebos are given to adult diabetic males who had suffered a recent amputation for diabetic lower extremity vascular disease. End points are major vascular events after at least 3 years of follow-up.Recruitment of 231 subjects was completed by May, 1980. Baseline characteristics are well matched in both groups. Mean age is 59.6 years, duration of diabetes 12.7 years, smoking history 33.3 pack years, and treatment with insulin 68%. Previous myocardial infarction, congestive heart failure, and/or cerebrovascular disease is present in 17-18% and retinopathy is present in 40% at entry. About 43% have more than one vascular complication at baseline.Mean duration of follow-up is now 18 months. Major vascular events in separate patients are: 40 amputations, 31 deaths, 5 myocardial infarctions. Numerous less serious vascular events have also occurred, as have multiple events in single patients. Therapy has been stopped in 17% of patients, but rarely due to drug side effects. Compliance with therapy has been good.We conclude that this study will provide important new information on the natural history of lower extremity vascular disease in diabetes. It will also provide definitive data about the efficacy of antiplatelet agents in diabetic vascular disease.

Download Full-text

Lipoprotein(a) and Cardiovascular Disease in Ethnic Chinese: The Chin-Shan Community Cardiovascular Cohort Study

Clinical Chemistry ◽

10.1373/clinchem.2007.090969 ◽

2008 ◽

Vol 54 (2) ◽

pp. 285-291 ◽

Cited By ~ 19

Author(s):

Kuo-Liong Chien ◽

Hsiu-Ching Hsu ◽

Ta-Chen Su ◽

Fung-Chang Sung ◽

Ming-Fong Chen ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Chinese Adults ◽

Vascular Events ◽

Community Based ◽

Lipoprotein A ◽

Ethnic Chinese ◽

Total Death ◽

Age Range

Abstract Background: Little is known about lipoprotein(a) [Lp(a)] as a predictor of vascular events among ethnic Chinese. We prospectively investigated the association of Lp(a) with cardiovascular disease and all-cause death in a community-based cohort. Methods: We conducted a community-based prospective cohort study of 3484 participants (53% women; age range, 35–97 years) who had complete lipid measurements and were free of a cardiovascular disease history at the time of recruitment. Over a median follow-up of 13.8-years, we documented 210 cases of stroke, 122 cases of coronary heart disease (CHD), and 781 deaths. Results: The incidences for each event increased appreciably with Lp(a) quartile for stroke and all-cause death, but not for CHD. Baseline Lp(a) concentration by quartile was not significantly associated with stroke, all-cause death, and CHD in multivariate analyses. The multivariate relative risk was significant for stroke at the 90th and 95th percentiles and for total death at the 95th and 99th percentiles. Conclusions: Our findings suggest a threshold relationship with little gradient of risk across lower Lp(a) values for stroke and all-cause death in Chinese adults.

Download Full-text

Incidence and characterization of venous thromboembolic events (VTE) in patients with pancreatic cancer: Effect of timing of VTE on survival.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.4037 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 4037-4037

Author(s):

Maithili A Shethia ◽

Aparna Hegde ◽

Xiao Zhou ◽

Michael J. Overman ◽

Saroj Vadhan-Raj

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Survival Analysis ◽

Kaplan Meier ◽

Hazard Ratios ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

One Year ◽

The Impact

4037 Background: Patients (pts) with pancreatic cancer are at high risk for VTE, and the occurrence of VTE can affect pts’ prognosis. The purpose of this study was to evaluate the incidence of VTE and the impact of timing of VTE (early vs. late) on survival. Methods: Medical record of 260 pts with pancreatic cancer, newly referred to UT MDACC during one year period from 1/1/2006 to 12/31/2006, were reviewed for the incidence of VTE during a 2-year follow-up period from the date of diagnosis. All VTE episodes were confirmed by radiologic studies. Survival analysis was conducted using Kaplan-Meier analysis and Cox proportional hazard models. Results: Of the 260 pts, 47 pts (18%) had 51 episodes of VTE during the 2-year follow-up. The median age of the pts with VTE was 61 years (range: 28-86) and 53% were males. Of the 47 pts with VTE, 27 (57%) had PE, 19 (40%) had DVT and 1 had concurrent PE/DVT. Three pts had recurrent VTE during the study period. Median follow-up time for OS was 192 days (range: 1-1652 days). Kaplan-Meier Survival analysis showed that those who developed VTE earlier (within 30 or 90 days) had shorter median overall survival (OS) compared with those who had VTE beyond these time points. The hazard ratios, 95% CI, and median OS at 1 year are summarized in the table below. Conclusions: The incidence of VTE is high in pts with pancreatic cancer. The timing of VTE had a significant impact on OS; pts who had an early development of VTE had a shorter overall survival. [Table: see text]

Download Full-text

Effect of Bariatric Surgery on Survival and Hospitalizations in Patients with Severe Obesity. A Retrospective Cohort Study

Nutrients ◽

10.3390/nu13093150 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3150

Author(s):

Enrica Migliore ◽

Amelia Brunani ◽

Giovannino Ciccone ◽

Eva Pagano ◽

Simone Arolfo ◽

...

Keyword(s):

Bariatric Surgery ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Proportional Hazards ◽

Severe Obesity ◽

Hospital Admissions ◽

Cox Proportional Hazards ◽

Hazard Ratios

Bariatric surgery (BS) confers a survival benefit in specific subsets of patients with severe obesity; otherwise, effects on hospital admissions are still uncertain. We assessed the long-term effect on mortality and on hospitalization of BS in patients with severe obesity. This was a retrospective cohort study, including all patients residing in Piedmont (age 18–60 years, BMI ≥ 40 kg/m2) admitted during 2002–2018 to the Istituto Auxologico Italiano. Adjusted hazard ratios (HR) for BS were estimated for mortality and hospitalization, considering surgery as a time-varying variable. Out of 2285 patients, 331 (14.5%) underwent BS; 64.4% received sleeve gastrectomy (SG), 18.7% Roux-en-Y gastric bypass (RYGB), and 16.9% adjustable gastric banding (AGB). After 10-year follow-up, 10 (3%) and 233 (12%) patients from BS and non-BS groups died, respectively (HR = 0.52; 95% CI 0.27–0.98, by a multivariable Cox proportional-hazards regression model). In patients undergoing SG or RYGB, the hospitalization probability decreased significantly in the after-BS group (HR = 0.77; 0.68–0.88 and HR = 0.78; 0.63–0.98, respectively) compared to non-BS group. When comparing hospitalization risk in the BS group only, a marked reduction after surgery was found for all BS types. In conclusion, BS significantly reduced the risk of all-cause mortality and hospitalization after 10-year follow-up.

Download Full-text

COVID-19 vaccine effectiveness among healthcare workers in Portugal: results from a hospital-based cohort study, December 2020 to November 2021

10.1101/2022.01.07.22268889 ◽

2022 ◽

Author(s):

Vânia Gaio ◽

Adriana Silva ◽

Palmira Amaral ◽

João Faro Viana ◽

Pedro Pinto Leite ◽

...

Keyword(s):

Cohort Study ◽

Healthcare Workers ◽

Vaccine Effectiveness ◽

Symptomatic Infection ◽

Cox Models ◽

Mainland Portugal ◽

Hazard Ratios ◽

Group Sex ◽

Tagus Valley

Introduction: Healthcare workers (HCW) were amongst the first prioritized for COVID-19 vaccination but data on COVID–19 vaccine effectiveness among HCW is still limited. This study aims to estimate the COVID–19 vaccine effectiveness (VE) against SARS–CoV–2 symptomatic infection among HCW from Portuguese hospitals. Methods: In this prospective cohort study, we analysed data from HCW (all professional categories) from two central hospitals in the Lisbon and Tagus Valley and Centre regions of mainland Portugal between December 2020 and November 2021. VE against symptomatic SARS–CoV–2 infection was estimated as one minus the confounder adjusted hazard ratios by Cox models considering age group, sex, presence of chronic disease and occupational exposure to patients diagnosed with COVID–19 as adjustment variables. Results: During the 11 months of follow up, the 2213 HCW contributed a total of 1950 person-years at risk and 171 SARS–CoV–2 events occurred. The COVID–19 incidence rate for unvaccinated HCW was 348.7 per 1000 person-years while for fully vaccinated HCW was 43.0 per 1000 person-years. We observed a VE against symptomatic SARS–CoV–2 infection of 73.9% (95% CI: 26.2–90.8%) for complete vaccination status. Conclusion: This cohort study found a high COVID-19 VE against symptomatic SARS–CoV–2 infection in Portuguese HCW, which is in concordance with previous studies from other countries. Monitoring of VE in this HCW cohort continues during the winter 2021/2022 to evaluate potential VE decay and booster vaccine effect. Keywords: Vaccine effectiveness, SARS–CoV–2 , COVID–19, symptomatic infection, healthcare workers.

Download Full-text

Underweight and mortality

Public Health Nutrition ◽

10.1017/s136898001500302x ◽

2015 ◽

Vol 19 (10) ◽

pp. 1751-1756 ◽

Cited By ~ 9

Author(s):

Joo Young Lee ◽

Hyeon Chang Kim ◽

Changsoo Kim ◽

Keeho Park ◽

Song Vogue Ahn ◽

...

Keyword(s):

Cohort Study ◽

Normal Weight ◽

Reverse Causation ◽

Men And Women ◽

Hazard Ratios ◽

All Cause Mortality ◽

Per Se ◽

Never Smokers ◽

Smoking And Health

AbstractObjectiveAccording to most prospective studies, being underweight (BMI<18·5 kg/m2) is associated with significantly higher mortality than being of normal weight, especially among smokers. We aimed to explore in a generally lean population whether being underweight is significantly associated with increased all-cause mortality.DesignProspective cohort study.SettingKorea Medical Insurance Corporation study with 14 years of follow-up.SubjectsAfter excluding deaths within the first 5 years of follow-up (1993–1997) to minimize reverse causation and excluding participants without information about smoking and health status, 94 133 men and 48 496 women aged 35–59 years in 1990 were included.ResultsWe documented 5411 (5·7 %) deaths in men and 762 (1·6 %) in women. Among never smokers, hazard ratios (HR) for underweight individuals were not significantly higher than those for normal-weight individuals (BMI=18·5–22·9 kg/m2): HR=0·87 (95 % CI 0·41, 1·84, P=0·72) for underweight men and HR=1·12 (95 % CI 0·76, 1·65, P=0·58) for underweight women. Among ex-smokers, HR=0·86 (95 % CI 0·38, 1·93, P=0·72) for underweight men and HR=3·77 (95 % CI 0·42, 32·29, P=0·24) for underweight women. Among current smokers, HR=1·60 (95 % CI 1·28, 2·01, P<0·001) for underweight men and HR=2·07 (95 % CI 0·43, 9·94, P=0·36) for underweight women.ConclusionsThe present study does not support that being underweight per se is associated with increased all-cause mortality in Korean men and women.

Download Full-text