Diabetes as a risk factor for stroke. A population perspective

Summary Stroke incidence, case fatality and mortality in diabetic patients were compared to non-diabetic subjects in a 35–74-year-old population in northern Sweden (target population 241,000). During an 8-year period, 1,544 stroke events in diabetic patients and 4,826 events in non-diabetic subjects were recorded. The crude incidence of stroke was 1,000 per 100,000 in the diabetic men vs 247 in the non-diabetic men (relative risk 4.1; 95% confidence interval 3.2–5.2). Among diabetic women, the crude incidence was 757 per 100,000 and 152 in non-diabetic women (relative risk 5.8; 95% confidence interval 3.7–6.9). The 28-day case fatality among men was similar in the diabetic and non-diabetic stroke patients (18.6 vs 17.1%; p=0.311), but significantly higher in diabetic women compared with non-diabetic women (22.2 vs 17.9%; p=0.02). When compared with the non-diabetic population, the overall mortality from stroke in the diabetic population (first and recurrent) was 4.4-times higher in male and 5.1-times higher in the female patients. Hypertension, atrial fibrillation, heart failure or myocardial infarction were all significantly more common in diabetic than in non-diabetic stroke patients. The population attributable risk, a crude estimate of all strokes ascribed to diabetes mellitus, was 18% in men and 22% in women. In Sweden, about 50 strokes are annually directly attributed to diabetes in a population of 100,000 in this age group.Abbreviations MONICA Multinational Monitoring of Trends and Determinants in Cardiovascular Disease - ICD International Classification of Diseases - CT computerised tomography - CI confidence interval - RR relative risk - CF case fatality     

Is diabetes an independent risk factor for mortality after myocardial infarction? The ARIC (Atherosclerosis Risk in Communities) Surveillance Study

Abstract. We investigated the age-, gender- and race-specific 1-year case fatality rates of diabetic and non-diabetic individuals with a myocardial infarction. Data were obtained from the Atherosclerosis Risk in Communities (ARIC) Surveillance Study, which monitors both hospitalized myocardial infarction and coronary heart disease (CHD) deaths in residents aged 35–74 years in four communities in the USA. The study population comprised 3242 hospitalized myocardial infarctions (HMIs) in diabetic subjects and 9826 HMIs in non-diabetic individuals between 1987 and 1997. Age-adjusted and gender- and race-specific odds ratios (OR) for 1-year case fatality comparing diabetic to non-diabetic patients were 2.0 (95% CI, 1.6–2.4) for white men and 1.4 (95% CI, 1.1–1.8) for white women. Further adjustment for severity of HMI, history of previous MI, stroke and hypertension, and therapy variables showed significantly higher case fatality in white diabetic men than in non-diabetic white men (OR=1.5; 95% CI, 1.2–1.9), but no significant association in the other race-gender groups. The age-adjusted odds of out of hospital death was significantly higher among white diabetic men (OR=1.7; 95% CI, 1.2–2.3), white women (OR=2.3; 95% CI, 1.4–3.8), and African-American women (OR=2.9; 95% CI, 1.5–5.9) as compared to their non-diabetic counterparts. In conclusion, diabetes is an independent factor for mortality within one year following a myocardial infarction among white men, and following out-of hospital coronary death in white men and women and in African-American women. It is possible that these differences could be explained, at least in part, by a less than optimal medical management of the high cardiovascular risk profile of these patients after hospital discharge.     

The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis

Aims/hypothesis Emerging data suggest that different indices of glycaemia are risk factors for clinical events. The aim of this analysis was to investigate the relationship between fasting plasma glucose or glycated haemoglobin (GHb) levels and incident cardiovascular (CV) outcomes, death, heart failure and overt nephropathy in diabetic and non-diabetic individuals enrolled in the Heart Outcomes Prevention Evaluation (HOPE) study.Materials and methods The adjusted 4.5-year risk of CV events (myocardial infarction or stroke or CV death), heart failure, death and overt nephropathy was analysed in relation to baseline and updated GHb levels (in 3,529 diabetic HOPE study participants) and baseline fasting plasma glucose levels (in 1,937 non-diabetic and 1,013 diabetic participants).Results In diabetic participants, a 1% absolute rise in the updated GHb predicted future CV events (relative risk [RR]=1.07, 95% CI 1.01–1.13; p=0.014), death (RR=1.12, 95% CI 1.05–1.19; p=0.0004), heart failure (RR=1.20, 95% CI 1.08–1.33; p=0.0008) and overt nephropathy (RR=1.26, 95% CI 1.17–1.36; p<0.0001) after adjusting for age, sex, diabetes duration, blood pressure, WHR, hyperlipidaemia and ramipril. Similarly, a 1 mmol/l rise in fasting plasma glucose was related to an increased risk of CV outcomes (RR=1.09, 95% CI 1.05–1.13; p<0.0001), death (RR=1.06, 95% CI 1.01–1.12; p=0.017), heart failure (RR=1.16, 95% CI 1.06–1.13; p=0.0007) and overt nephropathy (RR=1.34, 95% CI 1.23–1.45; p<0.0001) in the group composed of diabetic and non-diabetic individuals. The significant relationship between fasting plasma glucose and CV outcomes persisted after adjustment for diabetes status (RR=1.06, 95% CI 1.00–1.12; p=0.043).Conclusions/interpretation There is an independent progressive relationship between indices of glycaemia and incident CV events, renal disease and death. Clinical trials of glucose lowering to prevent these outcomes in diabetic and non-diabetic individuals are indicated.Listed by country in References 13 and 15.     

Incidence of and Mortality from Venous Thromboembolism in a Real-world Population: The Q-VTE Study Cohort

Background

The public health burden of venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, is not fully known, and contemporary incidence and mortality estimates are needed. We determined the incidence and case fatality of venous thromboembolism in a general population.

Methods

Using the administrative health care databases of the Canadian province of Québec, we identified all incident cases of deep vein thrombosis or pulmonary embolism between 2000 and 2009 and classified them as definite or probable venous thromboembolism. We formed 2 patient cohorts, one with definite cases and the other including cases with definite or probable venous thromboembolism that were followed until December 31, 2009.

Results

We identified 67,354 definite and 35,123 probable cases of venous thromboembolism. The age- and sex-adjusted incidence rates of definite or probable venous thromboembolism, deep vein thrombosis, and pulmonary embolism were 1.22 (95% confidence interval [CI], 1.22-1.23), 0.78 (95% CI, 0.77-0.79), and 0.45 (95% CI, 0.44-0.45) per 1000 person-years, respectively, while for definite venous thromboembolism it was 0.90 (95% CI, 0.89-0.90) per 1000 person-years. The 30-day and 1-year case-fatality rates after definite or probable venous thromboembolism were 10.6% (95% CI, 10.4-10.8) and 23.0% (95% CI, 22.8-23.3), respectively, and were slightly higher among definite cases. The 1-year survival rate was 0.47 (95% CI, 0.46-0.48) for cases with definite or probable venous thromboembolism and cancer, 0.93 (95% CI, 0.93-0.94) for cases with unprovoked venous thromboembolism, and 0.84 (95% CI, 0.83-0.84) for cases with venous thromboembolism secondary to a major risk factor. Similar survival rates were seen for cases with definite venous thromboembolism.

Conclusion

The risk of venous thromboembolism in the general population remains high, and mortality, especially in cancer patients with venous thromboembolism, is substantial.     

Pulmonary thromboembolism in Asians/Pacific Islanders in the United States: analysis of data from the National Hospital Discharge Survey and the United States Bureau of the Census

PURPOSE: To assess the rate of diagnosis of deep venous thrombosis, pulmonary embolism, and venous thromboembolism; the incidence in hospitalized patients; and mortality from pulmonary embolism among Asians/Pacific Islanders in the United States. METHODS: The number of patients discharged from hospitals with a diagnostic code for pulmonary embolism or deep venous thrombosis from 1990 through 1999 was obtained from the National Hospital Discharge Survey. Population estimates and deaths from pulmonary embolism from 1990 through 1998 were obtained from the United States Bureau of the Census. RESULTS: Rate ratios of 10-year age-adjusted rates of diagnosis of deep venous thrombosis, pulmonary embolism, and venous thromboembolism comparing Asians/Pacific Islanders with whites and African Americans ranged from 0.16 to 0.21. Rate ratios comparing incidences in hospitalized patients ranged from 0.32 to 0.42. The age-adjusted rate ratio of mortality in "others" (which included Asians/Pacific Islanders) was 0.29 (95% confidence interval [CI]: 0.01 to 0.87) compared with whites and 0.14 (95% CI: 0.0 to 0.58) compared with African Americans. CONCLUSION: Rates of deep venous thrombosis, pulmonary embolism, and venous thromboembolism; incidences in hospitalized patients; and the mortality rate from pulmonary embolism were markedly lower in Asians/Pacific Islanders than in whites and African Americans. Clinical assessment of the prior probability of venous thromboembolic disease at the bedside should probably be adjusted based on these ethnic differences.     

Risk of stroke in people with type 2 diabetes in the UK: a study using the General Practice Research Database

Aims/hypothesis Risk estimates for stroke in patients with diabetes vary. We sought to obtain reliable risk estimates for stroke and the association with diabetes, comorbidity and lifestyle in a large cohort of type 2 diabetic patients in the UK.Materials and methods Using the General Practice Research Database, we identified all patients who had type 2 diabetes and were aged 35 to 89 years on 1 January 1992. We also identified five comparison subjects without diabetes and of the same age and sex. Hazard ratios (HRs) for stroke between January 1992 and October 1999 were calculated, and the association with age, sex, body mass index, smoking, hypertension, atrial fibrillation and duration of diabetes was investigated.Results The absolute rate of stroke was 11.91 per 1,000 person-years (95% CI 11.41–12.43) in people with diabetes (n = 41,799) and 5.55 per 1,000 person-years (95% CI 5.40–5.70) in the comparison group (n = 202,733). The age-adjusted HR for stroke in type 2 diabetic compared with non-diabetic subjects was 2.19 (95% CI 2.09–2.32) overall, 2.08 (95% CI 1.94–2.24) in men and 2.32 (95% CI 2.16–2.49) in women. The increase in risk attributable to diabetes was highest among young women (HR 8.18; 95% CI 4.31–15.51) and decreased with age. No investigated comorbidity or lifestyle characteristic emerged as a major contributor to risk of stroke.Conclusions/interpretation This study provides risk estimates for stroke for an unselected population from UK general practice. Patients with type 2 diabetes were at an increased risk of stroke, which decreased with age and was higher in women. Additional risk factors for stroke in type 2 diabetic patients included duration of diabetes, smoking, obesity, atrial fibrillation and hypertension.     

Risk of Arterial Thromboembolism,Venous Thromboembolism,and Bleeding in Patients with Nephrotic Syndrome: A Population-Based Cohort Study

BackgroundAlthough venous thromboembolism is a well-known complication of nephrotic syndrome, the long-term absolute and relative risks of arterial thromboembolism, venous thromboembolism, and bleeding in adults with nephrotic syndrome remain unclarified.MethodsIn this matched cohort study, we identified every adult with first-time recorded nephrotic syndrome from admissions, outpatient clinics, or emergency department visits in Denmark during 1995-2018. Each patient was matched by age and sex with 10 individuals from the general population. We estimated the 10-year cumulative risks of recorded arterial thromboembolism, venous thromboembolism, and bleeding accounting for the competing risk of death. Using Cox models, we computed crude and adjusted hazard ratios (HRs) of the outcomes in patients with nephrotic syndrome versus comparators.ResultsAmong 3967 adults with first-time nephrotic syndrome, the 1-year risk of arterial thromboembolism was 4.2% (95% confidence interval [CI] 3.6-4.8), of venous thromboembolism was 2.8% (95% CI 2.3-3.3), and of bleeding was 5.2% (95% CI 4.5-5.9). The 10-year risk of arterial thromboembolism was 14.0% (95% CI 12.8-15.2), of venous thromboembolism 7.7% (95% CI 6.8-8.6), and of bleeding 17.0% (95% CI 15.7-18.3), with highest risks of ischemic stroke (8.1%), myocardial infarction (6.0%), and gastrointestinal bleeding (8.2%). During the first year, patients with nephrotic syndrome had increased rates of both arterial thromboembolism (adjusted HR [HR_adj] = 3.11 [95% CI 2.60-3.73]), venous thromboembolism (HR_adj = 7.11 [5.49-9.19]), and bleeding (HR_adj = 4.02 [3.40-4.75]) compared with the general population comparators after adjusting for confounders.ConclusionAdults with nephrotic syndrome have a high risk of arterial thromboembolism, venous thromboembolism, and bleeding compared with the general population. The mechanisms and consequences of this needs to be clarified.     

Periprocedural Bridging in Patients with Venous Thromboembolism: A Systematic Review

BackgroundVitamin K antagonists (VKA) are the most widely used anticoagulants, and bridging is commonly administered during periprocedural VKA interruption. Given the unclear benefits and risks of periprocedural bridging in patients with previous venous thromboembolism, we aimed to assess recurrent venous thromboembolism and bleeding outcomes with and without bridging in this population.MethodsWe performed a systematic review searching the PubMed and Embase databases from inception to December 7, 2017 for randomized and nonrandomized studies that included adults with previous venous thromboembolism requiring VKA interruption to undergo an elective procedure, and that reported venous thromboembolism or bleeding outcomes. Quality of evidence was graded by consensus.ResultsWe included 28 cohort studies (20 being single-arm cohorts) with, overall, 6915 procedures for analysis. In 27 studies reporting perioperative venous thromboembolism outcomes, the pooled incidence of recurrent venous thromboembolism with bridging was 0.7% (95% confidence interval [CI], 0.4%-1.2%) and 0.5% (95% CI, 0.3%-0.8%) without bridging. Eighteen studies reported major or nonmajor bleeding outcomes. The pooled incidence of any bleeding was 3.9% (95% CI, 2.0%-7.4%) with bridging and 0.4% (95% CI, 0.1%-1.7%) without bridging. In bridged patients at high thromboembolic risk, the pooled incidence for venous thromboembolism was 0.8% (95% CI, 0.3%-2.5%) and 7.5% (95% CI, 3.1%-17.4%) for any bleeding. Quality of available evidence was very low, primarily due to a high risk of bias of included studies.ConclusionsPeriprocedural bridging increases the risk of bleeding compared with VKA interruption without bridging, without a significant difference in periprocedural venous thromboembolism rates.     

Usefulness of D-Dimer Testing in Predicting Recurrence in Elderly Patients with Unprovoked Venous Thromboembolism

Background

Whether post-anticoagulation D-dimer levels are useful in predicting recurrence in elderly patients with unprovoked venous thromboembolism is unknown.

Venous thromboembolism in heart failure: preventable deaths during and after hospitalization

Objective

Our aim was to compare the clinical characteristics, prophylaxis, treatment, and outcomes of patients with venous thromboembolism with and without heart failure.

Methods

We studied patients with heart failure in the population-based Worcester Venous Thromboembolism Study of 1822 consecutive patients with validated venous thromboembolism.

Results

Of the 1822 patients with venous thromboembolism, 319 (17.5%) had a history of clinical heart failure and 1503 (82.5%) did not. Patients with heart failure were older (mean age 75 vs 62 years, P < .0001) and more likely to have been immobilized (65.2% vs 46.1%, P < .0001). Thromboprophylaxis was omitted in approximately one third of patients with heart failure who had been hospitalized for non-venous thromboembolism-related illness or had undergone major surgery within the 3 months before diagnosis. Patients with heart failure had a higher frequency of in-hospital death (9.7% vs 3.3%, P < .0001) and death within 30 days of venous thromboembolism diagnosis (15.6% vs 6.4%, P < .0001). Heart failure (adjusted odds ratio [OR] 2.04; 95% confidence interval [CI], 1.15-3.62) and immobility (adjusted OR 4.37; 95% CI, 2.42-7.9) were associated with an increased risk of in-hospital death. Heart failure (adjusted OR 1.57; 95% CI, 1.01-2.43) and immobility (adjusted OR 3.05; 95% CI, 2.01-4.62) also were independent predictors of death within 30 days of venous thromboembolism diagnosis.

Conclusion

High mortality was observed among patients with heart failure and venous thromboembolism both during and after hospitalization. Heart failure and immobility are potent risk factors for in-hospital death and death within 30 days in patients with venous thromboembolism.