Relationship between platelet aggregation and stroke risk after percutaneous coronary intervention: a PENDULUM analysis

In patients undergoing percutaneous coronary intervention (PCI) with a stent, high on-treatment platelet reactivity may be associated with an increased risk of stroke. This post hoc analysis of the PENDULUM registry compared the risk of post-PCI stroke according to on-treatment P2Y12 reaction unit (PRU) values. Patients aged ≥ 20 years who underwent PCI were stratified by baseline PRU (at 12 and 48 h post-PCI) as either high (HPR, > 208), optimal (OPR, > 85 to ≤ 208), or low on-treatment platelet reactivity (LPR, ≤ 85). The incidences of non-fatal ischemic and non-ischemic stroke through to 12 months post-PCI were recorded. Almost all enrolled patients (6102/6267 [97.4%]) had a risk factor for ischemic stroke, and most were receiving dual antiplatelet therapy. Of the 5906 patients with PRU data (HPR, n = 2227; OPR, n = 3002; LPR, n = 677), 47 had a non-fatal stroke post-PCI (cumulative incidence: 0.68%, ischemic; 0.18%, non-ischemic stroke). Patients with a non-fatal ischemic stroke event had statistically significantly higher post-PCI PRU values versus those without an event (P = 0.037). The incidence of non-fatal non-ischemic stroke was not related to PRU value. When the patients were stratified by PRU ≤ 153 versus > 153 at 12–48 h post-PCI, a significant difference was observed in the cumulative incidence of non-fatal stroke at 12 months (P = 0.044). We found that patients with ischemic stroke tended to have higher PRU values at 12–48 h after PCI versus those without ischemic stroke.Clinical trial registration: UMIN000020332.

Factors associated with fatal stroke in glioma patients: a population analysis

ImportanceBrain tumour patients have the highest stroke mortality rates among all cancer types, but the factors associated with fatal stroke in brain tumour remain unknown.ObjectiveWe aimed to examine to what extent brain tumour grade, a marker of biological aggressiveness, tumour size and cancer treatment each associated with stroke mortality in glioma. Gliomas include the most common malignant types of brain cancer.Design, setting, participantsA retrospective, observational cohort study using the US National Cancer Institute’s Surveillance Epidemiology and End Results program. We identified adult patients with a primary diagnosis of malignant gliomas in 2000 to 2018 (N=72,252). The primary outcome of interest was death from cerebrovascular disease. Adjusted hazard ratio (aHR) and 95% confidence interval (CI) were calculated using cause-specific Cox regression model to determine associations with tumour characteristics: grades II-IV, tumour size and cancer treatment (surgery, radiotherapy, chemotherapy) associated with stroke mortality after adjustment for age, sex, race, marital status and calendar years.ResultsIn patients with glioma, increased risk for stroke mortality was observed in patients with higher grade (Grade III: aHR=1.19, 95% CI=0.88-1.61, p>0.05; Grade IV: aHR=1.94, 95% CI=1.39-2.71 compared to Grade II, p<0.001), and those with larger brain tumours (size=3-6 cm: aHR=1.93, 95%CI 1.31 -2.85, p<0.001, size>9cm: aHR=2.07, 95% CI=1.40-3.06, p<0.001 compared to size < 3cm). Having treatment was associated with decreased risk: surgery (yes VS no: aHR= 0.65; p<0.01), radiation (yes VS no: aHR= 0.66, p<0.01), chemotherapy (yes VS no: aHR=0.49, p<0.001).ConclusionsHigher grade and tumour size are strongly associated with increased stroke mortality. This implicates tumour biology and/or the systemic tumour response which require further investigation in prospective studies to determine strategies to mitigate this risk.

Age at menarche, age at menopause, reproductive years and risk of fatal stroke occurrence among Chinese women: the Guangzhou Biobank Cohort Study

Background The relationship between women’s reproductive characteristics and stroke events is unclear. We aimed to investigate age at menarche, age at menopause and number of reproductive years in relation to fatal stroke occurrence in the Guangzhou Biobank Cohort Study. Methods In total, 16,504 postmenopausal women without stroke, heart disease or a cancer history at baseline were included and followed up for a median of 12.0 years. After review of available records, 222 stroke deaths were recorded. Cox proportional hazards regression was used to assess the associations between the risk of fatal stroke occurrence and age at menarche, age at menopause and number of reproductive years. Results In the whole cohort, compared with those aged 15 years at menarche, an increased risk of fatal stroke among women at menarche showed respectively in those aged 12 years (aHR (adjusted hazard ratio) = 1.86, 95% confidence interval (CI) 0.96–3.60), aged 13 years (aHR = 1.69, 95% CI 0.98–2.92), aged 17 years (aHR = 1.83, 95% CI 1.10–3.05) and aged ≥ 18 years (aHR = 1.66, 95% CI 1.03–2.70), wherein the associations revealed an atypically U-shaped; similar U-shaped association to the cohort of postmenopausal women born before 1940 released a range of incremental risks of fatal stroke in women at menarche aged ≤ 12 years (aHR = 3.68, 95% CI 1.68–8.05), aged 13 years (aHR = 2.11, 95% CI 1.02–4.34), aged 14 years (aHR = 2.07, 95% CI 1.04), aged 17 years (aHR = 2.30, 95% CI 1.20–4.39) and aged 18 years (aHR = 2.50, 95% CI 1.37–4.57), respectively. Compared with menopausal women aged 51–52 years, those aged < 43 years at menopause had an increased risk for fatal stroke among postmenopausal women born in and after 1940 (aHR = 1.64, 95% CI 0.97–2.78) and postmenopausal women born before 1940 (aHR = 1.97, 95% CI 1.05–3.69). Additionally, compared with those with 32–34 reproductive years, women with ≤ 28 reproductive years had an increased risk for fatal stroke in the whole cohort (aHR = 1.91, 95% CI 1.28–2.86) and the cohort of postmenopausal women born before 1940 (aHR = 1.79, 95% CI 1.15–2.80). Conclusions Younger and older age at menarche, younger age at menopause and fewer reproductive ages were related to an increased risk of fatal stroke in postmenopausal women.

Higher total white blood cell and neutrophil counts are associated with an increased risk of fatal stroke occurrence: the Guangzhou biobank cohort study

Background Chronic inflammatory diseases are linked to an increased risk of stroke events. The white blood cell (WBC) count is a common marker of the inflammatory response. However, it is unclear whether the WBC count, its subpopulations and their dynamic changes are related to the risk of fatal stroke in relatively healthy elderly population. Methods In total, 27,811 participants without a stroke history at baseline were included and followed up for a mean of 11.5 (standard deviation = 2.3) years. After review of available records, 503 stroke deaths (ischaemic 227, haemorrhagic 172 and unclassified 104) were recorded. Cox proportional hazards regression was used to assess the associations between the WBC count, its subpopulations and their dynamic changes (two-phase examination from baseline to the 1st follow-up) and the risk of fatal all stroke, fatal ischaemic stroke and fatal haemorrhagic stroke. Results (i) Regarding the WBC count in relation to the risk of fatal stroke, restricted cubic splines showed an atypically U-curved association between the WBC count and the risk of fatal all stroke occurrence. Compared with those in the lowest WBC count quartile (< 5.3*10^9/L), the participants with the highest WBC count (> 7.2*10^9/L) had a 53 and 67% increased risk for fatal all stroke (adjusted hazard ratio [aHR] = 1.53, 95% confidence interval (CI) 1.16–2.02, P = 0.003) and fatal haemorrhagic stroke (aHR = 1.67, 95% CI 1.10–2.67, P = 0.03), respectively; compared with those in the lowest quartile (< 3.0*10^9/L), the participants with the highest NEUT count (> 4.5*10^9/L) had a 45 and 65% increased risk for fatal all stroke (aHR = 1.45, 95% CI 1.10–1.89, P = 0.008) and fatal ischaemic stroke (aHR = 1.65, 95%CI 1.10–2.47 P = 0.02), respectively. With the additional adjustment for C-reactive protein, the same results as those for all stroke and ischaemic stroke, but not haemorrhagic stroke, were obtained for the WBC count (4 ~ 10*10^9/L) and the NEUT count (the NEUT counts in the top 1% and bottom 1% at baseline were excluded). (ii) Regarding dynamic changes in the WBC count in relation to the risk of fatal stroke, compared with the stable group (− 25% ~ 25%, dynamic changes from two phases of examination (baseline, from September 1st, 2003 to February 28th, 2008; 1st follow-up, from March 31st 2008 to December 31st 2012)), the groups with a 25% increase in the WBC count and NEUT count respectively had a 60% (aHR = 1.60, 95% CI 1.07–2.40, P = 0.02) and 45% (aHR = 1.45, 95% CI1.02–2.05, P = 0.04) increased risk of fatal all stroke occurrence. Conclusions The WBC count, especially the NEUT count, was associated with an increased risk of fatal all stroke occurrence. Longitudinal changes in the WBC count and NEUT count increase in excess of 25% were also associated with an increased risk of fatal all stroke occurrence in the elderly population.

189 Long-term outcomes of early-onset myocardial infarction with non-obstructive coronary artery disease

Aims Data regarding long-term prognosis of MINOCA are very limited and conflicting. Methods and results The Italian Genetic Study on early-onset MI enrolled 2000 patients who had a first MI before they were 45. The median follow-up was 19.9 years, the equivalent of 39 535 person-years. The composite primary endpoint was cardiovascular (CV) death, non-fatal MI, and non-fatal stroke (MACE); the secondary endpoint was rehospitalization for coronary revascularization. MINOCA was experienced by 317 patients (15.9%). The risk of MACE was not significantly different between MINOCA patients and those with obstructive coronary artery disease (MICAD, 27.8% vs. 37.5%; adj. HR: 0.79, 95% CI: 0.57–1.09; P = 0.15, Figure 1). There was no between-group difference in the rate of non-fatal MI (17.3% vs. 25.4%; adj. HR: 0.76, 95% CI: 0.52–1.13; P = 0.18), non-fatal ischaemic stroke (9.5% vs. 3.7%; adj. HR: 1.79, 95% CI: 0.87–3.70; P = 0.12), or all-cause mortality (14.1% vs. 20.7%; adj. HR: 0.73, 95% CI: 0.43–1.25; P = 0.26), but the rates of CV death (6.2% vs. 8.4%; adj. HR: 0.26, 95% CI: 0.08–0.86; P = 0.03) and coronary revascularization (6.7% vs. 27.7%; HR: 0.27, 95% CI: 0.15–0.47; P &lt; 0.001) were lower in the MINOCA group. Conclusions MINOCA is frequent in early-onset MI patients and is not benign with a long-term risk of MACE and overall mortality not significantly different from that of the MICAD patients. 189 Figure 1 Composite primary endpoint of CV death, non-fatal MI, and non-fatal stroke

Association Between Long-Term Visit-to-Visit Hemoglobin A1c and Cardiovascular Risk in Type 2 Diabetes: The ACCORD Trial

Background: To explore the association between visit-to-visit variability of glycated hemoglobin (HbA1c) and cardiovascular outcomes in the patients with type 2 diabetes mellitus (T2DM) of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study.Methods: We conducted a post-hoc analysis on the ACCORD population including 9,544 participants with T2DM. Visit-to-visit variability of HbA1c was defined as the individual SD, coefficient of variation (CV), and variability independent of the mean (VIM) across HbA1c measurements. The clinical measurements included primary outcome [the first occurrence of non-fatal myocardial infarction (MI), non-fatal stroke or cardiovascular death], total mortality, cardiovascular death, non-fatal MI event, non-fatal stroke, total stroke, heart failure, macrovascular events, and major coronary events (CHD).Results: Over a median follow-up of 4.85 years, 594 and 268 participants experienced all-cause mortality and cardiovascular mortality, respectively. After adjusting for baseline HbA1c levels and confounding factors, the adjusted hazard ratio (HR) comparing patients in the highest vs. the lowest quartile CV of HbA1c variability was 1.61 (95% CI 1.29–2.00) for the primary outcome. Similar trends for secondary outcome were also observed. There was no association between HbA1c fluctuation and non-fatal stroke. Noticeably, there was 66% greater risk for the all-cause mortality among patients in the highest vs. the lowest quartile (HR 1.66, 95% CI 1.27–2.17).Conclusions: Greater variability of HbA1c is associated with higher risk for cardiovascular complications and all-cause death in T2DM. Our study stresses the significance of well-controlled glycemic levels for improving cardiovascular outcomes. Further randomized clinical trials are required to confirm these findings.

Meta-analysis assessing cardiovascular outcomes with febuxostat versus allopurinol for patients with gout

Background Gout, the most common inflammatory arthritis in the USA, represents an established risk factor for cardiovascular disease and coronary artery disease mortality. In addition, patients with gout experience an increased risk for non-fatal myocardial infarction, while they might also feature increased risk for stroke. Recent real-world data also highlight the association between gout and atrial fibrillation, which inevitably augments cardiovascular burden. Allopurinol, a xanthine oxidase inhibitor, remains the uric acid-lowering treatment option of first choice, while febuxostat is prescribed, when allopurinol is contraindicated or not tolerated. Unfortunately, medication adherence among gout patients is poor, associated with age and related co-morbidities. Purpose We sought to determine the comparative efficacy of febuxostat versus allopurinol across surrogate cardiovascular outcomes of interest, by pooling data from the 2 dedicated cardiovascular outcome trials available so far. The motive for this analysis was the U.S. Food and Drug Administration (FDA) warning raised after the publication of the CARES trial, regarding the increased risk for cardiovascular and all-cause death with febuxostat compared to allopurinol. Methods We pooled data from the 2 dedicated cardiovascular outcome trials (CARES and FAST) and we assessed the following cardiovascular outcomes of interest: cardiovascular death, all-cause death, non-fatal myocardial infarction (MI), non-fatal stroke, fatal MI, fatal stroke, transient ischemic attack, hospitalization for heart failure, coronary revascularization, cerebrovascular revascularization and atrial fibrillation. Risk of bias was low across the included studies. Results Our analysis in a total of 12,318 patients with gout showed that febuxostat compared to allopurinol treatment does not confer significant risk reduction for any of the assessed, prespecified surrogate outcomes in a study population with significant cardiovascular co-morbidities (Figure 1). One third of patients enrolled in the FAST trial and 40% of the patients enrolled in the CARES trial had pre-existing cardiovascular disease, as depicted in Figure 2. Heterogeneity was low for the vast majority of the assessed outcomes, except for cardiovascular and all-cause death and fatal MI. Conclusions There is no significant difference across surrogate cardiovascular outcomes of interest between febuxostat and allopurinol in patients with gout and cardiovascular co-morbidities. Febuxostat seems to be a safe treatment alternative to allopurinol, despite initial concerns in terms of its cardiovascular safety. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

Higher Neutrophil-to-lymphocyte Ratio is Association with an Increased Risk of Fatal Stroke Occurrence in Older Chinese

Background: The neutrophil-to-lymphocyte ratio (NLR) has linked to a mortality risk of coronary heart disease. However, it is unclear whether the NLR is related to the risk of fatal stroke in a relatively healthy elderly population.Aims: To evaluate the association between the NLR and the risk of fatal stroke in elderly populations.Methods: In total, 27811 participants without a stroke history at baseline were included and followed up for a mean of 11.5 (standard deviation=2.3) years. After review of available records, 503 stroke deaths (ischaemic 227, haemorrhagic 172 and unclassified 104) were recorded. Cox proportional hazards regression was used to assess the relationship between the NLR and future risk of fatal stroke, fatal ischaemic stroke or fatal haemorrhagic stroke.Results: (1) Compared with those in the 1st quartile and after adjustments for a series of factors, those in the highest neutrophil (NEUT) quartile had a 45% and a 65% increased risk of fatal stroke (adjusted hazard ratio (aHR)=1.45, 95% confidence interval (CI) 1.10-1.89, P=0.008) and fatal ischaemic stroke (aHR=1.65, 95% CI 1.10-2.47, P=0.02), respectively; while no significant relationship was obtained between the lymphocyte (LYM) and the risk of fatal stroke. (2) The restricted cubic splines showed an increased trend of relationship between the NLR and the risk of fatal stroke occurrence. Compared with those in the lowest quartile (≤ 1.39), the participants with the highest NLR (≥ 2.24) had a 76% and a 115% increased risk of fatal stroke (aHR=1.76, 95% CI 1.33-2.32) and fatal ischaemic stroke (aHR=2.15, 95% CI 1.41-3.28), respectively; Similar associations for stroke and ischaemic stroke were obtained after further adjustment for C-reactive protein. (3) Compared with those in NLR ≤ 1.75, the participants in NLR > 1.75 had a 57% and a 91% increased risk of fatal stroke (aHR=1.57, 95%CI 1.20-2.06) and fatal ischaemic stroke (aHR=1.91, 95%CI 1.27-2.88), respectively. (3) As a continuous variable, the NLR presented an increased risk of fatal stroke (aHR=1.11 95%CI 1.06-1.17) and fatal ischaemic stroke (aHR=1.15 95%CI 1.09-1.21), respectively.Conclusions: Higher NLR was associated with an increased risk of fatal stroke and fatal ischaemic stroke occurrence in a relatively healthy elderly population.The clinicians should pay more attention to asymptomatic inflammatory characteristics in relatively healthy older population.

Age At Menarche, Age At Menopause, Reproductive Years and Risk of Fatal Stroke Occurrence Among Chinese Women: The Guangzhou Biobank Cohort Study

Background The relationship between women’s reproductive characteristics and stroke events is unclear. We aimed to investigate age at menarche, age at menopause and number of reproductive years in relation to fatal stroke occurrence in the Guangzhou Biobank Cohort Study. Methods In total, 16504 postmenopausal women without stroke, heart disease or a cancer history at baseline were included and followed up for a median of 12.0 years. After review of available records, 222 stroke deaths were recorded. Cox proportional hazards regression was used to assess the associations between the risk of fatal stroke occurrence and age at menarche, age at menopause and number of reproductive years. Results In the whole cohort, compared with those aged 15 years at menarche, women aged 17 years at menarche had an increased risk for fatal stroke (adjusted hazard ratio [aHR] = 1.83, 95% confidence interval (CI) 1.10–3.05) and fatal haemorrhagic stroke (HR = 2.65, 95% CI 1.14–6.18), and women aged ≥ 18 years at menarche had an increased risk for fatal stroke (HR = 1.66, 95% CI 1.03–2.70) and fatal ischaemic stroke (HR = 2.01, 95% CI 1.01–3.99). Among postmenopausal women born before 1940, women aged < 43 years at menopause had an increased risk for fatal stroke (HR = 1.97, 95% CI 1.05–3.69) compared with those aged 51–52 years at menopause. Additionally, in the whole cohort, women with ≤ 28 reproductive years had an increased risk for fatal stroke (HR = 1.91, 95% CI 1.28–2.86) and fatal ischaemic stroke (HR = 2.26, 95% CI 1.26–4.05) compared with those with 32–34 reproductive years; postmenopausal women born before 1940 had a similar risk for fatal stroke and fatal ischaemic stroke. Conclusions Older age at menarche, younger age at menopause and fewer reproductive ages were related to an increased risk of fatal stroke in postmenopausal women.

Cardio- and Cerebrovascular Outcomes of Postoperative Acute Kidney Injury in Noncardiac Surgical Patients With Hypertension

Background: The cardiovascular and cerebrovascular risk of postoperative acute kidney injury (AKI) in surgical patients is poorly described, especially in the hypertensive population.Methods: We conducted a retrospective cohort study among all hypertensive patients who underwent elective noncardiac surgery from January 1st, 2012 to August 1st, 2017 at the Third Xiangya Hospital. The primary outcomes were fatal stroke and fatal myocardial infarction (MI). The secondary outcomes were all-cause mortality.Results: The postoperative cumulative mortality within 3 months, 6 months, 1 year, 2 years, and 5 years were 1.27, 1.48, 2.15, 2.15, and 5.36%, for fatal stroke, and 2.05, 2.27, 2.70, 3.37, and 5.61% for fatal MI, respectively, in patients with postoperative AKI. Compared with non-AKI patients, those with postoperative AKI had a significantly higher risk of fatal stroke and fatal MI within 3 months [hazard ratio (HR): 5.49 (95% CI: 1.88−16.00) and 11.82 (95% CI: 4.56−30.62), respectively], 6 months [HR: 3.58 (95% CI: 1.43−8.97) and 9.23 (95% CI: 3.89−21.90), respectively], 1 year [HR: 3.64 (95% CI: 1.63−8.10) and 5.14 (95% CI: 2.50−10.57), respectively], 2 years [HR: 2.21 (95% CI: 1.03−4.72) and 3.06 (95% CI: 1.66−5.64), respectively], and 5 years [HR: 2.27 (95% CI: 1.30−3.98) and 1.98 (95% CI: 1.16−3.20), respectively]. In subgroup analysis of perioperative blood pressure (BP) lowering administration, postoperative AKI was significantly associated with 1-year and 5-year risk of fatal stroke [HR: 9.46 (95% CI: 2.85−31.40) and 3.88 (95% CI: 1.67−9.01), respectively] in patients with ACEI/ARB, and MI [HR: 6.62 (95% CI: 2.23−19.62) and 2.44 (95% CI: 1.22−4.90), respectively] in patients with CCB.Conclusion: Hypertensive patients with postoperative AKI have a significantly higher risk of fatal stroke and fatal MI, as well as all-cause mortality, within 5 years after elective noncardiac surgery. In patients with perioperative administration of ACEI/ARB and CCB, postoperative AKI was significantly associated with higher risk of fatal stroke and MI, respectively.