Flu Vaccine and Mortality in Hypertension: A Nationwide Cohort Study.

Background Influenza infection may increase the risk of stroke and acute myocardial infarction (AMI). Whether influenza vaccination may reduce mortality in patients with hypertension is currently unknown. Methods and Results We performed a nationwide cohort study including all patients with hypertension in Denmark during 9 consecutive influenza seasons in the period 2007 to 2016 who were prescribed at least 2 different classes of antihypertensive medication (renin-angiotensin system inhibitors, diuretics, calcium antagonists, or beta-blockers). We excluded patients who were aged <18 years, >100 years, had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer, or cerebrovascular disease. The exposure to influenza vaccination was assessed before each influenza season. The end points were defined as death from all-causes, from cardiovascular causes, or from stroke or AMI. For each influenza season, patients were followed from December 1 until April 1 the next year. We included a total of 608 452 patients. The median follow-up was 5 seasons (interquartile range, 2-8 seasons) resulting in a total follow-up time of 975 902 person-years. Vaccine coverage ranged from 26% to 36% during the study seasons. During follow-up 21 571 patients died of all-causes (3.5%), 12 270 patients died of cardiovascular causes (2.0%), and 3846 patients died of AMI/stroke (0.6%). After adjusting for confounders, vaccination was significantly associated with reduced risks of all-cause death (HR, 0.82; P<0.001), cardiovascular death (HR, 0.84; P<0.001), and death from AMI/stroke (HR, 0.90; P=0.017). Conclusions Influenza vaccination was significantly associated with reduced risks of death from all-causes, cardiovascular causes, and AMI/stroke in patients with hypertension. Influenza vaccination might improve outcome in hypertension.

Preoperative chronic beta-blocker prescription in elderly patients as a risk factor for postoperative mortality stratified by preoperative blood pressure: a cohort study.

BACKGROUND: Recent data suggest that beta blockers are associated with increased perioperative risk in hypertensive patients. We investigated whether beta blockers were associated with an increased risk in elderly patients with raised preoperative arterial blood pressure. METHODS: We conducted a propensity-score-matched cohort study of primary care data from the UK Clinical Practice Research Datalink (2004-13), including 84 633 patients aged 65 yr or over. Conditional logistic regression models, including factors that were significantly associated with the outcome, were constructed for 30-day mortality after elective noncardiac surgery. The effects of beta blockers (primary outcome), renin-angiotensin system (RAS) inhibitors, calcium-channel blockers, thiazides, loop diuretics, and statins were investigated at systolic and diastolic arterial pressure thresholds. RESULTS: Beta blockers were associated with increased odds of postoperative 30-day mortality in patients with systolic hypertension (defined as systolic BP >140 mm Hg; adjusted odds ratio [aOR]: 1.92; 95% confidence interval [CI]: 1.05-3.51). After excluding patients for whom prior data suggest benefit from perioperative beta blockade (patients with prior myocardial infarction or heart failure), rather than adjusting for them, the point estimate shifted slightly (aOR: 2.06; 95% CI: 1.09-3.89). Compared with no use, statins (aOR: 0.35; 95% CI: 0.17-0.75) and thiazides (aOR: 0.28; 95% CI: 0.10-0.78) were associated with lower mortality in patients with systolic hypertension. CONCLUSIONS: These data suggest that the safety of perioperative beta blockers may be influenced by preoperative blood pressure thresholds. A randomised controlled trial of beta-blocker withdrawal, in select populations, is required to identify a causal relationship.

Influenza Vaccine in Heart Failure.

BACKGROUND: Influenza infection is a serious event for patients with heart failure (HF). Little knowledge exists about the association between influenza vaccination and outcome in patients with HF. This study sought to determine whether influenza vaccination is associated with improved long-term survival in patients with newly diagnosed HF. METHODS: We performed a nationwide cohort study including all patients who were >18 years of age and diagnosed with HF in Denmark in the period of January 1, 2003, to June 1, 2015 (n=134 048). We collected linked data using nationwide registries. Vaccination status, number, and frequency during follow-up were treated as time-varying covariates in time-dependent Cox regression. RESULTS: Follow-up was 99.8% with a median follow-up time of 3.7 years (interquartile range, 1.7-6.8 years). The vaccination coverage of the study cohort ranged from 16% to 54% during the study period. In unadjusted analysis, receiving ≥1 vaccinations during follow-up was associated with a higher risk of death. After adjustment for inclusion date, comorbidities, medications, household income, and education level, receiving ≥1 vaccinations was associated with an 18% reduced risk of death (all-cause: hazard ratio, 0.82; 95% CI, 0.81-0.84; P<0.001; cardiovascular causes: hazard ratio, 0.82; 95% CI, 0.81-0.84; P<0.001). Annual vaccination, vaccination early in the year (September to October), and greater cumulative number of vaccinations were associated with larger reductions in the risk of death compared with intermittent vaccination. CONCLUSIONS: In patients with HF, influenza vaccination was associated with a reduced risk of both all-cause and cardiovascular death after extensive adjustment for confounders. Frequent vaccination and vaccination earlier in the year were associated with larger reductions in the risk of death compared with intermittent and late vaccination.

Association of Timing of Aortic Valve Replacement Surgery After Stroke With Risk of Recurrent Stroke and Mortality.

Importance: Timing of surgical aortic valve replacement (SAVR) in patients with aortic valve stenosis and previous stroke for the risk of recurrent stroke is insufficiently investigated. Objective: To evaluate the association of time elapsed between previous stroke and SAVR with the risk of recurrent perioperative stroke, major adverse cardiovascular events (MACE), and mortality among patients with aortic valve stenosis. Design, Setting, and Participants: This cohort study using data from Danish administrative registries included all patients with aortic valve stenosis older than 18 years who underwent SAVR between 1996 and 2014 (n = 14 030). Patients who received simultaneous mitral, tricuspid, or pulmonary valve surgery and patients with endocarditis 1 year prior to surgery were excluded. Data were analyzed from March 2017 to January 2018. Exposures: Time elapsed between prior stroke and SAVR (<3 months, 3-<12 months, ≥12 months, and no prior stroke). Main Outcomes and Measures: Thirty-day risks of MACE, ischemic stroke, and all-cause mortality reported as absolute events and multivariable adjusted odds ratios with 95% confidence intervals. Restricted cubic spline regression models were additionally applied on the subgroup with prior stroke. Results: Of the 14 030 included patients, 616 patients (190 [30.8%] women; mean [SD] age, 72.0 [9.1] years) with prior stroke underwent surgery, and 13 414 (4837 [36.1%] women; mean [SD] age, 69.8 [10.8] years) without prior stroke underwent surgery. The absolute risk of ischemic stroke was significantly increased in patients with stroke less than 3 months prior to surgery compared with patients with no prior stroke (18.4% [37 of 201] vs 1.2% [160 of 13 219]; odds ratio, 14.69; 95% CI, 9.69-22.27). Likewise, compared with patients without stroke, patients with stroke less than 3 months prior surgery were at significantly increased risk of MACE (23.3% [53 of 227] vs 5.7% [768 of 13 414]; odds ratio, 4.57; 95% CI, 3.24-6.44) but not all-cause mortality (6.8% [50 of 730] vs 3.6% [374 of 10 370]; odds ratio, 1.45; 95% CI, 0.83-2.54). Spline analyses supported a declining risk over time, reaching nadir after 2 to 4 months. Conclusions and Relevance: Previous stroke is a major risk factor of recurrent ischemic stroke and MACE in patients undergoing SAVR, especially if time elapsed between previous stroke and surgery is less than 3 months.

Cost-effectiveness of Intensive Blood Pressure Management.

Importance: Among high-risk patients with hypertension, targeting a systolic blood pressure of 120 mm Hg reduces cardiovascular morbidity and mortality compared with a higher target. However, intensive blood pressure management incurs additional costs from treatment and from adverse events. Objective: To evaluate the incremental cost-effectiveness of intensive blood pressure management compared with standard management. Design, Setting, and Participants: This cost-effectiveness analysis conducted from September 2015 to August 2016 used a Markov cohort model to estimate cost-effectiveness of intensive blood pressure management among 68-year-old high-risk adults with hypertension but not diabetes. We used the Systolic Blood Pressure Intervention Trial (SPRINT) to estimate treatment effects and adverse event rates. We used Centers for Disease Control and Prevention Life Tables to project age- and cause-specific mortality, calibrated to rates reported in SPRINT. We also used population-based observational data to model development of heart failure, myocardial infarction, stroke, and subsequent mortality. Costs were based on published sources, Medicare data, and the National Inpatient Sample. Interventions: Treatment of hypertension to a systolic blood pressure goal of 120 mm Hg (intensive management) or 140 mm Hg (standard management). Main Outcomes and Measures: Lifetime costs and quality-adjusted life-years (QALYs), discounted at 3% annually. Results: Standard management yielded 9.6 QALYs and accrued $155 261 in lifetime costs, while intensive management yielded 10.5 QALYs and accrued $176 584 in costs. Intensive blood pressure management cost $23 777 per QALY gained. In a sensitivity analysis, serious adverse events would need to occur at 3 times the rate observed in SPRINT and be 3 times more common in the intensive management arm to prefer standard management. Conclusions and Relevance: Intensive blood pressure management is cost-effective at typical thresholds for value in health care and remains so even with substantially higher adverse event rates.

Influence of age on perioperative major adverse cardiovascular events and mortality risks in elective non-cardiac surgery.

BACKGROUND AND AIMS: Advanced age increases the risk of perioperative cardiovascular complications and may pose reluctance to subject elderly patients to surgery. We examined the impact of high age on perioperative major adverse cardiovascular events (MACE) and mortality in a nationwide cohort of patients undergoing elective surgery. METHODS: All Danish patients aged ≥20years undergoing non-cardiac, elective surgery in 2005-2011 were identified from nationwide administrative registers. Risks of 30-day MACE (non-fatal ischemic stroke, non-fatal myocardial infarction, or cardiovascular death) and all-cause mortality were analyzed by multivariable logistic regression models (adjusted for comorbidities, revised cardiac risk index, cardiovascular pharmacotherapy, body mass index, and surgery type). RESULTS: A total of 386,818 procedures on 302,459 patients were included; mean age was 54.8years (min-max 20-104), and 44% were men. A total of 1297 (0.34%) had perioperative MACE and 1449 (0.37%) died. Advanced age was associated with increased risks of MACE (odds ratio [OR], 1.87; 95% CI, 1.78-1.98 per 10-year high) and mortality (OR, 1.87; 95% CI, 1.78-1.96 per 10-year high). A total of 21,511 procedures were performed on patients >80-90years old, and 1662 on patients >90years. The numbers of MACE and crude mortality rates were 331 (1.7%) and 388 (2.0%) among >80-90years old, and 50 (3.0%) and 67 (4.0%) for those aged >90years. CONCLUSION: The risk of mortality and major adverse cardiovascular events within 30days after surgery increased with advanced age. However, despite advanced age, the absolute event rates appeared to be relatively modest and around 4% for people aged above 90years.

Comparison of antiplatelet regimens in secondary stroke prevention: a nationwide cohort study.

BACKGROUND: In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent stroke associated with these three treatments. METHODS: Patients who were discharged with first-time ischemic stroke from 2007-2010, with no history of atrial fibrillation were identified from Danish nationwide registries. Hazard ratios (HRs) and 1-year risks of recurrent ischemic stroke and bleeding were calculated for each antiplatelet regimen. RESULTS: Among patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus the combination of acetylsalicylic acid and dipyridamole were 1.02 (95% confidence interval [CI]: 0.89-1.17) for ischemic stroke and 1.06 (95% CI: 0.83-1.35) for bleeding. Adjusted HRs for acetylsalicylic acid versus the combination of acetylsalicylic acid and dipyridamole were 1.48 (95% CI: 1.31-1.67) for stroke and 1.47 (95% CI: 1.18-1.82) for bleeding. Clopidogrel versus acetylsalicylic acid yielded HRs of 0.69 (95% CI: 0.59-0.81) and 0.72 (95% CI: 0.55-0.96) for stroke and bleeding, respectively. The 1-year predicted risks associated with acetylsalicylic acid, the combination of acetylsalicylic acid and dipyridamole, and clopidogrel were 11.1 (95% CI: 10.2-12.2), 7.7 (95% CI: 7.3-8.3), and 8.0 (95% CI: 6.9-8.7) for ischemic stroke, respectively; while, the risks for bleeding were 3.4 (95% CI: 2.8-3.9), 2.4 (95% CI: 2.1-2.7), and 2.4 (95% CI: 1.9-2.9), respectively. CONCLUSION: Clopidogrel and the combination of acetylsalicylic acid and dipyridamole were associated with similar risks for recurrent ischemic stroke and bleeding; whereas acetylsalicylic acid was associated with higher risks for both ischemic stroke and bleeding. The latter finding may partially be explained by selection bias.

Age-specific performance of the revised cardiac risk index for predicting cardiovascular risk in elective noncardiac surgery.

BACKGROUND: The revised cardiac risk index (RCRI) holds a central role in preoperative cardiac risk stratification in noncardiac surgery. Its performance in unselected populations, including different age groups, has, however, not been systematically investigated. We assessed the relationship of RCRI with major adverse cardiovascular events in an unselected cohort of patients undergoing elective, noncardiac surgery overall and in different age groups. METHODS AND RESULTS: We followed up all individuals ≥ 25 years who underwent major elective noncardiac surgery in Denmark (January 1, 2005, to November 30, 2011) for the 30-day risk of major adverse cardiovascular events (ischemic stroke, myocardial infarction, or cardiovascular death). There were 742 of 357,396 (0.2%), 755 of 74.889 (1.0%), 521 of 11,921 (4%), and 257 of 3146 (8%) major adverse cardiovascular events occurring in RCRI classes I, II, III, and IV. Multivariable odds ratio estimates were as follows: ischemic heart disease 3.30 (95% confidence interval, 2.96-3.69), high-risk surgery 2.70 (2.46-2.96), congestive heart failure 2.65 (2.29-3.06), cerebrovascular disease 10.02 (9.08-11.05), insulin therapy 1.62 (1.37-1.93), and kidney disease 1.45 (1.33-1.59). Modeling RCRI classes as a continuous variable, C statistic was highest among age group 56 to 65 years (0.772) and lowest for those aged >85 years (0.683). Sensitivity of RCRI class >I (ie, having ≥ 1 risk factor) for capturing major adverse cardiovascular events was 59%, 71%, 64%, 66%, and 67% in patients aged ≤ 55, 56 to 65, 66 to 75, 76 to 85, and >85 years, respectively; the negative predictive values were >98% across all age groups. CONCLUSIONS: In a nationwide unselected cohort, the performance of the RCRI was similar to that of the original cohort. Having ≥ 1 risk factor was of moderate sensitivity, but high negative predictive value for all ages.

Noncardiac surgery in patients with aortic stenosis: a contemporary study on outcomes in a matched sample from the Danish health care system.

BACKGROUND: Past research has identified aortic stenosis (AS) as a major risk factor for adverse outcomes in noncardiac surgery; however, more contemporary studies have questioned the grave prognosis. To further our understanding of this, the risks of a 30-day major adverse cardiovascular event (MACE) and all-cause mortality were investigated in a contemporary Danish cohort. HYPOTHESIS: AS is not an independent risk factor for adverse outcomes in noncardiac surgery. METHODS: All patients with and without diagnosed AS who underwent noncardiac surgery in 2005 to 2011 were identified through nationwide administrative registers. AS patients (n = 2823; mean age, 75.5 years, 53% female) were matched with patients without AS (n = 2823) on propensity score for AS and surgery type. RESULTS: In elective surgery, MACE (ie, nonfatal myocardial infarction, ischemic stroke, or cardiovascular death) occurred in 66/1772 (3.7%) of patients with AS and 52/1772 (2.9%) of controls (P = 0.19), whereas mortality occurred in 67/1772 (3.8%) AS patients and 51/1772 (2.9%) controls (P = 0.13). In emergency surgery, 163/1051 (15.5%) AS patients and 120/1051 (11.4%) controls had a MACE (P = 0.006), whereas 225/1051 (21.4%) vs 179/1051 (17.0%) AS patients and controls died, respectively (P = 0.01). Event rates were higher for those with symptoms (defined as use of nitrates, congestive heart failure, or use of loop diuretics), compared with those without symptoms (P < 0.0001). CONCLUSIONS: AS is associated with high perioperative rates of MACE and mortality, but perhaps prognosis is, in practice, not much worse for patients with AS than for matched controls. Symptomatic patients and patients undergoing emergency surgery are at considerable risks of a MACE and mortality.