Reduced Long-Term Relative Survival in Females and Younger Adults Undergoing Cardiac Surgery: A Prospective Cohort Study

<div><p>Objectives</p><p>To assess long-term survival and mortality in adult cardiac surgery patients.</p><p>Methods</p><p>8,564 consecutive patients undergoing cardiac surgery in Trondheim, Norway from 2000 until censoring 31.12.2014 were prospectively followed. Observed long-term mortality following surgery was compared to the expected mortality in the Norwegian population, matched on gender, age and calendar year. This enabled assessment of relative survival (observed/expected survival rates) and relative mortality (observed/expected deaths). Long-term mortality was compared across gender, age and surgical procedure. Predictors of reduced survival were assessed with multivariate analyses of observed and relative mortality.</p><p>Results</p><p>During follow-up (median 6.4 years), 2,044 patients (23.9%) died. The observed 30-day, 1-, 3- and 5-year mortality rates were 2.2%, 4.4%, 8.2% and 13.8%, respectively, and remained constant throughout the study period. Comparing observed mortality to that expected in a matched sample from the general population, patients undergoing cardiac surgery showed excellent survival throughout the first seven years of follow-up (relative survival ≥ 1). Subsequently, survival decreased, which was more pronounced in females and patients undergoing other procedures than isolated coronary artery bypass grafting (CABG). Relative mortality was higher in younger age groups, females and patients undergoing aortic valve replacement (AVR). The female survival advantage in the general population was obliterated (relative mortality ratio (RMR) 1.35 (1.19–1.54), p<0.001). Increasing observed long-term mortality seen with ageing was due to population risk, and younger age was independently associated with increased relative mortality (RMR per 5 years 0.81 (0.79–0.84), p<0.001)).</p><p>Conclusions</p><p>Cardiac surgery patients showed comparable survival to that expected in the general Norwegian population, underlining the benefits of cardiac surgery in appropriately selected patients. The beneficial effect lasted shorter in younger patients, females and patients undergoing AVR or other procedures than isolated CABG. Thus, the study identified three groups that need increased attention for further improvement of outcomes.</p></div

Standardized mortality ratios stratified on gender and age group (n = 8,380).

<p>Standardized mortality ratios stratified on gender and age group (n = 8,380).</p

Overview over cardiac operations performed at the Department of Cardiothoracic Surgery, Trondheim, Norway, from 2000 through 2014.

<p>A) Stratified on the surgical procedure(s) performed. B) Stratified on age at operation day. For A and B, the total number of procedures is given as reference. C) Cumulative observed mortality rates 30 days, 1, 3 and 5 years following surgery.</p

Risk factors associated with observed mortality.

<p>Risk factors associated with observed mortality.</p

Long-term observed survival.

<p>Unadjusted Kaplan-Meier survival curves for patients undergoing coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR). The number at risk (n) at the start of even follow-up years are provided.</p

Predictors of relative mortality.

<p>Estimated relative mortality ratios (RMR) with corresponding 95% confidence intervals (CI) for predictor variables of long-term relative mortality in patients undergoing cardiac surgery. A ratio of 1 indicates no difference. CABG, coronary artery bypass grafting.</p

Mannose-Binding Lectin Deficiency Is Associated with Myocardial Infarction: The HUNT2 Study in Norway

<div><h3>Objectives</h3><p>Mannose-binding lectin (MBL) and ficolins activate the complement cascade, which is involved in atherogenesis. Based on a pilot study, we hypothesized that functional polymorphisms in the MBL gene (<em>MBL2</em>) leading to dysfunctional protein are related to development of myocardial infarction (MI). The aim of the present study was to study polymorphisms in <em>MBL2</em> and ficolin genes in relation to the risk of MI.</p> <h3>Methods and Results</h3><p>Using the population-based HUNT Study in Norway, 57133 persons were followed up for a first-time MI from 1995–1997 until the end of 2008. The 370 youngest MI patients were matched by age (range 29–62 years) and gender to 370 controls. A younger population was selected because disease in this group might be less dependent on non-genetic risk factors. The study size was based on power calculation. Polymorphisms in <em>MBL2</em> and in the genes of ficolin-1, ficolin-2 and ficolin-3 were genotyped by pyrosequencing and related to the risk of MI, estimated as odds ratios (OR). Functional haplotypes were analyzed and stringent alpha levels of significance were set by permutation testing. Variant <em>MBL2</em> haplotypes causing MBL deficiency were associated with a two-fold higher risk of MI (OR 2.04, 95%CI 1.29–3.24). Adjustments for conventional cardiovascular risk factors did not substantially influence the association. The ficolins were not associated with MI risk.</p> <h3>Conclusion</h3><p>In a young to middle aged and relatively healthy Caucasian population, <em>MBL2</em> variants related to functional MBL deficiency were associated with a doubling of the risk for MI, independent of conventional risk factors. This supports that MBL deficiency may lead to increased atherosclerosis or development of vulnerable plaques.</p> </div

Baseline characteristics.

*<p>Body mass index (BMI).</p>†<p>Waist hip ratio (WHR).</p>‡<p>Myocardial infarction before 60 years in first-degree relatives.</p

Data on <i>MBL2</i> haplotypes and MBL plasma concentrations from the pilot study.

<p>Data on <i>MBL2</i> haplotypes and MBL plasma concentrations from the pilot study.</p

Conditional logistic regression analyses, <i>MBL2</i> functional groups.

*<p>26 pairs excluded because one or more missing values.</p>†<p>Adjusted for classical risk factors: Hypertension (BP>140/90 or current use of antihypertensive medication), body mass index (kg/m², continuous), hypercholesterolemia (total cholesterol >6.2 mmol/L), diabetes (yes/no) and smoking (never/former/current).</p>‡<p>Adjusted for Framingham risk score (age, HDL-cholesterol, total cholesterol, systolic blood pressure, smoking and diabetes).</p>§<p>3 pairs excluded because one or more missing values.</p