Samuli Lepojärvi

Preoperative C-reactive protein and outcome after coronary artery bypass surgery

BACKGROUND C-reactive protein (CRP) is a predictor of early and late outcome after coronary angioplasty, but there is scant data on its impact on the outcome after coronary artery bypass grafting (CABG). METHODS The predictive value of preoperative CRP was evaluated in a series of 764 patients who underwent on-pump CABG. RESULTS During the in-hospital stay, 13 patients (1.7%) died, 45 (4.5%) developed low cardiac output syndrome, and 28 (3.7%) suffered minor or major cerebrovascular complications. Patients with a preoperative serum concentration of CRP>/=1.0 mg/dL had a higher risk of overall postoperative death (5.3% vs 1.1%, p = 0.001), cardiac death (4.4% vs 0.8%, p = 0.002), low cardiac output syndrome (8.8% vs 3.7%, p = 0.01), and any cerebrovascular complication (4.4% vs 3.5%, p = 0.66). Preoperative serum concentration of CRP>/=1.0 mg/dL was significantly more frequent among patients with history of myocardial infarction, diabetes, lower limb ischemia, low left ventricular ejection fraction, NYHA class IV, and in those undergoing urgent or emergency operation. At multivariate analysis, preoperative serum concentration of CRP >/= 1.0 mg/dL (p = 0.01, O.R.: 6.97) and left ventricular ejection fraction (p = 0.01, O.R.: 0.95) were independent predictors of postoperative death. Postoperative mortality rate was 0.3% among patients with preoperative CRP < 1.0 mg/dL and an ejection fraction >/=50%, whereas it was 21.4% among those with a preoperative CRP >/= 1.0 mg/dL and an ejection fraction less than 50% (p < 0.0001). CONCLUSIONS Preoperative serum concentration of CRP in patients undergoing on-pump coronary artery bypass surgery is an important determinant of postoperative outcome.

Preoperative Warfarin Treatment and Outcome of Coronary Artery Bypass Graft Surgery

BACKGROUND The aim of this case-control study was to evaluate the outcome of isolated coronary artery bypass grafting (CABG) when using a short (median, 2 days) preoperative pause in home warfarin treatment. METHODS A consecutive series of 162 patients on long-term warfarin treatment (median international normalized ratio at the time of operation, 1.9) who underwent isolated CABG was compared with a matched control group of 162 patients with no oral anticoagulation. RESULTS The operative risk of warfarin-treated patients was higher (p=0.001) than in the control patients. The in-hospital mortality was comparable in the warfarin and control groups (3.7% versus 2.5%; p=0.52), and there were no significant differences in the postoperative blood loss (818 versus 758 mL), transfused red blood cells (2.1 versus 1.8 units), or reoperations owing to bleeding (5.6% versus 7.4%) between the groups. The warfarin group received more (p<0.0001) fresh-frozen plasma (1.9 versus 0.5 units), needed longer treatment in the intensive care unit (4.1 versus 2.9 days; p<0.0001), and tended to have an increased risk of postoperative stroke (4.9% versus 1.2%; p=0.10). A CHADS2 score greater than 2, but not the international normalized ratio level, was associated with an increased risk of stroke when adjusted for other important comorbidities. Comparable results were observed also in 107 propensity-matched pairs. CONCLUSIONS The risk of bleeding complications after isolated CABG is not increased when using a short preoperative pause in warfarin treatment. Better preventive strategies for stroke are needed, especially in patients with a high CHADS2 score.

Acute post-exercise change in blood pressure and exercise training response in patients with coronary artery disease

We tested the hypothesis that acute post-exercise change in blood pressure (BP) may predict exercise training responses in BP in patients with coronary artery disease (CAD). Patients with CAD (n = 116, age 62 ± 5 years, 85 men) underwent BP assessments at rest and during 10-min recovery following a symptom-limited exercise test before and after the 6-month training intervention (one strength and 3-4 aerobic moderate-intensity exercises weekly). Post-exercise change in systolic BP (SBP) was calculated by subtracting resting SBP from lowest post-exercise SBP. The training-induced change in resting SBP was −2 ± 13 mmHg (p = 0.064), ranging from −42 to 35 mmHg. Larger post-exercise decrease in SBP and baseline resting SBP predicted a larger training-induced decrement in SBP (β = 0.46 and β = −0.44, respectively, p < 0.001 for both). Acute post-exercise decrease in SBP provided additive value to baseline resting SBP in the prediction of training-induced change in resting SBP (R2 from 0.20 to 0.26, p = 0.002). After further adjustments for other potential confounders (sex, age, baseline body mass index, realized training load), post-exercise decrease in SBP still predicted the training response in resting SBP (β = 0.26, p = 0.015). Acute post-exercise change in SBP was associated with training-induced change in resting SBP in patients with CAD, providing significant predictive information beyond baseline resting SBP.

Exercise Capacity and Heart Rate Responses to Exercise as Predictors of Short-Term Outcome Among Patients With Stable Coronary Artery Disease

Although exercise capacity (EC) and autonomic responses to exercise predict clinical outcomes in various populations, they are not routinely applied in patients with coronary artery disease (CAD). We hypothesized that the composite index of EC and exercise heart rate responses would be a powerful determinant of short-term risk in CAD. Patients with angiographically documented stable CAD and treated with β blockers (n = 1,531) underwent exercise testing to allow the calculation of age- and gender-adjusted EC, maximal chronotropic response index (CRI), and 2-minute postexercise heart rate recovery (HRR, percentage of maximal heart rate). Cardiovascular deaths and hospitalization due to heart failure, registered during a 2-year follow-up (n = 39, 2.5%), were defined as the composite primary end point. An exercise test risk score was calculated as the sum of hazard ratios related to abnormal (lowest tertile) EC, CRI, and HRR. Abnormal EC, CRI, and HRR predicted the primary end point, involving 4.5-, 2.2-, and 6.2-fold risk, respectively, independently of each other. The patients with intermediate and high exercise test risk score had 11.1-fold (95% confidence interval 2.4 to 51.1, p = 0.002) and 25.4-fold (95% confidence interval 5.5 to 116.8, p <0.001) adjusted risk for the primary end point in comparison with the low-risk group, respectively. The addition of this risk score to the established risk model enhanced discrimination by integrated discrimination index and reclassification by categorical and continuous net reclassification index (p <0.001 for all). In conclusion, the composite index of EC and heart rate responses to exercise and recovery is a powerful predictor of short-term outcome in patients with stable CAD.

Association of sST2 and hs-CRP levels with new-onset atrial fibrillation in coronary artery disease

BACKGROUND The data on biomarkers as predictors of atrial fibrillation (AF) in patients with coronary artery disease (CAD) are limited. METHODS A total of 1946 patients with CAD were recruited to the ARTEMIS study. At baseline, the study patients underwent clinical and echocardiographic examinations and had laboratory tests. The patients (n=1710) with the information about the occurrence of new-onset AF during the follow-up were included in the present analysis. RESULTS During 5.7±1.5years of follow-up, 143 (8.4%) patients developed a new-onset AF. Higher values of soluble ST2 (sST2) (20.2±10.8 vs. 17.5±7.2ng/mL, p=0.005), high-sensitivity troponin T (hs-TnT) (11.9±10.2 vs. 10.3±8.3ng/L, p=0.005), high-sensitivity C-reactive protein (hs-CRP) (3.3±5.9 vs. 2.0±4.4mg/L, p<0.001) and brain natriuretic peptide (BNP) (85.6±77.5 vs. 64.9±73.5ng/L, p<0.001) had significant associations with the occurrence of new-onset AF. In the Cox clinical hazards model, higher age (p=0.004), greater weight (p=0.045), larger left atrial diameter (p=0.001), use of asthma/chronic obstructive pulmonary disease medication (p=0.001) and lack of cholesterol lowering medication (p=0.008) had a significant association with the increased risk of AF. When the biomarkers were tested in the Cox clinical hazards model, sST2 (HR=1.025, 95% CI=1.007-1.043, p=0.006) and hs-CRP (HR=1.027, 95% CI=1.008-1.047, p=0.006) retained their significant power in predicting AF. CONCLUSION A biomarker of fibrosis, sST2, and a biomarker of inflammation, hs-CRP, predict the risk of occurrence of new-onset AF in patients with CAD. These biomarkers contributed to the discrimination of the AF risk model, but did not improve it markedly.

Total testosterone levels, metabolic parameters, cardiac remodeling and exercise capacity in coronary artery disease patients with different stages of glucose tolerance

Objective and methods. The correlation between total testosterone levels, exercise capacity, and metabolic and echocardiographic parameters was studied in 1097 male subjects with coronary artery disease (CAD) and different stages of glucose tolerance. Results. Testosterone level was the lowest among diabetics as compared to prediabetics or controls (P < 0.001). Total and abdominal adiposity were the highest in the subjects with the lowest testosterone. Independent of adiposity, fasting glucose, insulin, and leptin were higher (P < 0.03 to < 0.001) among diabetic and control groups in the lowest, and HbA1c values (P < 0.001) higher among diabetics in the lowest, than in the highest testosterone tertile. Controls and prediabetic subjects with the lowest testosterone levels had the lowest HDL-cholesterol levels, and controls also the highest triglycerides. An association between low testosterone level and low maximal exercise capacity was observed in diabetics (P < 0.001) and controls (P < 0.03). Independent of adiposity and metabolic parameters, low testosterone levels were associated with the highest septal wall thickness (P < 0.03) among diabetics. Conclusion. A negative correlation between low testosterone and dysmetabolic features was observed. Independent of metabolic status, low plasma testosterone seems to be an indicator of impaired maximal exercise capacity and cardiac hypertrophy among CAD patients with type II diabetes.

Presence of atrial fibrillation is associated with liver stiffness in an elderly Finnish population

Background Chronic liver injury from different etiologies drives liver fibrosis. However, little is known about the associated factors, systemic factors in particular. Recently, non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation have been shown to be associated with each other. Thereby, we aimed to study the association between atrial fibrillation and liver stiffness. Study Extensive clinical measurements including echocardiography of the heart, transient elastography (TE) of the liver and the presence of atrial fibrillation were determined in elderly Finnish study subjects (n = 76, mean age 73 years) from OPERA (Oulu Project Elucidating the Risk of Atherosclerosis) study cohort. Half of the study subjects had non-alcoholic fatty liver disease, whereas others did not have any known hepatic morbidity. The present study was cross-sectional by nature. Results The subjects with atrial fibrillation had higher TE values (with atrial fibrillation TE = 9.3kPa, without atrial fibrillation TE = 6.3kPa, p = 0.018). When the cohort was divided to four subgroups (those without NAFLD or atrial fibrillation, with NAFLD but without atrial fibrillation, with both conditions, and with atrial fibrillation but without NAFLD), the TE value was the highest in the subjects with both conditions (5.3kPa, 7.4kPa, 10.8kPa and 7.8kPa, respectively, p = 0.019). Moreover, the higher the TE value, the more prevalent atrial fibrillation was (the atrial fibrillation prevalence by tertiles of TE 27% / 36% / 77%, p = 0.001). Likewise, the greater the TE value, the greater the left atrial diameter, a collateral of atrial fibrillation (left atrial diameters by tertiles of TE 39mm / 45mm / 48mm, p<0.001) was. All these p-values for continuous variables remained statistically significant even after adjustment for common clinically relevant risk factors. Conclusions There is an association between atrial fibrillation and liver stiffness. This novel association may have multiple explanations and mechanistic links, which are discussed here and need further studies, prospective studies in particular.

Leptin predicts short-term major adverse cardiac events in patients with coronary artery disease

Abstract Introduction: Leptin is an adipose tissue-derived hormone associated with cardiovascular risk factors. We examined whether leptin predicts major adverse cardiac events (MACE) in coronary artery disease (CAD) patients. Methods: Fasting plasma leptin levels were measured in 1327 male and 619 female CAD patients. The patients were followed up for two years. The primary endpoint (MACE) was the composite of a hospitalisation for congestive heart failure (CHF) or a cardiac death. The secondary endpoint was the composite of an acute coronary syndrome (ACS) or a stroke. Results: In regression analysis including established risk variables, high leptin levels were associated with a significantly increased risk of MACE (HR 3.37; 95%CI 1.64–6.90; p = 0.001) and ACS or stroke (HR 1.95; 95%CI 1.29–2.96; p = 0.002). Adding leptin to the risk model for MACE increased the C-index from 0.78 (95%CI 0.71–0.85) to 0.81 (0.74–0.88) and improved classification (NRI 0.36; 95%CI 0.13–0.60; p = 0.002) and discrimination of the patients (IDI 0.016; 95%CI 0.001–0.030; p = 0.031). Conclusions: High plasma leptin levels predict short-term occurrence of CHF or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible harmful effects of leptin should be thoroughly investigated. Key messages Leptin is a peptide hormone secreted mainly by adipose tissue. It has been associated with several cardiovascular risk factors. High leptin levels predict the short-term occurrence of congestive heart failure or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible detrimental effects of leptin on the cardiovascular system should be thoroughly investigated.