Olli-Pekka Piira

Determinants and Prognostic Value of Cardiovascular Autonomic Function in Coronary Artery Disease Patients with and without Type 2 Diabetes

OBJECTIVE Cardiovascular autonomic dysfunction is a common finding among patients with coronary artery disease (CAD) and type 2 diabetes (T2D). The reasons and prognostic value of autonomic dysfunction in CAD patients with T2D are not well known. RESEARCH DESIGN AND METHODS We examined the association between heart rate recovery (HRR), 24-h heart rate (HR) variability (SD of normal R-R interval [SDNN]), and HR turbulence (HRT), and echocardiographic parameters, metabolic, inflammatory, and coronary risk variables, exercise capacity, and the presence of T2D among 1,060 patients with CAD (mean age 67 ± 8 years; 69% males; 50% patients with T2D). Second, we investigated how autonomic function predicts a composite end point of cardiovascular death, acute coronary event, stroke, and hospitalization for heart failure during a 2-year follow-up. RESULTS In multiple linear regression model, exercise capacity was a strong predictor of HRR (R = 0.34, P < 0.001), SDNN (R = 0.33, P < 0.001), and HRT (R = 0.13, P = 0.001). In univariate analyses, a composite end point was predicted by reduced HRR (hazard ratio 1.7 [95% CI 1.1–2.6]; P = 0.020), reduced SDNN (2.0 [95% CI 1.2–3.1]; P = 0.005), and blunted HRT (2.1 [1.3–3.4]; P = 0.003) only in patients with T2D. After multivariate adjustment, none of the autonomic markers predicted the end point, but high-sensitivity C-reactive protein (hs-CRP) remained an independent predictor. CONCLUSIONS Cardiovascular autonomic function in CAD patients is associated with several variables, including exercise capacity. Autonomic dysfunction predicts short-term cardiovascular events among CAD patients with T2D, but it is not as strong an independent predictor as hs-CRP.

High serum fasting peptide YY (3–36) is associated with obesity-associated insulin resistance and type 2 diabetes

We studied whether serum fasting levels of active form of peptide YY (PYY), PYY(3-36), are associated with obesity and related phenotypes. The study population consisted of 428 patients with coronary artery disease and diagnosed type 2 diabetes and 440 patients with coronary artery disease but without evidence of diabetes from the ARTEMIS study. The patients were recruited from the consecutive series of patients undergoing coronary angiography in the Oulu University Hospital. The patients without diabetes underwent a 2-hour oral glucose tolerance test. PYY(3-36) levels were analyzed by human PYY(3-36) specific radioimmunoassay. Result suggested that when PYY(3-36) tertiles were considered, high serum fasting PYY(3-36) concentration was associated with high body mass index, waist circumference, hemoglobin A1c, fasting blood glucose, leptin, triglyceride (p for all p ≤ 0.001), serum insulin (p=0.013) and with a low high-density lipoprotein cholesterol (p=0.004) concentrations in the analyses adjusted for age, sex and study group. The link high PYY(3-36)-high insulin level was evident in subjects with normal glucose tolerance (p<0.05). The prevalence of diabetes was 72%, 46% and 30% in the highest, medium and lowest PYY(3-36) tertile (p<0.001). The PYY(3-36) concentrations (after adjustment for age, sex and body mass index) were higher in type 2 diabetics compared to subjects with impaired fasting glucose, impaired glucose tolerance and normal glucose tolerance (p<0.001 for trend). In conclusion, fasting PYY(3-36) concentrations in type 2 diabetic subjects are high. Although high PYY(3-36) is strongly linked to obesity and associated insulin resistance, the relation between PYY(3-36) and type 2 diabetes is independent of body fatness.

Serum 25-hydroxyvitamin D is associated with major cardiovascular risk factors and cardiac structure and function in patients with coronary artery disease

BACKGROUND AND AIMSnVitamin D deficiency has been associated with increased risk for cardiovascular (CV) disease, but the possible effects of Vitamin D on cardiac structure and function are not well characterized.nnnMETHODS AND RESULTSnThe correlation between 25-hydroxyvitamin D levels and metabolic and cardiac echocardiographic parameters was studied in ARTEMIS study population including 831diabetic and 659 non-diabetic patients with stable coronary artery disease (CAD). Low levels of Vitamin D were associated with high BMI (pxa0<xa00.001), high total and LDL cholesterol and triglyceride levels (pxa0<xa00.001 for all) in both diabetics and non-diabetics. Among non-diabetic patients, low Vitamin D was also associated independently with elevated systolic and diastolic blood pressure (pxa0<xa00.005). Low Vitamin D levels were independently associated with reduced left ventricular (LV) ejection fraction (pxa0<xa00.005) and increased left atrial diameter (pxa0<xa00.03) measured by cardiac ultrasound by 2-dimensional echo. In the non-diabetic group, low Vitamin D levels were associated with impaired LV filling (high E/E) (pxa0<xa00.03) and low E/A mitral flow pattern measured by Doppler echocardiography (pxa0<xa00.05). Among diabetics, low Vitamin D levels were also related to increased LV end-systolic diameter (pxa0<xa00.05) and right ventricular diameter (pxa0<xa00.005). The association between LV diastolic filling (E/E) and Vitamin D levels was significant (pxa0<xa00.01) after adjustment for the commonly recognized risk factors of diastolic dysfunction in linear regression analysis.nnnCONCLUSIONSnLow Vitamin D is associated with several major cardiovascular risk factors and cardiac structural changes including impaired systolic and diastolic function, which together may explain the association of low Vitamin D to worse cardiovascular outcome.

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.

Usefulness of Highly Sensitive Troponin as a Predictor of Short-Term Outcome in Patients With Diabetes Mellitus and Stable Coronary Artery Disease (from the ARTEMIS Study).

The aim of this study was to test the hypothesis that novel biomarkers may predict cardiac events in diabetic patients with stable coronary artery disease (CAD). Serum levels of highly sensitive troponin T (hs-TnT), B-type natriuretic peptide, highly sensitive C-reactive protein (hs-CRP), galectin-3, and soluble suppressor of tumorigenicity-2 (sST2) were analyzed in 1,137 patients with CAD and with type 2 diabetes, impaired glucose tolerance, or fasting glycaemia (diabetic group) and in 649 patients with normal glucose state. Cardiac death or hospitalization for congestive heart failure was the major end point during the follow-up of 2 years. Forty patients in the diabetic group (3.5%) and 9 patients in the nondiabetic group (1.4%) reached the primary end point. High hs-TnT level (≥14 ng/l) was the strongest predictor of the primary end point with hazard ratio of 24.5 (95% confidence interval 8.7 to 69.0; p <0.001) and remained so when adjusted for clinical variables, ejection fraction, renal, lipid, and glycemic status and other biomarkers (hazard ratio 9.9, 95% confidence interval 3.2 to 30.8; p <0.001). In the multivariate model, hs-CRP, B-type natriuretic peptide, and sST2 also predicted the primary end point in the diabetic group (p <0.01 for all). Only sST2 (p <0.001) and hs-CRP (p = 0.02) predicted the primary end point in nondiabetic group. The inclusion of hs-TnT in the model significantly improved discrimination (integrated discrimination improvement 0.050) and reclassification of the patients (net reclassification index 0.21). In conclusion, hs-TnT is a strong predictor of cardiac death or hospitalization for heart failure independently from traditional risk markers or other biomarkers in diabetic patients with stable CAD.

High plasma leptin levels are associated with impaired diastolic function in patients with coronary artery disease

BACKGROUND AND AIMSnObese subjects have elevated leptin levels, which have been associated with increased risk of cardiovascular events. Because leptin has direct cellular effects on various tissues, we tested the hypothesis that leptin levels are associated with cardiac structure or function in patients with coronary artery disease (CAD).nnnMETHODS AND RESULTSnThe study population consisted of 1 601 CAD patients, of whom 42% had type 2 diabetes mellitus. Plasma leptin was measured in fasted state and an echocardiography performed. Leptin levels were not related to LV dimensions or LV ejection fraction (NS for all), but higher leptin levels were associated with elevated E/E (9.43 vs. 11.94 in the lowest and the highest leptin quartile, respectively; p=0.018 for trend). Correspondingly, a decreasing trend was observed in E/A (1.15 vs. 1.06; p=0.037). These associations were independent of obesity and other relevant confounding variables.nnnCONCLUSIONnWe conclude that elevated plasma leptin levels are associated with impaired left ventricular diastolic function in patients with CAD independently of obesity and other confounding variables. Leptin may be one of the mechanistic links explaining the development of congestive heart failure in obese subjects.

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.

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.

MANTA versus ProGlide vascular closure devices in transfemoral transcatheter aortic valve implantation

BACKGROUNDnThe MANTA system is a novel vascular closure device (VCD) and its safety and efficacy were compared to the ProGlide VCD in patients undergoing transfemoral transcatheter aortic valve implantation (TAVI).nnnMETHODSnThis is a retrospective study including 222 patients who underwent transfemoral TAVI at three Finnish University Hospitals. The MANTA VCD was used in 107 patients and their outcome was compared with that of 115 patients in whom the arterial access was closed with the ProGlide VCD.nnnRESULTSnVARC-2 VCD failure occurred less frequently in the MANTA cohort (3.7% vs. 7.8%, pu202f=u202f0.378), but the difference did not reach statistical significance. When adjusted for the introducer outer diameter, the MANTA cohort had similar rates of VARC-2 major vascular complications (9.3% vs. 12.2%, adjusted: pu202f=u202f0.456), VARC-2 life-threatening/disabling bleeding (9.3% vs. 6.1%, adjusted: pu202f=u202f0.296) and need of invasive treatment of bleeding (4.7% vs. 7.0%, adjusted: pu202f=u202f0.416) compared to the ProGlide cohort. Additional VCDs were more frequently needed in the ProGlide cohort (58.3% vs. 1.9%, pu202f<u202f0.0001).nnnCONCLUSIONSnIn patients undergoing transfemoral TAVI, the MANTA VCD showed a similar risk of VARC-2 vascular and bleeding complications compared to the ProGlide VCD, but it reduced significantly the need of additional VCDs for completion of hemostasis.

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; pu2009=u20090.001) and ACS or stroke (HR 1.95; 95%CI 1.29–2.96; pu2009=u20090.002). 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; pu2009=u20090.002) and discrimination of the patients (IDI 0.016; 95%CI 0.001–0.030; pu2009=u20090.031). 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.