European Journal of Preventive Cardiology

The increasing prevalence of atrial fibrillation and novel therapeutic tools to prevent cardioembolic stroke has increased the need for risk markers.

This study explored the relationship between the midregional sequence of pro-atrial natriuretic peptide (MR-proANP) levels with the risk of atrial fibrillation and stroke, and whether measurement of MR-proANP improves the prediction of these outcomes.

MR-proANP was measured in fasting blood samples of 5130 subjects (69% men, mean age 69.2 ± 6.2 years) without a history of atrial fibrillation or stroke from the general population. The incidence of atrial fibrillation and stroke was monitored over a median follow-up of 5.6 years. C-statistics and net reclassification improvement was used to assess the predictive ability of MR-proANP in addition to conventional risk factors.

Log-normalized MR-proANP was significantly associated with the incidence of atrial fibrillation (n = 362; hazard ratio (HR); 95% confidence interval (CI) per 1 standard deviation (SD) 2.05, 1.86–2.27) and stroke from all causes (n = 195; HR 1.30; 95% CI 1.12–1.50). The HR for stroke events related to atrial fibrillation was 1.79 (95% CI 1.25–2.58) per 1 SD. MR-proANP significantly improved the prediction of atrial fibrillation when added to a risk score of conventional risk factors (C statistic 0.69 vs. 0.75), mainly by down-classifying subjects who did not develop atrial fibrillation. A smaller improvement in predictive ability was observed for stroke (C statistic 0.66 vs. 0.68).

High plasma levels of MR-proANP are associated with the incidence of atrial fibrillation and stroke in the middle-aged and elderly population. MR-proANP may be useful to identify individuals with an increased risk of atrial fibrillation.

Anaemia and iron deficiency are frequent following major surgery. The present study aims to identify the iron deficiency patterns in cardiac surgery patients at their admission to a cardiac rehabilitation programme, and to determine which perioperative risk factor(s) may be associated with functional and absolute iron deficiency.

This was a retrospective study on prospectively collected data.

The patient population included 339 patients. Functional iron deficiency was defined in the presence of transferrin saturation <20% and serum ferritin ≥100 µg/l. Absolute iron deficiency was defined in the presence of serum ferritin values <100 µg/l.

Functional iron deficiency was found in 62.9% of patients and absolute iron deficiency in 10% of the patients. At a multivariable analysis, absolute iron deficiency was significantly (p = 0.001) associated with mechanical prosthesis mitral valve replacement (odds ratio 5.4, 95% confidence interval 1.9–15) and tissue valve aortic valve replacement (odds ratio 4.5, 95% confidence interval 1.9–11). In mitral valve surgery, mitral repair carried a significant (p = 0.013) lower risk of absolute iron deficiency (4.4%) than mitral valve replacement with tissue valves (8.3%) or mechanical prostheses (22.5%). Postoperative outcome did not differ between patients with functional iron deficiency and patients without iron deficiency; patients with absolute iron deficiency had a significantly (p = 0.017) longer postoperative hospital stay (median 11 days) than patients without iron deficiency (median nine days) or with functional iron deficiency (median eight days).

Absolute iron deficiency following cardiac surgery is more frequent in heart valve surgery and is associated with a prolonged hospital stay. Routine screening for iron deficiency at admission in the cardiac rehabilitation unit is suggested.

In patients with heart failure, inflammation has been associated with worse functional capacity, but it is uncertain whether it could affect their response to exercise training. We evaluated whether inflammatory biomarkers are related to differential effect of exercise on the peak oxygen uptake (V˙O₂) among patients with heart failure.

Open, parallel group, randomized controlled trial.

Patients with heart failure and ejection fraction ≤0.4 were randomized into exercise training or control for 12 weeks. Patients were classified according to: 1) inflammatory biomarkers blood levels, defined as ‘low’ if both interleukin-6 and tumor necrosis factor-alpha blood levels were below median, and ‘high’ otherwise; and 2) galectin-3 blood levels, which also reflect pro-fibrotic processes.

Forty-four participants (50 ± 7 years old, 55% men, 25% ischemic) were allocated to exercise training (n = 28) or control (n = 16). Exercise significantly improved peak V˙O₂ among participants with ‘low’ inflammatory biomarkers (3.5 ± 0.9 vs. −0.7 ± 1.1 ml/kg per min, p = 0.006), as compared with control, but not among those with ‘high’ inflammatory biomarkers (0.4 ± 0.6 vs. −0.2 ± 0.7 ml/kg per min, p = 0.54, p for interaction = 0.009). Similarly, exercise improved peak V˙O₂ among participants with below median (2.4 ± 0.8 vs. −0.3 ± 0.9 ml/kg per min, p = 0.032), but not among those with above median galectin-3 blood levels (0.3 ± 0.7 vs. −0.7 ± 1.0 ml/kg per min, p = 0.41, p for interaction = 0.053).

In patients with heart failure, levels of biomarkers that reflect pro-inflammatory and pro-fibrotic processes were associated with differential effect of exercise on functional capacity. Further studies should evaluate whether exercise training can improve clinical outcomes in patients with heart failure and low levels of these biomarkers.

Patients suffering from heart failure (HF) may demonstrate an abnormal blood pressure response to exercise (ABPRE), which may revert to a normal one following medical treatment. It is assumed that this change correlates positively with prognosis and functional aspects. The aim of this study was to characterize patients with ABPRE and assess ABPRE normalization and the correlation with clinical and functional outcomes.

In the study, 651 patients with HF who underwent cardiac rehabilitation (CR) were examined. Patients who presented an ABPRE during stress testing were identified and divided into those who corrected their initial ABPRE following CR and those who did not.

Pre-rehabilitation ABPRE was present in 27% of patients, 68% of whom normalized their ABPRE following CR. Two parameters were independently predictive of failure to normalize the blood pressure response: female gender (odds ratio (OR) 3.5; 95% confidence interval (CI) 1.4–9.0) and decreased systolic function (OR 3.2; 95% CI 1.0–9.4). Patients with hypertrophic cardiomyopathy demonstrated higher rates of ABPRE normalization than patients with other causes of HF (93% vs. 62%, respectively, P = 0.03). The research population exhibited an average improvement in exercise capacity (4.7 to 6.4 metabolic equivalents (METS), P < .001), ejection fraction (35.4% to 37.7%, P < .001) and percentage of patients with New York Heart Association (NYHA) class 3–4 (50% to 43.4%, P = .123). The group who normalized their ABPRE exhibited greater improvement.

Amongst a population of patients suffering from HF, an ABPRE was normalized following CR in two thirds of patients. Female gender and a reduced systolic function independently predicted the failure to correct the ABPRE, while patients with hypertrophic cardiomyopathy demonstrated exceptionally high rates of normalization.

Exercise oscillatory ventilation in chronic heart failure has been suggested as a factor related to adverse cardiac events, aggravated prognosis and higher mortality. Exercise training is well known to affect exercise capacity and mechanisms of pathophysiology beneficially in chronic heart failure. Little is known, however, about the exercise training effects on characteristics of exercise oscillatory ventilation in chronic heart failure patients.

Twenty (out of 38) stable chronic heart failure patients exhibited exercise oscillatory ventilation (age 54 ± 11 years, peak oxygen uptake 15.0 ± 5.0 ml/kg per minute). Patients attended 36 sessions of high intensity interval exercise. All patients underwent cardiopulmonary exercise testing before and after the programme. Assessment of exercise oscillatory ventilation was based on the amplitude of cyclic fluctuations in breathing during rest and exercise. All values are mean ± SD.

Exercise training reduced (P < 0.05) the percentage of exercise oscillatory ventilation duration (79.0 ± 13.0 to 50.0 ± 25.0%), while average amplitude (5.2 ± 2.0 to 4.9 ± 1.6 L/minute) and length (44.0 ± 10.9 to 41.0 ± 6.7 seconds) did not change (P > 0.05). Exercise oscillatory ventilation patients also increased exercise capacity (P < 0.05).

A rehabilitation programme based on high intensity interval training improved exercise oscillatory ventilation observed in chronic heart failure patients, as well as cardiopulmonary efficiency and functional capacity.

Functional electrical stimulation of lower limb muscles is an alternative method of training in patients with chronic heart failure (CHF). Although it improves exercise capacity in CHF, we performed a randomised, placebo-controlled study to investigate its effects on long-term clinical outcomes.

We randomly assigned 120 patients, aged 71 ± 8 years, with stable CHF (New York Heart Association (NYHA) class II/III (63%/37%), mean left ventricular ejection fraction 28 ± 5%), to either a 6-week functional electrical stimulation training programme or placebo. Patients were followed for up to 19 months for death and/or hospitalisation due to CHF decompensation.

At baseline, there were no significant differences in demographic parameters, CHF severity and medications between groups. During a median follow-up of 383 days, 14 patients died (11 cardiac, three non-cardiac deaths), while 40 patients were hospitalised for CHF decompensation. Mortality did not differ between groups (log rank test P = 0.680), while the heart failure-related hospitalisation rate was significantly lower in the functional electrical stimulation group (hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.21–0.78, P = 0.007). The latter difference remained significant after adjustment for prognostic factors: age, gender, baseline NYHA class and left ventricular ejection fraction (HR 0.22, 95% CI 0.10–0.46, P < 0.001). Compared to placebo, functional electrical stimulation training was associated with a lower occurrence of the composite endpoint (death or heart failure-related hospitalisation) after adjustment for the above-mentioned prognostic factors (HR 0.21, 95% CI 0.103–0.435, P < 0.001). However, that effect was mostly driven by the favourable change in hospitalisation rates.

In CHF patients, 6 weeks functional electrical stimulation training reduced the risk of heart failure-related hospitalisations, without affecting the mortality rate. The beneficial long-term effects of this alternative method of training require further investigation.

Cardiovascular disease remains the major contributor to morbidity and mortality. In routine care for patients with an elevated cardiovascular risk or with symptomatic cardiovascular disease information is mostly collected in an unstructured manner, making the data of limited use for structural feedback, quality control, learning and scientific research.

The Utrecht Cardiovascular Cohort (UCC) initiative aims to create an infrastructure for uniform registration of cardiovascular information in routine clinical practice for patients referred for cardiovascular care at the University Medical Center Utrecht, the Netherlands. This infrastructure will promote optimal care according to guidelines, continuous quality control in a learning healthcare system and creation of a research database.

The UCC comprises three parts. UCC-1 comprises enrolment of all eligible cardiovascular patients in whom the same information will be collected, based on the Dutch cardiovascular management guideline. A sample of UCC-1 will be invited for UCC-2. UCC-2 involves an enrichment through extensive clinical measurements with emphasis on heart failure, cerebral ischaemia, arterial aneurysms, diabetes mellitus and elevated blood pressure. UCC-3 comprises on-top studies, with in-depth measurements in smaller groups of participants typically based on dedicated project grants. All participants are followed up for morbidity and mortality through linkage with national registries.

In a multidisciplinary effort with physicians, patients and researchers the UCC sets a benchmark for a learning cardiovascular healthcare system. UCC offers an invaluable resource for future high quality care as well as for first-class research for investigators.

In a modern perspective there is limited information on mortality by affected coronary vessels assessed by coronary angiography in patients with type 1 diabetes. The aim of the present study was to characterise distribution of coronary artery disease and impact on long-term mortality in patients with type 1 diabetes undergoing coronary angiography.

The design of this research was a nationwide population-based cohort study.

Individuals (n = 2776) with type 1 diabetes undergoing coronary angiography 2001–2013 included in the Swedish National Diabetes Registry and Swedish Coronary Angiography and Angioplasty Registry were followed for mortality until 31 December 2013 (mean 7.1 years). In 79% the indication was stable or acute coronary artery disease. Coronary artery disease was categorised into normal (21%), one- (23%), two- (18%), three- (29%) and left main-vessel disease (8%).

Mean age was 57 years and 58% were male. Mean diabetes duration was 35 years, glycated haemoglobin was 67 mmol/mol and 44% had normal or one-vessel disease. In multivariate Cox proportional analyses hazard ratio for mortality compared with normal findings was 1.09 (95% confidence interval 0.80–1.48) for one, 1.43 (1.05–1.94) for two, 1.47 (1.10–1.96) for three and 1.90 (1.35–2.68) for left main-vessel disease. Renal failure 2.29 (1.77–2.96) and previous heart failure 1.76 (1.46–2.13) were highly associated with mortality. Standard mortality ratio the first year was 5.55 (4.65–6.56) and decreased to 2.80 (2.18–3.54) after five years.

In patients with type 1 diabetes referred for coronary angiography mortality is influenced by numbers of affected coronary vessels. The overall mortality rate was higher compared with the general population. These results support early intensive prevention of coronary artery disease in this population.

Familial hypercholesterolemia is characterized by markedly increased low-density lipoprotein cholesterol and risk for premature atherosclerotic cardiovascular disease. Models of care vary and reflect differing health policies and resources. The availability of electronic databases may enable better identification and assessment of familial hypercholesterolemia in the community.

A regional healthcare database was utilized to identify patients with a high probability of familial hypercholesterolemia, clinically defined by age-dependent-peak low-density lipoprotein cholesterol cutoffs and exclusion of secondary causes of severe hypercholesterolemia. Clinical characteristics, low-density lipoprotein cholesterol goal attainment, and treatment gaps were investigated.

Probable familial hypercholesterolemia was diagnosed in 1932 of 685,314 individuals (1:355; median age 47 years). Atherosclerotic cardiovascular disease was present in 16.3% of adults (38% in males aged 50–74 years). Median peak low-density lipoprotein cholesterol was 264 mg/dl (interquartile range 252–288). Statins and/or ezetimibe were prescribed to 83% of patients and high-intensity statins to 53%, whereas prescriptions were filled in 57% and 40% cases respectively over the last six months, p < 0.001. Treatment gaps were wider among ethnic minorities, younger individuals, and those without atherosclerotic cardiovascular disease. Low-density lipoprotein cholesterol < 100 mg/dl was attained in 10.1% overall and 28.7% of those with atherosclerotic cardiovascular disease. Predictors of low-density lipoprotein cholesterol goal attainment included recent issue of high-intensity statins, presence of atherosclerotic cardiovascular disease, diabetes, older age and lack of smoking.

The population with high probability for familial hypercholesterolemia was characterized by low attainment of low-density lipoprotein cholesterol treatment goals despite high prescription rates of lipid-lowering medications. Low utilization of intensified therapies, non-adherence, and ethnic disparities were contributing factors. These findings emphasize the need to improve awareness and quality of care of familial hypercholesterolemia in the community.

To investigate the association between cardiorespiratory fitness (CRF) and muscle strength in late adolescence and the long-term risk of heart failure (HF).

A cohort was created of Swedish men enrolled in compulsory military service between 1968 and 2005 with measurements for CRF and muscle strength (n = 1,226,623; mean age 18.3 years). They were followed until 31 December 2014 for HF hospitalization as recorded in the Swedish national inpatient registry.

During the follow-up period (median (interquartile range) 28.4 (22.0–37.0) years), 7656 cases of first HF hospitalization were observed (mean ± SD age at diagnosis 50.1 ± 7.9 years). CRF and muscle strength were estimated by maximum capacity cycle ergometer testing and strength exercises (knee extension, elbow flexion and hand grip). Inverse dose–response relationships were found between CRF and muscle strength with HF as a primary or contributory diagnosis with an adjusted hazards ratio (95% confidence interval) of 1.60 (1.44–1.77) for low CRF and 1.45 (1.32–1.58) for low muscle strength categories. The associations of incident HF with CRF and muscle strength persisted, regardless of adjustments for the other potential confounders. The highest risk was observed for HF associated with coronary heart disease, diabetes or hypertension.

In this longitudinal study of young men, we found inverse and mutually independent associations between CRF and muscle strength with risk of hospitalization for HF. If causal, these results may emphasize the importance of the promotion of CRF and muscle strength in younger populations.

Circulating cardiac troponin levels increase following prolonged intense physical exercise. The aim of this study was to identify participants with highly elevated cardiac troponins after prolonged, high intensity exercise, and to evaluate these for subclinical coronary artery disease.

Ninety-seven recreational cyclists without known cardiovascular disease or diabetes, participating in a 91 km mountain bike race were included, 74 (76%) were males, age: 43 ± 10 years, race duration: 4.2 (3.6–4.7) h. Blood samples, rest electrocardiogram and physical examination were obtained 24 h prior to, and at 0, 3 and 24 h following the race. Median cardiac troponin I level at baseline: 3.4 (2.1–4.9) ng/l (upper limit of normal: 30.0 ng/l). There was a highly significant (p < 0.0001) increase in circulating cardiac troponin I in all participants: immediately following the race; 50.5 (28.5–71.9) ng/l, peaking at 3 h 69.3 (42.3–97.7) ng/l and declining at 24 h: 14.2 (8.5–27.9) ng/l. No cyclist had symptoms or rest electrocardiogram changes compatible with coronary artery disease during or following the race. Coronary artery disease was detected by coronary angiography in the three cyclists with the three of the four highest cardiac troponin values (>370 ng/l) at 3 and 24 h following the race. Computed tomographic coronary angiography was performed in an additional 10 riders with the subsequently highest cardiac troponin I values, without identifying underlying coronary artery disease.

This study suggests that there is a pathologic cardiac troponin I response following exercise in individuals with subclinical coronary artery disease. This response may be associated with an excessive cardiac troponin I increase at 3 and 24 h following prolonged high-intensity exercise.