European Journal of Preventive Cardiology

Training studies frequently use maximum inspiratory mouth occlusion pressure (PImax) as a therapeutic target and surrogate marker. For patients on β-blocker (BBL), prognostic data allowing this extrapolation do not exist. Furthermore, the effects of BBL, mainstay of modern chronic heart failure therapy, on respiratory muscle function remain controversial. Finally, no proper separate cutoff according to treatment exists.

Prospective, observational inclusion of patients with stable systolic chronic heart failure and recording of 1 year and all-time mortality for endpoint analysis.

In 686 patients, 81% men, 494 patients on BBL, PImax was measured along with clinical evaluation. The median follow-up was 50 months (interquartile range: 26–75 months).

Patients with or without BBL did not differ significantly for PImax, percentage of predicted PImax or other marker of disease severity. PImax was a significant (hazard ratio: 0.925; 95% confidence interval: 0.879–0.975; χ²: 8.62) marker of adverse outcome, independent of BBL-status or aetiology. Percentage of predicted PImax was not independent of PImax. The cutoff identified through receiver-operated characteristics for 1-year mortality was 4.14 kPa for patients on BBL and 7.29 kPa for patients not on BBL. When separated accordingly, 1-year mortality was 8.5 versus 21.4%, P = 0.02, for patients not on BBL and 4.3 versus 16.2%, P < 0.001, for patients on BBL.

This study fills the gap between trials targeting respiratory muscle on a functional basis and the resultant prognostic information with regard to BBL. BBL lowered the optimal PImax cutoff values for risk stratification without changing the measured values of PImax. This should be considered at inclusion and evaluation of trials and interpretation of exercise parameters.

Exercise training is known to be beneficial in chronic heart failure (CH F) patients but there is a lack of studies following patient groups for longer duration with maintenance training programs to defer deconditioning.

Study base consisted of all patients diagnosed with CHF in a 3-year period. Sixty-six patients with systolic CHF (ejection fraction < 45, New York Heart Association II-III) were randomized to 12 months of either usual care or home-based maintenance exercise with group training sessions every 2 weeks after an initial 8-week training program. The primary endpoint was maximum workload; secondary endpoints were 6-min walk test, incremental shuttle walk test, sit-to-stand test, quality of life, and serological markers.

Six patients died and 43 completed the study. The initial 8-week training was associated with small but significant improvement in all of the functional tests. In both groups there was a significant decline in the maximum workload the next 12 months (P = 0.03 and P < 0.001, respectively) but after an adjustment for difference between groups in baseline characteristics, maintenance intervention reduced the decline in the maximum workload by 8.0W (95% CI: 3.0–13.0, P = 0.002). No effect of maintenance intervention was observed for 6-min walk test, incremental shuttle walk test, sit-to-stand test, or quality of life. After 14 months changes in most markers of inflammation, endothelial damage, and glycemic control were more beneficial in the intervention group.

A low-cost maintenance intervention in CHF patients reduced the decline in the maximum workload compared with usual care but not in other measures of physical function. Results suggest beneficial effects of long-term maintenance training on glycemic control, inflammation, and endothelial function.

Lipid-lowering treatment has been proven to decrease the rate of cardiovascular events in high-risk patients with manifest coronary artery disease (CAD) or CAD equivalent risk profile. Current treatment guidelines recommend low-density lipoprotein-cholesterol (LDL-C) less than 100 mg/dl (optional < 70 mg/dl) as the target level for this high-risk population. Little is known about the ambulatory treatment of high-risk patients in clinical practice and the achievement of guideline recommended target values.

In the ‘2L cardio’ registry in Germany, 295 cardiologists enrolled 6711 consecutive patients with known CAD, and/or diabetes mellitus, peripheral arterial disease (summarized as ‘coronary risk equivalent’, CE), on chronic statin treatment. They recorded actual LDL-C values at entry, probable changes in therapy, and the expected LDL-C values using a lipid calculator based on an earlier observational study in a similar setting. The three groups comprised 2618 patients with CAD plus CE (39.0%; median LDL-C 112 mg/dl), 3436 patients with CAD only (51.2%; median LDL-C 108 mg/dl), and 657 with CE only (9.8%; median LDL-C 124 mg/dl). They had LDL-C levels less than 100 mg/dl in 36.2% [95% confidence intervals (CI): 34.3–38.1], 39.7% (CI: 38.0–41.4), and 27.2% (CI: 23.7–30.7), respectively. Statin doses at entry were usually in the lower to intermediate range (e.g. simvastatin median 25 mg/day). Cardiologists switched to another statin in 10.1% (9.4–10.8), increased the dose of statins (if same drug) in 22.2% (CI: 21.1–23.2) and/or added a cholesterol absorption inhibitor in 23.7% (CI: 22.7–24.7) of the patients. The cardiologists’ intervention improved expected LDL-C levels in the total cohort by a mean of 9.0 mg/dl, but the 100 mg/dl LDL-C target was only reached in 51.3% (CI: 50.0–52.5) of the total cohort. CE patients appeared undertreated in terms of antiplatelet drugs.

Through infrequent increases in statin doses and mainly through add-on of a cholesterol absorption inhibitor, cardiologists improved target level attainment. Compared with earlier studies in the outpatient setting, the treatment to target for LDL-C of high-risk CAD patients has improved, but is not satisfactory.

Evidence about the efficacy of statin treatment among patients after percutaneous coronary intervention

(PCI) is very limited. The rapid advancement in PCI technology and near universal use of adjunctive cardioprotective medications make it necessary to formally assess the effect of statin therapy on cardiac events after PCI.

This was a multicenter prospective cohort study.

Patients who received stent implantation and survived to hospital discharge from the National Heart, Lung, and Blood Institute Dynamic Registry from 2004 to 2006 formed the study cohort. Patients with cardiogenic shock, in-hospital adverse events [including myocardial infarction and coronary artery bypass graft surgery (CABG)], liver disease, renal disease, alcoholism, or drug abuse were excluded. The occurrences of death, CABG, and repeat PCI, and repeat revascularization were collected over 1-year follow-up.

Of the 3227 patients evaluated, 2737 (85%) were prescribed a statin at discharge. By 1-year follow-up, incident events were 98 deaths, 44 CABG, 290 repeat PCI procedures, and 328 repeat revascularizations. After propensity score adjustment, postdischarge statin therapy was associated with lower risks of death [hazard ratio (HR): 0.58, 95% confidence interval (CI): 0.36–0.93, P = 0.02], CABG (HR: 0.49, 95% CI: 0.24–1.00, P = 0.05), and repeat revascularization (HR: 0.74, 95% CI: 0.56–1.00, P = 0.05).

These results support the routine use of statin therapy after PCI.

Exertional oscillatory ventilation (EOV) occurs in many patients with chronic heart failure. Two different definitions of EOV have been proposed by Corrá and Leite. We aimed to compare the prevalence of EOV and its prognostic significance in patients with chronic heart failure using the two diagnostic approaches.

Patients underwent a symptom-limited, treadmill-based exercise test with metabolic gas exchange measurements using the modified Bruce protocol. EOV was defined (i) as cyclic fluctuations in ventilation lasting for more than 60% of exercise duration, with an amplitude of greater than 15% of the average amplitude of cyclic fluctuations at rest (Corrá) and/or (ii) as three or more regular oscillations with regularity defined if the standard deviation of three consecutive cycle lengths was within 20% of the average coupled with a minimal average amplitude of ventilatory oscillation of 5I (Leite).

Two hundred and forty patients (mean age 59 ± 13 years; 73% males; left ventricular ejection fraction 34 ± 6%; peak VO₂ 21.0 ± 4.6 ml/kg per min; VE/VCO₂ slope 35 ± 9) were included in the study. The prevalence of EOV was 25% using the Corrá method and 31% using the Leite method. Fifty percent of patients diagnosed with EOV by the Corrá criteria and 58% diagnosed by the Leite criteria had died at 12-month follow-up. EOV (Corrá) was a predictor of mortality independent of peak VO₂, VE/VCO₂ slope, left ventricular ejection fraction, age, and 6-min walk test distance. A hazard ratio (HR) of 6.3 (P < 0.0001; 95% confidence interval = 1.6–25.2) was evident for the Corrá method, which was higher than for the Leite method (HR = 4.9; P < 0.0001; 95% confidence interval = 2.6–18.2).

The prevalence of EOV was between 25 and 31% depending on the criteria used to define it. The presence of EOV was a powerful predictor of adverse outcome, and diagnosed with the Corrá criteria was associated with a higher HR than the Leite criteria.

The relationship between body mass index (BMI) and mortality in patients with established arterial disease remains controversial.

FRENA is an ongoing, observational registry of consecutive outpatients with coronary artery disease (CAD), cerebrovascular disease, or peripheral artery disease (PAD). We examined the prognostic importance of accepted BMI categories on outcome among patients in the FRENA registry.

In April 2008, 2274 patients (mean age, 66 years) had been enrolled, of whom 14 (0.6%) were underweight; 533 (23%) normal; 1051 (46%) overweight; and 676 (30%) were obese. Over a mean follow-up of 14 months, the incidence of major cardiovascular events (myocardial infarction, ischemic stroke, or critical limb ischemia) per 100 patient-years was: 7.1 [95% confidence interval (CI): 0.4–35]; 11 (95% CI: 8.4–14); 6.9 (95% CI: 5.6–8.5); and 8.5 (95% CI: 6.6–11), respectively. Their cardiovascular mortality was: 7.1 (95% CI: 0.4–35); 4.1 (95% CI: 5.9–11); 1.3 (95% CI: 0.9–2.3); and 1.5 (95% CI: 1.4–3.5), respectively. On multivariate analysis, the hazard ratio for cardiovascular mortality was: 2.2 (95% CI: 0.3–17); 1.0 (reference); 0.37 (95% CI: 0.20–0.69); and 0.37 (95% CI: 0.18–0.73), respectively. Survival benefit was only found in patients with CAD or PAD. Weight loss had little influence on outcome.

Patients with CAD or PAD (not those with cerebrovascular disease) have an inverse correlation between BMI and cardiovascular mortality, even after adjusting for confounding variables.

Exercise training reduces mortality in patients with coronary artery disease (CAD); however, the impact of habitual physical activity level (PAL) on vascular endothelial function and circulating endothelial progenitor cells (EPCs) remain unknown.

We assessed habitual PAL using a validated International Physical Activity Questionnaire in 116 patients (67.8 ± 9.5 years; 81% male) with stable CAD and preserved left ventricular ejection fraction ≥ 45%. The number of circulating CD34/KDR+ and CD133/KDR+ EPCs was determined by flow cytometry, and brachial artery flow-mediated dilation (FMD) was measured.

The mean PAL of CAD patients with 1644 MET min/week (where MET is metabolic equivalents). With higher habitual PAL tertiles, there were significant linear trends of increased FMD (P = 0.001) and CD133/KDR+ EPCs (P = 0.03), but not of CD34/KDR+ EPCs. Patients with the highest tertile of PAL were associated with an absolute increase of 1.89% in FMD (relative increase 68%, P = 0.003) and 0.12% in CD133/KDR+ EPCs (relative increase 44%, P = 0.01) compared with those in the lowest tertile of PAL, after adjusting for age, sex, presence of hypertension, diabetes mellitus, hypercholesterolemia, smoking, and the use of medications including statins. However, neither CD34/KDR+ nor CD133/KDR+ EPCs significantly correlated with FMD.

This study showed that higher habitual PAL in patients with CAD was associated with higher FMD and EPC count. Nonetheless, FMD only significantly correlated with increased PAL, but not EPC, suggesting that increased physical activity improves endothelial function through mechanisms other than increasing EPC count.

Single-pill amlodipine/atorvastatin targets the two most common modifiable cardiovascular risk factors, hypertension and dyslipidaemia. We evaluated the clinical utility of this single pill to help patients across Europe and Canada achieve country-specific targets for blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C).

Two 16-week, open-label studies conducted in 122 study centres across the United Kingdom and Canada (JEWEL 1) and 113 centres across 11 European countries (JEWEL 2).

Patients with uncontrolled BP and controlled/uncontrolled LDL-C qualifying for treatment according to local governing guidelines were administered single-pill amlodipine/atorvastatin with appropriate lifestyle modification. Eight dosages of amlodipine/atorvastatin (5/10–10/80 mg) were titrated to achieve country-specific BP and LDL-C targets. The primary outcome was the percentage of patients reaching country-specific BP and LDL-C targets in 16 weeks.

Among 2245 patients enrolled in the studies (JEWEL 1, n = 1138; JEWEL 2, n = 1107), 62.9% in JEWEL 1 and 50.6% in JEWEL 2 achieved both country-specific BP and LDL-C goals. BP was reduced by 20.4/10.7 and 21.8/12.6 mmHg in JEWEL 1 and JEWEL 2, respectively, and reductions in LDL-C were 0.90 mmol/l (34.8 mg/dl) and 1.09 mmol/l (42.2 mg/dl), respectively. The most common adverse events were peripheral oedema (11.0%), joint swelling (2.9%) and headache (2.9%), of which, only oedema was linked to study treatment.

Single-pill amlodipine/atorvastatin is an effective and well-tolerated treatment, which in a real-world setting helped more than half of the patients achieve both BP and LDL-C targets as recommended by local guidelines. Although fewer patients met their goals in JEWEL 2 than JEWEL 1, reductions in BP and LDL-C were slightly greater in JEWEL 2, suggesting that the observed differences are likely because of more stringent targets in Europe than in the UK/Canada.

Postmenopausal women have an increased risk of adverse cardiovascular (CV) events. Similarly, chronic kidney disease (CKD) is a well established risk factor for CV disease and mortality.

We evaluated the effect of renal function on the risk of death and CV events in 1500 southern Italian postmenopausal women.

Renal function was estimated (e) by glomerular filtration rate (e-GFR) by Modification of Diet in Renal Disease equation. We classified postmenopausal women in two groups of e-GFR (ml/min per 1.73 m²): ≥ 60 (group 1) and less than 60 (group 2). The primary endpoint was major adverse CV events (MACE). The secondary endpoints were total events (MACE + death from any cause), coronary events, and stroke. During the follow-up (mean = 72.6 months), there were 200 new CV morbid events. The rate of MACE (per 100 patient-years) was 1.88 and 2.98 in the two groups of e-GFR (P < 0.0001). On univariate analysis, the incident risk of CV events was inversely related with the e-GFR values; similarly, in multiple Cox regression model, only the e-GFR maintained an independent association with MACE and secondary end-points.

For the first time, we demonstrated that the reduction of e-GFR was associated with the increased risk of death and CV events, independently of traditional CV risk factors, menopause duration, and presence of metabolic syndrome.

The allele threonine (T) of the angiotensinogen has been associated with ventricular hypertrophy in hypertensive patients and soccer players. However, the long-term effect of physical exercise in healthy athletes carrying the T allele remains unknown. We investigated the influence of methionine (M) or T allele of the angiotensinogen and D or I allele of the angiotensin-converting enzyme on left-ventricular mass index (LVMI) and maximal aerobic capacity in young healthy individuals after long-term physical exercise training.

Prospective clinical trial.

Eighty-three policemen aged between 20 and 35 years (mean ± SD 26 ± 4.5 years) were genotyped for the M235T gene angiotensinogen polymorphism (TT, n = 25; MM/MT, n = 58) and angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism (II, n = 18; DD/DI, n = 65). Left-ventricular morphology was evaluated by echocardiography and maximal aerobic capacity (VO_2peak) by cardiopulmonary exercise test before and after 17 weeks of exercise training (50–80% VO_2peak).

Baseline VO_2peak and LVMI were similar between TT and MM/MT groups, and II and DD/DI groups. Exercise training increased significantly and similarly VO_2peak in homozygous TT and MM/MT individuals, and homozygous II and DD/DI individuals. In addition, exercise training increased significantly LVMI in TT and MM/MT individuals (76.5 ± 3 vs. 86.7 ± 4, P = 0.00001 and 76.2 ± 2 vs. 81.4 ± 2, P = 0.00001, respectively), and II and DD/DI individuals (77.7 ± 4 vs. 81.5 ± 4, P = 0.0001 and 76 ± 2 vs. 83.5 ± 2, P = 0.0001, respectively). However, LVMI in TT individuals was significantly greater than in MM/MT individuals (P = 0.04). LVMI was not different between II and DD/DI individuals.

Left-ventricular hypertrophy caused by exercise training is exacerbated in homozygous TT individuals with angiotensinogen polymorphism.

The oxygen uptake efficiency slope (OUES) is a newer ventilatory exercise parameter, used in the evaluation of healthy participants and patients with cardiovascular disease. However, few data about the reliability and reproducibility of OUES are available. Our study assessed intratest reliability and test-retest reproducibility of OUES in healthy participants.

Eighteen participants (age 28 ± 6 years, BMI 22.1 ± 1.9 kg/m², 10 men) performed two identical maximal exercise tests on a bicycle ergometer. To assess test-retest reproducibility, we performed Bland-Altman analysis and calculated the coefficient of repeatability of the main ventilatory variables.

OUES remained stable during the second part of the exercise test. Mean values varied 2.4 ± 4.0% between OUES calculated at 70% (OUES70) and at 100% of exercise duration. Mean variation decreased to 1.4 ± 2.3% when OUES was calculated at 90% of exercise duration (OUES90). The Bland-Altman 95% limits of agreement for OUES90 were +3 and –6%, those for OUES70 were +11 and –8%. The coefficient of repeatability for OUES was 597 ml/min or 18.7% of the average value of repeated OUES measurements. These results were similar to those of peak oxygen uptake and minute ventilation/carbon dioxide output. However, the test-retest reproducibility for submaximal-derived values of OUES was lower, as we noted higher coefficients of repeatability for OUES90 and OUES70, increasing up to 27% of the average of repeated values.

OUES shows excellent intratest reliability and has a test-retest reproducibility that is similar to that of peak oxygen uptake and minute ventilation/carbon dioxide output slope. However, its reproducibility becomes higher when it is calculated from increasing levels of achieved exercise intensity.

Low vitality, characterized by fatigue and lack of energy, is common among survivors of acute myocardial infarction (AMI) and has been shown to be associated with increased risk of primary and secondary cardiac events. The goal of this study was to determine whether an association between vitality and recurrent cardiac events (nonfatal MI, cardiac death) among acute MI survivors persists after controlling for possible physiological and psychological confounders.

Incident AMI survivors (n = 1328) from Erie and Niagara (New York) county hospitals were enrolled and followed up to 9 years. Vitality was measured by the Short Form-36 on a 0–100 scale approximately 4 months post-AMI. Cox proportional hazards models were developed to assess the vitality-recurrent event association controlling for traditional cardiovascular disease risk factors, index MI severity, and psychological correlates of vitality.

Low-vitality individuals at baseline were more likely females, of higher BMI, smoking, diabetic, less physically active, and to have worse depression scores. Vitality was not strongly associated with MI severity markers. Lower vitality scores were associated with increased risk of recurrent cardiac events: adjusted hazard ratios (95% CI) for vitality scores 51–79, 21–50, and ≤ 20 (compared with ≥ 80) were 1.2 (0.8, 1.8), 1.4 (0.9, 2.2), and 2.9 (1.5, 5.4), respectively (P _trend = 0.005).

Low vitality was associated with increased risk of recurrent cardiac events among AMI survivors after controlling for physiological and psychological confounders. Mechanistic links with vitality should be sought as interventional targets.

Few earlier studies have analysed smoking as a risk factor for myocardial infarction (MI) or stroke in type 2 diabetic patients.

A longitudinal study involved 13 087 female and male patients with type 2 diabetes from the Swedish National Diabetes Register with no previous MI or stroke at baseline, aged 30–74 years, and with data available for all analysed variables, followed up for mean 5.7 years.

Adjusted hazard ratios (HRs) for smoking and first-incident fatal/nonfatal MI, stroke and total mortality were 1.7 [95% confidence interval (CI): 1.4–2.0; P < 0.001], 1.3 (95% CI: 1.1–1.6; P = 0.006) and 1.8 (95% CI: 1.5–2.2; P < 0.001), respectively, by Cox regression analysis, adjusted for age, sex, diabetes duration, hypoglycaemic treatment, haemoglobin A_1c, blood pressure, body mass index, microalbuminuria, antihypertensive and lipid-lowering drugs. Adjusted HR was higher for fatal MI, 2.1 (95% CI: 1.7–2.7; P < 0.001), than for nonfatal MI, 1.4 (95% CI: 1.2–1.7; P < 0.001). The highest HRs were observed in more frequently smoking (22%), middle-aged patients (age < 60 years) for fatal/nonfatal MI, 2.3 (95% CI: 1.8–3.1; P < 0.001) and for total mortality, 2.5 (95% CI: 1.6–3.8, P < 0.001), whereas lower HRs were observed in older and less smoking patients. With predicted cessation of smoking in patients aged below 60 years, 24% (95% CI: 15–33%) of cases of fatal/nonfatal MI and 24% (11–37%) of cases of total mortality may have been prevented.

The risk for MI and total mortality associated with smoking is high in type 2 diabetes, especially in more frequently smoking, middle-aged patients, and was higher for MI than for stroke, and also higher for fatal than for nonfatal events. Smoking cessation would strongly affect risk reduction.