Abstract Background Prognosis after a myocardial infarction (MI) have improved consistently over the last decades. In parallel, the incidence of cardiovascular (CV) events has been reduced and life expectancy in people free from CV disease improved. Purpose To explore the long-term mortality and burden of cardiovascular disease in patients after a first MI compared to matched controls in a contemporary setting. Methods The Swedish case-control study PAROKRANK recruited 805 patients <75 years with a first MI and 805 age-, gender- and area-matched controls from 2010 to 2014. All participants were followed by means of registry-based information. The primary endpoint was the first of a composite of all-cause death, non-fatal MI, non-fatal stroke and heart failure hospitalization. Data on the outcomes were provided via linkage to the National Patient Registries and the Cause of Death Registry. Hazard Ratios (HR) for the first composite event were calculated by means of a Cox regression model, subsequently adjusted for smoking, education level and marital status at baseline. Event curves for the time-to-first event in patients and controls were computed by Kaplan-Meier curves and the two groups were compared by means of the log-rank test. Results Data from 804 patients and 800 controls (mean age in both groups 62 years; women 19%) were complete for an average period of 6.2 years (0.2–8.5 years). The total number of events was 211. Patients had a higher event rate than controls (log rank p<0.0001). Unadjusted HR for the primary outcome was 2.08 (95% confidence interval (CI) 1.56–2.77) while the adjusted HR was 2.04 (95% CI 1.52–2.73). Mortality did not differ significantly between patients (n=38; 4.7%) and controls (n=35; 4.4%). In total, 82.5% of the patients and 91.3% of the controls were event-free during follow-up. Conclusion This long-term follow-up of a contemporary, nationwide case-control cohort illustrates that the likelihood for CV events is higher in patients with a first MI compared to their matched controls while mortality did not differ. The access to high quality of care and cardiac rehabilitation might explain the low rates of adverse outcomes. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): AFA Insurance, Swedish Heart-Lung Foundation, Swedish Research Council, Swedish Society of Medicine, Stockholm County Council (ALF project and Steering committee KI/SLL for odontological research), and The Baltic Child Foundation. Figure 1. Kaplan-Meier curves

This study evaluated the effects of a behaviorally oriented cardiac rehabilitation and secondary prevention program on lifestyle changes and on coronary recurrence rates. Patients recently treated with percutaneous coronary intervention (PCI) were randomized to an intervention with an aggressive focus on lifestyle changes (smoking, diet, exercise, and stress; n=46) or to a standard-care control group (n=42). Results showed that the intervention group had significantly larger overall lifestyle changes than the control group after 12, 24, 36, and 60 months. The intervention group had significantly lower rates of all coronary events (acute myocardial infarction, coronary artery bypass graft, PCI, cardiac death; 30.4% vs. 53.7%), and of cardiovascular mortality (2.2% vs. 14.6%). The need for future large-scale and long-term evaluations of lifestyle-oriented secondary prevention interventions of this kind is emphasized.

The atherosclerotic process is an ongoing dynamic and progressive state arising from endothelial dysfunction and inflammation. Although suffering from an acute coronary artery disease, patients with Type II diabetes have a poor outcome compared with non-diabetic patients, which may only partly be explained by traditional risk factors. Our purpose was to compare non-traditional risk factors, such as endothelial function, C-reactive protein (CRP) and adiponectin, in Type II diabetic and non-diabetic patients following AMI (acute myocardial infarction). Twenty Type II diabetic patients were compared with 25 non-diabetic patients at baseline (1-3 days from the onset of chest pain) and at 60 days follow-up after an AMI. Using high-resolution ultrasound, brachial artery responses to FMD (flow-mediated vasodilatation; endothelium-dependent vasodilatation) and NTG (nitroglycerine-induced vasodilatation; endothelium-independent vasodilatation) were measured. Plasma levels of CRP and adiponectin were measured by ELISA. At baseline, FMD (1.9 compared with 3.2%; P=0.22) and CRP levels (6.95 compared with. 5.51 mg/l; P=0.40) did not differ between Type II diabetic and non-diabetic patients, whereas adiponectin levels were lower in Type II diabetic patients (2.8 compared with 5.0 ng/ml; P<0.05). At 60 days follow-up, there were significant differences in FMD (1.5 compared with 4.1%; P<0.02), CRP (4.23 compared with 1.46 mg/ml; P<0.01) and adiponectin (3.3 compared with 5.3 ng/ml; P<0.05) levels between Type II diabetic and non-diabetic patients. In contrast, NTG responses improved in both groups between baseline and follow-up (Type II diabetic patients, 9.7 compared with 13.2% respectively, P<0.05; non-diabetic patients, 7.9 compared with 12.4% respectively, P<0.01). These results show a persistent endothelium-dependent dysfunction and inflammatory activity in patients with Type II diabetes, but not in non-diabetic patients, after AMI. These findings may, in part explain, the poor outcome in coronary artery disease seen in Type II diabetes.

Tetrahydrobiopterin (BH(4)) is an essential cofactor of nitric oxide synthase that improves endothelial function in diabetics, smokers, and patients with hypercholesterolemia. Insulin resistance has been suggested as a contributing factor in the development of endothelial dysfunction via an abnormal pteridine metabolism. We hypothesized that BH(4) would restore flow-mediated vasodilation (FMD, endothelial-dependent vasodilation), which may affect insulin resistance in type 2 diabetic patients. Thirty-two subjects (12 type 2 diabetic subjects, 10 matched nondiabetic subjects, and 10 healthy unmatched subjects) underwent infusion of BH(4) or saline in a random crossover study. Insulin sensitivity index (S(I)) was measured by hyperinsulinemic isoglycemic clamp. FMD was measured using ultrasonography. BH(4) significantly increased S(I) in the type 2 diabetics [3.6 +/- 0.6 vs. 4.9 +/- 0.7 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P < 0.05], while having no effects in nondiabetics [8.9 +/- 1.1 vs. 9.0 +/- 0.9 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P = 0.92] or in healthy subjects [17.5 +/- 1.6 vs. 18 +/- 1.8 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P = 0.87]. BH(4) did not affect the relative changes in brachial artery diameter from baseline FMD (%) in type 2 diabetic subjects (2.3 +/- 0.8 vs. 1.8 +/- 1.0%, P = 0.42), nondiabetic subjects (5.3 +/- 1.1 vs. 6.6 +/- 0.9%, P = 0.32), or healthy subjects (11.9 +/- 0.6 vs. 11.0 +/- 1.0%, P = 0.48). In conclusion, BH(4) significantly increases insulin sensitivity in type 2 diabetic patients without any discernible improvement in endothelial function.

BACKGROUND:Myocardial tissue velocity and perfusion were studied in patients with severe angina pectoris following gene therapy by intramyocardial injection of phVEGF-A165 via thoracotomy. Plasma concentrations of VEGF-A increased postoperatively. Two months after treatment anginal status and myocardial tissue velocity improved and perfusion showed a tendency to improve. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy.OBJECTIVE:To study effects on myocardial tissue velocity and perfusion in patients with angina pectoris following intramyocardial injection of phVEGF-A165 via thoracotomy.DESIGN:Open label, phase I/II.METHODS:Six patients with Canadian Cardiovascular Society (CCS) angina pectoris functional class III - IV and with major defects at adenosine stress single-photon emission computerized tomography (SPECT) were studied. In addition to SPECT, coronary angiography and dobutamine stress echocardiography with tissue Doppler velocity imaging were performed before and two months after gene transfer.RESULTS:Plasma concentrations of VEGF-A increased 2 to 3 times (P < 0.04) over baseline from 2 to 14 days after injection with normalization after 4 weeks. The CCS class improved about 40%, from 3.3 +/- 0.2 to 2.0 +/- 0.3 (P < 0.02) and nitroglycerine consumption decreased 30 - 40%, from 44 +/- 17 to 15 +/- 5 tablets per week (P < 0.05). The maximal systolic myocardial tissue velocity increased in all patients about 25% (P < 0.02) but did not reach the reference range. Myocardial perfusion at SPECT improved in four of the six patients.CONCLUSIONS:Anginal status, myocardial tissue velocity and perfusion can be improved by phVEGF-A165 intramyocardial injection. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy.

A comprehensive, multifactorial lifestyle behavior change program was developed for rehabilitation and secondary prevention of subjects with coronary artery disease. The purpose of the present report is to describe this intervention model and to analyze results achieved in a first group of consecutive participants. Main inclusion criteria for the 292 subjects were a recent history of acute myocardial infarction, coronary artery bypass surgery, or percutaneous transluminal coronary angioplasty. The program commenced with a 4-week residential stay, with the focus on health education and the achievement of behavior change in major lifestyle areas. During the year of follow-up a systematic maintenance program included regular contact with a nurse. Morbidity and mortality was low. Self-reported quality of life improved and there were significant improvements in blood lipids, exercise capacity and body mass index. There were also significant changes both in psychological variables such as Type A behavior, anger, hostility, and in major lifestyle areas such as stress reactions, diet, exercise and smoking. These changes compared favorably with data from relevant samples from the Swedish normal population. This program had a considerable effect on a number of important factors for rehabilitation and secondary prevention of coronary artery disease.

A group of 93 coronary patients recently treated with percutaneous transluminal coronary angioplasty (PTCA) were randomly assigned to either an intervention or a control group. Subjects in the intervention group participated in a comprehensive behaviorally oriented program aimed at achieving significant long-term changes in risk factor–related lifestyle behavior. Assessments of lifestyle behaviors, psychological factors, biological risk factors, and rehabilitation as well as secondary prevention endpoints were carried out, at inclusion and after 12 months. Results showed that the intervention patients, as compared with controls, improved significantly on measures assessing smoking, exercise, and diet habits. These self-rated changes were confirmed by weight reductions and improved exercise capacity, as well as by between-group differences in subclinical chest pain during an exercise test. However, few effects were found on the different psychological variables, as well as on morbidity or return to work.

AIMSIn a multifactorial lifestyle behaviour programme, of 2 years duration, to study the maintenance of achieved behaviour and risk factor-related changes.METHODS AND RESULTSOut of a consecutive population of 151 patients treated with percutaneous transluminal angioplasty under 65 years of age, 87 were randomly allocated to an intervention group (n=46) or to a control group (n=41). The programme started with a 4 week residential stay, which was focused on health education and the achievement of behaviour change. During the first year of follow-up, a maintenance programme included regular contacts with a nurse, while no further rehabilitative efforts were offered during the second year. One patient died (control). During the second year the proportion of hospitalized patients was lower in the intervention group (4% vs 20%;P<0.05). Patients in the intervention group improved several lifestyle dependent behaviours: diet (index at 0, 12 and 24 months): 10.5+/-3. 4, 12.9+/-2.5 and 12.4+/-2.6 in the intervention group (I) vs 10. 1+/-3.2, 10.7+/-3.0 and 11.8+/-3.2 in the control group (C);P<0.05, exercise sessions per week: 2.5+/-2.3, 4.5+/-1.9 and 4.4+/-2.1 (I) vs 3.1+/-2.2, 3.5+/-2.3 and 3.7+/-2.7 (C);P<0.05, and smoking; 18%, 6% and 9% (I) vs 12%, 21% and 18% (C);P<0.05. This corresponded to improvement in exercise capacity (0, 12 and 24 months): 156+/-42, 174+/-49 and 165+/-47 W (I) vs 164+/-40, 163+/-49 and 156+/-48 watts (C);P<0.05. There were no significant differences between the two groups with regard to serum cholesterol levels at 0 and 24 months: 5. 4+/-0.8 and 5.2+/-0.9 mmol. l(-1)(I) vs 5.4+/-1.0 and 4.9+/-0.9 mmol. l(-1)(C); ns, low density lipoprotein cholesterol level: 3.6+/-0.8 and 3.4+/-0.8 mmol. l(-1)(I) vs 3.7+/-0.9 and 3.3+/-0.7 mmol. l(-1)(C); ns, triglyceride level: 2.2+/-1.6 and 1.8+/-1.3 mmol. l(-1)(I) vs 2.2+/-1.4 and 1.6+/-0.6 mmol. l(-1)(C); ns, body mass index (0, 12 and 24 months): 27.5+/-4.5, 27.0+/-4.3 and 27.4+/- 4.5 kg. m(-2)(I) vs 26.8+/-2.8, 26.9+/-2.7 and 26.9+/- 3.2 kg. m(-2)(C); ns, waist/hip ratio or blood pressure. The two groups did not differ in quality of life, or psychological factors. Return to work after 12 and 24 months was 74% and 78% (I) vs 68% and 61% (C); ns.CONCLUSIONThis rehabilitation programme influenced important lifestyle behaviour and reduced some, but not all, important risk factors

The aim of the study was to compare the effects of ischaemic and non-ischaemic training on aerobic performance. In 10 subjects, peak oxygen uptake (peak VO2) and time to fatigue (TTF) for one-legged exercise were measured before and after 4 weeks (4 times week-1) of one-legged training. Each training session started with one leg training for 45 min with 20% blood-flow reduction induced by local application of a supra-atmospheric external pressure of 50 mmHg (ischaemic leg; I-leg). We have previously shown that this decreases leg blood flow by about 20%. The contralateral leg (non-restricted-flow leg; N-leg), serving as a control, then trained with an identical power-output profile for 45 min but without flow restriction. In the I-leg the average training-induced increments in TTF and peak VO2 were 27 and 24%, respectively. In the N-trained leg TTF and peak-VO2 increased 10 and 14%, respectively. Both increments were significantly greater (P < 0.05) in the I-trained leg. Moreover, the performance increase in the I-trained leg was exaggerated (P < 0.05) in the ischaemic test condition, i.e. there was a specificity in the training response. In conclusion, ischaemia acts as an additive stimulus to training leading to an exaggerated increase in endurance and peak-VO2 compared to identical training without blood-flow restriction. The main explanation is probably an enhanced local adaptation in the I-trained leg.

Obesity and an enhanced insulin response to oral glucose tolerance test are associated with therapy resistance in hypertension. In order to explore this association further we studied the insulin sensitivity of subjects with essential hypertension resistant to triple drug therapy (RH), with the euglycemic insulin clamp technique. Well controlled hypertensives, matched for age, gender and body mass index (BMI) served as controls. Male subjects (7 RH and 7 controls) were further investigated by biopsies of Musculus Vastus lateralis since structural conditions in skeletal muscles might have a role in the above association. Irrespective of pre-study drug therapy, therapy-resistant hypertensives had a lower insulin sensitivity index than controls (p < 0.05). In spite of the BMI-match waist/hip ratio (WHR) in the RH males tended to be higher (p < 0.07). Insulin clearance tended to be lower in RH subjects (p = 0.09). BMI correlated with a reduced muscular capillary density (r = -0.77, p < 0.01). The average cross-sectional muscle fibre area was larger in RH subjects (p < 0.05). The mean muscle fibre area correlated with basal serum insulin (r = 0.63; p < 0.05). Rarefaction of the muscular capillary bed appears to be related to obesity. Larger muscle fibres might be an effect of the growth factor properties of insulin and could possibly correspond to hypertrophy of smooth muscle in the resistance vessels. This factor might contribute to the association of hyperinsulinemia and hypertension and attenuate the response to antihypertensive therapy.

Eight healthy men performed supine one-legged training on a bicycle ergometer 45 min per leg four times per week for 4 week. The ergometer and lower body were inside a pressure chamber, the opening of which was sealed at the level of the crotch. One leg trained with impeded leg blood flow (I-leg), induced by an increased (50 mmHg) chamber pressure, at the highest tolerable intensity. The contralateral leg trained at the same power under normal pressure (N-leg). Before and after training biopsies were taken from the vastus lateralis of both legs and maximal one-legged exercise tests were executed with both legs. Biopsies were repeated when the subjects had been back to their habitual physical activity for 3 months. Training increased exercise time to exhaustion, but more in the I-leg than in the N-leg. After training, the I-leg had higher activity of citrate synthase (CS), a marker of oxidative capacity, and lower activity of the M-subunit of lactate dehydrogenase isoenzymes. It also had a higher percentage of type-I fibres and a lower percentage of IIB fibres, larger areas of all fibre types and a greater number of capillaries per fibre. It is concluded that ischaemic training changes the muscle metabolic profile in a direction facilitating aerobic metabolism. An altered fibre-type composition may contribute, but is not enough prerequisite for the change.

Force (peak torque) of m. quadriceps femoris was measured during 60 repeated, voluntary dynamic knee extensions in 10 men before and after a 4-week training regimen of one-legged cycle exercise. Biopsies for histochemical analysis were obtained from the lateral vastus muscle after the training period. One leg was trained with the blood flow to the leg muscles reduced by local supra-atmospheric external pressure of 50 mmHg ('Ischaemic leg, I-leg'). Employing the same work-load profile the other leg was trained at normal atmospheric pressure ('Non-restricted-flow leg, N-leg'). In response to I-training, Maximum Peak Torque (MPT; the highest torque produced in any contraction) and Initial Peak Torque (IPT; the average peak torque of the initial 12 contractions) decreased by 8% (P < 0.01) and 9% (P < 0.001), respectively. Final Peak Torque (FPT; the average peak torque of the final 12 contractions) increased by 13% (P < 0.05) after I-training. No changes in MPT, IPT or FPT occurred following N-training. After training the proportion of slow-twitch fibres was higher (P < 0.05) and the mean slow-twitch fibre area was larger (P < 0.05) in the I-than in the N-trained leg. The results indicate that blood flow-restricted training, in contrast to non-restricted-flow training, decreases maximum voluntary dynamic force, possibly by inducing an increase in the share of the muscle cross-sectional area consisting of slow-twitch fibres. That flow-restricted training improves maintenance of force during short-term local exercise may reflect ischaemically induced changes in the metabolic characteristics of skeletal muscle.

Sundberg, C. J.; Eiken, O.; Esbjörnsson, M.; Nygren, A.; Jansson, E.; Kaijser, L. Author Information

Healthy young men executed supine one-legged cycle training four times per week for 4 wk with legs and the cycle ergometer inside a pressure chamber, the opening of which was sealed by a rubber membrane at the level of the crotch. Each training session started by training one leg under ischemic conditions induced by increased chamber pressure (50 mmHg) at the highest intensity tolerable for 45 min. Then the other leg was trained with the same power profile but normal atmospheric chamber pressure. Before and after the training period, both legs executed one-legged exercise tests under both normal and increased chamber pressure and muscle biopsies were taken from the vastus lateralis. Ischemic training increased performance more than normal training, the difference being greater for exercise executed under ischemic conditions. The difference in performance increase between the legs was paralleled by a greater muscle citrate synthase activity in the ischemically than in the normally trained leg.