Challenges in coronary heart disease prevention - experiences from a long-term follow-up study in Norway.

Objective. To determine longitudinal changes in lifestyle behaviour and lipid management in a chronic coronary heart disease (CHD) population. Design. A multi-centre cohort study consecutively included 1127 patients at baseline in 2014-2015, on average 16 months after a CHD event. Data were collected from hospital records, a questionnaire and clinical examination. Seven hundred and seven of 1021 eligible patients participated in a questionnaire-based follow-up in 2019. Data were analysed with univariate statistics. Results. After a mean follow-up of 4.7 years (SD 0.4) from baseline, the percentage of current smokers (15% versus 16%), obesity (23% versus 25%) and clinically significant symptoms of anxiety (21% versus 17%) and depression (13% versus 14%) remained unchanged, whereas the proportion with low physical activity increased from 53% to 58% (p < .001). The proportions with reduced physical activity level were similar in patients over and under 70 years of age. Most patients were still taking statins (94% versus 92%) and more patients used high-intensity statin (49% versus 54%, p < .001) and ezetimibe (5% versus 15%, p < .001) at follow-up. 73% reported ≥1 primary-care consultation(s) for CHD during the last year while 27% reported no such follow-up. There were more smokers among participants not attending primary-care consultations compared to those attending (19% versus 14%, p = .026). No differences were found for other risk factors. Conclusions. We found persistent suboptimal risk factor control in coronary outpatients during long-term follow-up. Closer follow-up and intensified risk management including lifestyle and psychological health are needed to improved secondary prevention and outcome of CHD. Trial registration: Registered at ClinicalTrials.gov: NCT02309255.Registered at 5 December 2014, registered retrospectively.

Preventable clinical and psychosocial factors predicted two out of three recurrent cardiovascular events in a coronary population.

BACKGROUND: The relative importance of lifestyle, medical and psychosocial factors on the risk of recurrent major cardiovascular (CV) events (MACE) in coronary patients' needs to be identified. The main objective of this study is to estimate the association between potentially preventable factors on MACE in an outpatient coronary population from routine clinical practice. METHODS: This prospective follow-up study of recurrent MACE, determine the predictive impact of risk factors and a wide range of relevant co-factors recorded at baseline. The baseline study included 1127 consecutive patients 2-36 months after myocardial infarction (MI) and/or revascularization procedure. The primary composite endpoint of recurrent MACE defined as CV death, hospitalization due to MI, revascularization, stroke/transitory ischemic attacks or heart failure was obtained from hospital records. Data were analysed using cox proportional hazard regression, stratified by prior coronary events before the index event. RESULTS: During a mean follow-up of 4.2 years from study inclusion (mean time from index event to end of study 5.7 years), 364 MACE occurred in 240 patients (21, 95% confidence interval: 19 to 24%), of which 39 were CV deaths. In multi-adjusted analyses, the strongest predictor of MACE was not taking statins (Relative risk [RR] 2.13), succeeded by physical inactivity (RR 1.73), peripheral artery disease (RR 1.73), chronic kidney failure (RR 1.52), former smoking (RR 1.46) and higher Hospital Anxiety and Depression Scale-Depression subscale score (RR 1.04 per unit increase). Preventable and potentially modifiable factors addressed accounted for 66% (95% confidence interval: 49 to 77%) of the risk for recurrent events. The major contributions were smoking, low physical activity, not taking statins, not participating in cardiac rehabilitation and diabetes. CONCLUSIONS: Coronary patients were at high risk of recurrent MACE. Potentially preventable clinical and psychosocial factors predicted two out of three MACE, which is why these factors should be targeted in coronary populations. TRIAL REGISTRATION: Registered at ClinicalTrials.gov: NCT02309255. Registered at December 5th, 2014, registered retrospectively.

The imprinting box of the Prader-Willi/Angelman syndrome domain.

A subset of mammalian genes is monoallelically expressed in a parent-of-origin manner. These genes are subject to an imprinting process that epigenetically marks alleles according to their parental origin during gametogenesis. Imprinted genes can be organized in clusters as exemplified by the 2-Mb domain on human chromosome 15q11-q13 and its mouse orthologue on chromosome 7c (ref. 1). Loss of this 2-Mb domain on the paternal or maternal allele results in two neurogenetic disorders, Prader-Willi syndrome (PWS) or Angelman syndrome (AS), respectively. Microdeletions on the paternal allele share a 4.3-kb short region of overlap (SRO), which includes the SNRPN promoter/exon1, cause PWS and silence paternally expressed genes. Microdeletions on the maternal allele share a 0.88-kb SRO located 35 kb upstream to the SNRPN promoter, cause AS and alleviate repression of genes on the maternal allele. Individuals carrying both AS and PWS deletions on the paternal allele show a PWS phenotype and genotype. These observations suggest that cis elements within the AS-SRO and PWS-SRO constitute an imprinting box that regulates the entire domain on both chromosomes. Here we show that a minitransgene composed of a 200-bp Snrpn promoter/exon1 and a 1-kb sequence located approximately 35 kb upstream to the SNRPN promoter confer imprinting as judged by differential methylation, parent-of-origin-specific transcription and asynchronous replication.

Airflows after inhalation of terbutaline sulphate aerosol from a 750-ml spacer for four weeks.

Terbutaline sulphate was administered to 40 adult asthmatic patients via an ordinary metered-dose inhaler (MDI) or one connected to a 750-ml spacer in an open, randomized, crossover study. Spirometry was obtained before the start of the study and again after four weeks of treatment with each inhaler. The patients recorded on a diary card the severity of their asthma symptoms and the peak expiratory flow rate (PEFR) in the morning before and after drug administration and in the evening. Preinhalation spirometric values were higher after four weeks with the 750-ml spacer than at the start of the study (P less than or equal to 0.05). Daily morning and evening PEFR values were higher after use of the 750-ml spacer than after use of the ordinary MDI (P less than 0.05). Daily symptom scores were generally low. A significantly better effect (P less than or equal to 0.05) with the 750-ml spacer was achieved only in daytime dyspnea. The investigators conclude that the attachment of a 750-ml spacer to an ordinary metered-dose inhaler can improve the efficacy of terbutaline sulphate in the long-term treatment of asthma.

Prevalence of hypertension among cadmium-exposed workers.

In a retrospective study of 311 male workers in an alkaline battery factory, the relationship between exposure to cadmium oxide and hypertension has been investigated. Blood pressure measurements, taken by the same physician, were available for a 30-yr period. When age-matched groups of hypertensive and normotensive workers were compared, employment time was significantly longer (P = .0109) in the hypertensive group. This indicates a possible relationship between exposure to cadmium oxide and the development of hypertension.

[Rehabilitation after myocardial infarction or coronary surgery: elderly patients may benefit as much as the younger ones]. / Rehabilitering efter hjärtinfarkt eller kranskärlskirurgi: äldre patienter har lika stor nytta av träning som yngre.

At most Swedish hospitals participation in cardiac rehabilitation programmes is restricted to patients of working age, although coronary patients predominately belong to the higher age groups. The article consists in a review of the benefits of cardiac rehabilitation to the elderly, such as enhanced quality of life and lower readmission rates, improvement in co-ordination, muscular strength and bone mineral constant, and a cardioprotective effect on risk factors. Cardiac rehabilitation programmes for the elderly, preferably organised in close so-operation between local hospitals, primary care facilities and patient organisations, might yield considerable individual and general health economic benefits.

Need cardiac rehabilitation be cost-effective?

In this article, the available health-economic literature in the field of comprehensive cardiac rehabilitation is reviewed. The effects of cardiac rehabilitation are well known, but cost-effectiveness studies are lacking in several important areas. The long-term effect on the number of life-years saved indicates that cardiac rehabilitation is a cost-effective use of health care resources, provided that cost-containing principles are applied in comprehensive programmes.

Cardiac rehabilitation: applying exercise physiology in clinical practice.

In this paper new insights into the beneficial effects of physical training for patients with coronary artery disease are reviewed. Endurance training as part of a comprehensive cardiac rehabilitation programme in combination with strength training, smoking cessation and lipid management may slow down and in some cases reverse the progress of coronary atherosclerosis. Thus, exercise training remains an invaluable tool in the hands of the clinical cardiologist dealing with chronic coronary care.

5-year results of a comprehensive rehabilitation programme after myocardial infarction.

A comprehensive cardiac rehabilitation programme has been offered to a non-selected consecutive group of patients who have survived an acute myocardial infarction (MI). The programme includes follow-up at a post-MI clinic, physical training in outpatient groups, the provision of information on smoking and diet, and psychological support to patients and their families. The intervention group, consisting of the 147 patients participating in the programme has been compared with a nonselected consecutive reference group of 158 patients receiving standard care. During the five-year follow-up there was no difference in cardiac mortality between the groups, but the recurrence rate of non-fatal MI (17.3 vs 33.3%. P = 0.02) and the rate of total cardiac events was lower in the intervention group (39.5 vs 53.2%, P = 0.05). There was an alteration of risk factors, as there were fewer smokers and uncontrolled hypertensives in the intervention group. Patients in the reference group used more sedatives and long-acting nitroglycerine and had a lower return-to-work rate during the study period. The programme proved to be particularly effective in the age group below 55 years, where a significantly lower rate of total cardiac events was observed and more patients returned to work than in the reference group. It is concluded that the combined effect of the comprehensive programme has contributed to the long-term results, and that the programme offers an effective and safe method of secondary prevention after MI.

Can high-risk patients after myocardial infarction participate in comprehensive cardiac rehabilitation?

Patients with large transmural infarctions (MI) and signs of congestive heart failure (CHF) are often excluded from physical training, because of the risk of malignant arrhythmia or cardiac overloading. From a non-selected MI population less than 65 years we enrolled 37 high-risk patients in a two-year comprehensive cardiac rehabilitation programme, including health education, follow-up at a post-MI clinic, and physical training in outpatient groups. The feasibility, effectiveness and safety of the physical training were evaluated: Twenty-one patients joined the physical training and participated with excellent compliance, reaching the preset levels of training. No adverse effects occurred during the 921 training sessions. The high-risk patients were compared with the remaining 228 patients and a subgroup of 86 low-risk patients with regard to mortality, morbidity, medication, effect on risk factors, exercise test performance and rate of return to work. The high-risk group showed a higher mortality (27.0 vs. 10.4%, p less than 0.05), a lower maximal work capacity at the exercise test 4 months after MI (126 W vs. 140 W, p less than 0.05), and a lower rate of early return to work (22.6 vs. 50% p less than 0.01) when compare with the low risk group. However, they showed a similar improvement in exercise test parameters. At the end of the programme a remarkable 63% had returned to work vs. 48.2% of the remaining patients. The reduction in smoking and the effect on blood pressure were equal in both groups. It is concluded that high-risk patients may well benefit from regular physical training in outpatient groups, if adequate medical supervision is available.

Long-term reduction of cardiac mortality after myocardial infarction: 10-year results of a comprehensive rehabilitation programme.

The long-term outcome of different methods of post-MI care has been studied in two non-selected groups of MI patients: an intervention group (n = 147), participating in a cardiac rehabilitation (CR) programme, was compared to a reference group receiving standard care (n = 158). The CR programme included a post-MI clinic, physical training, information on smoking and diet, and psychological support. After 5 years there was no difference in mortality (29.3 vs 31.6%), but the recurrence rate of non-fatal MI (17.3 vs 33.3%, P < 0.05) and of total cardiac events (39.5 vs 53.2%, P < 0.05) was lower in the intervention group, and more patients were still at work (51.8 vs 27.4% P < 0.01). After 10 years there was a reduction in total (42.2 vs 57.6% P < 0.01) and cardiac mortality (36.7 vs 48.1% P < 0.001). Fewer patients in the intervention group suffered from non-fatal reinfarction (28.6 vs 39.9%, P < 0.001). Among those patients who had not yet reached the age of retirement more patients had resumed employment (58.6 vs 22.0% P < 0.05). We conclude, that the secondary preventive effect of the programme has contributed to the higher rate of survival.

Cardiac rehabilitation: evaluation of a long-term programme of physical training for out-patients.

A community-based long-term cardiac rehabilitation programme (LTP) has been designed for patients who had completed a two-year hospital-based physical training programme after myocardial infarction (MI) and wished to continue with community-based group training sessions. Since the start of LTP 20% of all patients in a consecutive MI population less than 65 yrs have participated. The programme operates on a low-cost base. Its feasibility is supported by a high attendance rate and by the absence of adverse effects during more than 2,000 patient training hours. In order to evaluate LTP 20 participating MI patients were compared with 20 matched control patients, who had completed the hospital-based training, but did not participate in LTP. The main reason for participation was the need for continued group support and social contact (15/20). Reasons for not participating were preference to exercise at home (10/20), long distance (6/20) and working hours (4/20). When compared with the data of the hospital-based programme one year post MI, both groups showed 4 years (average) post MI a slight but significant increase of systolic blood pressure of 12 vs. 18 mmHg. Work performance levels had been maintained (132 vs. 136 W). No patients had started smoking and there were no differences between the groups as to leisure time activities. It is concluded that a long-term training programme can be provided safely and at low cost for those MI patients who need continued support in order to maintain the effectiveness of the hospital-based cardiac rehabilitation.

Cardiorespiratory adaptation of COPD patients to physical training on land and in water.

Physical training in water might be included in a comprehensive pulmonary rehabilitation programme, but data on the feasibility and safety of this technique in chronic obstructive pulmonary disease (COPD) patients are lacking. We studied cardiorespiratory parameters of 20 stable COPD patients (10 with forced expiratory volume in one second (FEV1) < 35% of predicted value, and 10 with FEV1 > or = 35% pred) on land and in a temperate-controlled pool (32 degrees C) both at rest and during a 15 min submaximal upper body muscle training programme. Compared to resting values on land, we found in water a decrease of systolic and diastolic blood pressure (14 and 6 mmHg, respectively), rate-pressure product (7%) and lung function (vital capacity (VC) 12%, FEV1 14%, peak expiratory flow (PEF) 18%). There were no differences in heart rate, breathing frequency or O2 saturation. The most strenuous exercise in water resulted in a slightly lower O2 saturation compared to work on land (95 and 93%, respectively), and an increase of Borg rating for dyspnoea from 4 to 5. In spite of the restriction of lung function in water, all patients (even those with FEV1 < 35% pred) performed the training in the pool well, without clinically relevant desaturation, arrhythmia or discomfort. No training session was discontinued due to dyspnoea. We conclude that a 15 min session of submaximal physical training in a pool with a water temperature of 32 degrees C is feasible and safe for nonhypoxaemic normotensive COPD patients without cardiac failure.

Clinical trial of a modified inhaler for pressurized aerosols.

Using spirometry, the effects on lung function of interposing a tube extension between a bronchodilator aerosol (terbutaline sulphate 0.25 mg) and the mouth and an ordinary aerosol have been compared. Both devices were administered with a delay of 2 s from actuating the aerosol to inhalation, thus simulating inability to coordinate properly. In 12 stable asthmatics it was found that attachment of the tube extension to the aerosol gave significantly better results for one-second forced vital capacity (FEV1.0) and forced vital capacity (FVC). The tube extension seems to be beneficial in patients with hand-lung dyscoordination.

Effects of cardiac rehabilitation after coronary artery bypass grafting on readmissions, return to work, and physical fitness. A case-control study.

In a case-control study 49 consecutive post-coronary artery bypass grafting (CABG) patients (10 f, 39 m) participating in a comprehensive rehabilitation programme were compared with 98 individually matched double control patients, receiving standard care. The rehabilitation programme, starting 6 weeks after surgery, consisted of follow-up at a coronary clinic, repeated health education, and physical training in out-patient groups. During the first year after CABG, fewer study group patients were readmitted to hospital (14% vs 32%, p less than 0.01) and on fewer occasions (1.1 vs 2.9, p less than 0.05). Fewer patients used anxiolytic drugs (0% vs 15%, p less than 0.01). At the one year post-CABG exercise test we found in the study group a tendency to a greater increase in work capacity, as compared with the values obtained at the preoperative exercise test (33 vs 25 W ns). There were no differences in the rates of returning to work (59% vs 64%). In a long-term follow-up study (av. 38 months post-CABG) the patients were asked to fill in a questionnaire evaluating perceived physical work capacity and training habits. The study group patients rated their physical work capacity higher, and more patients had continued with regular physical training (66% vs 46%, p = 0.05). There were fewer patients using anxiolytic drugs (9% vs 30%, p less than 0.01). Although the programme did not influence the return to work we conclude that it improved the quality of life of our patients as it entailed fewer readmissions and reduced the use of anxiolytic medication; in addition it promoted physical fitness and training habits.

Cardiac rehabilitation--a cost analysis.

This economic evaluation is based on a 5-year follow-up study comparing a comprehensive cardiac rehabilitation programme with standard care after myocardial infarction (MI). The intervention group consisted of 147 non-selected MI patients aged less than 65 years, who were participating in a rehabilitation programme consisting of follow-up at a post-MI clinic, health education and physical training in out-patient groups. The control group consisted of a non-selected MI-population aged less than 65 years (n = 158), who were receiving standard care. The rehabilitation programme did not increase the health-care costs of post-MI care, as the increase in cost due to participation in the programme was balanced by a decrease in readmissions for cardiovascular diseases. On average, the rehabilitated patient returned to work more frequently, resulting in decreased costs due to loss of production. The mean patient total cost of a 5-year MI follow-up was SEK 73,500 lower in the rehabilitated group. The outstanding winner of the rehabilitation programme was the Swedish National Health Insurance System (NHIS). It must be concluded that the comprehensive cardiac rehabilitation programme is a major strategy that leads to both lowered costs and positive health effects. The cardiac rehabilitation programme is therefore highly cost-effective.

The imprinting box of the mouse Igf2r gene.

Genomic imprinting is a phenomenon characterized by parent-of-origin-specific expression. The imprint is a mark established during germ-cell development to distinguish between the paternal and maternal copies of the imprinted genes. This imprint is maintained throughout embryo development and erased in the embryonic gonads to set the stage for a new imprint. DNA methylation is essential in this process as shown by the presence of differentially methylated regions (DMRs) in all imprinted genes and by the loss of imprinting in mice that are deficient in DNA methylation or upon deletion of DMRs. Here we show that a DMR in the imprinted Igf2r gene (which encodes the receptor for insulin-like growth factor type-2) that has been shown to be necessary for imprinting includes a 113-base-pair sequence that constitutes a methylation imprinting box. We identify two new cis-acting elements in this box that bind specific proteins: a de novo methylation signal and an allele-discrimination signal. We propose that this regulatory system, which we show to be involved in the establishment of differential methylation in the Igf2r DMR, represents a critical element in the imprinting process.