Plasma methylmalonic acid predicts risk of acute myocardial infarction and mortality in patients with coronary heart disease: A prospective 2-cohort study.

BACKGROUND: Elevated plasma methylmalonic acid (MMA) is reported in patients with established coronary heart disease (CHD) and is considered a marker of vitamin B12 deficiency. Moreover, MMA-dependent reactions have been linked to alterations in mitochondrial energy metabolism and oxidative stress, key features in the pathophysiology of cardiovascular diseases (CVDs). OBJECTIVES: We examined whether plasma MMA prospectively predicted the long-term risk of acute myocardial infarction (AMI) and mortality. METHODS AND RESULTS: Using Cox modeling, we estimated hazard ratios (HRs) for endpoints according to per 1-SD increment of log-transformed plasma MMA in two independent populations: the Western Norway Coronary Angiography Cohort (WECAC) (patients evaluated for CHD; n = 4137) and the Norwegian Vitamin Trial (NORVIT) (patients hospitalized with AMI; n = 3525). In WECAC and NORVIT, 12.8% and 18.0% experienced an AMI, whereas 21.8% and 19.9% died, of whom 45.5% and 60.3% from CVD-related causes during follow-up (range 3-11 years), respectively. In WECAC, age- and gender-adjusted HRs (95% confidence interval) were 1.18 (1.09-1.28), 1.25 (1.18-1.33), and 1.28 (1.17-1.40) for future AMI, total mortality, and CVD mortality, respectively. Corresponding risk estimates were 1.19 (1.10-1.28), 1.22 (1.14-1.31), and 1.30 (1.19-1.42) in NORVIT. These estimates were only slightly attenuated after multivariable adjustments. Across both cohorts, the MMA-risk association was stronger in older adults, women, and non-smokers. CONCLUSIONS: Elevated MMA was associated with an increased risk of AMI and mortality in patients with suspected or verified CHD.

Is the ongoing obesity epidemic partly explained by concurrent decline in cigarette smoking? Insights from a longitudinal population study. The Tromsø Study 1994-2016.

The increase of obesity coincides with a substantial decrease in cigarette smoking. We assessed post-cessation weight change and its contribution to the obesity epidemic in a general population in Norway. A total of 14,453 participants (52.6% women), aged 25-54 years in 1994, who attended at least two of four surveys in the Tromsø Study between 1994 and 2016, were included in the analysis. Hereof 77% participated in both the first and the last survey. Temporal trends in mean body mass index (BMI), prevalence of obesity (BMI ≥ 30 kg/m2) and daily smoking were estimated with generalized estimation equations. We assessed BMI change by smoking status (ex-smoker, quitter, never smoker, daily smoker), and also under a scenario where none quit smoking. In total, the prevalence of daily smoking was reduced over the 21 years between Tromsø 4 (1994-1995) and Tromsø 7 (2015-2016) by 22 percentage points. Prevalence of obesity increased from 5 - 12% in 1994-1995 to 21-26% in 2015-2016, where obesity in the youngest (age 25-44 in 1994) increased more than in the oldest (p < 0.0001). Those who quit smoking had a larger BMI gain compared to the other three smoking subgroups over the 21 years (p < 0.0001). The scenario where none quit smoking would imply a 13% reduction in BMI gain in the population, though substantial age-related differences were noted. We conclude that smoking cessation contributed to the increase in obesity in the population, but was probably not the most important factor. Public health interventions should continue to target smoking cessation, and also target obesity prevention.

Analyses of Increased Mortality in New and Known Diabetes in Patients with Coronary Disease Enrolled in the NORSTENT Randomized Study.

BACKGROUND: NORSTENT trial randomized 9,013 patients to percutaneous coronary intervention with drug-eluting stents (DES) or bare-metal stents (BMS) with a 5-year follow-up. Among the patients, 5,512 had measured either fasting glucose level or percent glycated hemoglobin (HbA1c) at the index procedure. That cohort constitutes the present study population analyzing mortality and evaluating treatment heterogeneity of randomized stent in diabetic versus nondiabetic subgroups. RESULTS: The cohort consisted of 4,174 (75.7%) patients without diabetes, 716 (13.0%) with known diabetes, and 622 (11.3%) with no diabetes in history but elevated fasting glucose level >7.0 mmol/L or HbA1c >6.5% and therefore defined as new diabetes. Patients with known diabetes had a significantly increased all-cause (hazard ratio [HR] 1.99, 95% CI 1.51-2.62, p < 0.001), cardiac (subhazard ratio [SHR] 2.47, 95% CI 1.55-3.93, p < 0.001), and noncardiac (SHR 1.74, 95% CI 1.23-2.44, p = 0.002) mortality after adjustment for baseline variables. In the follow-up of 5 years, patients with new diabetes, however, had a marginally increased all-cause (HR 1.40, 95% CI 1.01-1.93, p = 0.043) and significantly increased noncardiac mortality (SHR 1.52, 95% CI 1.06-2.20, p = 0.025), but no increase in cardiac mortality (SHR 1.06, 95% CI 0.53-2.12, p = 0.86) after the same adjustment. The majority of the mortality was cardiac in the first 1-2 years after intervention; thereafter, noncardiac mortality dominated. However, the time period for when noncardiac mortality became the dominating cause varied considerably and significantly between the groups. There was no heterogeneity in mortality in response to randomized stent between diabetics and nondiabetics. CONCLUSION: Known diabetes has increased cardiac and noncardiac mortality in contrast to new diabetes which is only associated with increased noncardiac mortality during the 5-year follow-up. Diabetic and nondiabetic patients have the same response to the treatment with BMS or DES.

Drug-eluting or bare-metal stents for percutaneous coronary intervention: a systematic review and individual patient data meta-analysis of randomised clinical trials.

BACKGROUND: New-generation drug-eluting stents (DES) have mostly been investigated in head-to-head non-inferiority trials against early-generation DES and have typically shown similar efficacy and superior safety. How the safety profile of new-generation DES compares with that of bare-metal stents (BMS) is less clear. METHODS: We did an individual patient data meta-analysis of randomised clinical trials to compare outcomes after implantation of new-generation DES or BMS among patients undergoing percutaneous coronary intervention. The primary outcome was the composite of cardiac death or myocardial infarction. Data were pooled in a one-stage random-effects meta-analysis and examined at maximum follow-up and a 1-year landmark. Risk estimates are reported as hazard ratios (HRs) with 95% CIs. This study is registered in PROSPERO, number CRD42017060520. FINDINGS: We obtained individual data for 26 616 patients in 20 randomised trials. Mean follow-up was 3·2 (SD 1·8) years. The risk of the primary outcome was reduced in DES recipients compared with BMS recipients (HR 0·84, 95% CI 0·78-0·90, p<0·001) owing to a reduced risk of myocardial infarction (0·79, 0·71-0·88, p<0·001) and a possible slight but non-significant cardiac mortality benefit (0·89, 0·78-1·01, p=0·075). All-cause death was unaffected (HR with DES 0·96, 95% CI 0·88-1·05, p=0·358), but risk was lowered for definite stent thrombosis (0·63, 0·50-0·80, p<0·001) and target-vessel revascularisation (0·55, 0·50-0·60, p<0·001). We saw a time-dependent treatment effect, with DES being associated with lower risk of the primary outcome than BMS up to 1 year after placement. While the effect was maintained in the longer term, there was no further divergence from BMS after 1 year. INTERPRETATION: The performance of new-generation DES in the first year after implantation means that BMS should no longer be considered the gold standard for safety. Further development of DES technology should target improvements in clinical outcomes beyond 1 year. FUNDING: Bern University Hospital.

The Effect of Drug-Eluting Stents on Target Lesion Revascularization in Native Coronary Arteries: Results from the NORSTENT Randomized Study.

BACKGROUND: The NORSTENT trial randomized 9,013 patients to percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) or bare-metal stent (BMS) with 5-year follow-up. No difference was found in the composite primary outcome of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularizations, which were reduced by DES. We report the occurrence of target lesion revascularization (TLR) in time and across demographic and clinical subgroups in patients with lesions in native coronary arteries (n = 8,782). RESULTS: Clinically driven TLR was performed on 488 (5.6%) of the 8,782 patients during 5 years of follow-up. Male gender, older age, visible thrombus in the lesion, and larger stent diameter were associated with less TLR; multivessel disease and longer stents were associated with a higher risk of TLR. There was a substantial and highly significant reduction of the risk of any TLR after 5 years in the DES group (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.36-0.52], p < 0.001). The effect of DES on TLR was limited in time to the first 2 years in the study with no evidence of a later rebound effect. The reduction in TLR after DES insertion was consistent across subgroups defined by gender, age, diabetes status, renal function, and lesion and stent characteristics. The number needed to treat with DES (vs. BMS) to prevent 1 TLR ranged from 4 to 110 across clinically relevant subgroups. CONCLUSION: DES have a time-limited effect on the rate of TLR, but with a substantial and highly significant reduction in the first 2 years after the procedure. This effect was found to be consistent across all important clinical subgroups.

Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease.

BACKGROUND: Limited data are available on the long-term effects of contemporary drug-eluting stents versus contemporary bare-metal stents on rates of death, myocardial infarction, repeat revascularization, and stent thrombosis and on quality of life. METHODS: We randomly assigned 9013 patients who had stable or unstable coronary artery disease to undergo percutaneous coronary intervention (PCI) with the implantation of either contemporary drug-eluting stents or bare-metal stents. In the group receiving drug-eluting stents, 96% of the patients received either everolimus- or zotarolimus-eluting stents. The primary outcome was a composite of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularization, stent thrombosis, and quality of life. RESULTS: At 6 years, the rates of the primary outcome were 16.6% in the group receiving drug-eluting stents and 17.1% in the group receiving bare-metal stents (hazard ratio, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P=0.66). There were no significant between-group differences in the components of the primary outcome. The 6-year rates of any repeat revascularization were 16.5% in the group receiving drug-eluting stents and 19.8% in the group receiving bare-metal stents (hazard ratio, 0.76; 95% CI, 0.69 to 0.85; P<0.001); the rates of definite stent thrombosis were 0.8% and 1.2%, respectively (P=0.0498). Quality-of-life measures did not differ significantly between the two groups. CONCLUSIONS: In patients undergoing PCI, there were no significant differences between those receiving drug-eluting stents and those receiving bare-metal stents in the composite outcome of death from any cause and nonfatal spontaneous myocardial infarction. Rates of repeat revascularization were lower in the group receiving drug-eluting stents. (Funded by the Norwegian Research Council and others; NORSTENT ClinicalTrials.gov number, NCT00811772 .).

Cardiovascular health and the modifiable burden of incident myocardial infarction: the Tromsø Study.

BACKGROUND: The American Heart Association has proposed an impact goal for the year 2020 to improve cardiovascular health by 20%. The objectives of the study were to assess the association between the proposed cardiovascular health metric score and incident myocardial infarction (MI) and to estimate the generalized impact fraction (GIF). METHODS: The health metric score was derived from ideal levels of six cardiovascular risk factors from the population-based Tromsø Study of 22,121 residents of Tromsø, Norway aged 30 to 79 years, examined in 1994-95, 2001, and 2007-08. Incident events of MI were recorded from the date of enrollment in 1994-95 to the end of 2010. Adjudication of hospitalized and out-of hospital events was performed by an independent endpoints committee based on data from hospital and out-of hospital journals, autopsy records and death certificates. Cox proportional hazard regression was used to estimate hazard ratios (HR). GIF was calculated from age stratified analysis using a case-load weighted-sum method. Bootstrapping was used to estimate 95% simulation intervals. RESULTS: A total of 1652 MIs accrued over an average of 14.7 person-years of follow-up. Few men (0.96%) and women (3.6%) had ideal levels in all 6 metrics. 64.7% (men) and 55.7% (women) had ideal levels in 2 or 3 metrics. The age-adjusted HR per point increase in health score was 0.65 (95% confidence interval: 0.61, 0.70) in men and 0.59 (0.54, 0.64) in women. A shift of 30% of subjects from low score levels ≤3 to scores ≥4 was estimated to prevent 13.7% (11.2, 16.2) of incident MI in men and 15.9% (12.1, 19.4) in women. CONCLUSIONS: The association between the health metric score and MI indicate that close to 15% of incident MIs could be prevented by attainable and realistic improvements in the health metrics.

Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals.

BACKGROUND: Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about possible cancer risks. We aimed to assess any effects on site-specific cancer rates in the randomised trials of folic acid supplementation, at doses higher than those from fortification. METHODS: In these meta-analyses, we sought all trials completed before 2011 that compared folic acid versus placebo, had scheduled treatment duration at least 1 year, included at least 500 participants, and recorded data on cancer incidence. We obtained individual participant datasets that included 49,621 participants in all 13 such trials (ten trials of folic acid for prevention of cardiovascular disease [n=46,969] and three trials in patients with colorectal adenoma [n=2652]). All these trials were evenly randomised. The main outcome was incident cancer (ignoring non-melanoma skin cancer) during the scheduled treatment period (among participants who were still free of cancer). We compared those allocated folic acid with those allocated placebo, and used log-rank analyses to calculate the cancer incidence rate ratio (RR). FINDINGS: During a weighted average scheduled treatment duration of 5·2 years, allocation to folic acid quadrupled plasma concentrations of folic acid (57·3 nmol/L for the folic acid groups vs 13·5 nmol/L for the placebo groups), but had no significant effect on overall cancer incidence (1904 cancers in the folic acid groups vs 1809 cancers in the placebo groups, RR 1·06, 95% CI 0·99­1·13, p=0·10). There was no trend towards greater effect with longer treatment. There was no significant heterogeneity between the results of the 13 individual trials (p=0·23), or between the two overall results in the cadiovascular prevention trials and the adenoma trials (p=0·13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast, or any other specific site. INTERPRETATION: Folic acid supplementation does not substantially increase or decrease incidence of site-specific cancer during the first 5 years of treatment. Fortification of flour and other cereal products involves doses of folic acid that are, on average, an order of magnitude smaller than the doses used in these trials. FUNDING: British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency.

Cardiovascular outcomes after curative prostate cancer treatment: A population-based cohort study.

Objective: To investigate differences in cardiovascular disease (CVD) morbidity and mortality after radical prostatectomy or definitive radiotherapy with or without androgen deprivation therapy (ADT). Materials and methods: We used population-based data from the Cancer Registry of Norway, the Norwegian Patient Registry and the Norwegian Cause of Death Registry including 19 289 men ≤80 years diagnosed with non-metastatic prostate cancer during 2010-2019. Patients were treated with radical prostatectomy or definitive radiotherapy. We used competing risk models to compare morbidity from overall CVD, acute myocardial infarction (AMI), cerebral infarction, thromboembolism, and CVD-specific mortality for the overall cohort and stratified by prognostic risk groups. Results: After a median follow-up time of 5.4 years (IQR 4.6 years), there were no differences in adjusted rates of AMI, cerebral infarction, and CVD-specific death between radical prostatectomy and definitive radiotherapy in any of the prognostic risk groups. Rates of overall CVD (0.82; 95% CI 0.76-0.89) and thromboembolism (0.30; 95% CI 0.20-0.44) were lower for definitive radiotherapy than radical prostatectomy during the first year of follow-up. After this overall CVD rates (1.19; 95% CI 1.11-1.28) were consistently higher across all risk groups in patients treated with definitive radiotherapy, but there were no differences regarding thromboembolism. Conclusions: During the first years after treatment, no differences were found in rates of AMI, cerebral infarction, and CVD-specific death between radiotherapy and radical prostatectomy in any of the prognostic risk groups. This suggests that ADT use in combination with radiotherapy may not increase the risks of these outcomes in a curative setting. The increased overall CVD rate for definitive radiotherapy after the first year indicates a possible relationship between definitive radiotherapy and other CVDs than AMI and cerebral infarction.

A Clinical Description of Chronic Pain in a General Population Using ICD-10 and ICD-11 (The HUNT Pain Examination Study).

The purpose was to present a total description, distribution, and ranking of chronic pain conditions in the general population. This was based on structured clinical examinations of a random sample from a population-based survey (HUNT3) with a calculated oversampling of participants with chronic pain. Supplemented with access to hospital reports, the examination was performed by experienced physicians and psychologists using a consistent definition of chronic pain as well as ICD-10- and the new ICD-11-classification. The main findings were that a higher proportion of the 551 participants had chronic pain assessed by clinical examination (399) than by self-report in a survey the same day (337). Among those with examination-verified chronic pain estimated from HUNT3 to represent 27.9% of the general population, 63% had chronic primary pain, 81% musculoskeletal pain, and 77% more than one chronic pain condition. When separating chronic primary from chronic secondary pain according to ICD-11, the weighted prevalence was 17.7% for chronic pain conditions of unknown and 10.2% of known cause. When all the participants' conditions were accounted for, the most prevalent was nonspecific low back (10.8%) and neck pain (7.6%). Participants with chronic primary pain did not have significantly more psychopathology than those with chronic secondary pain: 14.5% versus 12.5%. PERSPECTIVE: Since this study confirms the high prevalence in self-report surveys and indicates that two thirds of chronic pain conditions cannot be explained by underlying diseases, this huge health and societal problem should be solved primarily on a public health level directed toward prevention and rehabilitation.

Individual Patient Data Meta-analysis of Drug-eluting Versus Bare-metal Stents for Percutaneous Coronary Intervention in Chronic Versus Acute Coronary Syndromes.

New-generation drug-eluting stents (DES) strongly reduce restenosis and repeat revascularization compared with bare-metal stents (BMS) for percutaneous coronary intervention. There is residual uncertainty as to whether other prognostically relevant outcomes are affected by DES versus BMS concerning initial presentation (chronic coronary syndrome [CCS] vs acute coronary syndrome [ACS]). We performed an individual patient data meta-analysis of randomized trials comparing new-generation DES versus BMS (CRD42017060520). The primary outcome was the composite of cardiac death or myocardial infarction (MI). Outcomes were examined at maximum follow-up and with a 1-year landmark. Risk estimates are expressed as hazard ratio (HR) with 95% confidence interval (CI). A total of 22,319 patients were included across 14 trials; 7,691 patients (34.5%) with CCS and 14,628 patients (65.5%) with ACS. We found evidence that new-generation DES versus BMS consistently reduced the risk of cardiac death or MI in both patients with CCS (HR 0.83, 95% CI 0.70 to 0.98, p <0.001) and ACS (HR 0.83, 95% CI 0.75 to 0.92, p <0.001) (p-interaction = 0.931). This benefit was mainly driven by a similar reduction in the risk of MI (p-interaction = 0.898) for both subsets (HRCCS 0.80, 95% CI 0.65 to 0.97; HRACS 0.79, 95% CI 0.70 to 0.89). In CCS and ACS, we found a time-dependent treatment effect, with the benefit from DES accumulating during 1-year follow-up, without offsetting effects after that. In conclusion, patients with CCS were slightly underrepresented in comparative clinical trials. Still, they benefited similarly to patients with ACS from new-generation DES instead of BMS with a sustained reduction of cardiac death or MI because of lower event rates within 1 year.

Carotid plaque area and intima-media thickness in prediction of first-ever ischemic stroke: a 10-year follow-up of 6584 men and women: the Tromsø Study.

BACKGROUND AND PURPOSE: Carotid plaque and intima-media thickness (IMT) are recognized as risk factors for ischemic stroke, but their predictive value has been debated and varies between studies. The purpose of this longitudinal population-based study was to assess the risk of ischemic stroke associated with plaque area and IMT in the carotid artery. METHODS: IMT and total plaque area in the right carotid artery were measured with ultrasound in 3240 men and 3344 women aged 25 to 84 years who participated in a population health study in 1994 to 1995. First-ever ischemic strokes were identified through linkage to hospital and national diagnosis registries, with follow-up until December 31, 2005. RESULTS: Incident ischemic strokes occurred in 7.3% (n=235) of men and 4.8% (n=162) of women. The hazard ratio for 1 SD increase in square-root-transformed plaque area was 1.23 (95% CI, 1.09-1.38; P=0.0009) in men and 1.19 (95% CI, 1.01-1.41; P=0.04) in women when adjusted for other cardiovascular risk factors. The multivariable-adjusted hazard ratio in the highest quartile of plaque area versus no plaque was 1.73 (95% CI, 1.19-2.52; P=0.004) in men and 1.62 (95% CI, 1.04-2.53; P=0.03) in women. The multivariable-adjusted hazard ratio for 1 SD increase in IMT was 1.08 (95% CI, 0.95-1.22; P=0.2) in men and 1.24 (95% CI, 1.05-1.48; P=0.01) in women. There were no differences in stroke risk across quartiles of IMT in multivariable analysis. CONCLUSIONS: In the present study, total plaque area appears to be a stronger predictor than IMT for first-ever ischemic stroke.

Drug-Eluting or Bare-Metal Stents for Left Anterior Descending or Left Main Coronary Artery Revascularization.

Background New-generation drug-eluting stents (DES) reduce target-vessel revascularization compared with bare-metal stents (BMS), and recent data suggest that DES have the potential to decrease the risk of myocardial infarction and cardiovascular mortality. We evaluated the treatment effect of DES versus BMS according to the target artery (left anterior descending [LAD] and/or left main [LM] versus other territories [no-LAD/LM]). Methods and Results The Coronary Stent Trialist (CST) Collaboration gathered individual patient data of randomized trials of DES versus BMS for the treatment of coronary artery disease. The primary outcome was the composite of cardiac death or myocardial infarction. Hazard ratios (HRs) with 95% CIs were derived from a 1-stage individual patient data meta-analysis. We included 26 024 patients across 19 trials: 13 650 (52.4%) in the LAD/LM and 12 373 (47.6%) in the no-LAD/LM group. At 6-year follow-up, there was strong evidence that the treatment effect of DES versus BMS depended on the target vessel (P-interaction=0.024). Compared with BMS, DES reduced the risk of cardiac death or myocardial infarction to a greater extent in the LAD/LM (HR, 0.76; 95% CI, 0.68-0.85) than in the no-LAD/LM territories (HR, 0.93; 95% CI, 0.83-1.05). This benefit was driven by a lower risk of cardiac death (HR, 0.83; 95% CI, 0.70-0.98) and myocardial infarction (HR, 0.74; 95% CI, 0.65-0.85) in patients with LAD/LM disease randomized to DES. An interaction (P=0.004) was also found for all-cause mortality with patients with LAD/LM disease deriving benefit from DES (HR, 0.86; 95% CI, 0.76-0.97). Conclusions As compared with BMS, new-generation DES were associated with sustained reduction in the composite of cardiac death or myocardial infarction if used for the treatment of LAD or left main coronary stenoses. Registration URL: https://www.crd.york.ac.uk/PROSPERO; Unique identifier: CRD42017060520.

Employment status three years after percutaneous coronary intervention and predictors for being employed: A nationwide prospective cohort study.

BACKGROUND: Vocational support is recommended for patients in cardiac rehabilitation (CR), as returning to work is important in patients social readjusting after an acute coronary event. Information is lacking on whether CR leads to higher long-term employment after percutaneous coronary intervention (PCI). AIMS: The aims of this study were to determine employment status three years after PCI, to compare employment status between CR participants and CR non-participants and to assess predictors for employment. METHODS: We included first-time PCI patients from the NorStent trial, who were of working age (<63 years; n = 2488) at a three-year follow-up. Employment status and CR participation were assessed using a self-report questionnaire. Propensity score method was used in comparing employment status of CR participants and CR non-participants. RESULTS: Seventy per cent of participants who were <60 years of age at the index event were employed at follow-up and CR participation had no effect on employment status. Being male, living with a partner and attaining higher levels of education were associated with a higher chance of being employed, while being older, prior cardiovascular morbidity and smoking status were associated with lower chance of being employed at follow-up. CONCLUSION: Because a significant number of working-age coronary heart disease patients are unemployed three years after coronary revascularization, updated incentives should be implemented to promote vocational support. Such programmes should focus on females, patients lacking higher education and patients who are living alone, as they are more likely to remain unemployed.

Elevated plasma cystathionine is associated with increased risk of mortality among patients with suspected or established coronary heart disease.

BACKGROUND: Elevated circulating cystathionine levels are related to atherosclerotic cardiovascular disease, a leading cause of death globally. OBJECTIVE: We investigated whether plasma cystathionine was associated with mortality in patients with suspected or established coronary heart disease (CHD). METHODS: Data from 2 independent cohorts of patients with suspected stable angina pectoris (SAP) (3033 patients; median 10.7 y follow-up; 648 deaths) or acute myocardial infarction (AMI) (3670 patients; median 7.0 y follow-up; 758 deaths) were included. Hazard ratios with 95% CIs per SD increment of log-transformed cystathionine were calculated using Cox regression modeling. Endpoint data was obtained from a national health registry. RESULTS: Among patients with SAP, there was a positive association between plasma cystathionine and death (age- and sex-adjusted HRs [95% CI] per SD: 1.23 [1.14, 1.32], 1.29 [1.16, 1.44], and 1.17 [1.05, 1.29] for total, cardiovascular, and noncardiovascular mortality, respectively). Corresponding risk estimates were 1.28 (1.19, 1.37) for all-cause, 1.33 (1.22, 1.45) for cardiovascular, and 1.19 (1.06, 1.34) for noncardiovascular death among AMI patients. In both cohorts, estimates were slightly attenuated after multivariate adjustments for established CHD risk factors. Subgroup analyses showed that the relation between cystathionine and all-cause mortality in SAP patients was stronger among nonsmokers and those with lower plasma concentration of pyridoxal-5'-phosphate (P-interaction ≤ 0.01 for both). CONCLUSIONS: Elevated plasma cystathionine is associated with both cardiovascular and noncardiovascular mortality among patients with suspected or established CHD. The joint risk associations of high plasma cystathionine with lifestyle factors and impaired vitamin B-6 status on mortality need further investigation. This trial was registered at clinicaltrials.gov as NCT00354081 and NCT00266487.

Cardiac rehabilitation after percutaneous coronary intervention: Results from a nationwide survey.

AIM: The purpose of this study was to estimate the proportion of Norwegian coronary heart disease patients participating in cardiac rehabilitation programmes after percutaneous coronary intervention, and to determine predictors of cardiac rehabilitation participation. METHODS: Participants were patients enrolled in the Norwegian Coronary Stent Trial. We assessed cardiac rehabilitation participation in 9013 of these patients who had undergone their first percutaneous coronary intervention during 2008-2011. Of these, 7068 patients (82%) completed a self-administered questionnaire on cardiac rehabilitation participation within three years after their percutaneous coronary intervention. RESULTS: Twenty-eight per cent of the participants reported engaging in cardiac rehabilitation. Participation rate differed among the four regional health authorities in Norway, varying from 20%-31%. Patients undergoing percutaneous coronary intervention for an acute coronary syndrome were more likely to participate in cardiac rehabilitation than patients with stable angina (odds ratio 3.2; 95% confidence interval 2.74-3.76). A multivariate statistical model revealed that men had a 28% lower probability ( p<0.001) of participating in cardiac rehabilitation, and the odds of attending cardiac rehabilitation decreased with increasing age ( p<0.001). Contributors to higher odds of cardiac rehabilitation participation were educational level >12 years (odds ratio 1.50; 95% confidence interval 1.32-1.71) and body mass index>25 (odds ratio 1.19; 95% confidence interval 1.05-1.36). Prior coronary artery bypass graft was associated with lower odds of cardiac rehabilitation participation (odds ratio 0.47; 95% confidence interval 0.32-0.70) Conclusion: The estimated cardiac rehabilitation participation rate among patients undergoing first-time percutaneous coronary intervention is low in Norway. The typical participant is young, overweight, well-educated, and had an acute coronary event. These results varied by geographical region.

Cardiac rehabilitation and symptoms of anxiety and depression after percutaneous coronary intervention.

Background Anxiety and depression are related to coronary heart disease, and psychological support is recommended in cardiac rehabilitation. Purpose The aims of this study were: to compare the prevalence of anxiety and depression with respect to cardiac rehabilitation participation among patients who have been treated with percutaneous coronary intervention; to examine prevalence of anxiety and depression among percutaneous coronary intervention patients compared to the general population; and to identify predictors of symptomatic anxiety and depression among percutaneous coronary intervention patients. Methods We included 9013 patients undergoing first-time percutaneous coronary intervention. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale in a representative sample of 775 patients at baseline and after three years of follow-up, and in the entire cohort at three-year follow-up. Results Cardiac rehabilitation participants had more anxiety and depression than cardiac rehabilitation non-participants at baseline, and both groups had a more anxiety than the general population. The levels of anxiety and depression fell significantly during three years of follow-up, but the changes did not differ between cardiac rehabilitation participants and cardiac rehabilitation non-participants. Three years after percutaneous coronary intervention the prevalence of anxiety was 32% ( p < 0.001), higher among cardiac rehabilitation participants compared to cardiac rehabilitation non-participants. Female gender and younger age were associated with anxiety, whereas older age, lower levels of education and cardiovascular morbidity were associated with depression. Conclusion The levels of anxiety and depression were prevalent among percutaneous coronary intervention patients and the levels were not affected by cardiac rehabilitation participation. Anxiety is prevalent among female and younger patients, whereas depression is related to older age and cardiovascular co-morbidity.

Plasma cystathionine and risk of acute myocardial infarction among patients with coronary heart disease: Results from two independent cohorts.

BACKGROUND: Cystathionine is a thio-ether and a metabolite formed from homocysteine during transsulfuration. Elevated plasma cystathionine levels are reported in patients with cardiovascular disease; however prospective relationships with acute myocardial infarction (AMI) are unknown. We investigated associations between plasma cystathionine and AMI among patients with suspected and/or verified coronary heart disease (CHD). METHODS: Subjects from two independent cohort studies, the Western Norway Coronary Angiography Cohort (WECAC) (3033 patients with stable angina pectoris; 263 events within 4.8 years of median follow-up) and the Norwegian Vitamin Trial (NORVIT) (3670 patients with AMI; 683 events within 3.2 years of median follow-up) were included. RESULTS: In both cohorts, plasma cystathionine was associated with several traditional CHD risk factors (P < 0.001). Comparing the cystathionine quartile 4 to 1, age and gender adjusted hazard ratios (95% confidence intervals) for AMI were 2.08 (1.43-3.03) and 1.41 (1.12-1.76) in WECAC and NORVIT, respectively. Additional adjustment for traditional risk factors slightly attenuated the risk estimates, which were generally stronger in both cohorts among non-smokers, patients with higher age, and lower BMI or PLP status (P-interaction ≤ 0.04). Risk associations also tended to be stronger in patients not treated with B-vitamins. Additionally, in a subset of 80 WECAC patients, plasma cystathionine associated strongly negatively with glutathione, an important antioxidant and positively with lanthionine, a marker of H2S production (P < 0.001). CONCLUSIONS: Plasma cystathionine is associated with increased risk of AMI among patients with either suspected or verified coronary heart disease, and is possibly related to altered redox homeostasis.

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles.

BACKGROUND: Although choline metabolism has been associated with atherosclerotic heart disease, less research attention has been paid to the associations of choline and its oxidative metabolite betaine with cardiac arrhythmias. METHODS AND RESULTS: We evaluated associations of plasma concentrations and dietary intakes of choline and betaine with long-term atrial fibrillation (AF) risk in a community-based cohort, HUSK ([the Hordaland Health Study] n=6949), and validated the findings in 2 patient cohorts: the Western Norway Coronary Angiography Cohort (n=4164) and the NORVIT (Norwegian B-Vitamin) Trial (n=3733). Information on AF was obtained from the CVDNOR (Cardiovascular Disease in Norway) project. In HUSK, WECAC (Western Norway Coronary Angiography Cohort), and NORVIT, 552, 411, and 663 AF cases were identified during a median follow-up time of 10.9, 7.3, and, 8.7 years, respectively. Plasma concentrations of choline and betaine were significantly positively associated with later AF risk after multivariable adjustments in HUSK. Such associations were independently replicated in the 2 external prospective patient cohorts. The pooled hazard ratio was 1.13 (95% confidence interval 1.08-1.19, P<0.001) and 1.16 (95% confidence interval 1.10-1.22, P<0.001) per SD increment for log-transformed choline and betaine, respectively. Moreover, dietary intake of choline was marginally associated with AF risk (pooled hazard ratio 1.29, 95% confidence interval 1.01-1.66, fifth versus first quintile), whereas no significant association was observed between dietary betaine and AF risk. CONCLUSIONS: Our findings indicate that plasma concentrations as well as dietary intake of choline, but not betaine, are associated with subsequent risk of AF, suggesting a potential role of choline metabolism in the pathogenesis of AF. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov.Unique identifier: NCT00671346.