The Role of Long-Chained Marine N-3 Polyunsaturated Fatty Acids in Cardiovascular Disease

This paper reviews the current evidence regarding long-chained marine omega-3 polyunsaturated fatty acids (PUFAs) and cardiovascular disease (CVD), their possible mechanisms of action, and results of clinical trials. Also, primary and secondary prevention trials as studies on antiarrhythmic effects and meta-analyses are summarized. However, the individual bioavailability of n-3 PUFAs along with the highly different study designs and estimations of FAs intake or supplementation dosages in patient populations with different background intake of n-3 PUFAs might be some of the reasons for the inconsistent findings of the studies evaluating the impact of n-3 PUFAs on CVD. The question of an optimum dose of n-3 PUFAs or whether there exists adose-response relation for n-3 PUFA supplementation is widely discussed.Moreover, the difficulties in interpreting meta-analyses are clearly demonstrated by two recently published meta-analyses (Rizos et al. and Delgado Lista et al.), evaluating the efficacy of n-3 PUFAs on CVD, including 12 common studies, but drawing opposite conclusions. We definitely need more large-scale, randomized clinical trials of long duration, also reporting harmful effects of n-3 PUFAs.publishedVersio

No effect of plasma trimethylamine N-Oxide (TMAO) and plasma trimethyllysine (TML) on the association between choline intake and acute myocardial infarction risk in patients with stable angina pectoris

Plasma concentrations of trimethylamine N-oxide (TMAO) have been linked to cardiovascular disease (CVD) risk and mortality. TMAO is formed through the bacterial conversion of trimethylamine which is obtained either directly from food, generated from dietary precursors (e.g. choline) or derived from endogenous trimethyllysine (TML) production. In a previous article, we reported an increased risk of acute myocardial infarction with increased total choline intake in patients with stable angina pectoris. Due to the close link between TMAO, TML, choline metabolism and possibly CVD, we investigated whether plasma TMAO and TML modified the effect of total choline intake on acute myocardial infarction (AMI) risk in a post-hoc analysis. We found plasma TMAO and TML do not modify the association between higher dietary choline intake and increased AMI risk. Additionally, this association is not mediated via TMAO.publishedVersio

Associations between disease severity, coping and dimensions of health-related quality of life in patients admitted for elective coronary angiography – a cross sectional study

<p>Abstract</p> <p>Background</p> <p>In patients with suspected coronary artery disease (CAD), the overall aim was to analyse the relationships between disease severity and both mental and physical dimensions of health related quality of life (HRQOL) using a modified version of the Wilson and Cleary model.</p> <p>Methods</p> <p>Using a cross-sectional design, 753 patients (74% men), mean age 62 years, referred for elective cardiac catheterisation were included. The measures included 1) physiological factors 2) symptoms (disease severity, self-reported symptoms, anxiety and depression 3) self-reported functional status, 4) coping, 5) perceived disease burden, 6) general health perception and 7) overall quality of life. To analyse relationships, we performed linear and ordinal logistic regressions.</p> <p>Results</p> <p>CAD and left ventricular ejection fraction (LVEF) were significantly associated with symptoms of angina pectoris and dyspnea. CAD was not related to symptoms of anxiety and depression, but less depression was found in patients with low LVEF. Angina pectoris and dyspnea were both associated with impaired physical function, and dyspnea was also negatively related to social function. Overall, less perceived burden and better overall QOL were observed in patients using more confronting coping strategy.</p> <p>Conclusion</p> <p>The present study demonstrated that data from cardiac patients to a large extent support the suggested model by Wilson and Cleary.</p

Type 2 diabetes genes : present status and data from Norwegian studies

The worldwide rise in prevalence of type 2 diabetes has led to an intense search for the genetic risk factors of this disease. In type 2 diabetes and other complex disorders, multiple genetic and environmental factors, as well as the interaction between these factors, determine the phenotype. In this review, we summarize present knowledge, generated by more than two decades of efforts to dissect the genetic architecture of type 2 diabetes. Initial studies were either based on a candidate gene approach or attempted to fine-map signals generated from linkage analysis. Despite the detection of multiple genomic regions proposed to be linked to type 2 diabetes, subsequent positional fine-mapping of candidates were mostly inconclusive. However, the introduction of genome-wide association studies (GWAS), applied on thousands of patients and controls, completely changed the field. To date, more than 50 susceptibility loci for type 2 diabetes have been detected through the establishment of large research consortia, the application of GWAS on intermediary diabetes phenotypes and the use of study samples of different ethnicities. Still, the common variants identified in the GWAS era only explain some of the heritability seen for type 2 diabetes. Thus, focus is now shifting towards searching also for rare variants using new high-throughput sequencing technologies. For genes involved in the genetic predisposition to type 2 diabetes the emerging picture is that there are hundreds of different gene variants working in a complex interplay influencing pancreatic beta cell function/mass and, only to a lesser extent, insulin action. Several Norwegian studies have contributed to the field, extending our understanding of genetic risk factors in type 2 diabetes and in diabetes-related phenotypes like obesity and cardiovascular disease.publishedVersio

B-vitamin Treatment Modifies the Mortality Risk Associated with Calcium Channel Blockers in Patients with Suspected Stable Angina Pectoris: A Prospective Cohort Study

Background Calcium channel blockers (CCBs) are used for the treatment of cardiovascular disease (CVD), including angina pectoris, and hypertension; however, the effect on survival remains uncertain. CCBs impair fibrinolysis and have been linked to elevated plasma homocysteine (Hcy), a CVD risk marker. Objective We explored the association between CCB use and mortality in a large prospective cohort of patients with suspected stable angina pectoris (SAP), and potential effect modifications by Hcy-lowering B-vitamin treatment (folic acid, B12, and/or B6) as 61.8% of the patients participated in a randomized placebo-controlled B-vitamin intervention trial. Methods Patient baseline continuous characteristics according to CCB treatment were tested by linear regression. Hazard ratios (HRs) for mortality associated with CCB treatment, also according to B-vitamin intervention, were examined using Cox regression analysis. The multivariable model included CVD risk factors, medical histories, and the use of CVD medications. Results A total of 3991 patients (71.5 % men) were included, of whom 907 were prescribed CCBs at discharge. During 10.3 years of median follow-up, 20.6% died and 8.9% from cardiovascular- and 11.7% from non-cardiovascular causes. Patients treated with CCBs had higher plasma Hcy, fibrinogen levels, and erythrocyte sedimentation rate (all P<0.001). Furthermore, CCB use was positively associated with mortality, also after multivariable adjustments (HRs [95% CIs]: 1.34 [1.15,1.57], 1.35 [1.08,1.70], and 1.33 [1.09,1.64] for total, CVD, and non-CVD death, respectively). Numerically stronger associations were observed among patients not treated with B-vitamins (HR [95% CI]: 1.54 [1.25, 1.88], 1.69 [1.25, 2.30], and 1.41 [1.06, 1.86] for total, CVD deaths, and non-CVD deaths, respectively), whereas no association was seen in patients treated with B-vitamins (HR [95% CI]: 1.15 [0.91, 1.46], 1.09 [0.76, 1.57], and 1.20 [0.88, 1.65]). Conclusions In patients with suspected SAP, CCB treatment was associated with increased mortality risk primarily among patients not treated with B-vitamins.publishedVersio

Tryptophan catabolites as metabolic markers of vitamin B-6 status evaluated in cohorts of healthy adults and cardiovascular patients

Background Vitamin B-6 status is routinely measured as pyridoxal 5′-phosphate (PLP) in plasma. Low concentrations of PLP are associated with rheumatic, cardiovascular, and neoplastic diseases. We have previously shown that vitamin B-6 status affects the kynurenine (Kyn) pathway of tryptophan (Trp) catabolism. Objective This study aimed to comprehensively evaluate the use of Kyns as potential markers of functional vitamin B-6 status across 2 large cohorts. Methods We measured circulating concentrations of the first 6 metabolites in the Trp catabolic pathway by LC–MS-MS in the community-based Hordaland Health Study (HUSK; n = 7017) and cardiovascular patient–based Western Norway Coronary Angiography Cohort (WECAC; n = 4161). Cross-sectional and longitudinal associations of plasma PLP with Kyns were estimated using linear and nonlinear regression–based methods. Results 3′-Hydroxykynurenine (HK), a substrate, and all 4 products formed directly by the PLP-dependent enzymes kynurenine transaminase and kynureninase contributed to the explanation of circulating PLP in multivariable-adjusted regression models. The construct HK:(kynurenic acid + xanthurenic acid + 3′-hydroxyanthranilic acid + anthranilic acid), termed HK ratio (HKr), was related to plasma PLP with standardized regression coefficients (95% CIs) of −0.47 (−0.49, −0.45) and −0.46 (−0.49, −0.43) in HUSK and WECAC, respectively. Across strata of cohort and sex, HKr was 1.3- to 2.7-fold more sensitive, but also 1.7- to 2.9-fold more specific to changes in PLP than a previously proposed marker, HK:xanthurenic acid. Notably, the association was strongest at PLP concentrations < ∼20 nmol/L, a recognized threshold for vitamin B-6 deficiency. Finally, PLP and HKr demonstrated highly sex-specific and corroborating associations with age. Conclusions The results demonstrate that by combining 5 metabolites in the Kyn pathway into a simple index, HKr, a sensitive and specific indicator of intracellular vitamin B-6 status is obtained. The data also underscore the merit of evaluating alterations in Kyn metabolism when investigating vitamin B-6 and health.acceptedVersio

Food Sources Contributing to Intake of Choline and Individual Choline Forms in a Norwegian Cohort of Patients With Stable Angina Pectoris

Choline is an essential nutrient involved in a wide range of physiological functions. It occurs in water- and lipid-soluble forms in the body and diet. Foods with a known high choline content are eggs, beef, chicken, milk, fish, and selected plant foods. An adequate intake has been set in the US and Europe, however, not yet in the Nordic countries. A higher intake of lipid-soluble choline forms has been associated with increased risk of acute myocardial infarction, highlighting the need for knowledge about food sources of the individual choline forms. In general, little is known about the habitual intake and food sources of choline, and individual choline forms.publishedVersio

Serum trans fatty acids, asymmetric dimethylarginine and risk of acute myocardial infarction and mortality in patients with suspected coronary heart disease: a prospective cohort study

Quartiles of trans 16:1n7 and risk of acute myocardial infarction, cardiovascular death and all-cause mortality. (DOCX 20 kb

Association of dietary vitamin K and risk of coronary heart disease in middle-age adults: the Hordaland Health Study Cohort

Objective: The role of vitamin K in the regulation of vascular calcification is established. However, the association of dietary vitamins K1 and K2 with risk of coronary heart disease (CHD) is inconclusive. Design: Prospective cohort study. Setting: We followed participants in the community-based Hordaland Health Study from 1997 - 1999 through 2009 to evaluate associations between intake of vitamin K and incident (new onset) CHD. Baseline diet was assessed by a past-year food frequency questionnaire. Energy-adjusted residuals of vitamin K1 and vitamin K2 intakes were categorised into quartiles. Participants: 2987 Norwegian men and women, age 46–49 years. Methods: Information on incident CHD events was obtained from the nationwide Cardiovascular Disease in Norway (CVDNOR) Project. Multivariable Cox regression estimated HRs and 95% CIs with test for linear trends across quartiles. Analyses were adjusted for age, sex, total energy intake, physical activity, smoking and education. A third model further adjusted K1 intake for energy-adjusted fibre and folate, while K2 intake was adjusted for energy-adjusted saturated fatty acids and calcium. Results: During a median follow-up time of 11 years, we documented 112 incident CHD cases. In the adjusted analyses, there was no association between intake of vitamin K1 and CHD (HRQ4vsQ1 = 0.92 (95% CI 0.54 to 1.57), p for trend 0.64), while there was a lower risk of CHD associated with higher intake of energy-adjusted vitamin K2 (HRQ4vsQ1 = 0.52 (0.29 to 0.94), p for trend 0.03). Further adjustment for potential dietary confounders did not materially change the association for K1, while the association for K2 was slightly attenuated (HRQ4vsQ1 = 0.58 (0.28 to 1.19)). Conclusions: A higher intake of vitamin K2 was associated with lower risk of CHD, while there was no association between intake of vitamin K1 and CHD.publishedVersio

Heart Failure Complicating Acute Myocardial Infarction; Burden and Timing of Occurrence: A Nation-wide Analysis Including 86 771 Patients From the Cardiovascular Disease in Norway (CVDNOR) Project

Background: Coronary heart disease (CHD) represents often the underlying conditions for the development of heart failure (HF). We aimed at exploring the burden and timing of HF complicating an acute myocardial infarction (AMI), using the total population of AMI patients hospitalized during 2001–2009 in Norway. Methods and Results: A total of 86 771 patients with a first AMI during 2001–2009 and without previous HF were identified in the “Cardiovascular Disease in Norway” project and followed until HF development, death, or December 31, 2009. In 16 219 patients (18.7%), HF was present on admission or developed during hospitalization for the incident AMI. HF occurrence varied according to age (8.9%, 15.2%, and 25.6% among men and 10.2%, 16.8%, and 27.1% among women ages 25–54, 55–74, and 75–85 years). Among 63 853 patients discharged alive without HF, 8058 (12.6%) were hospitalized with or died because of HF during a median follow‐up time of 3.2 years. HF incidence rates (IRs) per 1000 person‐years during follow‐up were 31 (95% CI, 30–32) for men and 46 (95% CI, 44–47) for women (P<0.01). IRs of HF were highest during the first 6 months of follow‐up, after which they leveled off and remained stable until the end of follow‐up. Conclusions: In this nation‐wide cohort study, we observed that HF remains a frequent complication of the first AMI; both during the acute phase and shortly after the discharge from the hospital.publishedVersio