Epigenetics of Lipid Phenotypes

Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (eg, CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay between different classes of epigenetic processes in the lipid-related genomic regions. Although epigenetic findings hold the potential to explain the interindividual variability in lipid profiles as well as the underlying mechanisms, they have yet to be translated into effective therapies for dyslipidemia

Effectiveness of Statins as Primary Prevention in People With Different Cardiovascular Risk: A Population-Based Cohort Study

The purpose was to analyze statin effectiveness in a general population with differing levels of coronary heart disease (CHD) risk. Patients (35-74 years) without previous cardiovascular disease were included and stratified according to 10-year CHD risk ( < 5%, 5-7.4%, 7.5-9.9%, and 10-19.9%). New users were categorized according to their medical possession ratio (MPR). The main outcome was atherosclerotic cardiovascular disease (ASCVD) (myocardial infarction and ischemic stroke). In adherent patients (MPR 70%), statin treatment decreased ASCVD risk across the range of coronary risk (from 16-30%). The 5-year number needed to treat (NNT) was 470 and 204 in the risk categories < 5% and 5-7.4%, respectively, and 75 and 62 in the 7.5-9.9% category than in the 10-19.9% category, respectively. Statin therapy should remain a priority in patients at high 10-year CHD risk (10-19.9%). Most patients with intermediate risk could benefit from statin treatment, but the treatment decision should focus on the net benefit, safety, and patient preference, given the higher NNT

Panenteric capsule endoscopy identifies proximal small bowel disease guiding upstaging and treatment intensification in Crohn&#8217;s disease: A European multicentre observational cohort study

Background: Endoscopically defined mucosal healing in Crohn\u2019s disease is associated with improved outcomes. Panenteric capsule endoscopy enables a single non-invasive assessment of small and large bowel mucosal inflammation. Aims and methods: This multicentre observational study of patients with suspected and established Crohn\u2019s disease examined the feasibility, safety and impact on patient outcomes of panenteric capsule endoscopy in routine clinical practice. The potential role in assessment of disease severity and extent by a comparison with existing clinical and biochemical markers is examined. Results: Panenteric capsule endoscopy was performed on 93 patients (71 with established and 22 with suspected Crohn\u2019s disease). A complete examination occurred in 85% (79/93). Two cases (2.8%) of capsule retention occurred in patients with established Crohn\u2019s disease. Panenteric capsule resulted in management change in 38.7% (36/93) patients, including 64.6% (32/48) of those with an established diagnosis whose disease was active, and all three patients with newly diagnosed Crohn\u2019s disease. Montreal classification was upstaged in 33.8% of patients with established Crohn\u2019s disease and mucosal healing was demonstrated in 15.5%. Proximal small bowel disease upstaged disease in 12.7% and predicted escalation of therapy (odds ratio 40.3, 95% confidence interval 3.6\u2013450.2). Raised C-reactive protein and faecal calprotectin were poorly sensitive in detecting active disease (0.48 and 0.59 respectively). Conclusions: Panenteric capsule endoscopy was feasible in routine practice and the ability to detect proximal small bowel disease may allow better estimation of prognosis and guide treatment intensification. Panenteric capsule endoscopy may be a suitable non-invasive endoscopic investigation in determining disease activity and supporting management decisions

Endurance sport practice as a risk factor for atrial fibrillation and atrial flutter

Although the benefits of regular exercise in controlling cardiovascular risk factors have been extensively proven, little is known about the long-term cardiovascular effects of regular and extreme endurance sport practice, such as jogging, cycling, rowing, swimming, etc. Recent data from a small series suggest a relationship between regular, long-term endurance sport practice and atrial fibrillation (AF) and flutter. Reported case control studies included less than 300 athletes, with mean age between 40 and 50. Most series recruited only male patients, or more than 70% males, who had been involved in intense training for many years. Endurance sport practice increases between 2 and 10 times the probability of suffering AF, after adjusting for other risk factors. The possible mechanisms explaining the association remain speculative. Atrial ectopic beats, inflammatory changes, and atrial size have been suggested. Some of the published studies found that atrial size was larger in athletes than in controls, and this was a predictor for AF. It has also been shown that the left atrium may be enlarged in as many as 20% of competitive athletes. Other proposed mechanisms are increased vagal tone and bradycardia, affecting the atrial refractory period; however, this may facilitate rather than cause the arrhythmia. In summary, recent data suggest an association between endurance sport practice and atrial fibrillation and flutter. The underlying mechanism explaining this association is unclear, although structural atrial changes (dilatation and fibrosis) are probably present. Larger longitudinal studies and mechanistic studies are needed to further characterize the association to clarify whether a threshold limit for the intensity and duration of physical activity may prevent AF, without limiting the cardiovascular benefits of exercise

Impact of a partial smoke-free legislation on myocardial infarction incidence, mortality and case-fatality in a population-based registry: the REGICOR Study

Abstract Background and Objective Coronary heart disease (CHD) is the leading cause of death, and smoking its strongest modifiable risk factor. Our aim was to determine the impact of the Spanish 2006 partial smoke-free legislation on acute myocardial infarction (AMI) incidence, hospitalization and mortality rates, and 28-day case-fatality in Girona, Spain. Methods Using a population-based registry (the REGICOR Study), we compared population incidence, hospitalization, and mortality rates, and 28-day case-fatality in the pre- and post-ban periods (2002-2005 and 2006-2008, respectively) by binomial regression analysis adjusted for confounding factors. We also analyzed the ban's impact on the outcomes of interest using the AMI definitions of the American Heart Association (AHA)/European Society of Cardiology (ESC) and the World Health Organization (WHO)-Monitoring trends and determinants in cardiovascular diseases (MONICA). Results In the post-ban period, AMI incidence and mortality rates significantly decreased (relative risk [RR] = 0.89; 95% confidence interval [CI] = 0.81-0.97 and RR = 0.82; 95% CI = 0.71-0.94, respectively). Incidence and mortality rates decreased in both sexes, especially in women, and in people aged 65-74 years. Former and non-smokers (passive smokers) showed diminished incidence rates. Implementation of the ban was not associated with AMI case-fatality. Models tended to be more significant with the WHO-MONICA than with the AHA/ESC definition. Conclusions The 2006 Spanish partial smoke-free legislation was associated with a decrease in population AMI incidence and mortality, particularly in women, in people aged 65-74 years, and in passive smokers. These results clarify the association between AMI mortality and the enactment of a partial smoke-free legislation and reinforce the effectiveness of smoking regulations in preventing CH

Prevalence of Symptomatic and Asymptomatic Peripheral Arterial Disease and the Value of the Ankle-brachial Index to Stratify Cardiovascular Risk

AbstractObjectivesTo determine the prevalence of ankle-brachial index (ABI)<0.9 and symptomatic peripheral arterial disease (PAD), association with cardiovascular risk factors (CVRF), and impact of adding ABI measurement to coronary heart disease (CHD) risk screening.DesignPopulation-based cross-sectional survey of 6262 participants aged 35–79 in Girona, Spain.MethodsStandardized measurements (CVRF, ABI, 10-year CHD risk) and history of intermittent claudication (IC), CHD, and stroke were recorded. ABI<0.9 was considered equivalent to moderate-to-high CHD risk (≥10%).ResultsABI<0.9 prevalence was 4.5%. Only 0.62% presented low ABI and IC. Age, current smoker, cardiovascular disease, and uncontrolled hypertension independently associated with ABI<0.9 in both sexes; IC was also associated in men and diabetes in women. Among participants 35–74 free of cardiovascular disease, 6.1% showed moderate-to-high 10-year CHD risk; adding ABI measurement yielded 8.7%. Conversely, the risk function identified 16.8% of these participants as having 10-year CHD risk>10%. In participants 75–79 free of cardiovascular disease, the prevalence of ABI<0.9 (i.e., CHD risk≥10%) was 11.9%.ConclusionsABI<0.9 is relatively frequent in those 35–79, particularly over 74. However, IC and CHD risk≥10% indicators are often missing. Adding ABI measurement to CHD-risk screening better identifies moderate-to-high cardiovascular risk patients

Fiber-optic lossy mode resonance sensors

In the last 4 years, experimental evidences about the potential use of optical sensors based on Lossy Mode Resonances (LMR) have been presented in the literature. These LMR sensors have some similarities with Surface Plasmon Resonance (SPR) sensors, the gold standard in label-free, real-time biomolecular interaction analysis. In these new LMR sensors, if the non-metallic nanocladding of an optical waveguide fulfills the conditions explained in this work, coupling of light to the cladding modes happens at certain resonance wavelengths, which enables the use of LMR devices as refractometers and opens the door to diverse applications such as in biology and proteomics research. These highly sensitive refractometers have already shown sensitivities higher than 20,000 nm/RIU or 5x10-7 RIU and, given the youth of this field, it is expected to achieve even better values

Optical sensors based on lossy-mode resonances

Lossy-mode resonance (LMR)–based optical sensing technology has emerged in the last two decades as a nanotechnological platform with very interesting and promising properties. LMR complements the metallic materials typically used in surface plasmon resonance (SPR)–based sensors, with metallic oxides and polymers. In addition, it enables one to tune the position of the resonance in the optical spectrum, to excite the resonance with both transverse electric (TE) and transverse magnetic (TM) polarized light, and to generate multiple resonances. The domains of application are numerous: as sensors for detection of refractive indices voltage, pH, humidity, chemical species, and antigens, as well as biosensors. This review will discuss the bases of this relatively new technology and will show the main contributions that have permitted the optimization of its performance to the point that the question arises as to whether LMR–based optical sensors could become the sensing platform of the near future