Insomnia and left ventricular function – an echocardiography study

<p><i>Objectives</i>. Recently, studies have reported an association of insomnia with incident heart failure but its causal relation is still uncertain. In patients with heart failure, the left ventricular function is impaired and the deterioration may start long before the patient experiences any symptoms. As the first study, we examined the association of insomnia with left ventricular function using state-of-the art echocardiography methods. <i>Design</i>. In the echocardiography study, several indices of left ventricular function were examined in participants free from cardiovascular diseases, hypertension and diabetes. In total 788 participants with information on all relevant covariates were included. We calculated the least square mean of indices of left ventricular function associated with increasing number of insomnia symptoms (i.e. difficulties falling asleep, frequent awakenings and early awakenings), including systolic mitral annular excursion, peak velocities of systolic and diastolic motion of the mitral annulus and systolic deformation of the left ventricle. <i>Results</i>. We found no clear evidence that increasing number of insomnia symptoms is associated with any of the left ventricular function indices. <i>Conclusions</i>. The methods that were used are sensitive to detect preclinical HF, and therefore, our findings do not support a causal relation between insomnia symptoms and HF.</p

Conditional logistic regression analyses, <i>MBL2</i> functional groups.

*<p>26 pairs excluded because one or more missing values.</p>†<p>Adjusted for classical risk factors: Hypertension (BP>140/90 or current use of antihypertensive medication), body mass index (kg/m², continuous), hypercholesterolemia (total cholesterol >6.2 mmol/L), diabetes (yes/no) and smoking (never/former/current).</p>‡<p>Adjusted for Framingham risk score (age, HDL-cholesterol, total cholesterol, systolic blood pressure, smoking and diabetes).</p>§<p>3 pairs excluded because one or more missing values.</p

Mannose-Binding Lectin Deficiency Is Associated with Myocardial Infarction: The HUNT2 Study in Norway

<div><h3>Objectives</h3><p>Mannose-binding lectin (MBL) and ficolins activate the complement cascade, which is involved in atherogenesis. Based on a pilot study, we hypothesized that functional polymorphisms in the MBL gene (<em>MBL2</em>) leading to dysfunctional protein are related to development of myocardial infarction (MI). The aim of the present study was to study polymorphisms in <em>MBL2</em> and ficolin genes in relation to the risk of MI.</p> <h3>Methods and Results</h3><p>Using the population-based HUNT Study in Norway, 57133 persons were followed up for a first-time MI from 1995–1997 until the end of 2008. The 370 youngest MI patients were matched by age (range 29–62 years) and gender to 370 controls. A younger population was selected because disease in this group might be less dependent on non-genetic risk factors. The study size was based on power calculation. Polymorphisms in <em>MBL2</em> and in the genes of ficolin-1, ficolin-2 and ficolin-3 were genotyped by pyrosequencing and related to the risk of MI, estimated as odds ratios (OR). Functional haplotypes were analyzed and stringent alpha levels of significance were set by permutation testing. Variant <em>MBL2</em> haplotypes causing MBL deficiency were associated with a two-fold higher risk of MI (OR 2.04, 95%CI 1.29–3.24). Adjustments for conventional cardiovascular risk factors did not substantially influence the association. The ficolins were not associated with MI risk.</p> <h3>Conclusion</h3><p>In a young to middle aged and relatively healthy Caucasian population, <em>MBL2</em> variants related to functional MBL deficiency were associated with a doubling of the risk for MI, independent of conventional risk factors. This supports that MBL deficiency may lead to increased atherosclerosis or development of vulnerable plaques.</p> </div

Baseline characteristics.

*<p>Body mass index (BMI).</p>†<p>Waist hip ratio (WHR).</p>‡<p>Myocardial infarction before 60 years in first-degree relatives.</p

<i>MBL2</i> gene and haplotypes.

<p>Panel A: Simplified figure of the investigated <i>MBL2</i> polymorphisms. Wild type allele is <i>A.</i> Panel B: <i>MBL2</i> haplotypes and corresponding concentrations of functional MBL.</p

Data on <i>MBL2</i> haplotypes and MBL plasma concentrations from the pilot study.

<p>Data on <i>MBL2</i> haplotypes and MBL plasma concentrations from the pilot study.</p

Genotype frequencies for <i>FCN1</i>, <i>FCN2</i> and <i>FCN3</i>.

*<p><i>FCN1</i> recessive model: p = 0.069.</p>†<p>4 missing.</p

Characteristics according to cumulative number of insomnia for women.

<p>Characteristics according to cumulative number of insomnia for women.</p

Least square means and 95% confidence intervals for the cumulative insomnia symptoms and flow mediated dilation (%).

<p>Model 1: Adjusted for age and age squared.</p><p>Model 2: Adjusted for age, age squared, marital status, education, smoking, alcohol consumption, physical activity index, BMI, sleep-disordered breathing, snoring.</p><p>Model 3: Adjusted for the same variables as in model 2, and depression score and anxiety score.</p

Least square means and 95% confidence intervals for the insomnia symptoms and flow mediated dilation (%) in women.

<p>Model 1: Adjusted for age and age squared.</p><p>Model 2: Adjusted for age, age squared, marital status, education, smoking, alcohol consumption, physical activity index, BMI, sleep-disordered breathing, snoring.</p><p>Model 3: Adjusted for the same variables as in model 2, and depression score and anxiety score.</p