Sleep Apnea Syndrome: More Than Benign Snoring. Implications for the Cardiovascular System

Sleep disordered breathing is a rather common problem in the general population. Apnea during sleep can be divided into three types: central, obstructive and mixed. In central apneas there is lack of both airflow and respiratory efforts. It is recognized by its waxing-waning pattern of respiration called Cheyne- Stokes respiration. Central sleep apnea is most commonly seen in patients with heart failure and its prevalence among this group of patients is estimated to be as high as 30-40%. Obstructive sleep apnea occurs approximately in 5-15% of the general population. It usually affects middle-aged men with an increased body-mass index and a large neck circumference. It is characterized by repetitive complete or partial obstruction of the upper airway during sleep, which is followed by increasing and ineffective respiratory efforts. Sleep fragmentation in patients with sleep apnea syndrome results in sleepiness, fatigue, morning headaches and depression. This daytime presentation together with loud snoring, choking and pauses of respiration during sleep should make primary care physicians suspicious of sleep disordered breathing. The best method used for the diagnosis of sleep apnea syndrome is overnight polysomnography. The pathophysiologic mechanisms, which take place in sleep apnea, include sympathetic activation, hypercoagulability, inflammation and production of pro-inflammatory cytokines, endothelial dysfunction, oxidative stress and metabolic dysfunction. All these mechanisms are associated with the development and progression of cardiovascular disease. There is a strong linkage between sleep apnea and hypertension, systolic and diastolic dysfunction of the left ventricle, congestive heart failure, coronary artery disease, cardiac arrhythmias, stroke and pulmonary disease. Given the increased morbidity and mortality of patients with sleep apnea, an effective treatment must be started as soon as possible after the diagnosis is made. Currently, nasal continuous positive airway pressure constitutes first line therapy. This therapy improves both quality of sleep and cardiovascular and general outcomes

Impact of Cardiometabolic Risk Factors on Major Cardiovascular Events in Patients With Familial Combined Hyperlipidemia

Background: Familial combined hyperlipidemia (FCH) is an inherited lipid disorder associated with premature cardiovascular disease. It has not been established whether the cardiometabolic risk factors, which frequently accompany FCH, such as diabetes, metabolic syndrome (MetS) and hypertension, modulate cardiovascular risk in FCH patients. Methods and Results: In this single-center, retrospective study, 695 FCH patients with adequate follow-up were enrolled (mean age, 48.9 years; 455 male). Risk factors including lipid levels were evaluated before the initiation of treatment. Acute myocardial infarction (AMI) and cardiovascular death were recorded during a mean follow-up of 9 years. The combined endpoint (AMI and/or cardiovascular death) occurred in 41 patients (5.9% of the total). Those FCH patients who reached the combined endpoint had lower high-density lipoprotein cholesterol (HDL-C) than those who did not, but levels of other lipid variables were similar. Presence of hypertension, diabetes or MetS was a predictor of the combined endpoint on univariate Kaplan-Meier analysis (all P<0.005). Multivariate Cox proportional analysis showed that hypertension and MetS were associated with the combined endpoint independently of age, gender, HDL-C and presence of coronary artery disease at enrolment (adjusted hazard ratios [HRs], 3.00; 95% confidence interval [Cl]: 1.46-6.17, P=0.003; HR, 2.43; 95C1%; 1.11-5.33, P=0.026, respectively). Conclusions: Cardiometabolic risk factors such as hypertension and MetS are independent predictors of major cardiovascular events in FCH patients. (Circ J 2013; 77: 163-168

Novel germline mutations of the MEN1 gene in Greek families with multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder associated with mutations of the MEN1 gene and characterized by the combined occurrence of tumours of the parathyroid glands, the pancreatic islet cells and the anterior pituitary. To identify MEN1 gene mutations and characterize clinical manifestations in Greek patients with MEN1. We studied four unrelated index patients with MEN1, 17 relatives and 100 control subjects. Among the relatives, seven were clinically and/or biochemically affected, while 10 were unaffected. DNA extraction, polymerase chain reaction (PCR) and direct sequencing of the MEN1 exons 2-10 and exon/intron boundaries were performed according to standard procedures. We identified novel MEN1 gene mutations in three out of four index patients (75%) and in all affected (100%) relatives. Novel mutations included: a frameshift mutation in exon 4 (c.684_685insG) at codon 229 (index patient A); a frameshift mutation in exon 8 (c.1160_1170dupAGGAGCGGCCG) involving codons 387-390 (index patient B); and a missense mutation in exon 4 (c.776T > C), which substitutes leucine with proline at codon 259 (L259P) (index patient C). In the fourth index patient, a common polymorphism (D418D) was detected. This is the first report to reveal a high prevalence of novel MEN1 gene mutations among Greek MEN1 patients with apparent absence of genotype-phenotype correlation. Because of the small number of patients examined, the high prevalence detected might be a chance phenomenon

Arterial aging mediates the effect of TNF-α and ACE polymorphisms on mental health in elderly individuals: insights from IKARIA study.

Background: Aging is characterized by an insidious decline in cognitive function. Several genetic and lifestyle factors have been implicated in the increased risk or early onset of dementia. Aim: We sought to assess the role of tumor necrosis factor (TNF) and angiotensin-converting enzyme (ACE) polymorphisms on the development of impaired mental health in respect to indices of arterial aging in nonagenarian individuals. Design: 178 consecutive subjects above 75 years that permanently inhabit in the island of IKARIA, Greece were recruited. Methods: Aortic distensibility (AoD) was calculated and genetic evaluation was performed on the ACE Insertion/Deletion gene polymorphism (intron 16) and the G/A transition (position -308) of the TNF gene. Cognitive function was evaluated using the Mini-mental State Examination (MMSE). Results: The DD genotype for ACE was independently associated ( b  = -0.44, P = 0.007) with AD while AoD remained an independent determinant of mental status (OR = 1.82, P = 0.036). Interestingly though, when a combined genetic index (GI) was calculated for both genes (ACE and TNF), subjects being double homozygous (DD for ACE and GG for TNF) for these loci presented significantly decreased MMSE (adjusted OR = 0.259, P = 0.033). This GI independently associated with AD (beta coefficient = -0.785, P = 0.002). When AoD was included, GI lost its predictive role (OR = 0.784, P = 0.783) towards MMSE. AoD has marginal indirect mediating effect in the association of the GI with MMSE ( P = 0.07). Conclusion: Vascular aging may modulates the genetic substrate of elderly subjects on the risk for developing dementia