Monitoring of cerebral oximetry during head-up tilt test in adults with history of syncope and orthostatic intolerance.

Aims: We applied near-infrared-spectroscopy (NIRS) to measure absolute frontal cerebral tissue oxygen saturation (SctO2) during head-up tilt test (HUT) in patients investigated for unexplained syncope. Methods and results: Synchronized non-invasive beat-to-beat haemodynamic monitoring, ECG, SctO2 (NIRS; normal range: 60-80%), and peripheral oxygen saturation (left hand, SpO2) were applied during HUT in a random sample of patients with unexplained syncope. Tracings of 54 patients (mean-age: 55 ± 19 years, 39% male) with negative HUT, vasovagal syncope (VVS), or orthostatic hypotension (OH) were analysed. In 44 patients HUT was diagnostic, in 10 HUT was negative. Thirty-one experienced VVS. Of these, 6 had spontaneous and 25 nitroglycerin-induced syncope. Thirteen patients had orthostatic hypotension (OH). Although there was no significant change in mean-arterial pressure from baseline to 1 min before syncope or end of passive HUT phase (-1.4 ± 13.9 mmHg; P = 0.45), there was a significant fall in SctO2 during the same period (-3.2 ± 3.2%; P ≤ 0.001). Among patients who experienced syncope, a decrease in SctO2 from 71 ± 5% at baseline to 53 ± 9% (P < 0.001) at syncope was observed. During HUT, there was a significant difference in delta SctO2 between spontaneous VVS (-4.5 ± 3.0%) and negative HUT (-1.3 ± 1.9%; P = 0.021), but not between spontaneous VVS and OH (-5.4 ± 4.2%; P = 0.65). In spontaneous VVS, progressive decrease of SctO2 was independent of mean arterial pressure decrease (P = 0.22). Conclusions: Progressive decrease in cerebral tissue oxygenation independent of mean-arterial pressure may precede spontaneous vasovagal reflex during tilt. Patients experience syncope when SctO2 falls below 60%. These data confirm clinical utility of absolute cerebral oximetry monitoring for syncope investigation. We applied NIRS to measure frontal cerebral tissue oxygen saturation (SctO2) during head-up tilt test (HUT) in patients with unexplained syncope. In 44 of 54 patients, HUT was diagnostic. In patients with syncope, a significant SctO2-decrease was observed. Different patterns of SctO2 can be detected.

Gene variance in the nicotinic receptor cluster (CHRNA5-CHRNA3-CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers.

BACKGROUND: Genetic variation in the cluster on chromosome 15, encoding the nicotinic acetylcholine receptor subunits (CHRNA5-CHRNA3-CHRNB4), has shown strong associations with tobacco consumption and an additional risk increase in smoking-related diseases such as chronic obstructive pulmonary disease (COPD), peripheral artery disease and lung cancer. OBJECTIVES: To test whether rs1051730 (C/T), a tag for multiple variants in the CHRNA5-CHRNA3-CHRNB3 cluster, is associated with a change in risk of smoking-related mortality and morbidity in the Malmö Diet and Cancer study, a population-based prospective cohort study. METHODS: At baseline participants were classified as current (n = 6951), previous (n = 8426) or never (n = 9417) smokers. Cox-proportional hazards models were used to determine the correlation between rs1051730 and incidence of first COPD, tobacco-related cancer, other cancer and cardiovascular disease (CVD), and total mortality due to these causes, during approximately 14 years of follow-up. RESULTS: Amongst current smokers there were 480 first incident COPD events, 852 tobacco-related cancers, 810 other cancers and 1022 CVD events. A total of 1508 deaths occurred, including 500 due to CVD, 102 due to respiratory diseases and 677 due to cancer. In adjusted additive models, an increasing number of T alleles were associated with a gradual increase in total mortality, incident COPD and tobacco-related cancer, even after adjustment for smoking quantity. No significant associations were observed amongst never smokers. CONCLUSION: Our data suggest that gene variance in the CHRNA5-CHRNA3-CHRNB4 cluster is associated with an increased risk of death, incidence of COPD and tobacco-related cancer in smokers. These findings indicate an individual susceptibility to tobacco use and its complications; this may be important when targeting and designing smoking cessation therapies.

A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis.

OBJECTIVE: To assess whether or not a genetic risk score that was previously shown to be associated with myocardial infarction (MI) and coronary artery disease (CAD) is also associated with markers of carotid atherosclerosis. DESIGN: A total of 4022 middle-aged subjects from the general Swedish population were genotyped and individually assigned a genetic risk score based on 13 single-nucleotide polymorphisms (SNPs), previously associated with MI and CAD. The genetic score (Score-MI) was then related to carotid bulb intima-media thickness (IMT), common carotid artery (CCA) IMT and to the occurrence of carotid plaques in the study population. RESULTS: Score-MI was associated with IMT of the bulb (P < 0.001) and the CCA (P < 0.001) in unadjusted analyses, and with IMT of the bulb after adjustment for cardiovascular risk factors (P = 0.003). The effect size of Score-MI on IMT of the bulb was similar to that of LDL cholesterol. After adjustment for cardiovascular risk factors, Score-MI was also associated with the occurrence of carotid plaques (odds ratio per quintile of Score-MI = 1.11; 95% confidence interval 1.04-1.18; P = 0.001). In addition to SNPs with known effects on LDL levels, Score-MI showed nominal associations with increasing systolic blood pressure and decreasing C-reactive protein levels. CONCLUSIONS: This genetic risk score was independently associated with carotid bulb IMT and carotid plaques, providing evidence of an association with early markers of atherosclerosis. This might imply that the genetic MI risk conferred by the score is related to early atherosclerosis and that the risk score may identify at an early stage candidates at risk of developing intermediate phenotypes of atherosclerosis. Further studies should test whether or not assessing the genetic score could be valuable for early treatment decisions in these subjects.