Decreased role of neuropeptides in the microvascular function in migraine patients with polycystic ovary syndrome.

BACKGROUND AND AIMS: To understand pathophysiological mechanisms underlying migraine as a cardiovascular risk factor, we studied neuropeptide action and endothelial function as measures of peripheral microvascular function in middle-aged women with or without migraine. METHODS: We included women with the endocrine disorder polycystic ovary syndrome (PCOS), a population with supposed elevated cardiovascular risk, with and without comorbid migraine. In 26 women without and 23 women with migraine in the interictal phase (mean age 50.8 ± 2.9 years) local thermal hyperemia (LTH) of the skin of the volar forearm was measured cross-sectionally under control conditions, after inhibition of neuropeptide release by 5% lidocaine/prilocaine (EMLA) cream application, and after inhibition of nitric oxide formation by iontophoresis of NG-monomethyl-l-arginine (L-NMMA). Hereafter, changes in the natural logarithm of the reactive hyperemia index (lnRHI) and augmentation index (AI) during reperfusion after occlusion-derived ischemia were measured. RESULTS: While mean values under control conditions and L-NMMA conditions were similar, migraine patients had a significantly higher mean area of the curve (AUC) of the total LTH response after EMLA application than those without (86.7 ± 26.5% versus 67.9 ± 24.2%; p = 0.014). This was also reflected by a higher median AUC of the plateau phase under similar conditions in women with migraine compared to those without (83.2% (IQR[73.2-109.5]) versus 73.2% (IQR[54.3-92.0]); p = 0.039). Mean changes in lnRHI and AI scores were similar in both groups. CONCLUSIONS: In PCOS patients with migraine, neuropeptide action was lower compared with those without migraine. While larger studies are warranted, these findings provide a potential mechanism supporting previous findings that migraine may be independent from traditional risk factors, including atherosclerosis.

Trigeminovascular effects of propranolol in men and women, role for sex steroids.

OBJECTIVE: Assess whether propranolol modulates the trigeminovascular system in both men and women. METHODS: We investigated the effect of propranolol (80 mg, 90 min after oral administration, corresponding to Tmax ) on the increase in dermal blood flow of the forehead skin (innervated by the trigeminal nerve) by capsaicin application (0.6 mg/mL) and electrical stimulation (0.2-1.0 mA) before and after placebo (grapefruit juice) or propranolol (oral solution diluted in grapefruit juice) in a randomized, double-blind, placebo-controlled cross-over study, including healthy males (n = 10) and females on contraceptives (n = 11). Additionally, we compared our results with data from the Dutch IADB.nl prescription database by analyzing the change in triptan use after propranolol prescription in a population similar to our dermal blood flow study subjects (males and females, 20-39 years old). RESULTS: Dermal blood flow responses to capsaicin were significantly attenuated after propranolol, but not after placebo. When stratifying by sex, no significant changes in the capsaicin-induced dermal blood flow were observed in females after propranolol, whereas they remained significant in males. Dermal blood flow responses to electrical stimulation were not modified in any case. In our prescription database study, after propranolol, a more pronounced decrease in triptan use was observed in male patients than in female patients. INTERPRETATION: Propranolol (80 mg) inhibits capsaicin-induced increases in dermal blood flow in a sex-dependent manner. In patients, a more pronounced decrease in triptan use is observed in males when compared with females, suggesting an interaction between propranolol and sex steroids in the modulation of the trigeminovascular system.

Diagnosis of left ventricular hypertrophy using non-ECG-gated 15O-water PET.

AIM: To develop a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET). METHODS: We retrospectively pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n = 197) were performed with three different PET devices. A low-end scanner (66 scans) was used for method development, and remaining scans with newer devices for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall and calculation of LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n = 47) and WT to 2D-echocardiography (2DE, n = 36). PET accuracy was tested using linear regression, Bland-Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients. RESULTS: High correlations were found in the blinded analyses (r ≥ 0.87, P < 0.0001 for all). AUC for detecting increased LVM and WT (> 12 mm and > 15 mm) was ≥ 0.95 (P < 0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P < 0.0001). CONCLUSION: 15O-water PET might detect LV hypertrophy with high accuracy and precision.

Effects of successful percutaneous coronary intervention of chronic total occlusions on myocardial perfusion and left ventricular function.

AIMS: The aim of the present study was to investigate the effects of successful PCI CTO on absolute myocardial blood flow (MBF) and functional recovery. METHODS AND RESULTS: Patients with a documented CTO were prospectively examined for ischaemia and viability with [15O]H2O positron emission tomography (PET) and late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR). Sixty-nine consecutive patients, in whom PCI was successful, underwent follow-up PET and CMR after approximately 12 weeks to evaluate potential improvement of MBF as well as systolic function. After PCI, stress MBF in the CTO area increased from 1.22±0.36 to 2.40±0.90 mL·min-1·g-1 (p<0.001), whilst stress MBF in the remote area also increased significantly between baseline and follow-up PET (2.58±0.68 to 2.77±0.77 mL·min-1·g-1, p=0.01). The ratio of stress MBF between CTO and remote area was 0.49±0.13 at baseline and increased to 0.87±0.24 at follow-up (p<0.001). The MBF defect size of the CTO area decreased from 5.12±1.69 to 1.91±1.75 myocardial segments after PCI (p<0.001). Left ventricular ejection fraction (LVEF) increased significantly (46.4±11.0 vs. 47.5±11.4%, p=0.01) at follow-up. CONCLUSIONS: The vast majority of CTO patients with documented ischaemia and viability showed significant improvement in stress MBF and a reduction of ischaemic burden after successful percutaneous revascularisation with only minimal effect on LVEF.