Citations

Vascular reactivity may affect the stiffness characteristics of the arterial wall. We investigated the association between forearm microcirculatory and conduit artery function and measures of arterial stiffness in 527 asymptomatic non-Hispanic white adults without known cardiovascular disease. High-resolution ultrasonography of the brachial artery (ba) was performed to assess forearm microcirculatory function (ba blood flow velocity, local shear stress, and forearm vascular resistance at rest and during reactive hyperemia) and conduit artery function (ba flow-mediated dilatation [baFMD] and ba nitroglycerin-mediated dilatation [baNMD]). Arterial stiffness was assessed by cuff-derived brachial pulse pressure and aortic pulse wave velocity (aPWV) measured by applanation tonometry. In regression analyses that adjusted for heart rate, mean arterial pressure, height, cardiovascular risk factors, and hypertension medication and statin use, higher baseline ba systolic velocity and systolic shear stress were associated with greater pulse pressure ( P =0.0002 and P =0.006, respectively) and higher aPWV (each P <0.0001). During hyperemia, lower ba mean velocity and lower mean shear stress were associated with higher pulse pressure ( P =0.045 and P =0.036, respectively), whereas both systolic and mean velocity ( P <0.0001 and P =0.002, respectively) and systolic and mean shear stress ( P <0.0001 and P =0.003, respectively) were inversely associated with aPWV. baFMD was not associated with pulse pressure but was inversely associated with aPWV ( P =0.011). baNMD was inversely associated with pulse pressure ( P =0.0002) and aPWV ( P =0.008). Our findings demonstrate that impaired forearm microvascular function (in the form of elevated resting blood flow velocity and impaired flow reserve) and impaired brachial artery reactivity are associated with increased arterial stiffness.

Background— Previous studies that assessed the risk of life-threatening cardiac events in patients with congenital long-QT syndrome (LQTS) have focused mainly on the first 4 decades of life, whereas the clinical course of this inherited cardiac disorder in the older population has not been studied. Methods and Results— The risk of aborted cardiac arrest or death from age 41 though 75 years was assessed in 2759 subjects from the International LQTS Registry, categorized into electrocardiographically affected (corrected QT interval [QTc] ≥470 ms), borderline (QTc 440 to 469 ms), and unaffected (QTc <440 ms) subgroups. The affected versus unaffected adjusted hazard ratio for aborted cardiac arrest or death was 2.65 ( P <0.001) in the age range of 41 to 60 years and 1.23 ( P =0.31) in the age range of 61 to 75 years. The clinical course of study subjects displayed gender differences: Affected LQTS women experienced a significantly higher cumulative event rate (26%) than borderline (16%) and unaffected (12%) women ( P =0.001), whereas event rates were similar among the 3 respective subgroups of men (29%, 26%, and 27%; P =0.16). Recent syncope (<2 years in the past) was the predominant risk factor in affected subjects (hazard ratio 9.92, P <0.001), and the LQT3 genotype was identified as the most powerful predictor of outcome in a subset of 871 study subjects who were genetically tested for a known LQTS mutation (hazard ratio 4.76, P =0.02). Conclusions— LQTS subjects maintain a high risk for life-threatening cardiac events after age 40 years. The phenotypic expression of affected subjects is influenced by age-specific factors related to gender, clinical history, and the LQTS genotype.

Background— The congenital long-QT syndrome (LQTS) is an important cause of sudden cardiac death in children without structural heart disease. However, specific risk factors for life-threatening cardiac events in children with this genetic disorder have not been identified. Methods and Results— Cox proportional-hazards regression modeling was used to identify risk factors for aborted cardiac arrest or sudden cardiac death in 3015 LQTS children from the International LQTS Registry who were followed up from 1 through 12 years of age. The cumulative probability of the combined end point was significantly higher in boys (5%) than in girls (1%; P <0.001). Risk factors for cardiac arrest or sudden cardiac death during childhood included corrected QT interval [QTc] duration >500 ms (hazard ratio [HR]; 2.72; 95% confidence interval [CI], 1.50 to 4.92; P =0.001) and prior syncope (recent syncope [<2 years]: HR, 6.16; 95% CI 3.41 to 11.15; P <0.001; remote syncope [≥2 years]: HR, 2.67; 95% CI, 1.22 to 5.85; P =0.01) in boys, whereas prior syncope was the only significant risk factor among girls (recent syncope: HR, 27.82; 95% CI, 9.72 to 79.60; P <0.001; remote syncope: HR, 12.04; 95% CI, 3.79 to 38.26; P <0.001). β-Blocker therapy was associated with a significant 53% reduction in the risk of cardiac arrest or sudden cardiac death ( P =0.01). Conclusions— LQTS boys experience a significantly higher rate of fatal or near-fatal cardiac events than girls during childhood. A QTc duration >500 ms and a history of prior syncope identify risk in boys, whereas prior syncope is the only significant risk factor among girls. β-Blocker therapy is associated with a significant reduction in the risk of life-threatening cardiac events during childhood.