Predictors of the effects of smoking cessation on the endothelial function of conduit and digital vessels.

Smoking predisposes individuals to endothelial dysfunction. Flow-mediated dilation (FMD) and reactive hyperemia peripheral artery tonometry (RH-PAT) are used to assess endothelial function. However, whether smoking cessation demonstrates comparable effects on endothelial function evaluated by FMD and RH-PAT remains unclear. Thus, we aimed to evaluate the effects of smoking cessation on endothelial function evaluated simultaneously by FMD and RH-PAT and clarify the factors associated with these effects. Fifty-eight consecutive current smokers (mean ± standard deviation; age, 64 ± 11 years) who visited our smoking cessation outpatient department and succeeded with smoking cessation were enrolled. Twenty-one continued smokers were enrolled as age- and sex-matched controls. Clinical variables, FMD, and natural logarithmic transformation of the reactive hyperemia index (Ln-RHI) were examined before and 20 weeks after treatment initiation. In 58 smokers who succeeded with smoking cessation, FMD significantly improved (3.80 ± 2.24 to 4.60 ± 2.55%; p = 0.013), whereas Ln-RHI did not (0.59 ± 0.28 to 0.66 ± 0.22; p = 0.092). Spearman's rank correlation coefficient between changes in FMD and Ln-RHI was -0.004, and the intraclass correlation coefficient for a two-way mixed effects model was <0.001 (p = 0.499). In multivariate analysis, the presence of an increase in FMD was inversely correlated with the Brinkman index and changes in systolic blood pressure (SBP), whereas Ln-RHI was positively correlated with changes in SBP and inversely correlated with baseline body mass index. These factors may predict the varying effects of smoking cessation on the endothelial function of the conduit and digital vessels.

Predictors of endothelial function improvement in patients with mild hypertriglyceridemia without evidence of coronary artery disease treated with purified eicosapentaenoic acid.

BACKGROUND AND AIMS: Eicosapentaenoic acid (EPA) has been reported to reduce cardiovascular risk in patients with hypertriglyceridemia. Although several mechanisms underlying the effects of EPA have been demonstrated, those responsible for its beneficial role in patients with hypertriglyceridemia without evidence of coronary artery disease (CAD) have not been fully elucidated. We sought to clarify the main factors associated with EPA administration that led to improved endothelial function. METHODS: Forty-seven consecutive patients with mild hypertriglyceridemia (mean age, 59 ± 13 years) without evidence of CAD were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-four patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed between FMD changes and clinical variables. RESULTS: EPA treatment decreased triglyceride levels (from 224.6 ± 58.8 to 151.8 ± 54.5 mg/dl, p < 0.001) and increased FMD (from 4.21% ± 1.91% to 6.21% ± 2.30%, p < 0.001). Multivariate analysis showed that the change in FMD was associated with the baseline high-density lipoprotein cholesterol (HDL-C) level (ß = -0.331, p = 0.027) and the change in EPA/arachidonic acid (AA) ratio (ß = 0.301, p = 0.048). CONCLUSIONS: EPA treatment improved triglyceride levels and FMD in patients with mild hypertriglyceridemia and without evidence of CAD. The baseline HDL-C level and the change in EPA/AA ratio predicted FMD improvement. The beneficial effects of EPA on triglyceride-rich lipoproteins and vascular endothelium may help improve endothelial function.

Greater nighttime blood pressure variability is associated with left atrial enlargement in atrial fibrillation patients with preserved ejection fraction.

Left atrial enlargement is an independent risk factor for ischemic stroke in patients with atrial fibrillation. Little is known regarding the association between nighttime blood pressure variability and left atrial enlargement in patients with atrial fibrillation and preserved ejection fraction. The study population consisted of 140 consecutive patients with atrial fibrillation (mean age 64 ± 10 years) with preserved ejection fraction (≥50%). Nighttime blood pressure was measured at hourly intervals, using a home blood pressure monitoring device. Nighttime blood pressure variability was expressed as the standard deviation of all readings. Left atrial volume index was measured using the modified Simpson's biplane method with transthoracic echocardiography. Multiple regression analysis indicated that nighttime mean systolic/diastolic blood pressure and its variability remained independently associated with left atrial enlargement after adjustment for age, sex, anti-hypertensive medication class, and left ventricular mass index (P < 0.01). When patients were divided into four groups according to nighttime blood pressure and its variability, the group with higher nighttime blood pressure and its variability had significantly larger left atrial volume than the group with lower nighttime blood pressure and its variability (46.6 ml/m2 vs. 35.0 ml/m2, P < 0.0001). Higher nighttime blood pressure and its variability are associated with left atrial enlargement. The combination of nighttime blood pressure and its variability has additional predictive value for left atrial enlargement. Intensive intervention for these high-risk patients may avoid or delay progression of left atrial enlargement and reduce the risk of stroke.

Relationship between tissue Doppler measurements of left ventricular diastolic function and silent brain infarction in patients with non-valvular atrial fibrillation.

AIMS: Left ventricular (LV) diastolic function assessed by tissue Doppler imaging (TDI) is reported to be associated with left atrial (LA) blood stasis in patients with non-valvular atrial fibrillation (AF). This study aimed to evaluate the relationship of diastolic TDI parameters with silent brain infarction (SBI) on brain magnetic resonance imaging (MRI), and in turn the risks of subsequent stroke or dementia, in non-valvular AF patients. METHODS AND RESULTS: The study population consisted of 171 neurologically asymptomatic patients with non-valvular AF who underwent transoesophageal echocardiography (TOE) (128 men; mean age, 63 ± 11 years). We measured diastolic TDI parameters by transthoracic echocardiography, and also screened for SBI employing brain MRI. Early transmitral flow velocity (E) and mitral annular velocity by TDI (e') were measured, and E/e' ratios were calculated. An increased tertile of the E/e' ratio was significantly related to high prevalences of LA abnormalities detected by TOE (32% vs. 12% vs. 9%; P =0.002) and SBI on brain MRI (46% vs. 23% vs. 14%; P < 0.001). In multivariate logistic regression analyses after adjustment for age, hypertension, chronic kidney disease, and CHA2DS2-VASc score ≥2, the E/e' ratio ≥12.4 was found to be an independent predictor of the presence of SBI (OR 3.98, 95% CI 1.74-9.07; P = 0.001). CONCLUSIONS: Impaired LV diastolic function evaluated by increased E/e' ratio was closely associated with the presence of SBI independent of CHA2DS2-VASc score. TDI measurements are non-invasive and useful for risk stratification of the early stage of cerebral damages in patients with non-valvular AF.

Plaque surface irregularity and calcification length within carotid plaque predict secondary events in patients with coronary artery disease.

BACKGROUND AND AIMS: Although comprehensive risk factor modification is recommended, a uniform management strategy does not necessarily prevent secondary events in patients with coronary artery disease (CAD). Therefore, identification of high-risk patients who may benefit from more intensive interventions may improve prognosis. Carotid ultrasound can reliably identify systemic atherosclerosis, and carotid plaque and intima-media thickness (IMT) are known independent risk factors for CAD. However, it is unclear whether findings on carotid ultrasound can improve prediction of secondary CAD events. METHODS: The study population comprised 146 consecutive patients with CAD (mean age, 66 ± 9 years; 126 with angina pectoris, 20 with acute myocardial infarction). IMT, plaque score, plaque area, plaque surface irregularity, and calcification length (calculated by summing the calcified lesions within each plaque accompanied by acoustic shadow) were measured at baseline. Patients were followed for 10 years to ascertain secondary CAD events defined as hard major adverse cardiovascular events (MACE; cardiac death and acute myocardial infarction) and as total MACE (hard MACE and angina pectoris with coronary revascularization). RESULTS: Multiple regression analysis demonstrated that calcification length (p < 0.05) and plaque surface irregularity (p < 0.01) remained independently associated with total MACE after adjustment for age, sex, diabetes mellitus, dyslipidemia, hypertension, chronic kidney disease, smoking, and multivessel CAD. CONCLUSIONS: These findings suggest that the combination of calcification length and plaque surface irregularity has additional value beyond traditional risk classification. Intensive intervention for these high-risk patients may avoid or delay progression of atherosclerosis towards secondary CAD events.

Low-flow mediated constriction incorporated indices as indicators of cardiovascular risk in smokers.

BACKGROUND AND AIMS: Low-flow-mediated constriction (L-FMC), the endothelial response to reduced blood flow by forearm compression, is present in some smokers. The differences between smokers with and without L-FMC are unclear. It is also unknown whether flow-mediated total dilation (FMTD) or modified flow-mediated dilation (mFMD), both of which incorporate information concerning L-FMC, could be used to estimate cardiovascular risk. We sought to clarify the clinical factors associated with the presence of L-FMC in smokers according to sex and examine whether L-FMC incorporated indices would be better than a conventional index to estimate cardiovascular risk in smokers. METHODS: In total, 140 consecutive smokers (58 ± 13 years old) with no coronary heart disease and 48 non-smokers, who comprised the age- and sex-matched control group, were enrolled. RESULTS: L-FMC was demonstrated in 33.6% (47/140) and 25% (12/48) of the smokers and non-smokers, respectively. In male smokers, the predictors of the presence of L-FMC were age (p = 0.014), body mass index (BMI) (p = 0.045), and baseline brachial arterial diameter (Dbase) (p = 0.048). In female smokers, there were no predictors of the presence of L-FMC. The correlations between the Framingham risk score (FRS) and %FMTD (r = -0.34) and between FRS and %mFMD (r = -0.33) were stronger than that between FRS and conventional flow-mediated dilation (%cFMD) (r = -0.20). CONCLUSIONS: Independent predictors of the presence of L-FMC were age, BMI, and Dbase in male smokers. L-FMC incorporated indices may be good alternatives to cFMD to estimate cardiovascular risk.

Higher visit-to-visit intra-dialytic blood pressure is associated with the progression of aortic valve stenosis in chronic hemodialysis patients.

Aortic valve stenosis (AS) is a frequent complication contributing to poor prognosis in chronic hemodialysis (CHD) patients. High blood pressure (BP) is known to be associated with AS progression in the general population. In CHD patients, however, BP varies during and between hemodialysis sessions with ultrafiltration volume or inter-dialytic weight gain; therefore it is difficult to characterize the BP status with a conventional single measurement. Our purpose was to clarify the BP variables affecting AS progression in CHD patients. We retrospectively enrolled 32 consecutive CHD patients with AS [aortic valve area (AVA), 1.3 ± 0.3 cm(2); mean age 69 ± 8 years] who had serial transthoracic echocardiographic studies at least 6 months apart (mean 23 ± 9 months). AS progression was evaluated using absolute reduction in AVA per year. Pre-dialytic and intra-dialytic (every hour during sessions) BPs throughout the 3 consecutive visits were used to determine each patient's BP status. We calculated the mean values of pre-dialytic and intra-dialytic BPs and their variability. In univariate analysis, mean visit-to-visit pre-dialytic and intra-dialytic BP were associated with AS progression, whereas all variables of BP variability were not. Multiple regression analysis indicated that only mean visit-to-visit intra-dialytic systolic and diastolic BP remained independently associated with AS progression after adjustment for age, sex, hypertension, hypercholesterolemia, diabetes mellitus, and serum parathyroid hormone (p < 0.05). Although BP regulation in CHD patients is complex and multifactorial, mean visit-to-visit intra-dialytic BP was independently associated with AS progression. Prospective studies are necessary before considering intra-dialytic BP as a potential target for therapy.

Effects of Night Shift Work on Nighttime Blood Pressure among Healthy Young Female Medical Workers.

Background Although night shift is an independent risk factor of cardiovascular disease (CVD), the underlying mechanisms have not been understood. Nocturnal blood pressure (BP) and increased BP variability are associated with CVD. However, little is known regarding the impact of night shift on nocturnal BP variables. Methods The study population consisted of 30 healthy female medical shift workers (mean age, 28±6 years) with flexible blood vessels (mean cardio-ankle vascular index, 5.8±0.9). Nocturnal BP variables were measured after day and night shifts using a home BP monitoring device. Similarly, sleep status (total sleep time, sleep efficiency, and snoring) were measured using a noncontact radiofrequency sensor. Results Nocturnal diastolic BP variability (7.0±5.3 mm Hg vs 4.7±2.7 mm Hg; p<0.01) was significantly higher after night shift than after day shift, whereas no significant differences in systolic BP variables, mean diastolic BP, and sleep status were observed. Conclusions Among young healthy women with flexible blood vessels, night shift increased nighttime diastolic BP variability, rather than systolic BP variables independent of sleep disorder. These findings imply that increased nighttime diastolic BP variability derived from night shift might stimulate an early- stage atherosclerotic process that predisposes patients to future CVD.

Vascular Functional and Morphological Alterations in Smokers during Varenicline Therapy.

BACKGROUND: Varenicline has been reported to achieve high rates of smoking cessation. It remains undetermined whether varenicline therapy improves vascular function in smokers. METHODS: Consecutive Seventy-two smokers (age 57 ± 12 years) who succeeded in complete smoking cessation and 46 normal healthy volunteers (age 24 ± 3 years) with no cardiovascular risk factors were enrolled into this study. Vascular function and structure were assessed by flow-mediated dilation (FMD), nitroglycerin-induced vasodilation, and brachial artery intima-media thickness (baIMT) at baseline and 20 weeks after the initiation of varenicline therapy in smokers. FMD and baIMT were measured simultaneously using a semi-automatic vessel wall-tracking software program. 75 µg dose of a nitroglycerin tablet were sublingually administered for the nitroglycerin-induced vasodilation measurement. RESULTS: Exhaled-carbon monoxide concentration decreased significantly (20.0 ± 11.1 ppm at baseline vs 1.9 ± 1.5 ppm after 20 weeks, p < 0.001). FMD was significantly improved after 20 weeks (4.09% ± 1.83% at baseline vs 4.77% ± 2.33% after 20 weeks, p = 0.010), whereas nitroglycerin-induced vasodilation and baIMT were not significantly changed. CONCLUSIONS: Smoking cessation with varenicline therapy significantly increased FMD without significant changes of nitroglycerin-induced vasodilation or baIMT from baseline to 20 weeks. It appears to improve vascular function in smokers, which depends on endothelial function rather than on vascular smooth muscle function or changes in vascular structure.