Central Systolic Blood Pressure as a Risk Factor for Accelerated Progression of Arterial Stiffness.

AIMS: In the arterial tree, a pressure gradient of the systolic blood pressure (SBP) is observed from the center to the periphery, with the pressure being higher in the periphery because of pressure wave reflection. However, this gradient is attenuated, with elevation of the central SBP (cSBP), in cases with abnormal pressure wave reflection in the arterial tree. It remains unclear if increase of the cSBP might be an independent risk factor for accelerated progression of arterial stiffness. We conducted this prospective observational study using latent growth curve model (LGCM) analyses to examine if elevated cSBP might be an independent risk factor for accelerated progression of the arterial stiffness in middle-aged Japanese men. METHODS: In this 9-year prospective observational study, we analyzed the data of 3862 middle-aged Japanese men (43±10years old) without cerebrocardiovascular disease at the study baseline who had undergone repeated annual measurements of the brachial-ankle pulse wave velocity (baPWV) and cSBP, as represented by the second peak of the radial pressure waveform (SBP2) in radial pressure waveform analysis. RESULTS: During the follow-up period (6.3±2.5years), significant increases of both the baPWV and SBP2 were observed in all the subjects. Analysis using the LGCM confirmed that the SBP2, a marker of the cSBP (B=0.260, P＜0.001), was a significant determinant of the slope of the annual changes of the baPWV during the study period. CONCLUSIONS: Our finding may appear to confirm elevated cSBP as an independent risk factor for accelerated progression of the arterial stiffness in middle-aged Japanese men.

The ability of contemporary cardiologists to judge the ischemic impact of a coronary lesion visually.

BACKGROUND: Landmark trials showed that invasive pressure measurement (Fractional Flow Reserve, FFR) was a better guide to coronary stenting than visual assessment. However, present-day interventionists have benefited from extensive research and personal experience of mapping anatomy to hemodynamics. AIMS: To determine if visual assessment of the angiogram performs as well as invasive measurement of coronary physiology. METHODS: 25 interventional cardiologists independently visually assessed the single vessel coronary disease of 200 randomized participants in The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial (ORBITA). They gave a visual prediction of the FFR and Instantaneous Wave-free Ratio (iFR), denoted vFFR and viFR respectively. Each judged each lesion on 2 occasions, so that every lesion had 50 vFFR, and 50 viFR assessments. The group consensus visual estimates (vFFR-group and viFR-group) and individual cardiologists' visual estimates (vFFR-individual and viFR-individual) were tested alongside invasively measured FFR and iFR for their ability to predict the placebo-controlled reduction in stress echo ischemia with stenting. RESULTS: Placebo-controlled ischemia improvement with stenting was predicted by vFFR-group (p < 0.0001) and viFR-group (p < 0.0001), vFFR-individual (p < 0.0001) and viFR-individual (p < 0.0001). There were no significant differences between the predictive performance of the group visual estimates and their invasive counterparts: p = 0.53 for vFFR vs FFR and p = 0.56 for viFR vs iFR. CONCLUSION: Visual assessment of the angiogram by contemporary experts, provides significant additional information on the amount of ischaemia which can be relieved by placebo-controlled stenting in single vessel coronary artery disease.

Longitudinal Associations between Alcohol Intake and Arterial Stiffness, Pressure Wave Reflection, and Inflammation.

AIMS: This prospective observational study, which utilized repeated annual measurements performed over a 9-year period, applied mixed model analyses to examine age-related differences in longitudinal associations between alcohol intake and arterial stiffness, pressure wave reflection, and inflammation. METHODS: In 4016 middle-aged (43±9 years) healthy Japanese male employees, alcohol intake, brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), and serum C-reactive protein (CRP) levels were measured annually during a 9-year study period. RESULTS: The estimated marginal mean baPWV (non-drinkers=1306 cm/s, mild-moderate drinkers=1311 cm/s, and heavy drinkers=1337 cm/s, P＜0.01) and that of rAI showed significant stepped increases in an alcohol dose-dependent manner in the entire cohort, but an increase in rAI was not observed in subjects aged ≥ 50 years. The estimated slope of the annual increase in baPWV, but not rAI, was higher for heavy drinkers than for non-drinkers (slope difference, 1.84; P＜0.05), especially for subjects aged ＜50 years (slope difference, 2.84; P＜0.05). CONCLUSION: In middle-aged male Japanese employees, alcohol intake may attenuate inflammatory activity. While alcohol intake may exacerbate the progression of arterial stiffening in a dose-dependent manner without mediating inflammation, especially in subjects under 50 years of age, it may promote pressure wave reflection abnormalities with aging at earlier ages without further exacerbation at older ages.

Association of the severity of vascular damage with discordance between the fractional flow reserve and non-hyperemic pressure ratios.

BACKGROUND: While there is a discordance between fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPRs) in some cases, the mechanisms underlying these discordances have not yet been fully clarified. We examined whether vascular damage as assessed by measurement of the brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, or ankle brachial pressure index (ABI), a marker of atherosclerotic arterial stenosis, might be associated with their discordances. METHODS: FFR and NHPRs were measured in 283 consecutive patients (69 ±â€¯10 years old). Based on previously established cut-off values of the two markers (i.e. +/- = FFR ≤/> 0.80 or =NHPRs ≤/> 0.89), the study participants were divided into four groups (the + and - signs denoting "predictive of significant stenosis" and "not predictive of significant stenosis," respectively): the FFR+/NHPRs+ group (n = 124), FFR-/NHPRs+ group (n = 16), FFR+/NHPRs- group(n = 65), and FFR-/NHPRs- group (n = 78). The baPWV and ABI were also measured in all the participants, and values of <2000 cm/s and ≥1.00 of the baPWV and ABI, respectively, were considered as representing relatively less advanced atherosclerotic systemic vascular damage. RESULTS: The prevalence of subjects with ABI ≥1.00 was higher in the FFR+/NHPRs- group than in the FFR-/NHPRs- group (p < 0.05). When the study subjects were divided into 2 groups, namely, the FFR+/NHPRs- group and the combined group, the prevalence of ABI ≥1.00 and that of baPWV <2000 cm/s were higher in the FFR+/NHPRs- group as compared with those in the combined group (p < 0.05). The results of binary logistic regression analysis demonstrated that ABI ≥1.00 was associated with a significant odds ratio (2.34, p < 0.05) for the FFR+/NHPRs- discordance. CONCLUSION: The FFR+/NHPRs- discordance appears to be observed in patients with relatively less advanced atherosclerotic systemic vascular damage. Thus, ABI ≥1.00 may be a marker of the presence of the FFR+/NHPRs- discordance.

Lifelong Heterogeneous Contribution of Cardiovascular Risk Factors to Slow and Fast Progression of Arterial Stiffness.

BACKGROUND: Although some cardiovascular risk factors (CVRFs) are known to be associated with increased arterial stiffness, increased arterial stiffness does not mediate the cardiovascular risk associated with all CVRFs. Here, based on long-term repeated-measurement data, we examined the association of the lifelong status of each CVRF with the rate of progression of arterial stiffness. METHODS: We utilized the data from annual health checkups with the brachial-ankle pulse wave velocity measurements over a 16-year period in middle-aged Japanese occupational cohort. RESULTS: Totally, 29 090 brachial-ankle pulse wave velocity data were obtained during the follow-up of 3763 subjects ranging in age from around 30 to 70 years. Smoking, heavy alcohol intake, hypertension, diabetes, hypertriglyceridemia, and hyperuricemia were independently associated with the fast progression of arterial stiffness. Also, lower values in nondisease range in blood pressure, glycosylated hemoglobin A1c, triglyceride, and uric acid were independently associated with the slow progression of arterial stiffness. For body mass index and low-density lipoprotein cholesterol, no clear associations with the progression of arterial stiffness were observed. CONCLUSIONS: The present prospective study provided more robust epidemiological evidence for the heterogeneity of the significance of contribution of lifelong status of each CVRF to the slow and fast rate of progression of arterial stiffness. These findings suggest the important need to examine, in further studies, the effects of global early interventions to control the levels of the culprit CVRFs, even from middle age, not only to prevent a fast progression of the arterial stiffness but also to maintain a relatively slow progression of arterial stiffness.

Nutritional Status and Sleep Quality Are Associated with Atrial Fibrillation in Patients with Obstructive Sleep Apnea: Results from Tokyo Sleep Heart Study.

The prevalence of obstructive sleep apnea (OSA) in patients with atrial fibrillation (AF) has been observed to be much higher than in control participants without AF. Limited data exist regarding the prevalence of AF in patients with OSA. The clinical characteristics, nutritional status, and sleep parameters associated with AF in patients with OSA remain unclear. In this study, we aimed to determine the prevalence and factors associated with AF in patients with OSA from a large Japanese sleep cohort (Tokyo Sleep Heart Study). This was a single-center explorative cross-sectional study. Between November 2004 and June 2018, we consecutively recruited 2569 patients with OSA who underwent an overnight full polysomnography at our hospital. They were assessed using a 12-lead ECG and echocardiography. The clinical characteristics, sleep parameters, and medical history were also determined. Of the OSA patients, 169 (6.6%) had AF. Compared with the non-AF patients, OSA patients with AF were older and male, and they had higher prevalence of a history of alcohol consumption, hypertension, chronic kidney disease, and undernutrition, as well as a reduced ejection fraction. With regard to the sleep study parameters, OSA patients with AF had reduced slow-wave sleep and sleep efficiency, as well as higher periodic limb movements. There were no significant differences in the apnea-hypopnea index or hypoxia index between the two groups. The logistic regression analysis demonstrated that age (OR = 4.020; 95% CI: 1.895-8.527; p < 0.001), a history of alcohol consumption (OR = 2.718; 95% CI: 1.461-5.057; p = 0.002), a high CONUT score (OR = 2.129; 95% CI: 1.077-4.209; p = 0.030), and reduced slow-wave sleep (OR = 5.361; 95% CI: 1.505-19.104; p = 0.010) were factors significantly related to AF. The prevalence of AF in patients with OSA was 6.6%. Age, a history of alcohol consumption, undernutrition, and reduced sleep quality were independent risk factors for the presence of AF in patients with OSA, regardless of the severity of OSA.

Bidirectional Longitudinal Relationships Between Arterial Stiffness and Hypertension Are Independent of Those Between Arterial Stiffness and Diabetes: A Large-Scale Prospective Observational Study in Employees of a Japanese Company.

Background Hypertension and diabetes frequently coexist; however, it has not yet been clarified if the bidirectional longitudinal relationships between arterial stiffness and hypertension are independent of those between arterial stiffness and diabetes. Methods and Results In this 16-year prospective observational study, 3960 middle-aged employees of a Japanese company without hypertension/diabetes at the study baseline underwent annual repeated measurements of blood pressure, serum glycosylated hemoglobin A1c levels, and brachial-ankle pulse wave velocity. By the end of the study period, 664, 779, 154, and 406 subjects developed hypertension, prehypertension, diabetes, and prediabetes, respectively. Increased brachial-ankle pulse wave velocity at the baseline was associated with a significant odds ratio (per 1 SD increase) for new onset of prehypertension/hypertension with (2.45/3.28; P<0.001) or without (2.49/2.76; P<0.001) coexisting prediabetes/diabetes, but not for new onset of prediabetes/diabetes without coexisting hypertension. Analyses using the latent growth curve model confirmed the bidirectional relationships between brachial-ankle pulse wave velocity and hypertension, but no such relationship was observed between brachial-ankle pulse wave velocity and abnormal glucose metabolism. Conclusions In middle-aged employees of a Japanese company, while bidirectional relationships were found to exist between increased arterial stiffness and hypertension, such a relationship was not found between increased arterial stiffness and diabetes. Therefore, it appears that increased arterial stiffness may be associated with the development of hypertension but not with that of diabetes.

Longitudinal Association of Arterial Stiffness and Pressure Wave Reflection with Decline of the Cardiac Systolic Performance in Healthy Men.

AIMS: This prospective observational study aimed to examine the individual longitudinal associations of the increases in the arterial stiffness and pressure wave reflection with the decline in the cardiac systolic performance during the study period in healthy middle-aged Japanese men. METHODS: In 4016 middle-aged Japanese healthy men (43±9 years), the brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), and pre-ejection period/ejection time (pre-ejection period (PEP)/ET) were measured annually during a 9-year study period. RESULTS: The baPWV, rAI, and PEP/ET showed steady annual increases during the study period. According to the results of multivariate linear regression analyses, both the baPWV and rAI measured at the baseline showed significant independent associations with the PEP/ET measured at the baseline (baPWV: beta=0.17, p＜0.01 and rAI: beta=0.11, p＜0.01), whereas neither showed any association with the PEP/ET measured at the end of the study period. The results of the mixed-model linear regression analysis of the repeated-measures data collected over the 9-year study period revealed that the baPWV, but not the rAI, showed a significant longitudinal association with the PEP/ET (estimate=0.69 x 10-4, p＜0.01). CONCLUSION: In apparently healthy middle-aged Japanese men, the annual increase of the arterial stiffness, rather than the annual increase of the pressure wave reflection, appears to be more closely associated with the annual decline of the cardiac systolic performance as assessed by the systolic time interval.

Association of pulse wave velocity and pressure wave reflection with the ankle-brachial pressure index in Japanese men not suffering from peripheral artery disease.

BACKGROUND AND AIMS: We examined the cross-sectional and longitudinal association of arterial stiffness and pressure wave reflection with the ankle-brachial pressure index (ABI) in middle-aged Japanese subjects free of peripheral artery disease (PAD). METHODS: ABI, brachial-ankle pulse wave velocity (baPWV) and radial augmentation index (rAI) were measured annually during the 9-year observation period in 3066 men (42 ± 9 years old) with ABI ≥1.00 at baseline of the study period, and not taking any antihypertensive medication. RESULTS: In the cross-sectional assessments, mediation analysis demonstrated that baPWV showed both direct and indirect (via the rAI) associations with ABI, and rAI showed both direct and indirect (via the heart-arm difference of systolic blood pressure) associations with the ankle-arm difference of systolic blood pressure, both at study baseline and end of study period. Mixed model linear regression analysis of the repeated-measurement data obtained over the 9-year observation period demonstrated that annual increase of baPWV (estimate = 0.73 × 10-4, p < 0.01) and rAI (estimate = 0.33 × 10-3, <0.01) was associated with ABI. When baPWV and rAI were entered into the same model, only baPWV showed a significant longitudinal association with ABI. CONCLUSION: In middle-aged Japanese men free of PAD, arterial stiffness may contribute to ABI directly and via pressure wave reflection. Pressure wave reflection may contribute to ABI directly and, at least in part, via attenuation of peripheral pulse pressure amplification.

Mediation of Arterial Stiffness for Hyperuricemia-Related Decline of Cardiac Systolic Function in Healthy Men.

Background: This prospective observational study examined whether hyperuricemia may be associated with impaired left ventricular (LV) systolic function and increased cardiac load resulting from increased arterial stiffness. Methods and Results: In 1,880 middle-aged (mean [±SD] age 45±9 years) healthy men, serum uric acid (UA) levels, pre-ejection period/ejection time (PEP/ET) ratio, serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and brachial-ankle pulse wave velocity (baPWV) were measured at the start and end of the 3-year study period. Linear regression analysis revealed that serum UA levels measured at baseline were significantly associated with the PEP/ET ratio, but not with serum NT-proBNP levels, measured at baseline (ß=0.73×10-1, P<0.01) and at the end of the study period (ß=0.68×10-1, P<0.01). The change in the PEP/ET ratio during the study period was significantly greater in the High-UA (UA >7 mg/dL in 2009 and 2012) than Low-UA (UA ≤7 mg/dL in 2009 and 2012) group. Mediation analysis demonstrated both direct and indirect (via increases in baPWV) associations between serum UA measured at baseline and the PEP/ET ratio measured at the end of the study period. Conclusions: In healthy middle-aged Japanese men, hyperuricemia may be associated with an accelerated decline in ventricular systolic function, both directly and indirectly, via increases in arterial stiffness.

Heart rate modulates the relationship of augmented systolic blood pressure with the blood natriuretic peptide levels.

AIMS: Augmented central systolic blood pressure (cSBP), which is known to affect the cardiac afterload, is an independent risk factor for cardiovascular disease. While an inverse relationship is known to exist between the heart rate (HR) and the cSBP, it has not yet been clarified if the HR also modulates the association between the cSBP and the cardiac afterload. The present study was conducted to clarify whether the association of the cSBP with the serum levels of the N-terminal fragment B-type natriuretic peptide (NT-proBNP) differs between subjects with high and low HRs, using data obtained from the same subjects on two occasions (2009 and 2012) so as to confirm their consistency. METHODS AND RESULTS: The radial augmentation index, systolic pressure at the second peak of the radial pressure waveform (SBP2), and serum NT-proBNP levels were measured and analysed in a worksite cohort of 2000 middle-aged men in 2009 and in 2012. The subjects were divided into three groups by the HR (i.e. ≤69, 70-79, and ≥80 b.p.m.). While the serum NT-proBNP levels were similar among the three groups, the radial augmentation index increased (from 61 ± 12% to 72 ± 13%, P < 0.01 in 2009 and from 61 ± 13% to 73 ± 12%, P < 0.01 in 2012) and the SBP1-2 decreased (from 18 ± 7 to 13 ± 7 mmHg, P < 0.01 in 2009 and from 19 ± 7 to 13 ± 6 mmHg, P < 0.01 in 2012) significantly with decreasing HR. After the adjustment, the SBP2 showed a significant association with the serum NT-proBNP levels in the overall study population [non-standardized coefficient (B) = 0.005, standard error (SE) = 0.001, P < 0.01 in 2009 (n = 2257) and B = 0.004, SE = 0.001, P < 0.01 in 2012 (n = 1986)]. In subgroup analyses, the SBP2 showed a significant association with the serum NT-proBNP levels [B = 0.004, SE = 0.002, P = 0.02 in 2009 (n = 1291) and B = 0.005, SE = 0.001, P < 0.01 in 2012 (n = 1204)] only in the subject group with an HR of ≤69 b.p.m. CONCLUSIONS: In middle-aged Japanese men, the relationship between the cSBP and the cardiac afterload appears to differ depending on the HR; the results of our analysis showed that the relationship between the cSBP and the cardiac overload may be more pronounced and strongly significant in patients with low HRs as compared with patients with high HRs.

A case report of myocardial ischemia improvement despite early bypass graft occlusion: Efficiency of physiological reassessment.

Patients with functional ischemia often do not complain of chest symptoms even in early occlusion after coronary artery bypass grafting (CABG). The clinical evidence indicating the necessity of revascularization for these patients is unclear. A 70-year-old man who underwent 3 stent implant procedures to treat repeated in-stent restenosis to the left anterior descending artery (LAD) felt effort-related chest pain. Coronary angiography revealed that the patient's jailed diagonal had severe stenosis with delay and the LAD had intermediate stenosis. The instantaneous wave-free ratio (iFR) value of the LAD equalled 0.75. The patient underwent sequential CABG, where the left internal mammary artery (LIMA) to the LAD and diagonal artery grafts were performed. Although his effort-related chest pain disappeared, coronary and bypass angiography did not show flow competition in the diagonal branch and early occlusion in the LIMA to LAD graft was confirmed. The physiological assessment of the LAD did not reveal myocardial ischemia (iFR = 0.89 and fractional flow reserve = 0.87). This case highlights the importance of physiological assessment to detect cases of early graft occlusion. Although the LAD was not perfused from the CABG, the iFR value improved dramatically and pharmacological therapy without revascularization was successful for this patient. .