Inverse association between obesity and aortic pressure augmentation is attenuated in women: the Wakuya study.

OBJECTIVE: Pressure wave reflection predicts cardiovascular events in the general population. Obesity is negatively associated with pressure wave reflection. Muscular arterial diameter (responsible for pressure wave reflection) increases with obesity, and obesity-dependent dilation of muscular arteries is attenuated in women compared with men. We investigated the sex differences in the cross-sectional relationship between obesity and pressure wave reflection in a general population cohort. METHODS: Tonometric pressure waveforms were recorded in 928 adults (mean age, 56 ±â€Š10 years) to estimate the aortic augmentation index. The BMI was calculated using height and body weight, and waist circumference was recorded at the umbilical level. RESULTS: Aortic augmentation index was significantly higher in women than in men. Indices of obesity (BMI and waist circumference) were negatively correlated with the aortic augmentation index in both men and women, even after adjusting for mean arterial pressure (both P  < 0.001). Sex and BMI had no synergistic effect on the aortic augmentation index. However, when waist circumference was substituted for BMI, sex and waist circumference had a reciprocal influence on decreasing the aortic augmentation index independent of age, mean arterial pressure, diabetes, and hyperlipidemia (interaction, P  = 0.045). CONCLUSION: The negative correlation between overweight/obesity and aortic pressure augmentation from peripheral wave reflection is inhibited in women more than in men. Sex differences in aortic pressure augmentation are greater in individuals with central (abdominal) obesity than in those with general obesity.

Being overweight worsens the relationship between urinary sodium excretion and albuminuria: the Wakuya study.

BACKGROUND/OBJECTIVES: (Micro)albuminuria (a manifestation of renal microvascular damage) is an independent predictor of mortality risk, even when the urinary albumin/creatinine ratio is ≥ 10 mg/g in the general population. Excessive sodium intake and obesity are strong predictors of cardiovascular disease. However, the effect of obesity on the relationship between sodium intake and albuminuria is not fully understood. SUBJECTS/METHODS: The purpose of the present study was to investigate the cross-sectional relationships among dietary sodium intake, obesity, and albuminuria in a general population cohort. Subjects were 928 apparently healthy adults. Body mass index was calculated using the height and body weight. Urinary sodium/creatinine and albumin/creatinine ratios were measured in spot urine samples. Estimated 24-h urinary sodium/creatinine ratio (e24UNa/Cr) was assessed using age, height, body weight, and spot urinary sodium/creatinine ratio. RESULTS: Both the body mass index and e24UNa/Cr positively correlated with the urinary albumin/creatinine ratio (both, P < 0.001), and had a synergistic effect on increasing urinary albumin/creatinine ratio independent of age, sex, mean arterial pressure, and diabetes (interaction P = 0.04). When subjects were divided into 6 groups according to the tertiles of e24UNa/Cr and body mass index < (normal-weight) or ≥ 25 (overweight), the prevalence rate of urinary albumin/creatinine ratio ≥ 10 mg/g increased with rising e24UNa/Cr and being overweight (P < 0.001). CONCLUSION: An increase in body mass index increases the positive association between urinary sodium excretion and (micro)albuminuria in the general population. Excess sodium intake may strengthen cardiovascular risk by increasing (micro)albuminuria, particularly in overweight individuals.

Aortic diastolic pressure decay explains sex-related differences in the subendocardial viability ratio: the Wakuya study.

OBJECTIVE: Coronary heart disease is the leading cause of mortality in women. Despite a higher risk of heart failure after the first myocardial infarction in women compared with men, the sex-specific mechanisms are unknown. We hypothesized that myocardial ischemia is attributable to sex-related diastolic alterations in the central hemodynamics. METHODS: We investigated the subendocardial viability ratio (myocardial oxygen supply/demand) and aortic diastolic pressure decay index in 962 apparently healthy adults (mean age, 56 ±â€Š10 years). Using noninvasive applanation tonometry, the subendocardial viability ratio, aortic diastolic pressure decay index, and aortic augmentation index were estimated in all participants. The aortic diastolic pressure decay index was quantified by fitting an exponential curve: P(t) = P0e-λt (λ, decay index; P0, end-systolic pressure; t, time from end-systole). RESULTS: Women showed a significantly higher aortic diastolic pressure decay index, even after adjusting for age, hypercholesterolemia, and diabetes, and a significantly lower subendocardial viability ratio than men (P < 0.001). Analysis demonstrated a mediating effect of the aortic decay index on the sex-related differences in the subendocardial viability ratio (71%), despite different effects of the augmentation index (5%). CONCLUSION: These results suggest that the predisposition of women to coronary heart disease is more likely attributable to impaired myocardial perfusion caused by accelerated aortic diastolic pressure decay, rather than increased myocardial load due to augmented aortic systolic pressure.

Central-to-peripheral stiffness gradients determine diastolic pressure and flow fluctuation waveforms: time domain analysis of femoral artery pulse.

OBJECTIVE: Blood pressure fluctuates during diastole to create a dicrotic wave but the mechanistic origin remains poorly understood. We sought to investigate the characteristics and determinants of diastolic pressure and flow fluctuations with a focus on stiffness gradients between the central aorta and peripheral arteries. METHODS: Using applanation tonometry and duplex ultrasound, pulse waveforms were recorded on the femoral artery in 592 patients (age: 55 ±â€Š14 years) to estimate the diastolic pressure fluctuation as a residual wave against the mono-exponential decay and the diastolic flow fluctuation as a bidirectional (forward and reverse) velocity wave. The radial, carotid, and dorsalis pedis pressures were also recorded to measure the peripheral/aortic pulse pressure (PP) and pulse wave velocity (PWV) ratios. RESULTS: There were close resemblances between the femoral pressure and flow fluctuation waveforms. The pressure and flow fluctuations were mutually correlated in relative amplitude as indexed to the total pulse height (r = 0.63), and the former temporally followed the latter. In multivariate-adjusted models, higher peripheral/aortic PP and PWV ratios were independently associated with greater pressure and flow fluctuation indices (P < 0.001). Mediation analysis revealed that the associations of PP and PWV ratios with the pressure fluctuation index were largely mediated by the flow fluctuation index [indirect/total effect ratio: 57 (95% CI 42-80)% and 54 (30-100)%, respectively]. CONCLUSION: These results suggest that central-to-peripheral pulse amplification and stiffness gradients contribute to triphasic flow fluctuations and dicrotic pressure waves. Diminished or inverted stiffness gradients caused by aortic stiffening may thus reduce diastolic runoff leading to ischemic organ damage.

Albuminuria Intensifies the Link Between Urinary Sodium Excretion and Central Pulse Pressure in the General Population: The Wakuya Study.

BACKGROUND: Central pulse pressure (cPP) is responsible for the hemodynamics of vital organs, and monitoring this parameter is important for cardiovascular disease (CVD) prevention. Excess sodium intake and (micro)albuminuria (a manifestation of renal microvascular damage) are known to be strong predictors of CVD. We sought to investigate the cross-sectional relationships among dietary sodium intake, albuminuria, and cPP in a general population cohort. METHODS: The subjects were 933 apparently healthy adults (mean age, 56 ± 10 years). Radial pressure waveforms were recorded with applanation tonometry to estimate mean arterial pressure (MAP), cPP, forward and backward pressure amplitudes, and augmentation index. The urinary sodium/creatinine and albumin/creatinine ratios were measured in spot urine samples. RESULTS: Both the urinary sodium/creatinine and albumin/creatinine ratios were positively correlated with cPP, even after adjusting for MAP (P < 0.001). Moreover, both ratios had a synergistic influence on increasing the cPP independent of age, sex, estimated glomerular filtration rate, hyperlipidemia, and diabetes (interaction P = 0.04). A similar synergistic influence was found on the forward pressure amplitude, but not on the backward pressure amplitude or augmentation index. The overall results were not altered when the urinary albumin/creatinine ratio was replaced with the existence of chronic kidney disease (CKD). CONCLUSIONS: (Micro)albuminuria strengthens the positive association between urinary sodium excretion and cPP and systolic forward pressure. Excess sodium intake may magnify the cardiovascular risk by widening the aortic pulsatile pressure, particularly in the presence of concomitant CKD.

Concurrent analogous organ damage in the brain, eyes, and kidneys in malignant hypertension: reversible encephalopathy, serous retinal detachment, and proteinuria.

Malignant hypertension, a form of hypertensive emergency, causes acute damage in vital organs such as the brain, eyes, and kidneys. We aimed to examine the concurrency of acute hypertensive damage across the target organs to elucidate the underlying analogous pathophysiology. This single-center retrospective study evaluated the characteristics of organ damage, short-term clinical course, and interorgan relationships in patients with malignant hypertension treated between 2008 and 2019. Baseline characteristics of 20 patients who met our inclusion criteria were mean age 48 ± 13 years and blood pressure 222 ± 18/142 ± 16 mmHg; the median estimated glomerular filtration rate and urinary protein level were 49 mL/min/1.73 m2 (interquartile range [IQR] 27-79) and 1.9 g/g creatinine (IQR 0.2-4.0), respectively. Posterior reversible encephalopathy syndrome (PRES) was found in 60% of patients with major involvement and a wide variety of distribution patterns in the brainstem. In the fundus, serous retinal detachment was found in 60% of patients. Patients with PRES and serous retinal detachment showed higher levels of urinary protein than those without symptoms (P = 0.007 and 0.02, respectively), and proteinuria >1 g/g creatinine highly complicated both PRES and serous retinal detachment (91%). Matrix analysis also showed that the three symptoms were highly associated with each other. These results demonstrate the close relationship and concurrency of hypertensive acute organ damage in the brain, eyes, and kidneys. A common analogous mechanism, such as hyperperfusion-induced capillary leakage in each organ, implies an underlying pathophysiology of PRES, serous retinal detachment, and proteinuria.

Carotid Flow Augmentation, Arterial Aging, and Cerebral White Matter Hyperintensities.

Objective- Aortic stiffness and pressure wave reflection are associated with age-related cerebral microvascular disease, but the underlying mechanism remains obscure. We hypothesized that cerebral (carotid) flow alterations potentially mediate these associations. Approach and Results- Doppler waveforms were recorded in 286 patients with hypertension to measure the carotid flow augmentation index (FAIx) as the late/early-systolic velocity amplitude ratio. Tonometric waveforms were recorded to estimate the aortic pressure AIx (PAIx), aortic compliance, and carotid-femoral and carotid-radial pulse wave velocities. Additionally, white matter hyperintensities on brain magnetic resonance imaging were evaluated using the Fazekas scale. With increasing age, the carotid late systolic velocity increased, whereas the early systolic velocity decreased, although the aortic augmented pressure increased in parallel with the incident wave height ( P<0.001). Both FAIx and PAIx increased with age, but the age-dependent curves were upwardly concave and convex, respectively. FAIx increased exponentially with increasing PAIx ( r=0.71). Compared with PAIx, FAIx was more closely ( P≤0.001) correlated with the aortic pulse wave velocity, aortic compliance, and elastic/muscular pulse wave velocity ratio. FAIx was associated with white matter hyperintensities scores independently of confounders including age, sex, diabetes mellitus, hypercholesterolemia, and aortic pulse wave velocity ( P=0.01), and was more predictive of white matter hyperintensities presence than PAIx. Conclusions- Carotid FAIx had closer associations with age, aortic stiffness, and cerebral white matter hyperintensities than aortic PAIx. These results indicate that carotid flow augmentation (enhanced by aortic stiffening and pressure wave reflection from the lower body) causes microcerebrovascular injury potentially through increasing cerebral flow pulsations, but this detrimental effect is greater than that estimated from PAIx.

High central blood pressure is associated with incident cardiovascular events in treated hypertensives: the ABC-J II Study.

It is not established whether central blood pressure (BP) evaluated by a radial pulse wave analysis is useful to predict cardiovascular prognoses. We tested the hypothesis that central BP predicts future cardiovascular events in treated hypertensive subjects. We conducted a multicenter, observational cohort study of 3566 hypertensives being treated with antihypertensive medications at 27 institutions in Japan. We performed the radial pulse wave analyses using applanation tonometry in all subjects. The primary outcome was the incidence of any of the following: stroke, myocardial infarction (MI), sudden cardiac death, and acute aortic dissection. The mean age of the subjects was 66.0 ± 10.9 years, and 50.6% were male. The mean brachial SBP and central SBP were 138 ± 18 mm Hg and 128 ± 19 mm Hg, respectively. When the central SBP was divided into quintiles, the number of events was least in the 2nd quintile, and we set it as the reference. In the Cox regression analysis adjusting for age, sex, body mass index, creatinine, diabetes, use of ß-blocker, and history of MI/stroke, the patients in the 3rd (hazard ratio (HR) 3.55, 95% confidence interval 1.29-9.78, p = 0.014), 4th (HR 4.12, 95% CI 1.53-11.10, p = 0.005), and 5th quintiles (HR 2.87, 95% CI 1.01-8.18, p = 0.048) had a significantly higher incidence of cardiovascular events compared to the 2nd quintile. The results were essentially unchanged when brachial DBP was additionally adjusted. In conclusion, in treated hypertensives, high central SBP was associated with worse cardiovascular outcomes.

Association Between Change in Central Nocturnal Blood Pressure and Urine Albumin-Creatinine Ratio by a Valsartan/Amlodipine Combination: A CPET Study.

BACKGROUND: We aimed to assess the association of changes in brachial or central nocturnal systolic blood pressure (SBP) with change in urine albumin-creatinine ratio (UACR) by a valsartan/amlodipine combination (80/5 mg) therapy in hypertensive patients. METHODS: Twenty-three patients (age range, 47-78 years; mean, 68.0 years; 35% men, 65% with chronic kidney disease) with clinic brachial BP ≥140/90 mm Hg were treated with valsartan/amlodipine combination therapy for 16 weeks. At baseline and 16 weeks later, we measured brachial and central nocturnal SBP using an oscillometric Mobil-O-Graph device and UACR by spot urine in 23 patients. RESULTS: The changes in brachial nocturnal SBP (r = 0.445, P = 0.033) and those in central nocturnal SBP (r = 0.616, P = 0.002) were significantly associated with change in UACR by intervention. In multivariable-adjusted multiple regression analyses including changes in both brachial and central nocturnal SBP jointly, only central nocturnal SBP change retained a statistically significant association with change in UACR (ß = 0.919, P = 0.020). CONCLUSIONS: Lowering central nocturnal SBP by a valsartan/amlodipine combination therapy was associated with reduction of UACR, independently of brachial nocturnal SBP reduction. Central nocturnal SBP may be a therapeutic target to protect the kidney. A larger scale interventional study will be needed to confirm the kidney protection conferred by lowering central nocturnal SBP. CLINICAL TRIALS REGISTRATION: Trial Number UMIN000013519.

Low frequency of cervicocranial artery involvement in Japanese with renal artery fibromuscular dysplasia compared with that of Caucasians.

BACKGROUND: Fibromuscular dysplasia (FMD), which usually affects the renal artery, also affects the carotid, vertebral, and intracranial arteries. Previous studies have shown a high prevalence of concomitant renal artery and cervicocranial lesions in FMD patients. However, the analyzed subjects were mostly Caucasians in Western countries. METHOD: We performed a retrospective analysis to examine the prevalence of cervicocranial vascular lesions in Japanese FMD patients with renal artery involvement at a single institution. The presence of cervicocranial lesions was evaluated by Doppler echography and magnetic resonance angiography. We compared this prevalence with that reported in the literature. RESULT: Thirty-one Japanese FMD patients with renal artery lesions were studied. The mean age was 30 ± 12 years, 71% were women, and 16% were smokers; all patients were Asians and had hypertension. Multifocal, tubular, and unifocal types of renal lesions were found in 52, 35, and 13% of patients, respectively. Bilateral renal lesions were found in 13% of patients. None of the patients had a cervical vascular lesion associated with FMD. Only two patients (8%) had a lesion in the intracranial artery, of which one was a known case of moyamoya disease. CONCLUSION: These findings suggest that cervical artery involvement and intracranial artery involvement are not common in renal FMD patients in Japan, which is in contrast to the data reported for Caucasian patients in Western countries. Ethnic differences could influence the occurrence of cervicocranial lesions. A study with a larger sample size should be performed to validate these findings.

Central diastolic pressure decay mediates the relationship between aortic stiffness and myocardial viability: potential implications for aortosclerosis-induced myocardial ischemia.

OBJECTIVE: Stiffening of the aorta often precedes coronary events, but little is known about the aetiological mechanism. We hypothesized that the predisposition to myocardial ischemia could be attributable to aortosclerosis-induced alterations in the central haemodynamics during diastole. METHODS: Using noninvasive tonometry and ultrasonography, we investigated the arterial pressure pulse waveforms, pulse wave velocities (PWVs) and compliance in 222 patients with hypertension. The diastolic pressure decay was quantified by fitting a mono-exponential curve as P(t) =  P0e [λ: decay index; P0: end-systolic pressure; t: time from end-systole]. The myocardial oxygen supply/demand balance was estimated from the subendocardial viability index (SVI). RESULTS: The aortic pressure decay fit to an exponential curve significantly (R = 0.98 ±â€Š0.02) and more closely than the radial pressure decay (P < 0.001). The aortic decay index (median, 0.59 s) was associated with the aortic PWV and compliance (but not with the peripheral PWV or resistance), even after controlling for age, sex, renal function, diabetes and hypercholesterolemia (P < 0.001). Also, both the aortic PWV and compliance (together with the augmentation index) were related to the SVI, although these relationships were no longer significant after accounting for the decay index. Mediation analysis revealed substantial mediating effects of the decay index on the relationship between aortic PWV or compliance and SVI (75-100%), despite the lack of similar effects of the augmentation index. CONCLUSION: Aortic stiffening with reduced compliance potentially impairs myocardial viability by accelerating the diastolic exponential decay (rather than through enhancing late-systolic augmentation) of the central blood pressure, thus predisposing hypertensive patients to ischemic heart disease.

Selective embolization therapy for intrarenal artery stenosis causing renovascular hypertension: Efficacy and follow-up renal imaging.

We report the case of a young woman treated with selective renal embolization for renovascular hypertension caused by intrarenal artery stenosis and show follow-up imaging of the treated kidney. An 18-year-old woman had renin-dependent hypertension with intrarenal artery stenosis caused by fibromuscular dysplasia. A middle branch artery was nearly occluded, resulting in segmental renal ischemia with excessive renin secretion. Because our angioplasty attempt for revascularization failed as a result of technical difficulty, we performed selective embolization of the diseased vessel by anhydrous ethanol. The embolization promptly ameliorated hyperreninemia and resistant hypertension without deterioration of renal function. Findings from magnetic resonance imaging showed disappearance of the blood flow in the embolized area corresponding to the ischemic lesion that had been revealed by diffusion-weighted imaging. Thus, selective embolization can be effective in treating renovascular hypertension by intrarenal stenosis for which angioplasty is not feasible. Additionally, renal magnetic resonance imaging is useful for evaluating the causative ischemic lesion and embolized area.

Central Hemodynamics for Management of Arteriosclerotic Diseases.

Arteriosclerosis, particularly aortosclerosis, is the most critical risk factor associated with cardiovascular, cerebrovascular, and renal diseases. The pulsatile hemodynamics in the central aorta consists of blood pressure, flow, and stiffness and substantially differs from the peripheral hemodynamics in muscular arteries. Arteriosclerotic changes with age appear earlier in the elastic aorta, and age-dependent increases in central pulse pressure are more marked than those apparent from brachial pressure measurement. Central pressure can be affected by lifestyle habits, metabolic disorders, and endocrine and inflammatory diseases in a manner different from brachial pressure. Central pulse pressure widening due to aortic stiffening increases left ventricular afterload in systole and reduces coronary artery flow in diastole, predisposing aortosclerotic patients to myocardial hypertrophy and ischemia. The widened pulse pressure is also transmitted deep into low-impedance organs such as the brain and kidney, causing microvascular damage responsible for lacunar stroke and albuminuria. In addition, aortic stiffening increases aortic blood flow reversal, which can lead to retrograde embolic stroke and renal function deterioration. Central pressure has been shown to predict cardiovascular events in most previous studies and potentially serves as a surrogate marker for intervention. Quantitative and comprehensive evaluation of central hemodynamics is now available through various noninvasive pressure/flow measurement modalities. This review will focus on the clinical usefulness and mechanistic rationale of central hemodynamic measurements for cardiovascular risk management.