Severity of obstructive sleep apnea is associated with the nocturnal fluctuation of pulse rate, but not with that of blood pressure, in older hypertensive patients receiving calcium channel blockers.

AIM: Obstructive sleep apnea (OSA) is associated with increased variability in nocturnal blood pressure (BP). Calcium channel blockers (CCB) are superior to other classes of antihypertensives in decreasing BP variability. We investigated whether OSA severity is associated with nocturnal BP variability in older hypertensive patients treated with CCB. METHODS: We measured home systolic and diastolic BP and pulse rate (PR) automatically during sleep at an interval of an hour once a week using an electronic sphygmomanometer in 29 hypertensive patients (aged ≥65 years) receiving CCB. We calculated the coefficient of variation (CV) from four consecutive measurements. All patients underwent a home-based portable sleep study. RESULTS: We found no difference in PR, BP or CV of BP between the patients with no-to-mild OSA and with moderate-to-severe OSA, categorized by the respiratory disturbance index (RDI) and 3% oxygen desaturation index (ODI). The CV of PR in patients with moderate-to-severe OSA was higher than the patients with no-to-mild OSA categorized by 3% ODI (P = 0.01). Body mass index was correlated with RDI and 3% ODI (r = 0.56 and 0.43, respectively). The CV of BP did not correlate to RDI or 3% ODI. The CV of PR was positively correlated both with RDI and with 3% ODI (r = 0.41 and 0.42, respectively). CONCLUSIONS: The severity of OSA was associated with PR variability, but not with BP variability, in older patients receiving CCB. Our results suggest the need for future studies to determine whether CCB can suppress the influence of OSA on BP fluctuation during sleep. Geriatr Gerontol Int 2019; 19: 604-610.

Ankle-brachial index measured by oscillometry is predictive for cardiovascular disease and premature death in the Japanese population: An individual participant data meta-analysis.

BACKGROUND AND AIMS: The ankle-brachial index (ABI) is a predictor of cardiovascular disease (CVD) and premature death. However, few studies on this marker are available in the general Asian populations. This study aimed to investigate the association between ABI measured with oscillometry and the risk of these outcomes. METHODS: We conducted an individual participant data meta-analysis in 10,679 community-dwelling Japanese individuals without a history of CVD. The primary outcome was a composite of CVD events and all-cause mortality. RESULTS: During an average of 7.8 years of follow-up, 720 participants experienced the primary outcome. The multivariable-adjusted hazard ratios (HRs) of the primary outcome significantly increased with a lower ABI. The HRs were 1.07 (95% confidence interval [CI] 0.91-1.27) for ABI of 1.00-1.09, HR 1.37 (95% CI 1.04-1.81) for ABI of 0.91-0.99, and HR 1.60 (95% CI 1.06-2.41) for ABI of ≤0.90, compared with ABI of 1.10-1.19. Furthermore, a high ABI (≥1.30) was associated with a greater risk of outcome (HR 2.42 [95% CI 1.14-5.13]). Similar tendencies were observed for CVD events alone and all-cause mortality alone. Addition of ABI to a model with the Framingham risk score marginally improved the c-statistics (p = 0.08) and integrated discrimination improvement (p < 0.05) for the primary outcome. CONCLUSIONS: The present study suggests that lower and higher ABI are significantly associated with an increased risk of CVD and all-cause mortality in the Japanese population. The ABI, which is easily measured by oscillometry, may be incorporated into daily clinical practice to identify high-risk populations.

Simultaneously Measured Interarm Blood Pressure Difference and Stroke: An Individual Participants Data Meta-Analysis.

We conducted individual participant data meta-analysis to examine the validity of interarm blood pressure difference in simultaneous measurement as a marker to identify subjects with ankle-brachial pressure index <0.90 and to predict future cardiovascular events. We collected individual participant data on 13 317 Japanese subjects from 10 cohorts (general population-based cohorts, cohorts of patients with past history of cardiovascular events, and those with cardiovascular risk factors). Binary logistic regression analysis with adjustments identified interarm blood pressure difference >5 mm Hg as being associated with a significant odds ratio for the presence of ankle-brachial pressure index <0.90 (odds ratio, 2.19; 95% confidence interval, 1.60-3.03; P<0.01). Among 11 726 subjects without a past history of cardiovascular disease, 249 developed stroke during the average follow-up period of 7.4 years. Interarm blood pressure difference >15 mm Hg was associated with a significant Cox stratified adjusted hazard ratio for subsequent stroke (hazard ratio, 2.42; 95% confidence interval, 1.27-4.60; P<0.01). Therefore, interarm blood pressure differences, measured simultaneously in both arms, may be associated with vascular damage in the systemic arterial tree. These differences may be useful for identifying subjects with an ankle-brachial pressure index of <0.90 in the overall study population, and also a reliable predictor of future stroke in subjects without a past history of cardiovascular disease. These findings support the recommendation to measure blood pressure in both arms at the first visit.

Comparison between L-type and N/L-type calcium channel blockers in the regulation of home blood-pressure variability in elderly hypertensive patients.

Recent studies suggest that L-type calcium channel blockers (CCBs) contribute to reducing blood pressure (BP) variability. We investigated whether inhibition of the N-type calcium channel has an additional effect on BP variability by comparing the effect of L-type and L/N-type CCBs on home BP variability in elderly hypertensive patients. Twenty-six hypertensive patients (≥65 years) were subjected to repeated changes with the administration of amlodipine (L-type CCB) and cilnidipine (L/N-type CCB) every 2 months. They measured the home BP in the morning and evening, and the coefficient of variation (CV) was calculated. We measured the brachial-ankle pulse wave velocity (baPWV) and urinary catecholamine excretion as an index of the arterial stiffness and sympathetic nerve activity, respectively. There was no difference in the effect of both drugs on the CV in the morning and evening, while amlodipine was associated with a modestly higher pulse rate and lower BP than cilnidipine. By comparing individual patient data for the CV with each drug, we found that higher urinary catecholamine excretion was associated with the effectiveness of cilnidipine over amlodipine in the BP variability in the morning, which was not the case in the evening. In contrast, lower baPWV was associated with the effectiveness of amlodipine over cilnidipine on BP variability in the evening. Lower baPWV was also associated with lower BP variability in the evening. Cilnidipine has a similar capacity as amlodipine in reducing home BP variability, but the underlying mechanisms in reducing BP variability may differ.

A klotho gene single nucleotide polymorphism is associated with the onset of stroke and plasma klotho concentration.

Klotho protects against development of multiple age-related disorders, including cardiovascular diseases. We assessed whether a human klotho single nucleotide polymorphism (SNP) rs650439 is associated with the onset of stroke in hypertensive patients and plasma klotho concentration in the general population. Five hundred and twenty-three patients with hypertension were analyzed for both the presence of rs650439 and onset of stroke. We found that hypertensive patients with the TT genotype of rs650439 (n=52) had a higher incidence of stroke than those with AT (n=257) and AA (n=214) genotypes. Multivariate analysis indicated that the TT genotype was the only risk factor associated with increased incidence of stroke. Plasma klotho concentrations were measured in a general population (age=70±1 years) to assess the association between rs650439 and plasma klotho concentration. A significant trend was observed in the elderly population where plasma klotho concentration decreased as the T alleles in rs650439 increased. Subjects with a TT genotype had lower plasma klotho concentrations than those with AT+AA genotypes. In conclusion, TT genotype of klotho SNP (rs650439) is correlated with an increased incidence of stroke in hypertensive patients, and the mechanism underlying this correlation might involve the effect of rs650439 T allele on plasma klotho concentrations.

Proposed Cutoff Value of Brachial-Ankle Pulse Wave Velocity for the Management of Hypertension.

BACKGROUND: The optimal cutoff values of the brachial-ankle pulse wave velocity (baPWV) for predicting cardiovascular disease (CVD) were examined in patients with hypertension.Methods and Results:A total of 7,656 participants were followed prospectively. The hazard ratio for the development of CVD increased significantly as the baPWV increased, independent of conventional risk factors. The receiver-operating characteristic curve analysis showed that the optimal cutoff values for predicting CVD was 18.3 m/s. This cutoff value significantly predicted THE incidence of CVD. CONCLUSIONS: The present analysis suggests that the optimal cutoff value for CVD in patients with hypertension is 18.3 m/s.

Brachial-Ankle Pulse Wave Velocity and the Risk Prediction of Cardiovascular Disease: An Individual Participant Data Meta-Analysis.

An individual participant data meta-analysis was conducted in the data of 14 673 Japanese participants without a history of cardiovascular disease (CVD) to examine the association of the brachial-ankle pulse wave velocity (baPWV) with the risk of development of CVD. During the average 6.4-year follow-up period, 687 participants died and 735 developed cardiovascular events. A higher baPWV was significantly associated with a higher risk of CVD, even after adjustments for conventional risk factors (P for trend <0.001). When the baPWV values were classified into quintiles, the multivariable-adjusted hazard ratio for CVD increased significantly as the baPWV quintile increased. The hazard ratio in the subjects with baPWV values in quintile 5 versus that in those with the values in quintile 1 was 3.50 (2.14-5.74; P<0.001). Every 1 SD increase of the baPWV was associated with a 1.19-fold (1.10-1.29; P<0.001) increase in the risk of CVD. Moreover, addition of baPWV to a model incorporating the Framingham risk score significantly increased the C statistics from 0.8026 to 0.8131 (P<0.001) and also improved the category-free net reclassification (0.247; P<0.001). The present meta-analysis clearly established baPWV as an independent predictor of the risk of development of CVD in Japanese subjects without preexisting CVD. Thus, measurement of the baPWV could enhance the efficacy of prediction of the risk of development of CVD over that of the Framingham risk score, which is based on the traditional cardiovascular risk factors.

Factors associated with the severity of obstructive sleep apnea in older adults.

AIM: Epidemiological studies have shown that severe obstructive sleep apnea (OSA) is associated with higher mortality when compared with mild to moderate OSA. Because aging is a well-known risk factor for OSA, we aimed to elucidate the underlying factors associated with the severity of OSA in elderly patients. METHODS: Patients who underwent polysomnography were divided into the non-elderly group (aged <65 years; n = 44) and the elderly group (aged ≥65 years; n = 46). The severity of OSA was determined by the apnea hypopnea index (AHI), and each group was subdivided into two groups: mild to moderate OSA (5 < AHI < 30) and severe OSA (AHI ≥30) . In the elderly group, geriatric assessments to evaluate physical and neuropsychiatric function were carried out. RESULTS: All patients had OSA as diagnosed by an AHI >5. Whereas body mass index was positively correlated with AHI in both groups, age was correlated with AHI only in the elderly group. Body mass index and age were higher in severe OSA than mild to moderate OSA in the elderly group. Unexpectedly, no significant difference was observed in physical strength, cognitive function, apathy scale, depression scale or activities of daily living between mild to moderate OSA and severe OSA in the elderly group. Binary logistic regression analysis showed that male sex, body mass index and aging were independent risk factors of severe OSA in the elderly group. CONCLUSIONS: Our findings suggest that aging increases the severity of OSA in elderly patients, even if they are physically active and neuropsychiatrically unimpaired. Geriatr Gerontol Int 2017; 17: 614-621.

Prognostic impact of regional arterial stiffness in hypertensive patients.

Many reports have shown that brachial-ankle pulse wave velocity (baPWV) and carotid-femoral PWV are prognostic factors for cardiovascular diseases. We evaluated heart-carotid PWV, heart-femoral PWV (hfPWV), and femoral-ankle PWV (faPWV) using carotid and femoral sensors. Our objectives were to reveal correlations among PWVs and to determine the clinical importance of the respective PWVs in predicting the cardiovascular events. This prospective cohort study included 338 patients with essential hypertension (mean age 61.3 ± 0.7, mean follow-up period 6.5 ± 0.1 years) whose regional PWVs were measured. Primary end points were stroke, cardiovascular diseases (CVD), and death. Kaplan-Meier analysis showed that subjects with higher faPWV and baPWV had a significantly higher incidence of stroke (p = 0.0288 and 0.0277, respectively), subjects with higher hfPWV had a significantly higher incidence of CVD (p = 0.0212), subjects with higher baPWV and hfPWV had a significantly higher incidence of stroke + CVD (p = 0.0070 and 0.0463, respectively), and subjects with higher baPWV had a significantly higher mortality rate (p = 0.0367). Cox proportional hazard model revealed that baPWV was a significant risk factor for stroke + CVD after adjustment for traditional risk factors (relative risk: 14.50, p = 0.0288). Higher baPWV may be a risk factor for stroke and CVD, but the prognostic impact of regional PWVs is still unclear in patients with hypertension.

The influence of aging on the diagnosis of primary aldosteronism.

Primary aldosteronism (PA) is common in young or middle-aged hypertensive patients, but PA among the elderly has recently become more common. As salt sensitivity increases with age, plasma renin activity (PRA) tends to decrease, whereas the aldosterone-to-renin ratio (ARR) tends to increase in the elderly. The aim of this study was to clarify the influence of aging on the diagnosis of PA. We retrospectively evaluated 155 consecutively admitted patients who were not taking antihypertensive medications or calcium channel blockers and α blockers that underwent PRA and plasma aldosterone concentration (PAC) measurements. The study subjects included 13 PA and 69 essential hypertensive (EHT) patients aged over 65 years, and 32 PA and 41 EHT patients under aged 65 years. Our study clarified the influence of aging through screening and confirmatory tests for the diagnosis of PA. Our results showed the ARR cutoff value for a screening test to be 556 (area under the curve: AUC=0.906), its sensitivity and specificity to be 84.6% and 89.9%, respectively, and the likelihood ratio to be 8.34 in the elderly, whereas the ARR cutoff value was 272 in the non-elderly. In the saline infusion test, the mean PAC was 86.6 ± 41.8 pg ml(-1) in the elderly and 158.1 ± 116.5 pg ml(-1) in the non-elderly (P = 0.04). There was no influence from age in both the captopril challenge test and the furosemide upright test. Aging may influence PA screening and saline infusion tests; thus, we should consider the influence of aging in the diagnosis of elderly subjects with PA.

Alteration of vascular function is an important factor in the correlation between visit-to-visit blood pressure variability and cardiovascular disease.

OBJECTIVE: To assess how visit-to-visit variability of SBP correlates with systemic atherosclerotic change and various prognoses. BACKGROUND: Visit-to-visit SBP variability correlates with cardiovascular events. However, the mechanisms underlying the impact of visit-to-visit SBP variability on prognoses are poorly understood. METHODS AND RESULTS: A total of 485 patients with essential hypertension from the Non-Invasive Atherosclerotic Evaluation in Hypertension (NOAH) study cohort were included. We analyzed the correlation between visit-to-visit SBP variability and multiple clinical parameters. Next, we prospectively examined the correlation of SBP variability and frequency of cardiovascular disease (CVD) and total mortality. Patients with higher SBP variability exhibited significantly higher rates of statin use, as well as higher pulse wave velocity (PWV), left-ventricular mass index (LVMI), plaque score, and resistive index of the common carotid artery; these patients also exhibited lower estimated glomerular filtration rate. Kaplan-Meier analysis demonstrated that patients with higher SBP variability have a significantly higher incidence of CVD and mortality rate. The hazard ratio of SBP variability for incidence of CVD was greatly diminished after adjustment for intima-media thickness, plaque score, and resistive index, and was slightly diminished after adjustment for PWV and LVMI. Visit-to-visit SBP variability remained an independent risk factor for mortality after adjustment. CONCLUSION: Visit-to-visit SBP variability correlates significantly with systemic atherosclerotic change, incidence of CVD, and mortality rate. Altered arterial functions, such as macrovascular atherosclerosis and vascular resistance, are responsible for the correlations between visit-to-visit SBP variability and incidence of CVD.

Carotid plaque score and intima media thickness as predictors of stroke and mortality in hypertensive patients.

The mean intima media thickness (IMT) and plaque score from carotid ultrasonography are both widely used to evaluate macrovascular atherosclerotic change. The present study sought to examine which parameter more effectively predicts patient prognosis. This hospital-based cohort study included 356 patients with essential hypertension (mean age: 62.4 ± 0.6). We investigated how the mean IMT and plaque score correlated with various parameters, including pulse wave velocity (PWV), and we assessed the ability of the mean IMT and plaque score to predict cardiovascular events and total mortality. The mean IMT and plaque score significantly correlated with systemic atherosclerotic change, target organ damage, age and PWV. Subjects with a higher mean IMT and subjects with higher plaque scores showed higher frequencies of stroke and total mortality. In addition, subjects with marginal thickening of the intima media (mean ≥ 0.7) showed a significantly higher frequency of stroke than subjects with a mean IMT of <0.7. After adjustment for traditional risk factors, plaque score was significantly and independently predictive of stroke, and the predictive ability of the plaque score for the onset of stroke was equivalent to that of PWV. The mean IMT and plaque score showed a nonsignificant trend of higher risk of mortality after adjustment for traditional risk factors. The mean IMT and plaque score were significantly correlated with systemic atherosclerotic change. We revealed that plaque score predicted the onset of stroke more accurately than the mean IMT, and the accuracy of this prediction was equivalent to that from PWV in hypertensive patients. We also showed that marginal thickening of the intima media (as measured by mean IMT) may be a predictor of stroke.

Incidence and risk factors for very late recurrence of atrial fibrillation after radiofrequency catheter ablation.

AIMS: Although several prognostic factors for atrial fibrillation (AF) recurrence after catheter ablation (CA) have been reported, predictors of very late recurrence (VLR; initial recurrence >12 months after ablation) remain unidentified. This study investigated clinical variables predictive of VLR after CA for AF. METHODS AND RESULTS: This retrospective single-centre cohort study evaluated data from 1016 consecutive drug-refractory AF patients who underwent single CA for AF from July 2004 to May 2010. After excluding 324 patients with a short follow-up period (<1 year) and 300 patients with recurrence within a year of CA, 392 patients were included. Study subjects were divided into two groups on the basis of VLR presence. Preoperative clinical variables were evaluated as predictors of VLR using the Cox proportional hazards model. The annual rate of VLR was 7.6% after single CA. Univariate analysis revealed that hypertension [hazard ratio (HR) 1.77, 95% confidence interval (CI) 0.93-3.37, P = 0.08], obesity (HR 1.84, 95% CI 0.98-3.45, P = 0.06), long-standing persistent AF (HR 2.35, 95% CI 1.08-5.11, P = 0.03), and abnormally high preoperative C-reactive protein (CRP) levels >0.5 mg/dL (HR 4.28, 95% CI 2.03-9.03, P < 0.0001) were associated with VLR. In the multivariate model, only abnormally high preoperative CRP level was an independent predictor of VLR (HR 4.9, 95% CI 2.3-10.7, P < 0.0001). CONCLUSION: Even after a year without AF, VLR occurred annually in 7.6% cases. Continued vigilance for VLR after CA is clinically desirable, especially for patients with abnormally high preoperative CRP levels.

-374 T/A polymorphism in RAGE gene is associated with onset of diabetes mellitus, atherosclerosis, and renal dysfunction in patients with hypertension.

Receptor of advanced glycation end products (RAGE) is reportedly linked with chronic inflammatory diseases due to aging or diabetes. The aim of this study was to show how -374 T/A RAGE has an impact on systemic vascular damage and renal function. The study subjects were a total of 468 essential hypertension patients from the Non-Invasive Atherosclerotic Evaluation in Hypertension (NOAH) study cohort. We prospectively examined the association of -374 T/A RAGE with their prognoses and investigated the correlation between -374 T/A RAGE and multiple clinical parameters. Kaplan-Meier analysis did not show a significant association of -374 T/A RAGE with total mortality or the prevalence of cardiovascular events. Carriers of the A allele showed a significantly higher prevalence of diabetes mellitus (DM) and lower estimated glomerular filtration rate (eGFR) than subjects without this allele. In subjects with DM, carriers of the A allele showed a significantly lower eGFR. These significant correlations were only seen in male subjects. Carriers of the A allele of -374 T/A RAGE show an independent risk of atherosclerosis and reduced renal function in male hypertensive patients with DM.

Cause of very late recurrence of atrial fibrillation or flutter after catheter ablation for atrial fibrillation.

The major mechanism underlying the early recurrence of atrial fibrillation (AF) after ablation is mainly reconnection of the isolated pulmonary vein (PV); however, the mechanism responsible for very late recurrence (VLR) has not been fully elucidated. The purpose of the present study was to investigate the mechanism underlying VLR. The study population included 150 consecutive patients with AF who underwent a second session of catheter ablation because of recurrence. We divided them into 2 groups according to the point of initial AF recurrence: the late recurrence group (LR group, initial recurrence 3 to 12 months after ablation, n = 124) and the VLR group (initial recurrence >12 months after ablation, n = 26). We identified PVs with ectopic foci (trigger PVs) in the first procedure and checked their electrical reconnection in the second procedure. The prevalence of PV reconnection and trigger PV reconnection were significantly lower in the VLR group than in LR group (LR vs VLR, 90% vs 69% and 48% vs 27%, p = 0.007 and p = 0.045, respectively). In the VLR group, left ventricular systolic and diastolic function were significantly worse than in the LR group, and more patients in the VLR group required non-PV trigger ablation in the second session than did those in the LR group (30% vs 54%, p = 0.034). In conclusion, electrical PV reconnection contributed less to VLR than to LR. Progression of the AF substrate might be an important mechanism responsible for VLR.

Differences between daytime and nighttime blood pressure variability regarding systemic atherosclerotic change and renal function.

Recently, new parameters related to hypertension, such as variability in blood pressure and ambulatory arterial stiffness index (AASI), were demonstrated to correlate with arteriosclerotic change. In this study, we investigated the correlation between circadian variability in blood pressure/AASI and renal function. We also investigated differences in the clinical impact of 24 h, daytime and nighttime blood pressure variability on renal and systemic atherosclerotic changes. We analyzed data from 120 patients who underwent renal Doppler ultrasonography (RDU) and ambulatory blood pressure monitoring (ABPM) at our hospital ward, and investigated the correlation between circadian variability in blood pressure/AASI and renal function, including resistive index (RI) evaluated with RDU, which is thought to be a good indicator of renal vascular resistance. Subjects with higher circadian variability in systolic blood pressure (SBP) had significantly higher RI. Daytime variability in SBP correlated more strongly with RI than nighttime variability. Meanwhile, only nighttime variability, but not daytime variability, in SBP was related to carotid atherosclerosis. Similarly, AASI was significantly correlated with RI. Circadian variability in SBP and AASI were both significantly correlated with renal function. Daytime SBP s.d. was especially more strongly correlated with renal vascular resistance, and nighttime SBP s.d. was significantly correlated with intima-media thickness (IMT) and plaque score. These results indicate that evaluating both daytime and nighttime blood pressure variability enables an assessment of pathological conditions in hypertensive patients to prevent cardiovascular diseases.

Adiponectin single nucleotide polymorphism is a genetic risk factor for stroke through high pulse wave pressure: a cohort study.

AIM: Adiponectin is a key molecule involved in metabolic syndrome. Single nucleotide polymorphisms (SNPs) in the ADIPOQ gene encoding adiponectin correlate with various diseases, such as diabetes mellitus; however, there is insufficient information about ADIPOQ SNPs and the onset of cardiovascular events. METHODS: This hospital-based cohort study included 353 patients with essential hypertension (mean age, 62.9±0.6; mean follow-up period. 7.9±0.2 years) in whom ADIPOQ SNPs encoding G276T, I164T, A349G, and/or G967A amino acid changes were detected. We analyzed the correlation between ADIPOQ SNPs and various parameters, including pulse wave velocity (PWV), and assessed whether these SNPs could be risk factors for the onset of stroke, cardiovascular disease, and mortality. RESULTS: Subjects with the T allele of G276T showed significantly lower HDL cholesterol, and significantly higher HbA1c and brachial-ankle PWV (baPWV). Kaplan-Meier analysis revealed that subjects with the T allele of G276T had a significantly higher frequency of stroke (p= 0.0489). The Cox proportional hazard model showed that the T allele of G276T was an independent and significant risk factor for stroke after adjusting for traditional risk factors (relative risk: 1.879, p= 0.0479); however, when adjusted for traditional risk factors and baPWV, the relative risk was significantly diminished (relative risk: 0.710, p= 0.4937). G276T was significantly correlated with dyslipidemia and glucose metabolism. CONCLUSION: The T allele of G276T was a significant and independent risk for the onset of stroke, and mediated the incidence of stroke through increased arterial stiffness.

Cut-off value of brachial-ankle pulse wave velocity to predict cardiovascular disease in hypertensive patients: a cohort study.

AIM: Arterial stiffness has been reported to correlate with cardiovascular disease (CVD). Brachial-ankle pulse wave velocity (baPWV) is easy to measure and has been used as a marker to evaluate arterial stiffness. The objective of the present study was to determine the cut-off value of baPWV for predicting cardiovascular prognosis in a prospective cohort study. METHODS: Four hundred forty patients with essential hypertension were analyzed in study 1 with a mean follow-up of 6.3±0.1 years. Four hundred patients from study 1 who did not have a past history of CVD and/or stroke were analyzed in study 2 with a mean follow-up of 6.4±0.1 years. Stroke, CVD, and death were the primary endpoints. RESULTS: Receiver operating characteristic (ROC) curve analysis revealed that 1750.0 cm/sec is an appropriate cut-off value for baPWV to predict the onset of stroke, CVD, stroke+CVD, and total mortality (area under curve: 0.576-0.719). A baPWV higher than 1750.0 may also be a significant and independent risk factor for the onset of CVD+stroke (relative risk: 2.048 (1.176-3.616), p= 0.0113 in study 1; relative risk: 1.920 (1.028-3.634), p=0.0408 in study 2). CONCLUSIONS: The present study indicates that 1750.0 cm/sec could be a useful cut-off value for baPWV to predict cardiovascular prognosis.

Influence of renin angiotensin system gene polymorphisms on visit-to-visit blood pressure variability in hypertensive patients.

BACKGROUND: Visit-to-visit blood pressure (BP) variability has been reported to be a major risk for cardiovascular events. Renin angiotensin system (RAS) gene polymorphisms are reportedly genetic risk factors for cardiovascular diseases and arterial stiffness. In this study, we aimed to reveal the relationship between visit-to-visit BP variability and RAS gene polymorphisms. METHODS: Study subjects included 427 essential hypertension patients from the Non-Invasive Atherosclerotic Evaluation in Hypertension study cohort, whose BP was measured during at least six outpatient visits. We analyzed the correlation between visit-to-visit variability in systolic BP (SBP) and RAS gene polymorphisms. RESULTS: We identified angiotensinogen M235T, angiotensin II type 1 receptor A1166C, and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms. Only ACE I/D polymorphisms were correlated with variability in diastolic BP; no gene polymorphisms were correlated with variability in SBP. CONCLUSIONS: RAS gene polymorphisms, especially ACE I/D polymorphisms, might genetically influence the visit-to-visit BP variability in hypertensive patients.