Significance of blood pressure variability in normotensive individuals as a risk factor of developing hypertension.

PURPOSE: Visit-to-visit blood pressure variability is a strong predictor of the incidence of cardiovascular events and target organ damage due to hypertension. The present study investigated whether year-to-year blood pressure variability predicts the risk of hypertension in the Japanese general population. MATERIALS AND METHODS: This study analysed 2806 normotensive individuals who participated in our physical check-up program for five years in a row from 2008 to 2013. The average, standard deviation, coefficient of variation, average real variability, and highest value of systolic blood pressure in the five consecutive visits were determined and used as baseline data. The participants were followed up for the next 6 years with the development of 'high blood pressure', an average blood pressure level of ≥140/90 mmHg or the use of antihypertensive medications, as the endpoint. RESULT: During follow-up, 'high blood pressure' developed in 389 participants (13.9%, 29.5 per 1 000 person-years). The incidence increased across the quartiles of standard deviation and average real variability, while the average and highest systolic blood pressure had the most prominent impact on the development of 'high blood pressure'. Multivariate logistic regression analysis adjusted for possible risk factors indicated that the average, standard deviation, average real variability, and highest blood pressure, but not the coefficient of variation of systolic blood pressure, were significant predictors of 'high blood pressure'. CONCLUSION: Increased year-to-year blood pressure variability predicts the risk of hypertension in the general normotensive population. The highest blood pressure in the preceding years may also be a strong predictor of the risk of hypertension.

What is the context A relatively high blood pressure level recorded by chance is not usually examined further, especially in cases where the blood pressure values recorded in different opportunities were within normal levels.However, high blood pressure observed by chance may be a result of increased blood pressure variability.Increased blood pressure variability predicts incident hypertension in patients with diabetes, but clinical significance of increased blood pressure variability in the general population with normal blood pressure has not been studied.What is new The impact of blood pressure variability on the development of hypertension in the normotensive general population was investigated.The present study demonstrated that increased blood pressure variability was the significant predictor of the development of hypertension in the general population.What is the impact Increased year-to-year blood pressure variability as well as the highest blood pressure observed by chance in the preceding years is a strong predictor of the development of hypertension in the general normotensive population.

Association Between Aortic Stiffness and Exercise Tolerance in Patients at the Risk Stage of Heart Failure.

BACKGROUND: The number of patients with heart failure (HF) has increased, and it is crucial to prevent the development of HF in patients at risk of HF. The present study aimed to risk stratify patients in Stage A and B HF based on associations between exercise-induced changes in aortic stiffness and exercise tolerance.Methods and Results: Patients in Stage A and B HF who performed a cardiopulmonary exercise test were enrolled in the study (n=106; median age 65.0 years [interquartile range 52.8-73.0 years]). Exercise tolerance was examined by the percentage of predicted peak oxygen consumption (%V̇O2peak). The ascending aortic pressure waveform was estimated non-invasively. Aortic stiffness was assessed using the augmentation index (AIx) and reflection magnitude (RM). Multivariable regression analysis showed that AIx measured both before and after exercise was significantly associated with %V̇O2peak (ß=-0.221 [P=0.049] and ß=-0.342 [P=0.003], respectively). When participants were divided into %V̇O2peak subgroups using a cut-off value of 60%, RM decreased immediately after exercise and remained lower 5 min after exercise in the group with preserved exercise tolerance, but recovered to baseline levels 5 min after exercise in the group with reduced exercise tolerance. CONCLUSIONS: Exercise-induced increases in aortic stiffness were associated with exercise tolerance in patients at risk of HF, suggesting that exercise-induced changes in aortic stiffness may be useful to stratify high-risk patients.

Impact of malondialdehyde-modified low-density lipoprotein on clinical outcomes after fractional flow reserve-guided deferral of revascularization.

Cardiovascular events can occur after deferred revascularization, and malondialdehyde-modified low-density lipoprotein (MDA-LDL) has been suggested to be an atherogenic marker. We investigated the relationship between serum MDA-LDL levels and clinical outcomes in patients with fractional flow reserve (FFR)-guided deferral of revascularization. Among 3084 patients undergoing coronary angiography, we retrospectively analyzed 127 patients with intermediate stenosis and deferred revascularization based on FFR > 0.80. Median follow-up interval was 30.4 months, and serum MDA-LDL was measured prior to the measurement of FFR. We evaluated the composite of major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, ischemia-driven deferred lesion revascularization, and any revascularization. MACEs occurred in 18 (14.2%) patients. The MACE group presented with significantly higher MDA-LDL levels than the non-MACE group (134.9 ± 33.3 U/L vs. 95.6 ± 32.2 U/L, P < 0.001). In analysis of the receiver operating characteristics curve for the prediction of MACEs, MDA-LDL presented a significantly larger area under the curve than low-density lipoprotein-cholesterol (LDL-C; 0.810 vs. 0.687, P = 0.042). Univariate Cox regression analysis indicated a significant relationship between MACEs and MDA-LDL (per 10 U/L, HR 1.20; P = 0.004), as did the multivariate model (per 10 U/L, HR 1.17; P = 0.019). When compared according to the median LDL-C (98 mg/dL), the MACE group had significantly higher MDA-LDL in both the high (147.2 ± 27.3 U/L vs. 113.9 ± 31.2 U/L, P = 0.001) and low (103.2 ± 27.3 U/L vs. 80.2 ± 24.0 U/L, P = 0.045) LDL-C groups. Serum MDA-LDL levels were associated with cardiac events in patients with deferral of revascularization based on FFR.

Current status and recent changes in blood pressure and dietary salt consumption in Japanese individuals.

Purpose: Treatment of hypertension has recently shown remarkable advances. It is quite important to survey the current general status of blood pressure (BP) and recent changes to verify whether people are benefitting from these advances. The present study aimed to investigate the current status of, and recent changes in, BP, the prevalence and treatment rate of hypertension, the achievement rate of target BP, and salt intake in Japanese individuals. Methods: Recent changes in salt intake as well as BP, the prevalence and treatment rate of hypertension, and the rate of achievement of target BP were investigated in participants in our yearly physical checkup program from 2009 to 2018 (n = 79,789). Individual salt intake was assessed by estimating 24-hour urinary sodium excretion using a spot urine sample. Results: The prevalence of hypertension did not change, but the treatment rate of hypertension (from 64% to 75%) and the achievement rate of the target BP improved during the period (from 35% to 57%). BP decreased, prominently in hypertensive participants under antihypertensive treatment (from 133 ± 14/84 ± 9 to 128 ± 13/76 ± 10 mmHg). Salt intake did not decline noticeably during the 10 years of observation. Conclusions: The prevalence of hypertension did not change, but the treatment rate of hypertension and the achievement rate of the target BP improved during a recent 10-year period. These findings suggest that improved pharmacological management of hypertension resulted in a gradual reduction in BP levels, but lifestyle modification has not yet really taken root in the Japanese general population.

Increased Serum Malondialdehyde-Modified Low-Density Lipoprotein and Coronary Angiographic Progression After Drug-Eluting Stent Implantation in Patients With Stable Angina.

BACKGROUND: Cardiac events can occur after drug-eluting stent (DES) implantation due to coronary plaque progression at non-stented sites. Malondialdehyde-modified low-density lipoprotein (MDA-LDL) is suggested to be an atherogenic marker. This study investigated the relationship between serum MDA-LDL and angiographic progression after DES implantation.Methods and Results:In total, 207 patients who underwent percutaneous coronary intervention (PCI) using DES and follow-up coronary angiography were retrospectively analyzed. MDA-LDL was serially measured before PCI and at follow up. Persistent high MDA-LDL was defined as a MDA-LDL level more than the median value both before PCI and at follow up. Angiographic progression was assessed by serial analysis of quantitative coronary angiography. Angiographic progression occurred in 35 patients (16.9%). MDA-LDL before PCI was significantly higher in the progression group than the non-progression group in all patients (143.4±35.8 U/L vs. 103.0±33.5U/L, P<0.001) and in patients with controlled LDL-cholesterol (LDL-C <100 mg/dL both before PCI and at follow up; 121.8±32.7 U/L vs. 84.9±24.9 U/L, P<0.001). There were positive correlations between % diameter stenosis changes and serum MDA-LDL before PCI in all patients (r=0.33, P<0.01) and those with controlled LDL-C (r=0.23, P=0.04). In multivariate logistic regression analysis, persistent high MDA-LDL was an independent predictor of plaque progression. CONCLUSIONS: Increased serum MDA-LDL was associated with angiographic progression after DES implantation.

Home blood pressure on winter mornings could be exaggerated: A comparison with summer mornings.

PURPOSE: Self-measured blood pressure at home (HBP) is quite important for the management of hypertension. We hypothesized that winter HBP measured according to the recommendation of the guidelines, but not HBP measured inside bed before getting up, is elevated in response to cold ambient temperatures in winter. This study aimed to investigate differences in HBP measured before and after getting up in winter and summer.Methods: Hypertensive subjects whose blood pressure was stably controlled were enrolled (n = 46, 73 years). They were instructed to measure HBP while in bed just after waking (HBP-bed), in addition to the ordinary HBP measurement in the morning (HBP-morning) according to the guidelines. The mean value of HBP for 7 consecutive days before the day of a regular hospital visit was considered as the HBP of each subject, and characteristics of the winter and summer BPs were investigated.Results: HBP-morning was significantly higher (P < .001) in winter than in summer, but HBP-bed was lower in winter than in summer (P < .05). HBP-morning was significantly higher than HBP-bed in winter, while HBP-morning was not different from HBP-bed in summer, resulting in greater changes in HBP after getting up in winter than in summer (P < .0001). Changes in HBP after getting up were significantly correlated with serum creatinine levels and the urinary albumin-to-creatinine ratio.Conclusions: These findings imply that elevated HBP-morning in winter reflects the response of BP to cold after getting up. Seasonal profiles of HBPs before and after getting up should be noted in the management of hypertension.

Factors associated with longitudinal changes in serum concentrations of Mac-2 binding protein: A prospective 3-year observational study.

BACKGROUND AND AIMS: Mac-2 binding protein (M2BP) plays an important role in cell adhesion. In a recent cross-sectional study we reported that serum M2BP concentrations may reflect silent atherosclerosis. The aim of the present prospective follow-up study was to investigate possible relationships between changes in concentrations of M2BP and other factors over a >3-year period. METHODS AND RESULTS: The present study enrolled subjects who visited Enshu hospital from 2014 to 2015 for a periodic physical check-up and then attended for another physical check-up after >3 years (n = 174). Factors affecting changes in M2BP concentrations were investigated at both baseline and follow-up. Subjects with liver dysfunction, a history of hepatic disease, malignant neoplasm, or cardiovascular events at baseline were excluded. Univariate and multivariate regression analyses showed that changes in serum M2BP concentrations during the follow-up period were significantly associated with changes in low-density lipoprotein cholesterol (LDL-C), triglyceride, and oxidative stress marker derivatives of reactive oxygen metabolites (d-ROM) concentrations. Moreover, the increase in LDL-C was significantly greater in subjects in whom M2BP concentrations increased during the follow-up period. Logistic regression analysis with an endpoint of increased M2BP revealed that increased LDL-C was an independent determinant of an increase in M2BP during the follow-up period. CONCLUSION: During the observation period of >3 years, serum M2BP concentrations were increased in subjects who also exhibited increases in levels of metabolic parameters, especially LDL-C, and the oxidative stress marker d-ROM. These results support that serum M2BP reflects one of the contributors to the progression of silent atherosclerosis.

The impact of intraday glucose variability on coronary artery spasm in patients with dysglycemia.

Impaired glucose metabolism is associated with an increased risk of cardiovascular complications, and coronary artery spasm is thought to underlie the development of coronary artery disease. Intraday glucose variability (GV) accelerates oxidative stress and inflammatory cytokine release, but its impact on coronary artery spasm remains unclear. This study investigated the relationship between intraday GV and coronary artery spasm. The study included 50 patients with dysglycemia and suspected coronary spastic angina. GV was analyzed by 24-h monitoring of the blood glucose concentration using a flash glucose monitoring system. The mean amplitude of glycemic excursion (MAGE) was calculated as an index of GV. Coronary artery spasm was assessed using the intracoronary acetylcholine provocation test. Coronary spasm was defined as acetylcholine-induced total or subtotal coronary occlusion. Changes in vessel diameter in response to acetylcholine were evaluated with quantitative coronary angiography. Coronary artery spasms were observed in 21 patients (42%). MAGE was significantly higher in patients with spasms compared to those without spasms (127.5 ± 33.5 vs. 91.4 ± 37.6, p < 0.01). Regression analysis showed a positive correlation between MAGE levels and coronary diameter changes induced by acetylcholine (r = 0.47, p < 0.01). In multiple regression analysis, MAGE was independently associated with acetylcholine-induced coronary diameter change (ß = 0.47, p < 0.01). Intraday GV was associated with coronary artery spasm in patients with dysglycemia.

Dietary Salt Intake is a Significant Determinant of Impaired Kidney Function in the General Population.

BACKGROUND/AIMS: Kidney dysfunction is an important risk factor for cardiovascular disease and end-stage renal disease. This study investigated whether dietary salt intake predicts deterioration of kidney function in the general population. METHODS: In all, 12 126 subjects with a normal estimated glomerular filtration rate (eGFR ≥60 mL/min per 1.73m2) attending an annual check-up were enrolled in the study and were followed-up for a median of 1754 days; the endpoint was the development of impaired kidney function (eGFR < 60 mL/min per 1.73m2). Individual salt intake was estimated using spot urine analysis. RESULTS: At baseline, mean (± SD) salt intake and eGFR were 10.6 ± 3.4 g/day and 80.8 ± 12.9 mL/min per 1.73m2, respectively. During the follow-up period, 1384 subjects (25.2 per 1000 person-years) developed impaired kidney function. Multivariate Cox hazard regression analysis revealed salt intake as a significant predictor of the new onset of kidney impairment (hazard ratio 1.045; 95% confidence interval 1.025-1.065). Subjects were divided into two groups based on salt intake; the incidence of impaired kidney function was higher in the group with high than low salt intake (P < 0.001, log-rank test). Multivariate Cox hazard regression analysis indicated a 29% increased risk of developing impaired kidney function in the high-salt group. Multivariate linear regression analysis showed a significant correlation between salt intake and yearly decline in eGFR (ß = 0.060, P < 0.001). CONCLUSION: Salt intake is associated with the development of impaired kidney function in the general population, independent of its effects on blood pressure. Salt restriction may help prevent the development of impaired kidney function.

Impact of malondialdehyde-modified low-density lipoprotein on coronary plaque vulnerability in patients not receiving lipid-lowering therapy: a whole coronary analysis with multislice-computed tomography.

Vulnerable plaque disruption was suggested as a primary cause of acute coronary syndrome. This study investigated the impact of malondialdehyde-modified low-density lipoprotein (MDA-LDL) on whole coronary plaque vulnerability, based on multislice-computed tomography (MSCT). We included 197 patients that were not receiving lipid-lowering therapy. We retrospectively analyzed MSCT and MDA-LDL measurements. We defined a CT-derived vulnerable plaque as a plaque with a remodeling index > 1.10 and a mean CT density value < 30 HU. Vulnerable plaques were detected in 60 patients (30%). Patients with vulnerable plaques had significantly higher MDA-LDL levels than patients without vulnerable plaques (151.3 ± 42.3 vs. 118.5 ± 41.7 U/L, p < 0.01). A univariate regression analysis showed that vulnerable plaques were significantly related to MDA-LDL levels [10 U/L groups, odds ratio (OR): 1.19; p < 0.01] and in a multivariate model (10 U/L groups, OR: 1.18; p < 0.01). Patients with multivessel vulnerable plaques had significantly higher MDA-LDL levels than those with single-vessel involvement or no vulnerable plaque (172.4 ± 28.5 vs. 142.8 ± 44.2 vs. 118.5 ± 41.7 U/L, respectively; p < 0.01). MDA-LDL difference was observed for all LDL tertiles (bottom; 128.9 ± 41.1 vs. 97.3 ± 25.0 U/L, p < 0.01, middle; 142.6 ± 42.7 vs. 122.5 ± 35.1 U/L, p = 0.05, top; 166.0 ± 38.1 vs. 143.5 ± 51.6 U/L, p = 0.05). Increased MDA-LDL levels were associated with the presence and extent of vulnerable plaques, regardless of LDL levels.

MicroRNA in atherothromobosis: is it useful as a disease marker?

Atherosclerosis is one of the major causes of death. Data from animal experiments suggest that atherosclerosis involves an inflammatory process of the vascular wall under hyperlipidemia. Atherothrombosis can become a serious complication of atherosclerosis leading to acute cardiovascular events such as myocardial infarction and stroke. Clinical applications to use this knowledge remain scarce. The plasma levels of vascular endothelium-enriched microRNA (miRNAs) in patients with atherosclerotic vascular disease could serve as a disease marker. In our laboratory vascular endothelium-enriched miRNA (miR-126) level was analyzed using quantitative RT polymerase chain reaction analysis (qRT-PCR) in plasma from patients with suspected coronary artery disease (CAD) according to the chest symptom or findings of electrocardiogram, or middle-aged male smokers. Endothelial function for peripheral small vessels was assessed using End-PAT 2000 and expressed as reactive hyperemia peripheral arterial tonometry (RH-PAT) index. In patients with suspected CAD miR-126 was not significantly changed in CAD patients. However, miR-126 was decreased in CAD patients who also have high levels of low-density lipoprotein (LDL) cholesterol. Interestingly, miR-126 was increased when LDL cholesterol was high in patients who did not have evident CAD on coronary angiography even though they have risk factors for CAD. In smokers serum cotinine levels were inversely correlated with endothelial function expressed as RH-PAT index and positively correlated with levels of metabolic parameters such as non-high-density lipoprotein (HDL) cholesterol and insulin resistance. More than half of the smokers could not completely attain smoking cessation and, thus, the RH-PAT index was not improved 8 weeks after the instruction of smoking cessation. However, changes in the RH-PAT index showed a significant correlation with those in systolic blood pressure. In smokers who completely attained smoking cessation, both RH-PAT index and plasma miR-126 values were increased. Thus, among patients with suspected CAD or subjects with coronary risk factors plasma levels of endothelium-enriched circulating miR-126 could be substantially altered. The results suggest a potential usefulness of miR-126 as a sensitive biomarker in assessing endothelial damage. Measurement of microRNA may serve as a useful tool for laboratory assays to determine high-risk patients for atherothromobotic vascular diseases.

A case report of asymptomatic aortic thrombosis incidentally detected by computed tomography in apparently healthy subject with a history of cancer surgery.

BACKGROUND: Aortic thrombosis is a rare disease and only a few cases of the disease, especially associated with chemotherapy for malignant diseases and/or blood diseases, have been previously reported. Although Virchow's triad for thrombogenesis, namely hypercoagulability, blood flow stasis, and vessel wall injury, is the major factor promoting the formation of thrombosis, the detailed mechanism of the disease has not been well established. CASE PRESENTATION: We report a case of aortic thrombosis incidentally detected by computed tomography and then regressed by pharmacotherapy using warfarin. This case is an apparently healthy man in a postoperative state after lung cancer surgery with decreased protein-C activity. CONCLUSIONS: A case of aortic thrombosis without an obvious abnormality of the aorta was incidentally identified. A few cases of aortic thrombosis in healthy aortas have been reported to be associated with chemotherapy or blood diseases, however our present case did not had such a background. Although the detailed mechanism remains to be elucidated, this case suggests that aortic thrombosis can develop in apparently healthy subjects with a history of cancer surgery.

Central blood pressure reflects left ventricular load, while brachial blood pressure reflects arterial damage.

OBJECTIVES: The present study investigated whether brachial and central blood pressures have differential impact on the cardiovascular system in the general population. METHODS: The study included 706 subjects (59 ± 10 years) who visited our hospital for a physical check-up. Brachial blood pressure and radial artery pressure waveforms were recorded using an automated device, and the pressure corresponding to the radial late systolic peak (SBP2) was taken as central blood pressure. The concentration of B-type natriuretic peptide and the intima-media thickness of the carotid artery were measured and a cross-sectional analysis was performed. RESULTS: Brachial blood pressure was 128 ± 18/74 ± 12 (mean blood pressure, 92 ± 13) mmHg and SBP2 was 120 ± 19 mmHg. Although both brachial systolic blood pressure and SBP2 correlated with B-type natriuretic peptide in a univariate analysis, only SBP2 independently correlated with B-type natriuretic peptide after adjustment for possible factors. In contrast, brachial systolic blood pressure, but not SBP2, independently correlated with carotid artery intima-media thickness. CONCLUSIONS: Central blood pressure is more closely associated with left ventricular load than brachial blood pressure, while brachial blood pressure is more strongly associated with vascular damage than central blood pressure.

Impact of medical checkup parameters on major adverse cardiovascular events in the general Japanese population.

Medical checkups play a role in the identification of individuals at increased cardiovascular risk. However, the impact of each medical examination parameter on the incidence of major adverse cardiovascular events (MACE) has not been intensively studied. Here we assessed the predictors of MACE among parameters examined during medical checkups in the general Japanese population. A total of 13,522 individuals (mean age, 52.8 ± 12.3 years) who participated in our medical checkup program from 2008 to 2015 were followed up for a median of 1,827 days with the endpoint of MACE. MACE included cardiovascular death, non-fatal myocardial infarction, angina, decompensated heart failure, stroke, and other cardiovascular events requiring hospitalization. Possible associations between MACE and baseline clinical test parameters were investigated. During follow-up, MACE occurred in 196 participants. Participants with hypertension, diabetes mellitus, dyslipidemia, or metabolic syndrome were at increased risk of MACE on the univariate analysis. Multivariate Cox hazard analysis demonstrated that male sex, age, systolic blood pressure, and baseline B-type natriuretic peptide level were independently correlated with future MACE after the adjustment for confounders; the impact of B-type natriuretic peptide was most prominent among the investigated variables. These results suggest that B-type natriuretic peptide level obtained during a medical checkup examination is an independent and strong predictor of MACE. The inclusion of BNP as part of medical checkup parameters may improve the ability to identify individuals at increased cardiovascular risk and prevent cardiovascular disease among them.

Dietary salt intake predicts future development of metabolic syndrome in the general population.

Excessive dietary salt consumption is one of the most important risk factors for hypertension. Metabolic disorders often coexist with hypertension, and excess salt intake has been reported to underlie metabolic disorders, such as insulin resistance. Therefore, we tested the hypothesis that excessive dietary salt causes metabolic syndrome in the general population. In total, 13886 subjects who participated in our medical checkup were enrolled, and salt intake was assessed using a spot urine sample. The characteristics of participants with metabolic syndrome (n = 1630) were examined at baseline, and then participants without metabolic syndrome (n = 12256) were followed up with the endpoint being the development of metabolic syndrome. The average estimated salt intake in our participants was 8.72 ± 1.93 g/day. A significant association between salt intake and metabolic syndrome was obtained from the logistic regression analysis, and salt intake increased as the number of metabolic disorders in an individual increased at baseline (P < 0.001). During the median follow-up period of 52 months, 1669 participants developed metabolic syndrome. Kaplan-Meier analysis demonstrated an increased risk of metabolic syndrome across quartiles of baseline salt intake (log-rank, P < 0.001). In the Cox proportional hazard regression analysis where salt intake was taken as a continuous variable, salt intake at baseline was an independent predictor of developing metabolic syndrome. These results suggest that excessive salt intake is significantly associated with the development of metabolic syndrome in the general population. Salt may play an important role in the development of metabolic disorders and hypertension.

Cumulative Cigarette Consumption is Associated with Cardio-Ankle Vascular Index (CAVI) Mediated by Abdominal Obesity Assessed by A Body Shape Index (ABSI): A Cross-Sectional Study.

AIM: To elucidate the mechanism by which cigarette smoking causes vascular damage, we examined the relationship between cumulative cigarette consumption and abdominal obesity, and the possible mediating effect of smoking on arterial stiffness. METHODS: Cross-sectional data from 19499 never smokers and 5406 current smokers receiving health screening was analyzed. Abdominal obesity was assessed by ABSI, and arterial stiffness by CAVI. High CAVI was defined as CAVI ≥ 9.0. RESULTS: Current smoker showed higher ABSI than never smokers after propensity score matching. Cumulative cigarette consumption expressed in pack-years correlated with ABSI (Rs: 0.312 in men, 0.252 in women), and was also extracted as an independent factor associated with ABSI by multiple regression analysis. A linear relationship between pack-year and CAVI was observed (Rs: 0.544 in men, 0.423 in women). Pack-year had almost equal discriminatory power in predicting high CAVI in both sexes (C-statistic: 0.774 in men, 0.747 in women), and the best cut-offs of pack-year for high CAVI were 24.5 in men and 14.7 in women. Bivariate logistic regression models revealed that the association between pack-year higher than cut-off and high CAVI was independent of traditional risks. A mediating effect of ABSI (mediation rate: 9.9% in men and 11.2% in women), but not waist circumference (WC), on the association of pack-year with CAVI was observed, after adjusting for traditional risks. CONCLUSION: Cumulative cigarette smoking in pack-years was independently associated with ABSI. ABSI partially mediates the association between pack-year and CAVI, suggesting that abdominal obesity partially mediates smoking-related vascular dysfunction.

Various Obesity Indices and Arterial Function Evaluated with CAVI - Is Waist Circumference Adequate to Define Metabolic Syndrome?

Obesity has been known to relate to various diseases and metabolic disorders. Since the implication of body shape has been mentioned, obesity can be divided into visceral obesity and subcutaneous obesity. The former is considered the upstream pathophysiology of metabolic syndrome (MetS), and has been emphasized worldwide for the prevention of cardiovascular diseases in the last quarter century. However, some prospective studies have shown that cardiovascular mortality and morbidity are not necessarily higher in patients with MetS compared to those without. Recently, cardio-ankle vascular index (CAVI) has been established as an indicator of arteriosclerosis. This parameter is independent of blood pressure at the measuring time, and reflects systemic arterial stiffness from the aortic origin to the ankle. However, since CAVI is not necessarily high in MetS patients, attempts have been made to clarify this unexpected phenomenon. In several studies, CAVI was found to correlate negatively with body mass index (BMI), and also with waist circumference (WC) which is a widely used representative visceral obesity index. On the other hand, a body shape index (ABSI) is also a visceral obesity index designed to be minimally associated with BMI, and is calculated by dividing WC by an allometric regression of weight and height. Replacing high WC with high ABSI in MetS diagnosis promoted the identification of MetS patients with increased CAVI in cross-sectional studies on Japanese and Korean populations. Additionally, the incidence of MetS diagnosed using high ABSI was associated with significant increase in CAVI after 1 year of observation. Enhanced predictive ability for renal function decline by replacing WC with ABSI in MetS diagnosis was also observed in a longitudinal study in Japanese urban residents. These findings suggest that MetS diagnosis using high ABSI instead of high WC as a visceral obesity index needs to be reconsidered. However, further research is desirable on Caucasian, whose body shape differs slightly from that of Asians.

Blood pressure variability and the development of hypertensive organ damage in the general population.

Increasing blood pressure variability (BPV) has been reported to be a strong predictor of cardiovascular events in patients with hypertension. However, the effects of BPV in the general population have not been intensively studied. The present study was designed to investigate a possible relationship between year-to-year BPV and hypertensive target organ damage (TOD) in a relatively low-risk general population. A total of 5489 consecutive patients (mean age 58.6 ± 10.7 years) who visited our hospital for an annual physical checkup for five consecutive years during 2008-2013 were enrolled in this study. The average systolic and diastolic blood pressures and pulse pressure were calculated, as well as standard deviation, coefficient of variation, and average real variability in blood pressures. Cross-sectional analysis was conducted and subjects without TOD at baseline (n = 3115) were followed up (median 1827 days) with the endpoint of TOD, defined as left ventricular hypertrophy on electrocardiogram or declining glomerular filtration rate. At baseline, BPV was closely associated with TOD. During follow-up, left ventricular hypertrophy and declining glomerular filtration rate developed in 189 and 400 subjects, respectively. Although the standard deviation for systolic blood pressure and pulse pressure predicted future development of TOD in a univariate analysis, BPV was not a significant determinant of incident TOD in adjusted Cox hazard models. These results suggest that year-to-year BPV is a marker of the presence of TOD in the general population but does not independently predict future TOD.

Impact of glucose variability on coronary plaque vulnerability in patients with dysglycemia: A whole coronary analysis with multislice computed tomography.

BACKGROUND: Dysglycemia is associated with an increased risk of acute coronary syndrome caused by the disruption of vulnerable plaques. The relationship between glycemic variability (GV), which is a component of impaired glucose metabolism, and coronary plaque vulnerability has not been fully elucidated. This study investigated the impact of GV on whole coronary plaque vulnerability using multislice computed tomography (MSCT). METHODS: We analyzed 88 patients with dysglycemia who underwent 24 h blood glucose monitoring and MSCT. The mean amplitude of glycemic excursion (MAGE) was calculated as an index of the GV. We defined a CT-derived vulnerable plaque as a plaque with a remodeling index > 1.10 and a mean CT density < 30 HU. We calculated the percentage of low-attenuation plaque (% LAP) as the ratio of the low-attenuation component (CT density < 30HU) volume to the total vessel volume. RESULTS: Vulnerable plaques were detected in 27 patients (31%). Patients with vulnerable plaques had higher MAGE (110.0 ± 40.7 vs. 71.7 ± 21.7, p < 0.01) than patients without vulnerable plaques. A univariate logistic regression analysis showed that vulnerable plaques were associated with the MAGE [odds ratio (OR) 1.04, 95% confidence interval (CI), 1.02-1.07, p < 0.01]. In a multivariate model, the MAGE (OR 1.05, 95% CI 1.02-1.07) remained a significant predictor of vulnerable plaque presence. Patients with multivessel-vulnerable plaques had higher MAGE values than those with single-vessel involvement or no vulnerable plaques (132.3 ± 39.4 vs. 102.2 ± 39.7, vs. 71.7 ± 21.7, p < 0.01). The regression analysis showed a positive correlation between MAGE levels and the % LAP (r = 0.55, p < 0.01). In a multiple linear regression analysis, the MAGE was independently associated with the % LAP (ß = 0.42, p < 0.01). CONCLUSIONS: Increased GV is associated with the presence and extent of vulnerable plaques.