Sex-specific associations between serum uric acid levels and risk of hypertension for different diagnostic reference values of high blood pressure.

The association between uric acid (UA) and hyperuricemia with 5-year hypertension incidence using different blood pressure (BP) diagnostic references in men and women without cardiometabolic diseases is unknown. We used the checkup data from Kagoshima Kouseiren Hospital. All participants with hypertension or on BP medication, diabetes, dyslipidemia, obesity, estimated glomerular filtration rate<60 ml/min/1.73m2, metabolic syndrome, history of gout, and UA-lowering medication were excluded. UA was categorized into sex-specific quartiles and hyperuricemia was defined as UA > 7 mg/dl in men and UA > 6 mg/dl in women. We performed multivariate logistic regression to assess the effects of UA on hypertension development. The 5-year hypertension incidence was defined as subsets of BP ≥ 140/90 mmHg in cohort 1 and BP ≥ 130/80 mmHg in cohort 2. The study enrolled 21,443 participants (39.8%, men) in cohort 1 and 15,245 participants (36.5%, men) in cohort 2. The incidence of hypertension in cohorts 1 and 2 over 5 years was 16.3% and 29.7% in men and 10.9% and 21.4% in women, respectively. When comparing the fourth to the first UA quartile, there was an association with hypertension in men in cohort 1, with odds ratio (OR): 1.36 (95% confidence interval [CI], 1.13-1.63, p < 0.01) and cohort 2, OR: 1.31 (95%CI, 1.09-1.57, p < 0.01), respectively, but not in women. Additionally, an association between hyperuricemia and hypertension was observed in men only in cohort 1, with OR: 1.23 (95%CI, 1.07-1.42, p = 0.02), and in women in cohort 2, OR: 1.57 (95%CI, 1.14-2.16, p < 0.01). The effect of UA on the development of hypertension is influenced by sex and incidence differs with the BP reference used. Uric acid effect on the development of hypertension is affected by sex and incidence differs with the BP reference used.

Development of predictive equation and score for 5-year metabolic syndrome incidence in Japanese adults.

BACKGROUND: Predicting metabolic syndrome (MetS) is important for identifying high-risk cardiovascular disease individuals and providing preventive interventions. We aimed to develop and validate an equation and a simple MetS score according to the Japanese MetS criteria. METHODS: In total, 54,198 participants (age, 54.5±10.1 years; men, 46.0%), with baseline and 5-year follow-up data were randomly assigned to 'Derivation' and 'Validation' cohorts (ratio: 2:1). Multivariate logistic regression analysis was performed in derivation cohort and scores were assigned to factors corresponding to ß-coefficients. We evaluated predictive ability of the scores using area under the curve (AUC), then applied them to validation cohort to assess reproducibility. RESULTS: The primary model ranged 0-27 points had an AUC of 0.81 (sensitivity: 0.81, specificity: 0.81, cut-off score: 14), and consisted of age, sex, blood pressure (BP), body mass index (BMI), serum lipids, glucose measurements, tobacco smoking, and alcohol consumption. The simplified model (excluding blood tests) ranged 0-17 points with an AUC of 0.78 (sensitivity: 0.83, specificity: 0.77, cut-off score: 15) and included: age, sex, systolic BP, diastolic BP, BMI, tobacco smoking, and alcohol consumption. We classified individuals with a score <15 and ≥15 points as low- and high-risk MetS, respectively. Furthermore, the equation model generated an AUC of 0.85 (sensitivity: 0.86, specificity: 0.55). Analysis of the validation and derivation cohorts yielded similar results. CONCLUSION: We developed a primary score, an equation model, and a simple score. The simple score is convenient, well-validated with acceptable discrimination, and could be used for early detection of MetS in high-risk individuals.

Clinical significance of atherosclerotic risk factors differs in early and advanced stages of plaque formation: A longitudinal study in the general population.

BACKGROUND: Carotid plaque is a well-known prognostic factor for cardiovascular diseases. It is unclear which risk factors are associated with the transformation of carotid plaque over time. In this longitudinal study, we examined the risk factors related to carotid plaque progression. METHODS: We enrolled 738 men without medication (mean age: 55 ± 10 years) who underwent the first and second health examinations. We measured carotid plaque thickness (PT) at three points of the right and left carotid artery. Plaque score (PS) was calculated by summing all the PTs. We divided the PS into three groups: None-group (PS <1.1), Early-group (1.1 ≤ PS <5.1), and Advanced-group (PS ≥5.1). We analyzed the relationship between PS progression and parameters such as age, body mass index, systolic blood pressure (SBP), fasting blood sugar, low-density lipoprotein cholesterol (LDL-C), and smoking and exercise habits. RESULTS: In multivariable logistic regression analysis, age and SBP were independent factors for PS progression from none to early stages (age, OR 1.07, p = 0.002; SBP, 10 mmHg, OR 1.27, p = 0.041). Age, follow-up period and LDL-C were independently associated factors for PS progression from early to advanced stages (age, OR 1.08,p < 0.001; follow-up period OR1.19, p = 0.041; LDL-C, 10 mg/dL, OR 1.10, p = 0.049). CONCLUSIONS: SBP was independently associated with the progress of early atherosclerosis, while LDL-C was independently associated with the progression of advanced atherosclerosis in the general population. Further studies are needed to assess whether early control of SBP and LDL-C levels can reduce the occurrence of future cardiovascular events.

Development of a risk prediction score and equation for chronic kidney disease: a retrospective cohort study.

Chronic kidney disease (CKD) is a risk factor for end-stage renal disease and contributes to increased risk of cardiovascular disease morbidity and mortality. We aimed to develop a risk prediction score and equation for future CKD using health checkup data. This study included 58,423 Japanese participants aged 30-69 years, who were randomly assigned to derivation and validation cohorts at a ratio of 2:1. The predictors were anthropometric indices, life style, and blood sampling data. In derivation cohort, we performed multivariable logistic regression analysis and obtained the standardized beta coefficient of each factor that was significantly associated with new-onset CKD and assigned scores to each factor. We created a score and an equation to predict CKD after 5 years and applied them to validation cohort to assess their reproducibility. The risk score ranged 0-16, consisting of age, sex, hypertension, dyslipidemia, diabetes, hyperuricemia, and estimated glomerular filtration rate (eGFR), with area under the curve (AUC) of 0.78 for the derivation cohort and 0.79 for the validation cohort. The CKD incidence gradually and constantly increased as the score increased from ≤ 6 to ≥ 14. The equation consisted of the seven indices described above, with AUC of 0.88 for the derivation cohort and 0.89 for the validation cohort. We developed a risk score and equation to predict CKD incidence after 5 years in Japanese population under 70 years of age. These models had reasonably high predictivity, and their reproducibility was confirmed through internal validation.

Cutoff Values of Brachial-Ankle Pulse Wave Velocity for Atherosclerotic Risks by Age and Sex in the Japanese General Population.

AIM: In this study, we aim to analyze the correlation between brachial-ankle pulse wave velocity (baPWV) and Suita score or Framingham risk score and obtain the cutoff value of baPWV by sex and age for cardiovascular risk, as assessed by these scores in the large Japanese annual health checkup data. METHODS: In total, 25,602 participants (14,539 men and 11,063 women), who had their annual health checkups, were included in this study. Cutoff values of baPWV for the moderate- and high-risk groups stratified by sex and age were obtained using a receiver operating characteristic (ROC) curve analysis. RESULTS: As per our findings, the Suita score demonstrated better correlations with baPWV than the Framingham risk score in both sexes (men, Suita score R2=0.41 and Framingham risk score R2=0.37; women, Suita score R2=0.54 and Framingham risk score R2=0.33). The ROC curve analysis demonstrated the cutoff values of baPWV for moderate- and high-risk groups estimated using the Suita score, and they are as follows: in men, the baPWV cutoff values were 1,350 cm/s in the 40s, 1,430 cm/s in the 50s, 1,520 cm/s in the 60s, and 1,880 cm/s in the 70s. In women, the baPWV cutoff values were 1,350 cm/s in the 40s, 1,430 cm/s in the 50s, 1,570 cm/s in the 60s, and 1,800 cm/s in the 70s. CONCLUSIONS: We demonstrated that baPWV significantly correlated with the Suita score or Framingham risk score in both men and women, with the former presenting a stronger correlation than the latter. We propose the cutoff values of baPWV for moderate- and high-risk groups estimated using the Suita score.

Insufficient blood pressure control is independently associated with increased arterial stiffness.

Hypertension is a risk factor for atherosclerosis. Achieving the therapeutic target value of blood pressure (BP) prevents the onset of cardiovascular events; however, it is not clear how antihypertensive drug use and BP control status relate to arterial stiffness. The purpose of this study is to investigate the relationship between BP control status with or without antihypertensive drugs and arterial stiffness. Nine hundred eighty individuals (mean age: 68 ± 11 years) who participated in a community-based cohort study were enrolled. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). Higher BP was defined as a systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. Participants were divided into four groups: normal, non higher BP without antihypertensive drugs (n = 421); untreated, higher BP without antihypertensive drugs (n = 174); good control, non higher BP with antihypertensive drugs (n = 209); and poor control, higher BP with antihypertensive drugs (n = 176). In multivariable logistic analysis adjusted for age, sex, dyslipidemia and diabetes mellitus medication use, obesity, smoking, alcohol drinking, and heart rate at the CAVI measurement for a high CAVI-using a borderline cutoff value of 8.0-the other three groups were significantly associated with a high CAVI when compared with the normal group. By contrast, multivariable logistic analysis of a high CAVI using an abnormal cutoff value of 9.0 demonstrated that the poor control and untreated groups were significantly associated with a high CAVI, whereas the good control group was not. In conclusion, even with antihypertensive drugs, poor BP control is independently associated with a high CAVI.

Assessment of Future Hypertension Risk by Sex Using Combined Body Mass Index and Waist-to-Height Ratio.

Background: Body mass index (BMI) and the waist-to-height ratio (WHtR) are widely used anthropometric indices of obesity to predict cardiovascular risks. However, the usefulness of combining WHtR and BMI values to predict hypertension risk by sex has not been well elucidated. Methods and Results: This cohort study enrolled 45,921 participants (mean [±SD] age 53.8±10.5 years; 47.0% men) without hypertension from among those undergoing annual health checkups. Participants were divided into 4 categories based on median BMI and WHtR values, and the 5-year incidence of hypertension was assessed for both sexes using logistic regression analysis. Mean (±SD) BMI and WHtR values were 23.5±3.1 kg/m2 and 0.50±0.05, respectively, in men and 22.4±3.3 kg/m2 and 0.53±0.06, respectively, in women. Among the women, those with high BMI and low WHtR had an increased risk of hypertension compared with those with low BMI and low WHtR (odds ratio [OR] 1.37, P<0.001); however, the same result was not found in men (OR 1.14, P=0.080). In both sexes, the incidence of hypertension was higher among participants with low BMI and high WHtR than among those with low BMI and low WHtR (men: OR 1.26, P<0.001; women: OR 1.15, P=0.048). Conclusions: Using WHtR and BMI together provides a better hypertension risk assessment. Among men, those with a high BMI had no increased hypertension risk when WHtR was low.

The relationship between day-to-day variability in home blood pressure measurement and multiple organ function.

Blood pressure variability (BPV) is associated with the prognosis of cardiovascular diseases. However, it is unclear how BPV is related to various organs. The aim of this study is to investigate the association between BPV and multiple organ functions. A total of three hundred fifteen participants (114 males; mean age: 70 ± 9 years) participated in a community health checkup held in Tarumizu City. Home blood pressure (BP) was measured using a HEM-9700T (OMRON Healthcare, Kyoto, Japan). Day-to-day BPV was evaluated by the coefficient of variation (CV) of home BP measured in the morning for one month. N-terminal pro B-type natriuretic peptide (NT-pro BNP) and high-sensitivity (hs-)troponin T were measured as cardiac biomarkers. Liver stiffness and renal function were evaluated using the Fibrous-4 (Fib4) index and estimated glomerular filtration rate (eGFR), respectively. NT-pro BNP and hs-troponin T were divided by the median value. Fib4 index greater than 2.67 and eGFR less than 60 mL/min/1.73 m2 were defined as high Fib4 index and low eGFR, respectively. In a multivariable logistic regression analysis, the CV of systolic BP was significantly associated with high NT-pro BNP, high Fib 4 index, and low eGFR, but not with high hs-troponin T. In contrast, the CV of diastolic BP was not associated with low eGFR, and the other three biomarkers had the same results as systolic BP. In conclusion, day-to-day BPV of systolic BP is independently associated with NT-pro BNP, eGFR, and Fib4 index, but not with hs-troponin T. In contrast, diastolic BPV was not found to be associated with eGFR.

Development of a risk prediction score for hypertension incidence using Japanese health checkup data.

Hypertension is a risk factor for cardiovascular disease. We developed a simple scoring method for predicting future hypertension using health checkup data. A total of 41,902 participants aged 30-69 years without baseline hypertension who underwent annual health checkups (mean age, 52.3 ± 10.2 years; male, 47.7%) were included. They were randomly assigned to derivation (n = 27,935) and validation cohorts (n = 13,967) at a ratio of 2:1. In the derivation cohort, we performed multivariable logistic regression analysis and assigned scores to each factor significantly associated with 5-year hypertension. We evaluated the predictive ability of the scores using area under the curve (AUC) analysis and then applied them to the validation cohort to assess their validity. The score including items requiring blood sampling ranged from 0 to 14 and included seven indicators (age, body mass index, blood pressure, current smoking, family history of hypertension, diabetes, and hyperuricemia). The score not including items requiring blood sampling ranged from 0 to 12 and included five indicators (the above indicators, except diabetes and hyperuricemia). The score not including items requiring blood sampling was better; blood sampling did not improve diagnostic ability. The AUC of the score not including items requiring blood sampling was 0.76, with a sensitivity and specificity of 0.82 and 0.60, respectively, for scores ≥6 points. The incidence of hypertension gradually and constantly increased (from 0.9 to 49.6%) as the score increased from 0 to ≥10. Analysis in the validation cohort yielded similar results. We developed a simple and useful clinical prediction model to predict the 5-year incidence of hypertension among a general Japanese population. The model had reasonably high predictive ability and reproducibility.

J-shaped curve for the association between serum uric acid levels and the prevalence of blood pressure abnormalities.

Low and high serum uric acid levels are associated with an increased risk of cardiovascular diseases. However, whether there is a similar association between serum uric acid levels and blood pressure abnormalities has not yet been elucidated. Data from 236,221 individuals (age, 56.0 ± 15.0 years; 107,146 men) who underwent routine health checkups were analyzed. Participants with a serum uric acid level ≤2.0 mg/dL were separated, and the remaining participants were divided into quartiles according to their serum uric acid levels. Among each group, the proportions of participants with high blood pressure (≥130/80 mmHg, and/or medication) and hypertension (≥140/90 mmHg, and/or medication), were calculated. The adjusted odds ratio of each group compared to the group with the lowest proportion of blood pressure abnormalities was calculated. The participants were divided into five groups according to their serum uric acid levels, ≤2.0, 2.1-4.0, 4.1-5.0, 5.1-6.0, and ≥6.1 mg/dL, and the prevalence of high blood pressure was 49.0, 44.6, 52.3, 58.6, and 65.3% and that of hypertension was 31.0, 27.4, 33.5, 38.7, and 43.8%, respectively. Compared to the second-lowest serum uric acid group (2.1-4.0 mg/dL), groups with higher serum uric acid levels (4.1-5.0, 5.1-6.0, and ≥6.1 mg/dL), as well as the group with the lowest serum uric acid level (≤2.0 mg/dL), showed significantly higher odds ratios for high blood pressure and hypertension. High and low serum uric acid levels were significantly associated with an increased prevalence of high blood pressure and followed a J-shaped curve.

Gender differences in the risk factors associated with atherosclerosis by carotid intima-media thickness, plaque score, and pulse wave velocity.

Cardiovascular disease (CVD) remains the leading cause of death, but the risk factors for CVD differ between men and women. Although carotid intima-media thickness (IMT), carotid plaque, and pulse wave velocity (PWV) are useful atherosclerotic parameters, patient backgrounds have differed in previous reports. Therefore, this study aimed to investigate gender differences in associations between these three parameters and traditional risk factors in the same population. We enrolled 3888 participants (women: 743) who underwent routine health checkups. High IMT, high carotid plaque score (PS), or high brachial-ankle PWV (baPWV) were defined by the median values for each gender. We analyzed the association between each parameter and atherosclerotic risk factors, such as obesity, smoking, blood pressure (BP) elevation, impaired fasting glucose (IFG), and dyslipidemia (DL). In both sexes, BP elevation was the only common risk factor for high IMT, high PS, and high baPWV in the multivariate logistic regression analysis adjusted for age. In men, IFG and DL were common risk factors for the three parameters. Furthermore, obesity was an additional risk factor for high IMT and smoking was an additional risk factor for high IMT and high PS. In contrast, in women, obesity, DL, or IFG was an additional risk factor for high IMT, high PS, or high baPWV, respectively. The risk factors for IMT, PS, and baPWV differ in in men and women. The management for atherosclerotic risk factors on early stage should be considered in terms of gender-specific risk factors.

The relationship between home blood pressure measurement and room temperature in a Japanese general population.

Blood pressure (BP) is influenced by various factors, and it is known that temperature and BP have a negative relationship. However, few reports have examined the relationship between BP and temperature throughout the day in the same participant over time. Therefore, this study aimed to investigate the relationship between BP and temperature in the morning and evening in the same participants during a time period of ~1 year. In total, 401 participants, who participated in a community-based health checkup survey in Tarumizu, Japan, were enrolled. Five participants were excluded due to missing data. All participants measured their BP and the room temperature at home using a blood pressure monitor (HEM-9700T, OMRON Healthcare, Kyoto, Japan). The mean systolic BP (SBP) and diastolic BP (DBP) in the morning were significantly higher than the mean of the measurements taken in the evening (SBP: morning vs. evening 128 ± 15 mmHg vs. 122 ± 14 mmHg, P < 0.0001; DBP: morning vs. evening 77 ± 10 mmHg vs. 72 ± 8 mmHg, P < 0.0001). Using a linear mixed model with participants as a random effect, SBP and DBP were significantly associated with temperature in both the morning and evening. In the morning, in almost every month except July, a significant association between SBP and temperature was observed. However, there was a significant relationship between evening BP and temperature in all months. In conclusion, BP was significantly related to temperature in both the morning and evening during the year-long study. Furthermore, BP and temperature were significantly associated in all months except morning measurements in July.

Association of risk factors for atherosclerosis, including high-sensitivity C-reactive protein, with carotid intima-media thickness, plaque score, and pulse wave velocity in a male population.

Intima-media thickness (IMT), plaque score (PS), and brachial-ankle pulse wave velocity (baPWV) are noninvasive parameters used for the evaluation of atherosclerosis. There have been no reports investigating the associations between IMT, PS, or baPWV and known risk factors for atherosclerosis in the same participants. This study aimed to compare the contributing risk factors among IMT, PS, and baPWV. We enrolled 3128 male participants who underwent health checkups. Carotid ultrasonography was used to measure IMT and PS, and baPWV was measured using an automatic device. We analyzed the association between these parameters and risk factors for atherosclerosis including obesity, smoking, alcohol, high blood pressure (BP), impaired fasting glucose (IFG), dyslipidemia (DL), and high-sensitivity C-reactive protein (hs-CRP). Multivariate logistic regression analysis revealed high IMT (>0.9 mm) to be independently associated with high BP. The presence of atherosclerosis (PS ≥ 1.1 mm) was independently associated with high BP, IFG, and DL. In addition, advanced atherosclerosis (PS ≥ 5.1 mm) showed a significant association with high BP, IFG, DL, log hs-CRP, and smoking. High baPWV (≥1600 cm/s) was significantly correlated with high BP, IFG, and log hs-CRP. IMT, PS, and baPWV were all associated with different risk factors among male Japanese participants. Only high BP was a common risk factor for all three parameters. Furthermore, hs-CRP was associated with advanced atherosclerosis but not with the presence of atherosclerosis.

Sex Differences in the Effects of Weight Reduction on Future Blood Pressure Elevation in a Mildly Obese Middle-Aged Population.

Background: The effectiveness of weight loss (WL) in preventing blood pressure (BP) elevation is common knowledge; however, the effect of sex differences is not known. Methods and Results: Health checkup data from Kagoshima Kouseiren Medical Healthcare Center for middle-aged participants (40-49 years old) with mild obesity (body mass index [BMI] 25.0-29.9 kg/m2) who had examination data for 2 follow-up time-points (after 3 and 10 years) were analyzed. Propensity score (PS) matching using data from the first examination was used to match participants with a decrease in BMI ≥1.0 kg/m2 at 3 years (WL group) with those with a BMI decrease <1.0 kg/m2 or weight gain (non-WL group). BP values were compared after 3 and 10 years between the 2 groups, as was the prevalence of hypertension after 10 years. PS matching resulted in 232 men and 160 women in each group. Among women, systolic BP (SBP) and hypertension prevalence after 10 years were significantly lower in the WL than non-WL group (P<0.01 and P<0.05, respectively). There were no significant differences in SBP and hypertension prevalence after 10 years in men in the 2 groups. Conclusions: There were sex differences in the effectiveness of WL in preventing future BP elevation in mildly obese middle-aged participants: WL prevented future BP elevation and hypertension onset in women, but not in men.

A case of acute coronary syndrome caused by delayed coronary ischemia after transcatheter aortic valve implantation.

An 84-year-old female patient suffered from dyspnea due to severe aortic stenosis. Several comorbidities and her advanced age made her acceptable for transcatheter aortic valve implantation (TAVI). The TAVI procedure was performed via a femoral access and a 26-mm CoreValve prosthesis (Medtronic, Minneapolis, MN, USA) was implanted. The prosthesis was deployed at a high position because of short distance between the annulus base and coronary arteries. Aortic angiography indicated normal contrast flow into both coronary arteries. Six months later she was readmitted to our hospital because of acute coronary syndrome. Although selective intubation of coronary arteries could not be achieved because of high valve position, both coronary arteries seemed to be well contrasted. As a consequence, the second coronary angiography was undertaken because of recurring chest pains. The aortic root angiogram showed a decreased contrast flow into both coronary arteries. During the examination she deteriorated rapidly, developed cardiopulmonary arrest, and a percutaneous cardiopulmonary support and an intra-aortic balloon pump needed to be inserted. She was then transferred to the operating room for aortic valve replacement. This is the first case of delayed coronary ischemia after TAVI, necessitating the removal of an implanted CoreValve and its replacement with a new prosthetic valve. .