Development of a risk prediction model for incident hypertension in a working-age Japanese male population.

The aim of this study was to develop a risk prediction model for incident hypertension in a Japanese male population. Study participants included 15,025 nonhypertensive Japanese male workers (mean age, 38.8±8.9 years) who underwent an annual medical checkup at a company. The participants were followed-up for a median of 4.0 years to determine new-onset hypertension, defined as a systolic blood pressure (BP) ⩾140 mm Hg, a diastolic BP ⩾90 mm Hg, or the initiation of antihypertensive medication. Participants were divided into the following two cohorts for subsequent analyses: the derivation cohort (n=12,020, 80% of the study population) and the validation cohort (n=3005, the remaining 20% of the study population). In the derivation cohort, a multivariate Cox proportional hazards model demonstrated that age, body mass index, systolic and diastolic BP, current smoking status, excessive alcohol intake and parental history of hypertension were independent predictors of incident hypertension. Using these variables, a risk prediction model was constructed to estimate the 4-year risk of incident hypertension. In the validation cohort, the risk prediction model demonstrated high discrimination ability and acceptable calibration, with a C-statistic of 0.861 (95% confidence interval 0.844, 0.877) and a modified Hosmer-Lemeshow χ2 statistic of 15.2 (P=0.085). A risk score sheet was constructed to enable the simple calculation of the approximate 4-year probability of incident hypertension. In conclusion, a practical risk prediction model for incident hypertension was successfully developed in a working-age Japanese male population.

Serum cystatin C, creatinine-based estimated glomerular filtration rate, and the risk of incident hypertension in middle-aged men.

BACKGROUND: The aim of this study was to examine the predictive value of serum cystatin C (CysC) and that of creatinine-based estimated glomerular filtration rate (eGFRCreat) for the risk of incident hypertension in a middle-aged male population. METHODS: Serum CysC levels were measured in 904 nonhypertensive, Japanese male subjects (mean age = 44±6 years) who received an annual general health examination in a company. Serum creatinine levels were simultaneously measured, and eGFRCreat was calculated. Subjects were followed-up for a maximum period of 4 years, and annual blood pressure measurements were recorded. RESULTS: During the follow-up period, 124 subjects developed hypertension, defined as systolic/diastolic blood pressure ≥140/90 mmHg or use of antihypertensive medications. In the Kaplan-Meier analysis, both the third quintile of CysC and that of eGFRCreat showed the lowest 4-year cumulative incident rate of hypertension. The multiadjusted hazard ratio for incident hypertension was significantly increased in the highest quintile of CysC compared with the third quintile (2.60; 95% confidence interval (CI) = 1.41-4.77; P = 0.002), as well as compared with the lowest 4 quintiles combined (1.89; 95% CI = 1.26-2.84; P = 0.002). However, eGFRCreat did not show significant hazard ratios for incident hypertension in any of the adjusted models. CONCLUSIONS: Elevated serum CysC levels could predict the risk of incident hypertension in this study population with a maximum follow-up period of 4 years. In contrast, eGFRCreat did not show predictive value for the risk of incident hypertension.

Oscillometric measurement of brachial artery cross-sectional area and its relationship with cardiovascular risk factors and arterial stiffness in a middle-aged male population.

An enlarged arterial diameter is associated with an increased risk for cardiovascular disease. This study examined the relationship of noninvasively measured brachial artery cross-sectional area with cardiovascular risk factors and arterial stiffness in a middle-aged male population. Absolute volumetric changes of the brachial artery were measured with a newly developed oscillometric method during a general health examination in 387 men (mean age: 38±9 years) without known cardiovascular disease. Based on the measurement, the estimated area (eA) of the brachial artery at end-diastole was obtained. Brachial artery volume elastic modulus (VE) and brachial-ankle pulse wave velocity (baPWV) were simultaneously measured as indices of arterial stiffness by the same device. The relationships of eA with cardiovascular risk factors, including age, obesity, hypertension, dyslipidemia, impaired fasting glucose/diabetes mellitus (IFG/DM), hyperuricemia, smoking and their associated continuous variables, as well as VE and baPWV, were examined. Overall, the mean eA was 12.9 ± 2.9 mm². The eA was significantly higher in subjects with obesity, hypertension or IFG/DM than in those without each of these risk factors. In a multiple linear regression analysis, body mass index (ß=0.31, P<0.001), age (ß=0.25, P<0.001), systolic blood pressure (ß=0.16, P=0.004) and pulse rate (ß=-0.13, P=0.005) were independent determinants of eA. In contrast, neither VE nor baPWV were selected as independent determinants of eA. In conclusion, enlarged brachial artery cross-sectional area was significantly associated with cardiovascular risk factors such as age, body mass index and systolic blood pressure, but it was not associated with increased arterial stiffness.

A 17-year-old girl with Klippel-Weber syndrome complicated with a pulmonary thromboembolism and RV thrombus.

A 17-year-old girl with multiple areas of skin hemangiomas that had been present since birth was referred to our institution complaining of sudden onset of dyspnea. Enhanced CT demonstrated a pulmonary thromboembolism and transthoracic echocardiogram showed a thrombus-like echo in the right ventricle. CT further revealed thrombi in the inferior vena cava (IVC) and peripheral vein. The thrombi, especially those in the RV, were highly life-threatening; therefore, immediate thrombectomy was performed and an IVC filter was placed. Because no major complications occurred, the patient was discharged 34 days after admission. In such young women, carefully using anticoagulation therapy and planning pregnancy are recommended.

Impact of prediabetic status on coronary atherosclerosis: a multivessel angioscopic study.

OBJECTIVE: To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity. RESEARCH DESIGN AND METHODS: Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups. RESULTS: Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs ≥2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09-55.6], P = 0.005; and OR 4.13 [95% CI 1.01-17.0], P = 0.049, respectively). CONCLUSIONS: Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself.

Links between sleep disordered breathing, coronary atherosclerotic burden, and cardiac biomarkers in patients with stable coronary artery disease.

BACKGROUND: Sleep disordered breathing (SDB) is highly prevalent in patients with cardiovascular disease, although it is not clear whether SDB has any link to coronary atherosclerotic burden in patients with stable coronary artery disease (CAD). This study sought to analyze the links between SDB, coronary atherosclerotic burden, and cardiac biomarkers in stable CAD patients. METHODS AND RESULTS: We studied 83 consecutive patients who underwent coronary angiography or scheduled percutaneous coronary intervention. SDB was evaluated by an ambulatory polysomnographic monitoring device. Coronary atherosclerotic burden was evaluated by the Gensini score, and myocardial stress/injury were assessed by measuring plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hs-TnT). Patients with an apnea hypopnea index (AHI)≧15 events/h (n=32) showed significantly higher Gensini score (35.7±38.0 vs 20.1±19.7, p=0.033) than those with AHI<15. The higher AHI group showed significantly higher NT-proBNP (275.8±402.6 pg/ml vs 131.9±146.3 pg/ml, p=0.047) and hs-TnT levels (0.011±0.005 ng/ml vs 0.008±0.003 ng/ml, p=0.015). Furthermore it was revealed that AHI significantly correlated with the Gensini score (r=0.253, p=0.036), NT-proBNP (r=0.266, p=0.027), and hs-TnT (r=0.274, p=0.023), and multiple stepwise linear regression analysis revealed that AHI (ß=0.257, p=0.029) and history of smoking (ß=0.244, p=0.038) were independently correlated with Gensini score among clinical and SDB-related parameters. CONCLUSIONS: Severity of SDB has a significant link to the severity of coronary atherosclerotic burden, which also reflected elevated NT-proBNP and hs-TnT as silent myocardial ischemia and minute myocardial injury even in stable CAD patients.

The possibility of delayed arterial healing 5 years after implantation of sirolimus-eluting stents: serial observations by coronary angioscopy.

BACKGROUND: Although very late stent thrombosis occurs several years after implantation of sirolimus-eluting stent (SES), the morphologic changes of the stent beyond 2 years have not yet been systematically studied in living patients. The late vascular response to SES was therefore evaluated by serial angioscopic studies at 2 and 5 years after stent implantation. METHODS: A total of 17 patients with 17 SES underwent a repeated angioscopy procedure at 2 and 5 years. Neointimal stent coverage (NSC) was classified as follows: grade 0, presence of uncovered struts; grade 1, visible struts through a thin neointima; or grade 2, complete neointimal coverage without visible struts. For each patient, the minimum and maximum NSC grade and the existence of in-stent thrombus were recorded. RESULTS: The minimum and maximum NSC grade did not increase between the 2 and 5 years (0.59 ± 0.51 vs 0.88 ± 0.70, P = .17, and 1.82 ± 0.39 vs 1.94 ± 0.24, P = .30, respectively). The prevalence of patients with uncovered struts did not significantly decrease from 2 to 5 years (41% vs 29%, P = .49). During the follow-up period, 3 of 6 thrombi disappeared, whereas new thrombus formation was found in 3 patients without any clinical symptoms. In-stent thrombus did not decrease (35% vs 35%, P > .99). CONCLUSIONS: The current serial angioscopic study suggests that incomplete NSC and the prevalence of latent thrombus within the SES segments did not decrease from 2 to 5 years. The risk of stent thrombosis related to incomplete healing of SES may continue for an extended period.

Successful blood pressure control with additive administration of eplerenone, an aldosterone receptor blocker, in a patient with bilateral renovascular hypertension treated with angioplasty.

A 29-year-old woman with refractory hypertension who previously suffered from subarchnoid hemorrhage visited our facility. The diagnosis of renovascular hypertension due to fibromuscular dysplasia was made based on a high level of plasma renin activity (PRA) and aldosterone concentration (AC), and computed tomographic image of bilateral renal artery stenosis/obstruction. Angioplasty, which could be performed only to the left renal artery, failed to regain sufficient BP control. The addition of eplerenone, an aldosterone receptor blocker, to the conventional antihypertensive drugs successfully and safely lowered BP and preserved the renal function despite the persistence of high PRA and AC values.

Relation of smoking status to serum levels of N-terminal pro-brain natriuretic peptide in middle-aged men without overt cardiovascular disease.

Cigarette smoking impairs arterial function and promotes atherosclerosis. However, whether smoking status is associated with cardiac overload has not yet been fully examined, particularly from an epidemiologic viewpoint. The present study examined the relation of smoking status to serum levels of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), a marker of cardiac overload, in middle-aged men without overt cardiovascular disease. Serum NT-pro-BNP levels were measured in a work-site based population of 969 men (mean age 44 ± 6 years) who did not have any history or presence of cardiovascular disease. Smoking status was evaluated by self-reported questionnaire. Four hundred fifty-nine, 222, and 288 subjects were never, former, and current smokers, respectively. NT-pro-BNP levels were significantly higher in current smokers (21.7 ± 2.3 pg/ml) than in never smokers (17.9 ± 2.1 pg/ml, p <0.001). This significant difference was maintained even after adjusting for age, obesity, heart rate, hypertension, dyslipidemia, impaired fasting glucose/diabetes mellitus, left ventricular hypertrophy, estimated glomerular filtration rate, high-sensitivity C-reactive protein, alcohol consumption, and regular exercise. Current smokers had an increased odds ratio (3.04, 95% confidence interval 1.64 to 5.61, p <0.001) for elevated NT-pro-BNP (>54.5 pg/ml) compared to never smokers, even after adjusting for the studied variables. In contrast, former smokers did not show a significantly increased odds ratio for elevated NT-pro-BNP. NT-pro-BNP levels showed a weak, but significant negative correlation with duration of smoking cessation (partial r = -0.15, p = 0.034) in former smokers. In conclusion, these results suggest that cigarette smoking increases cardiac overload, whereas smoking cessation ameliorates these conditions.

Relationship between LDL-C reduction after coronary revascularization and prevention of recurrence of cardiovascular events.

PURPOSE: The purpose of our study was to optimize lipid-lowering therapy in patients undergoing coronary revascularization and to determine whether the percentage change in low-density lipoprotein-cholesterol (LDL-C) level in the 3 months after coronary revascularization could be used as a predictor of the time to recurrence of coronary artery disease (CAD). METHODS: Biochemical values of patients undergoing lipid-lowering therapy after receiving coronary revascularization at the Nippon Medical School Chiba Hokusoh Hospital, Japan, were retrospectively investigated. Recurrence of a cardiovascular event (CVE) was defined by death, myocardial infarction, or angina caused by coronary revascularization more than 3 months after the first event. RESULTS: Of 171 patients under secondary preventive care who had at least one recurrence of a CVE, 75 showed evidence of objective stenotic lesions on coronary angiography. Among these 75 patients, exclusion of those in whom coronary revascularization had not been performed at disease onset, balloon dilatation had been used, serum lipid levels had not been measured, or coronary revascularization had been applied to restenosis left 44 patients suitable for inclusion in the study group. Although the mean value of high density lipoprotein-cholesterol did not change in the 3 months after coronary revascularization, that of (LDL-C) significantly decreased. A significant positive correlation was identified between % decrease in LDL-C and number of days to CVE recurrence. The average LDL-C value (102.8+/-21.7 mg/dL) in the group of patients with no recurrence within 5 years was significantly lower than that (135.3+/-46.1 mg/dL) in the recurrence group (P = 0.0088). The % of patients achieving the LDL-C target level (non-recurrence group vs. recurrence group: 50.0% vs. 16.7%; P = 0.032) and the % decrease in LDL-C (31.0%+/-12.6% vs. 9.6+/-21.0%, P = 0.0012) were significantly greater in the non-recurrence group than in the recurrence group. CONCLUSIONS: From our present study, a decrease in LDL-C 3 months after revascularization surgery reduces the rate of CVE relapse. The % LDL-C decrease could serve as a useful predictor of CVE recurrence, in addition to LDL-C values and achievement of the LDL-C target level.

Association between high-sensitivity cardiac troponin T levels and the predicted cardiovascular risk in middle-aged men without overt cardiovascular disease.

BACKGROUND: A slight elevation of cardiac troponin T (TnT) levels in the circulating blood can be detected by the recently developed, high-sensitivity TnT (hsTnT) assay. However, it remains unclear whether a slight elevation of hsTnT is associated with an increased cardiovascular risk in subjects without overt cardiovascular disease (CVD). METHODS: The serum hsTnT levels were measured in a work site-based population of 1,072 middle-aged males (mean age 44 years) without any history or presence of CVD. The lower detection limit of the hsTnT assay used in the present study was 0.002 ng/mL. The association of the hsTnT levels with cardiovascular risk factors and the predicted CVD risk, as determined by the Framingham CVD risk prediction score, were examined. RESULTS: Detectable hsTnT levels were seen in 867 subjects (80.9%). The highest value of the hsTnT was 0.020 ng/mL. Among various cardiovascular risk factors, age, blood pressure, estimated glomerular filtration rate, current smoking, and left ventricular hypertrophy were independent determinants of hsTnT levels. The odds ratio for a high predicted CVD risk (10-year risk > or =20%) in the highest tertile of hsTnT (> or =0.005 ng/mL) in comparison to the lowest tertile (< or =0.002 ng/mL) was 3.98 (95% CI 1.72-9.24, P = .001) after adjusting for multiple potential confounders. CONCLUSIONS: The present study showed the hsTnT levels to be significantly associated with several cardiovascular risk factors and the predicted CVD risk in middle-aged men without overt CVD, thus suggesting the usefulness of measuring hsTnT to identify high-risk subjects in the primary prevention of CVD.

Radial arterial wave reflection is associated with the MEGA risk prediction score, an indicator of coronary heart disease risk, in middle-aged men with mild to moderate hypercholesterolemia.

AIM: The present study examined the association between the radial augmentation index (AI), a marker of arterial wave reflection, and the MEGA risk prediction score (MEGA score), an indicator of coronary heart disease (CHD) risk, in middle-aged men with mild to moderate hypercholesterolemia. METHODS: Radial AI was measured during a company health examination in 266 men (age: 47+/-5 years) with total cholesterol levels ranging 220-270 mg/dL who were not taking antihypertensive, lipid-lowering, or antidiabetic agents. The MEGA score was calculated based on sex, age, low- and high-density lipoprotein cholesterol, blood pressure, glucose level, and smoking status. The higher MEGA score indicates increased CHD risk. A MEGA score > or = 22 corresponds to a 5-year CHD risk > or = 2.5% and we defined a MEGA score > or = 22 as a high estimated CHD risk. RESULTS: The mean AI was 74.4+/-12.6%. A high estimated CHD risk was seen in 32 subjects (12.0%). After adjusting for height and heart rate, the AI was higher in subjects with a high estimated CHD risk (81.5+/-10.6%) than in those without (73.4+/-10.4%, p<0.001). The odds ratio for high estimated CHD risk in the highest tertile of AI was 8.14 (p=0.002) in comparison to the lowest tertile, after adjusting for multiple potential confounders which did not constitute the MEGA score. CONCLUSION: The radial AI was positively associated with the estimated risk of CHD. These results suggest the usefulness of radial AI as a risk marker for future onset of CHD in middle-aged men with mild to moderate hypercholesterolemia.

Relationship between neointimal coverage of sirolimus-eluting stents and lesion characteristics: a study with serial coronary angioscopy.

BACKGROUND: Delayed neointimal coverage after the implantation of a drug-eluting stent (DES) is thought to be related to their potential for developing late-stent thrombosis. However, few studies have shown which factor affects the neointimal coverage after DES implantation. We hypothesized that the extent of neointimal coverage after DES implantation is affected by the underlying lesion characteristics because arterial wall components are reported to determine the transport and distribution of the drugs. METHODS: Thirty-seven coronary artery lesions treated with a single sirolimus-eluting stent (SES) were evaluated in 37 patients with stable coronary artery disease. Angioscopy was performed before, immediately after, and 6 months after stenting to examine the existence of yellow plaque, thrombus, complex plaque, and intramural hemorrhage and the degree of neointimal coverage at 6-month follow-up. This was classified either as a noncoverage group (stent struts were predominantly exposed or visible through a thin neointima) or as a coverage group (stent struts were predominantly covered by neointimal hyperplasia and thus invisible). RESULTS: Twenty-one lesions were classified into the noncoverage group, and 16 lesions the coverage group. The frequency of preexistent yellow plaques was significantly higher in the noncoverage group than that in the coverage group (67% vs 19%, P = .007). A multivariate logistic regression analysis showed the preexistence of yellow plaque was the only independent factor behind less neointimal coverage at 6 months after SES implantation (odds ratio 19.5, 95% confidence interval 1.58-240.50, P = .020). CONCLUSIONS: The preexistence of yellow plaque may be associated with decreased neointimal coverage of SES.

Obesity as an independent influential factor for reduced radial arterial wave reflection in a middle-aged Japanese male population.

This study aimed to examine whether obesity, including abdominal obesity, is an influential factor for radial arterial wave reflection, as expressed by the augmentation index (AI), in middle-aged Japanese men. Radial arterial pressure waveform was measured using automated applanation tonometry in 828 men (mean age: 47+/-5 years) during an annual health examination at a company. Radial AI was calculated from the waveforms. AI appeared to be similar between subjects with and without obesity (body mass index (BMI) >or=25 and <25 kg m(-2), respectively). However, after adjusting for age, height, heart rate, mean blood pressure, low- and high-density lipoprotein cholesterol, fasting plasma glucose, white blood cell count and other potential confounders, AI was significantly lower in subjects with obesity (71.6%, 95% confidence interval (CI); 70.2-73.0%) than in those without (75.2%, 95% CI; 74.4-76.0%, P<0.001). In a multiple linear regression analysis, BMI was negatively associated with AI (beta=-0.20, P<0.001); other factors associated with AI were heart rate (beta=-0.56), mean blood pressure (beta=0.44), height (beta=-0.24), age (beta=0.15), current smoking (beta=0.09), white blood cell count (beta=0.06) and low-density lipoprotein cholesterol (beta=0.06). Similar associations were found when waist circumference (WC, an index of abdominal obesity) was substituted for BMI in the analysis (beta=-0.12, P<0.001). BMI closely correlated with WC (r=0.87), thus suggesting that approximately 76% (a square of 0.87) of BMI can be explained by WC. In conclusion, although it does not have a major impact, obesity, including abdominal obesity, may be an influential factor for reduced radial AI, independently of well-known confounders, in middle-aged Japanese men.