Evaluation of risk for incident hypertension using glomerular filtration rate in the normotensive general population.

OBJECTIVES: The present study tested the hypothesis that glomerular filtration rate can predict the onset of hypertension in individuals with normal blood pressure in the general population. METHODS: Normotensive individuals (n = 7684) who visited our hospital for a routine physical examination were enrolled in the study (4907 men; mean age 52.1 ±â€Š11.1 years) and were followed up with the endpoint being the development of hypertension. The relationship between estimated glomerular filtration rate at baseline and the incidence of hypertension was evaluated. RESULTS: During the follow-up period (median 4.0 years; actual follow-up 30 624 person-years), hypertension developed in 2031 participants (66.3 per 1000 person-years). After adjustment for possible risk factors, the hazard ratio of incident hypertension (first tertile as reference) in the second and third tertiles was 1.03 (95% confidence interval 0.92-1.16) and 1.40 (95% confidence interval 1.26-1.57), respectively. Multivariate Cox proportional hazard regression analysis, in which estimated glomerular filtration rate was taken as a continuous variable and adjustments were made for known risk factors, also indicated that baseline estimated glomerular filtration rate independently predicted the onset of hypertension (P < 0.0001). Furthermore, multiple regression analysis revealed that a longitudinal increase in SBP was significantly associated with baseline estimated glomerular filtration rate after adjustment for known risk factors (P < 0.01). CONCLUSION: Estimated glomerular filtration rate in normotensive individuals is a good predictor of the onset of hypertension in the general population.

Brachial-ankle pulse wave velocity predicts increase in blood pressure and onset of hypertension.

BACKGROUND: The present study was designed to test the hypothesis that brachial-ankle pulse wave velocity (baPWV) predicts longitudinal increases in blood pressure (BP) and new onset of hypertension in individuals with normal BP. METHODS: baPWV was measured using a semiautomated device in 2,496 participants (27-84 years) without hypertension who visited our hospital for a yearly health check-up. They were followed up for 4 years with the endpoint being development of hypertension. RESULTS: During the follow-up period (median, 733 days; actual follow-up, 5,215 person-years), hypertension developed in 698 participants (133.8/1,000 person-years). Kaplan-Meier analysis revealed that risk for hypertension was increased across the tertiles of baseline baPWV. The hazard ratio (first tertile as reference) was 2.02 (95% confidence interval (CI) 1.55-2.64) and 3.49 (95% CI 2.66-4.57) in the second and third tertiles, respectively, after adjustment for possible risk factors. Multivariate Cox proportional hazard regression analysis adjusted for known risk factors, where baPWV was used as a continuous variable, also indicated that the baseline value of baPWV independently predicted new onset of hypertension (P < 0.001). Furthermore, baseline baPWV was significantly associated with a longitudinal increase in BP after adjustment for known risk factors in multiple regression analysis (P < 0.001). CONCLUSION: This study provides the first evidence that baPWV is an independent predictor of longitudinal increases in BP as well as of new onset of hypertension.

B-type natriuretic peptide levels and cardiovascular risk in patients with diastolic dysfunction on chronic haemodialysis: cross-sectional and observational studies.

BACKGROUND: Elevated B-type natriuretic peptide (BNP) levels are predictive of cardiovascular events in patients on chronic maintenance haemodialysis, even in those without apparent cardiovascular disorders when they start dialysis. In the present study, we tested the hypothesis that left ventricular diastolic dysfunction increases BNP levels and can predict cardiovascular events in patients on chronic haemodialysis without apparent cardiac disease. METHODS: Patients on chronic maintenance haemodialysis in a stable condition and with normal systolic function were enrolled (n=98). BNP concentrations were measured, and left ventricular diastolic function was assessed using echocardiography after the first dialysis session of the week. Then, they were followed up for 2 years with the end point being the incidence of cardiovascular events. RESULTS: At baseline, left ventricular diastolic dysfunction was detected in 39 of 98 patients. After adjustment for known risk factors, multivariable regression analysis demonstrated that diastolic dysfunction was a significant predictor of increased BNP levels (P<0.05). During the follow-up period, 17 patients experienced cardiovascular events. Kaplan-Meier analysis demonstrated that the incidence of cardiovascular events was higher in patients with (28.2%) than without (10.2%) left ventricular diastolic dysfunction (log-rank, P<0.01). Univariate Cox proportional hazards regression analysis indicated that diastolic dysfunction and BNP were significant predictors of cardiovascular events (hazard ratio 3.63 and 4.87, respectively; P<0.05). CONCLUSIONS: Left ventricular diastolic dysfunction is associated with increased BNP levels and an increased risk of cardiovascular events in patients on haemodialysis.

Does B-type natriuretic peptide predict the new onset of hypertension?

Increased B-type natriuretic peptide (BNP) expression precedes the development of hypertension in spontaneously hypertensive rats. We therefore tested the hypothesis that elevated plasma BNP levels predict the onset of hypertension in normotensive subjects. Japanese normotensive participants who were at our hospital for a yearly physical check-up (mean age 52.7 years, 35.9% women, n=5,026) were enrolled in the study. Blood pressure and BNP were measured at baseline and subjects were followed up for 5 years (median 1,114 d), with the endpoint being the development of hypertension. We evaluated the relationship between plasma BNP levels at baseline and the incidence of hypertension during the follow-up period. Hypertension was defined as systolic or diastolic blood pressure > or =140 or > or =90 mmHg, respectively, or the use of antihypertensive medications. During the follow-up period, hypertension developed in 23.4% (77.0 per 1,000 person-years) and 14.9% (51.0 per 1,000 person-years) of male and female subjects, respectively. Cox proportional hazard regression analysis demonstrated that after adjustment for known risk factors, the risk of hypertension was increased from the first to fourth quartiles of baseline BNP levels. However, after additional adjustment for baseline blood pressure, BNP did not predict the new onset of hypertension. Baseline BNP levels are closely associated with the risk of hypertension in individuals with normal blood pressure, but the prediction of hypertension with BNP is largely dependent on baseline blood pressure. Measurements of BNP may serve as a complementary method for the prediction or confirmation of hypertension.

Metabolic disorders predict development of hypertension in normotensive Japanese subjects.

Each component of the metabolic syndrome is not necessarily clustered coincidentally. Thus, subjects who have obesity, dyslipidemia or impaired glucose tolerance may be at high risk for the development of hypertension. We studied the predictive value of the following for the development of hypertension: obesity (body mass index > or =25.0 kg/m2), dyslipidemia (high-density lipoprotein-cholesterol <40 mg/dL, triglyceride > or =150 mg/dL, or use of anti-dyslipidemic drugs), high normal blood pressure (130 mmHg < or = systolic <140 mmHg, or 85 mmHg < or = diastolic <90 mmHg), and impaired glucose tolerance (fasting plasma glucose > or =110 mg/dL or use of anti-diabetic agents). This observational study included 5,785 subjects without hypertension recruited from participants in our health checkup program. They were followed up for 1,097+/-365 d, with the endpoint being the development of hypertension. During the follow-up, hypertension developed in 1,168 subjects (74.1 per 1,000 person-years). The incidence of hypertension was higher in subjects who had obesity (106.2 vs. 67.8), dyslipidemia (96.1 vs. 69.0), high normal blood pressure (166.0 vs. 40.1), or impaired glucose tolerance (130.5 vs. 65.3 per 1,000 person-years) than in those without these disorders at baseline. The risk of hypertension was increased as the number of metabolic disorders in an individual increased. Multiple regression analysis indicated that obesity, high normal blood pressure, and impaired glucose tolerance remained independent predictors of the onset of hypertension. Thus, the presence of individual components of the metabolic syndrome predicts the development of hypertension. Prediction of the development of hypertension may lead to effective prevention of both hypertension and resulting cardiovascular diseases.

Pioglitazone produces rapid and persistent reduction of vascular inflammation in patients with hypertension and type 2 diabetes mellitus who are receiving angiotensin II receptor blockers.

Inhibition of the renin-angiotensin system reportedly exerts potent antiatherogenic effects by reducing vascular inflammation. We tested the hypothesis that pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, further reduces vascular inflammation in patients receiving angiotensin II receptor blockers. Patients with hypertension who had developed type 2 diabetes mellitus were randomly assigned to receive either pioglitazone (15 mg/d, n = 20) or voglibose, an alpha-glucosidase inhibitor (0.6 mg/d, n=19) for 6 months, and changes in their serum concentrations of C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were monitored. Pioglitazone, but not voglibose, reduced CRP levels within 1 month (-51%+/-7%, mean+/-SEM; P<.001). C-reactive protein levels were decreased after 6 months of treatment with either pioglitazone or voglibose, with the former being more effective (-57%+/-8% vs -9%+/-18%; P<.05). The levels of ICAM-1 and VCAM-1 were significantly reduced after 1 month of pioglitazone therapy (-9%+/-3% and -8%+/-3%, respectively; both P<.05), with the beneficial effects persisting throughout the study period. In contrast, the levels of ICAM-1 and VCAM-1 were not altered during the study period in patients on voglibose. There was no correlation between the reduction of hemoglobin A1c and that of CRP, ICAM-1, or VCAM-1. These results suggest that augmentation with pioglitazone further reduces vascular inflammation in patients with hypertension and diabetes who are receiving angiotensin II receptor blockers. This may contribute to the reduction of cardiovascular events in this at-risk population.

Candesartan, an angiotensin II type-1 receptor blocker, reduces cardiovascular events in patients on chronic haemodialysis--a randomized study.

BACKGROUND: Cardiovascular events are the major determinants of the prognosis of patients on chronic haemodialysis. The present study was designed to investigate whether candesartan, an angiotensin II type-1 receptor blocker, reduces the incidence of cardiovascular events in these patients. METHODS: A total of 80 chronic haemodialysis patients (male/female, 47/33; mean age +/- SEM, 61 +/- 1 years) in stable condition and with no clinical evidence of cardiac disorders were enrolled. Patients were randomly assigned candesartan 4-8 mg/day (candesartan group; n = 43) or nothing (control group; n = 37), and followed for 19.4 +/- 1.2 months with as endpoint cardiovascular events such as fatal/nonfatal myocardial infarction, unstable angina pectoris, congestive heart failure, severe arrhythmia and sudden death. RESULTS: Both groups exhibited similar clinical characteristics at baseline. During follow-up, cardiovascular events occurred in seven patients in the candesartan group and 17 in the control group. Kaplan-Meier analysis revealed that cardiovascular events and mortality rates were significantly (P < 0.01) higher in the control group than in the candesartan group (45.9 vs 16.3% and 18.9 vs 0.0%, respectively). CONCLUSIONS: Candesartan therapy significantly reduces cardiovascular events and mortality in patients on chronic maintenance haemodialysis and therefore improves the prognosis of these patients.

Usefulness of Tc-99m methoxyisobutylisonitrile scintigraphy for evaluating congestive heart failure.

BACKGROUND: Evidence is accumulating that technetium 99m methoxyisobutylisonitrile (MIBI) is not retained in the impaired myocardium. The purpose of this study was to determine whether the severity of congestive heart failure (CHF) can be evaluated by use of the washout rate (WR) of MIBI. METHODS AND RESULTS: Seventeen patients with CHF and ten healthy volunteers were enrolled in this study. MIBI and iodine 123 metaiodobenzylguanidine (MIBG) scintigraphy techniques were performed, and the WR was calculated. The blood was also sampled for the measurement of levels of brain natriuretic peptide, which is a powerful predictor of the severity of CHF. The WR of MIBI was higher in CHF patients (31.2%+/-6.3%) than in healthy volunteers (25.2%+/-4.7%) (P<.05). There were positive correlations between the WR of MIBI and brain natriuretic peptide levels (r=0.723, P<.0001) and a negative correlation between the WR of MIBI and the left ventricular ejection fraction (r=-0.545, P<.01). The WR of MIBI was correlated with that of MIBG (r=0.603, P<.01). CONCLUSIONS: MIBI scintigraphy is useful in evaluating the severity of congestive heart failure.

Circulating levels of myocardial proteins predict future deterioration of congestive heart failure.

BACKGROUND: This study was designed to test whether circulating levels of myocardium-specific proteins serve as useful markers for the prognosis of patients with congestive heart failure. METHODS AND RESULTS: Seventy-eight patients with congestive heart failure from dilated cardiomyopathy but in a stable condition were enrolled, and their blood was sampled for measurements of myosin light chain-I (MLC-I), troponin T (TnT), heart fatty-acid-binding protein (H-FABP), and creatine kinase isoenzyme MB (CK-MB). The patients were then followed up for 951 +/- 68 days, with the endpoint being acute deterioration. A univariate analysis revealed that MLC-I, TnT, H-FABP, and CK-MB were significant predictors for acute deterioration of heart failure. Application of the Kaplan-Meier method using cutoff values determined by analysis of receiver operating characteristics curves demonstrated that the incidence of acute deterioration was significantly higher in patients with higher values of MLC-I (61.9%), TnT (52.4%), H-FABP (50.0%), or CK-MB (38.6%) than in those with lower values of these markers (15.8%, 20.4%, 13.6%, and 16.1%, respectively). CONCLUSIONS: Increased circulating levels of the specific myocardial proteins are related to a higher probability of future acute deterioration of congestive heart failure in patients in a stable condition associated with dilated cardiomyopathy.

Effect of nifedipine on C-reactive protein levels in the coronary sinus and on coronary blood flow in response to acetylcholine in patients with stable angina pectoris having percutaneous coronary intervention.

The effects of nifedipine on inflammation and endothelial function in the coronary circulation were studied in patients who had angina pectoris (n = 17). Long-term treatment with nifedipine (nifedipine CR, 20 mg/day for 4 months) decreased levels of C-reactive protein in the coronary sinus (from 0.35 +/- 0.09 mg/dl to 0.07 +/- 0.01 mg/dl, mean +/- SEM, p <0.05) and enhanced acetylcholine-induced increases in coronary blood flow. Thus, nifedipine is effective in decreasing inflammation and incresing endothelial function in the coronary circulation.

Increased endogenous endothelin-1 in coronary circulation is associated with restenosis after coronary angioplasty.

BACKGROUND: The relationship between vasoactive substances, including endothelin-1, nitric oxide, serotonin, angiotensin II and noradrenaline, and coronary restenosis after percutaneous transluminal coronary angioplasty (PTCA) is not clear. OBJECTIVE: To determine whether any vasoactive substance may be a marker of coronary restenosis after PTCA. METHODS: Twenty-nine patients with angina pectoris underwent elective PTCA. Three months after PTCA, coronary angiography was performed again to study the patency of the lesions. Seven patients had coronary restenosis (greater than 50% stenosis) (restenosis group) and the rest of the patients were without restenosis (patency group). Their blood samples were obtained from the coronary sinus before, immediately after and three months after PTCA. RESULTS: Endothelin-1 levels obtained immediately after PTCA (3.44+/-0.26 pg/mL) and three months after PTCA (3.57+/-0.29 pg/mL) were significantly higher than those obtained before PTCA (3.00+/-0.26 pg/mL) in the restenosis group, but not in the patency group (3.34+/-0.15 pg/mL, 3.02+/-0.17 pg/mL and 3.14+/-0.18 pg/mL, respectively). A transient decrease in nitrite/nitrate levels was observed immediately after PTCA in both groups. The serotonin levels three months after PTCA were significantly decreased in the patency group, but not in the restenosis group, and the levels of angiotensin II and noradrenaline did not change in either group throughout the study. CONCLUSIONS: Among several vasoactive substances, endothelin-1 seems to be associated with the process of coronary restenosis after PTCA. Increased endothelin-1 levels in the coronary circulation after PTCA may indicate an increased risk of coronary restenosis.

Asian variant of CD5+ intravascular large B-cell lymphoma with splenic infarction.

A 57-year-old man was admitted with fever and epigastralgia, and presented with splenomegaly and pancytopenia. A CT scan revealed splenic infarctions. There were no lymphadenopathies, skin lesions, or neurological abnormalities. A splenectomy was performed. Bone marrow involvement with hemophagocytosis was noted. The diagnosis of Asian variant of intravascular diffuse large B-cell lymphoma was based on intravascular and sinusoidal distribution of large CD5+ B cells. The patient died of the disease 11 months after onset. To our knowledge, this is the first report of AIVL that presented with splenic infarction. This distinct lymphoma should be included in the differential diagnosis of splenic infarction.

Increased circulating levels of natriuretic peptides predict future cardiac event in patients with chronic hemodialysis.

BACKGROUND/AIMS: Cardiovascular events are the major determinant of the prognosis in patients with chronic hemodialysis. The present study was designed to investigate whether increased plasma levels of atrial or brain natriuretic peptides (ANP or BNP) predict future cardiac events in such patients. METHODS: Fifty-three patients undergoing chronic hemodialysis without clinical symptoms suggestive of cardiac disorders were enrolled and their blood was sampled for ANP and BNP measurements. Electrocardiograms demonstrated left ventricular hypertrophy in 28 patients but no other abnormal findings. We followed them up for 11.3 +/- 0.2 months. The endpoint was cardiac events. RESULTS: Cardiac events occurred in 13 patients (CE group). Both ANP and BNP levels were higher in CE group than in patients without cardiac events (ANP: 118 +/- 21 vs. 56 +/- 5 pg/ml, BNP: 769 +/- 204 vs. 193 +/- 25 pg/ml, respectively). Receiver operating characteristics curve revealed that the cut-off levels of ANP and BNP were 58 and 390 pg/ml, respectively. Using the Kaplan-Meier method, the incidence of cardiac events was significantly greater in patients with higher levels of ANP (50.0 vs. 0.0%) or BNP (72.7 vs. 11.9%) than in those with lower levels of the peptides. CONCLUSIONS: Elevated levels of ANP or BNP indicate an increased risk of cardiac events and these peptides are clinically useful to predict cardiac events in patients with hemodialysis.

Effect of troglitazone on endothelial function in type 2 diabetic patients.

Lysophosphatidylcholine (lysoPC), a component of oxidized low-density lipoprotein cholesterol (LDL-C), has been reported to impair nitric oxide production and endothelium-dependent vasorelaxation. The effects of troglitazone (CAS 97322-87-7), which is an antidiabetic agent with antioxidant properties, on serum levels of lysoPC and nitrite/nitrate (NOx) have been studied. Eight patients with Type 2 diabetes (non-insulin dependent diabetes mellitus, NIDDM) were studied (age: 61.5 +/- 2.8 years; diabetes duration: 10.2 +/- 1.6 years). They were additionally given troglitazone (200 mg once daily) since their fasting plasma glucose (FPG) and HbA1c levels had been increased in spite of conventional medications. Before and after 12 weeks of treatment with troglitazone their blood pressure, FPG, HbA1c, lipid profiles and NOx were measured. Troglitazone treatment had a slight depressor effect (decreasing the blood pressure from 133 +/- 5/72 +/- 3 to 127 +/- 4/68 +/- 1 mmHg; p < 0.05). FPG and HbA1c were significantly decreased with the therapy (181 +/- 10 to 160 +/- 10 mg/dl; p < 0.05 and 9.1 +/- 0.6 to 8.1 +/- 0.5%; p < 0.05, respectively). In contrast, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and LDL-C were maintained within normal limits throughout the study. Although lysoPC and NOx levels were not altered, a negative correlation between lysoPC and NOx levels was observed. These results suggest that troglitazone is a beneficial agent improving FPG and HbA1c levels in NIDDM patients, while its effects on serum lysoPC and NOx levels, at least for 12 weeks, seem to be minimal.