The impact of cigarette smoking on 24-hour blood pressure, inflammatory and hemostatic activity, and cardiovascular risk in Japanese hypertensive patients.

The aim of the study was to assess the impact of current smoking on 24-hour blood pressure (BP) and inflammatory and hemostatic activity and thereby the incidence of cardiovascular disease (CVD) in Japanese hypertensive patients. A total of 810 hypertensive patients (mean age 72 years; 38% men) were prospectively followed-up (2799 person-years). During the follow-up, 66 cases of CVD occurred (stroke, 55; myocardial infarction, 7; both, 4). At baseline, the current smokers (n=166) had higher levels of high-sensitivity C-reactive protein (hs-CRP) (0.21 mg/dL vs 0.14 mg/dL) and plasminogen activator inhibitor-1 (PAI-1) (46.1 ng/mL vs 37.8 ng/mL; both P=.001), but not of 24-hour BP, compared with nonsmokers. Using a Cox regression analysis, current smoking was independently associated with an increased risk of CVD (hazard ratio [HR], 2.6; P<.01), and the risk was substantially higher in women (HR, 6.1; P<.001) than in men (HR, 1.4; P=.41). The CVD risk of current smokers was magnified when it was accompanied with high hs-CRP (highest quartile range, ≥0.40 mg/L) or PAI-1 levels (≥58.9 ng/mL) compared with that in smokers with low hs-CRP or PAI-1 levels (both P<.05). Among hypertensive patients, current smokers had increased risk of CVD events, and the increase was more prominent when accompanied by circulatory inflammatory and hemostatic abnormalities.

Association of home and ambulatory blood pressure changes with changes in cardiovascular biomarkers during antihypertensive treatment.

BACKGROUND: Our aim was to assess whether home blood pressure (HBP) and ambulatory BP monitoring measurement (ABPM), in addition to office BP (OBP) predict changes of cardiovascular biomarkers during antihypertensive treatment. METHODS: Two hundred and fifty-two hypertensive patients (mean age, 68 years; men: 41%) underwent measurements of OBP, HBP, ABPM, and cardiovascular biomarkers (urinary albumin excretion (UAE) and brain natriuretic peptide (BNP)) before and after 6 months of treatment with candesartan (± thiazide-diuretics). RESULTS: During the intervention, the OBP, HBP, daytime and night-time BP, and UAE levels were all significantly reduced (all P < 0.01). BNP was reduced only in the patients using diuretics (P = 0.003). For predicting the treatment-induced change in UAE, each of home systolic BP (SBP) and night-time SBP changes, but not daytime SBP change, had independent and significant value beyond OBP measurement (both P < 0.05). In contrast, for predicting the treatment-induced change in BNP, night-time SBP changes, but not home or daytime SBP changes, had significant value beyond OBP measurement (both P < 0.05). Patients who achieved a reduction in all three SBP parameters (office, home, and night-time SBP; n = 122) showed a more significant reduction of UAE compared with those who did not (-52.6 vs. -32.5%; P = 0.001), and patients who achieved a reduction in both office and night-time SBP (n = 134) showed a more significant reductions of BNP than those who did not (-12.9 vs. +12.8%; P < 0.05). CONCLUSIONS: HBP and ABPM measurements, particularly night-time SBP values provide additional information for predicting treatment-induced changes of cardiovascular biomarkers when used in conjunction with office SBP measurement during antihypertensive treatment.

The relationship between the morning blood pressure surge and low-grade inflammation on silent cerebral infarct and clinical stroke events.

OBJECTIVE: Morning blood pressure surge (MBPS) has been shown to be a risk factor for cardiovascular disease and is associated with vascular remodeling. This study investigated whether the cerebrovascular risk of MBPS is modified by low-grade inflammation. METHODS: We evaluated ambulatory BP, high sensitivity C-reactive protein (hsCRP), and brain MRI at baseline in 514 Japanese hypertensive patients, and followed them for the incidence of stroke for an average of 41 months (range: 1-68 months, 1751 person-years). RESULTS: MBPS was significantly correlated with the hsCRP level in patients with the highest quartile of MBPS, but not in the other quartiles. The odds ratio for silent cerebral infarcts (SCIs) was significantly higher only in patients in the highest quartile of MBPS with higher (above median) hsCRP [odds ratio 2.74, 95% confidence interval (CI) 1.42-5.30] in comparison with those in other quartiles of MBPS and with lower (below median) hsCRP. Conversely, being in the highest quartile of MBPS and having a higher hsCRP were independently and additively associated with an increased risk for clinical stroke events (both the highest quartile of MBPS and the higher hsCRP; hazard ratio [HR] 5.77, 95%CI 2.11-15.81, only the highest quartile of MBPS; HR 3.03, 95%CI 0.89-10.33, only the higher hsCRP; HR 2.89, 95%CI 1.12-7.47), even after adjusting for confounding factors. CONCLUSION: Exaggerated MBPS and increased low-grade inflammation independently increase the risk of stroke, while the relationship between exaggerated MBPS and the presence of SCIs is slightly affected by low-grade inflammation.

Synergistic effect of chronic kidney disease and high circulatory norepinephrine level on stroke risk in Japanese hypertensive patients.

OBJECTIVE: Evidence is now available about the association between chronic kidney disease (CKD) and stroke. However, less is known about the underlying mechanisms, and there is currently no reliable marker for identifying stroke-prone high-risk patients among CKD patients. METHODS: A total of 514 hypertensive patients aged >50 years (mean, 72.3 years; 37% men) underwent 24-h BP monitoring and measurement of circulatory high-sensitivity C-reactive protein (hs-CRP) and norepinephrine at baseline. CKD was defined as eGFR<60 ml/min/1.73 m(2) using the Cockcroft-Gault equation. RESULTS AND CONCLUSION: During an average of 41 months (1751 person-years), there were 43 stroke events. Compared with hypertensive patients without CKD, those with CKD (n=225) had higher levels of sleep systolic BP (SBP) (125 mmHg vs. 129 mmHg), circulatory hs-CRP (0.12 mg/L vs. 0.20 mg/L) and norepinephrine (332.2 pg/ml vs. 372.8 pg/ml; all P<0.05). On multivariable analysis, the hazard ratio (HR) (95% CI) for stroke in CKD vs. non-CKD was 2.7 (1.2-6.9) (P<0.05). CKD, as well as the baseline presence of silent cerebral infarction, sleep SBP increase, and high hs-CRP level (highest quartile: ≥0.42 mg/L) were independently and additively associated with stroke events; above all, there was a synergistic effect of CKD and high norepinephrine level (highest quartile: ≥538 pg/ml) on stroke risk (all P<0.05). Among hypertensive patients with CKD, those within the highest quartiles of norepinephrine had a greater stroke risk compared to those who were in the lower quartiles of norepinephrine (HR (95% CI): 2.2 (1.0-4.5); P=0.045). In conclusion, CKD is an independent predictor of stroke in Japanese hypertensive patients; in particular, hypertensive patients with CKD and a high norepinephrine level have a synergistically augmented stroke risk.

Additional impact of morning haemostatic risk factors and morning blood pressure surge on stroke risk in older Japanese hypertensive patients.

AIMS: Stroke events occur most frequently in the morning hours. Impaired haemostatic activity and morning blood pressure (BP) surge, defined as the morning BP increase from sleep, have individually been associated with stroke risk in general or hypertensive populations. However, their combined impact on the risk of a stroke remains unknown. METHODS AND RESULTS: A total of 514 hypertensive patients aged > 50 years (mean 72.3 years; 37% men) underwent 24 h BP monitoring, measurement of haemostatic risk factors [plasma fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and prothrombin fragment 1+2(F1+2)], and brain MRI at baseline. The incidence of stroke was prospectively ascertained. During an average of 41 months (1751 person-years), there were 43 stroke events (ischaemic, 30; haemorrhagic, 5; undefined, 8). On multivariable analysis adjusted for confounding factors, the hazard ratio [HR (95% confidence interval (CI)] for stroke in the highest vs. lower quartiles of PAI-1 was 2.5 (1.3-4.6), that for F1+2 was 2.6 (1.4-5.0), and that for the morning BP surge was 1.2 (1.1-1.4; all P< 0.01). In particular, the ratio was substantially higher in cases with the highest quartile of both PAI-1 and F1+2 levels compared with those with the lower quartiles of both parameters (HR: 8.2; 95% CI: 3.7-18.2; P< 0.001). Among the patients with the highest quartile of the morning BP surge (n= 128), the multivariable HR (95% CI) for the highest vs. lower quartiles of PAI-1 was 3.4 (1.3-9.1) and that for F1+2 was 3.3 (1.3-8.7) (both P< 0.05). CONCLUSION: High levels of plasma PAI-1 and F1+2, as well as an excessive morning BP surge, are independently and additively associated with an increased risk of stroke in older hypertensive patients.