Fang-Fei Wei

Beat-to-Beat, Reading-to-Reading, and Day-to-Day Blood Pressure Variability in Relation to Organ Damage in Untreated Chinese

Whether target organ damage is associated with blood pressure (BP) variability independent of level remains debated. We assessed these associations from 10-minute beat-to-beat, 24-hour ambulatory, and 7-day home BP recordings in 256 untreated subjects referred to a hypertension clinic. BP variability indices were variability independent of the mean, maximum–minimum difference, and average real variability. Effect sizes (standardized &bgr;) were computed using multivariable regression models. In beat-to-beat recordings, left ventricular mass index (n=128) was not (P≥0.18) associated with systolic BP but increased with all 3 systolic variability indices (+2.97–3.53 g/m2; P<0.04); the urinary albumin-to-creatinine ratio increased (P⩽0.03) with systolic BP (+1.14–1.17 mg/mmol) and maximum–minimum difference (+1.18 mg/mmol); and pulse wave velocity increased with systolic BP (+0.69 m/s; P<0.001). In 24-hour recordings, all 3 indices of organ damage increased (P<0.03) with systolic BP, whereas the associations with BP variability were nonsignificant (P≥0.15) except for increases in pulse wave velocity (P<0.05) with variability independent of the mean (+0.16 m/s) and maximum–minimum difference (+0.17 m/s). In home recordings, the urinary albumin-to-creatinine ratio (+1.27–1.30 mg/mmol) and pulse wave velocity (+0.36–0.40 m/s) increased (P<0.05) with systolic BP, whereas all associations of target organ damage with the variability indices were nonsignificant (P≥0.07). In conclusion, while accounting for BP level, associations of target organ damage with BP variability were readily detectable in beat-to-beat recordings, least noticeable in home recordings, with 24-hour ambulatory monitoring being informative only for pulse wave velocity.

Setting thresholds to varying blood pressure monitoring intervals differentially affects risk estimates associated with white-coat and masked hypertension in the population

Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ≥140/≥90, ≥130/≥80, ≥135/≥85, and ≥120/≥70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice.

Blood flow pattern in the middle cerebral artery in relation to indices of arterial stiffness in the systemic circulation.

BACKGROUND The brain is perfused at high-volume flow throughout systole and diastole. We explored the association of blood flow in the middle cerebral artery (MCA) with the pulsatile components of blood pressure in the systemic circulation and indices of arterial stiffness. METHODS We enrolled 334 untreated subjects (mean age, 50.9 years; 45.4% women) who had been referred for ambulatory blood pressure monitoring to Ruijin Hospital, Shanghai, China. We measured the MCA pulsatility index (PI) by transcranial Doppler ultrasonography. The indices of arterial stiffness included pulse pressure (brachial (bPP) and central (cPP) measured at the office and 24-h ambulatory (24-h PP)) and carotid-femoral (cf-PWV) and brachial-ankle (ba-PWV) pulse wave velocity. Effect sizes, expressed per 1 s.d., were adjusted for sex, age, heart rate, and mean pressure. RESULTS Women had faster MCA blood flow than men (68.0 vs. 58.3 cm/s), but lower PI (75.4 vs. 82.3%; P < 0.001). The five arterial stiffness indices were intercorrelated (r ≥ 0.37; P < 0.001). PI increased (P ≤ 0.045) with bPP (+6.78%), cPP (+5.56%), 24-h PP (+7.58%), cf-PWV (+1.59%), and ba-PWV (+3.46%). In explaining PI variance, bPP ranked first (partial r(2) = 0.25), 24-h PP second (0.20) and cPP third (0.14). In models including both cf-PWV and ba-PWV, only the latter was significant (-0.19%; P = 0.84 vs. +3.54%; P < 0.001). In models including both bPP and ba-PWV, only the former contributed to PI variance (+6.98%; P < 0.001 vs. -0.24%; P = 0.78). CONCLUSION MCA blood flow is closely associated with the pulsatile pressure in the systemic circulation, which depends on arterial stiffness as measured by PWV.

Ambulatory Hypertension Subtypes and 24-Hour Systolic and Diastolic Blood Pressure as Distinct Outcome Predictors in 8341 Untreated People Recruited From 12 Populations

Background— Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood pressure are scarce. Methods and Results— We recorded 24-hour blood pressure and health outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP24≥80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs⩽1.54; P≥0.18), but was associated with a higher risk of fatal combined with nonfatal cardiovascular, cardiac, or coronary events (HRs≥1.75; P⩽0.0054). Isolated systolic hypertension (SBP24≥130 mm Hg) and mixed diastolic plus systolic hypertension were associated with increased risks of all aforementioned end points (P⩽0.0012). Below age 50, DBP24 was the main driver of risk, reaching significance for total (HR for 1-SD increase, 2.05; P=0.0039) and cardiovascular mortality (HR, 4.07; P=0.0032) and for all cardiovascular end points combined (HR, 1.74; P=0.039) with a nonsignificant contribution of SBP24 (HR⩽0.92; P≥0.068); above age 50, SBP24 predicted all end points (HR≥1.19; P⩽0.0002) with a nonsignificant contribution of DBP24 (0.96⩽HR⩽1.14; P≥0.10). The interactions of age with SBP24 and DBP24 were significant for all cardiovascular and coronary events (P⩽0.043). Conclusions— The risks conferred by DBP24 and SBP24 are age dependent. DBP24 and isolated diastolic hypertension drive coronary complications below age 50, whereas above age 50 SBP24 and isolated systolic and mixed hypertension are the predominant risk factors.

Prevalence, awareness, treatment and control of hypertension in elderly Chinese

We studied the prevalence, awareness, treatment and control of hypertension in an elderly Chinese population. The study subjects (age ⩾60 years) were recruited from a suburban town of Shanghai from 2006 to 2008. We administered a standardized questionnaire to collect information on medical history, the use of medications and lifestyle. We measured blood pressure three times consecutively using a validated Omron 7051 oscillometric device (Kyoto, Japan) after the subjects had rested for at least 5 min in the sitting position. We defined hypertension as a blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or as the use of antihypertensive drugs. The 3949 participants (mean age of 68.3 years) included 2185 (55.3%) women, 182 (4.6%) obese subjects (body mass index ⩾30 kg m−2) and 366 (9.3%) diabetic patients. The prevalence of hypertension was 59.4%. In the 2345 hypertensive patients, the awareness, treatment and control (<140/90 mm Hg) rates were 72.5%, 65.8% and 24.4%, respectively. In the 1542 treated hypertensive patients, 1196 (77.6%) used fixed-dose combinations of thiazide and reserpine or clonidine (n=1157, 75.0%) or of an angiotensin receptor blocker and hydrochlorothiazide (n=1) or free combinations (n=38, 2.5%), and 346 (22.4%) used a monotherapy of short-acting calcium channel blockers (n=217, 14.1%) or other classes of antihypertensive drugs (n=129, 8.3%). The corresponding control rates were 37.3% and 36.4%, respectively. In a stepwise logistic regression, the risk of uncontrolled hypertension was higher with older age (+10 years, odds ratio (OR) 1.19, P=0.03), female sex (OR 1.40, P=0.01), obesity (OR 2.35, P=0.0002) and heavy drinking (⩾300 g per week, OR 2.18, P=0.0007). In conclusion, in elderly Chinese, the prevalence of hypertension is high. In spite of reasonably high awareness and treatment rates, the control rate remains low, most likely due to an unhealthy lifestyle and the underuse and/or underdose of antihypertensive drugs.

Brachial-Ankle Pulse Wave Velocity as a Predictor of Mortality in Elderly Chinese

Pulse wave velocity (PWV) is a measure of arterial stiffness and predicts cardiovascular events and mortality in the general population and various patient populations. In the present study, we investigated the predictive value of brachial-ankle PWV for mortality in an elderly Chinese population. Our study subjects were older (≥60 years) persons living in a suburban town of Shanghai. We measured brachial-ankle PWV using an automated cuff device at baseline and collected vital information till June 30, 2013, during follow-up. The 3876 participants (1713 [44.2%] men; mean [±SD] age, 68.1±7.3 years) included 2292 (59.1%) hypertensive patients. PWV was on average 17.8 (±4.0) m/s and was significantly (P<0.0001) associated with age (r=0.48) and in unadjusted analysis with all-cause (n=316), cardiovascular (n=148), stroke (n=46), and noncardiovascular mortality (n=168) during a median follow-up of 5.9 years. In further adjusted analysis, we studied the risk of mortality according to the decile distributions of PWV. Only the subjects in the top decile (23.3–39.3 m/s) had a significantly (P⩽0.003) higher risk of all-cause mortality (hazard ratio relative to the whole study population, 1.56; 95% confidence interval, 1.16–2.08), especially in hypertensive patients (hazard ratio, 1.86; 95% confidence interval, 1.31–2.64; P=0.02 for the interaction between PWV and hypertension). Similar trends were observed for cardiovascular, stroke, and noncardiovascular mortality, although statistical significance was not reached (P≥0.08). In conclusion, brachial-ankle PWV predicts mortality in elderly Chinese on the conditions of markedly increased PWV and hypertension.

Risk stratification by ambulatory blood pressure monitoring across JNC classes of conventional blood pressure.

BACKGROUND Guidelines propose classification of conventional blood pressure (CBP) into normotension (<120/<80 mm Hg), prehypertension (120-139/80-89 mm Hg), and hypertension (≥140/≥90 mm Hg). METHODS To assess the potential differential contribution of ambulatory blood pressure (ABP) in predicting risk across CBP strata, we analyzed outcomes in 7,826 untreated people recruited from 11 populations. RESULTS During an 11.3-year period, 809 participants died (276 cardiovascular deaths) and 639, 383, and 225 experienced a cardiovascular, cardiac, or cerebrovascular event. Compared with normotension (n = 2,639), prehypertension (n = 3,076) carried higher risk (P ≤ 0.015) of cardiovascular (+41%) and cerebrovascular (+92%) endpoints; compared with hypertension (n = 2,111) prehypertension entailed lower risk (P ≤ 0.005) of total mortality (-14%) and cardiovascular mortality (-29%) and of cardiovascular (-34%), cardiac (-33%), or cerebrovascular (-47%) events. Multivariable-adjusted hazard ratios (HRs) for stroke associated with 24-hour and daytime diastolic ABP (+5 mm Hg) were higher (P ≤ 0.045) in normotension than in prehypertension and hypertension (1.98 vs.1.19 vs.1.28 and 1.73 vs.1.09 vs. 1.24, respectively) with similar trends (0.03 ≤ P ≤ 0.11) for systolic ABP (+10 mm Hg). However, HRs for fatal endpoints and cardiac events associated with ABP did not differ significantly (P ≥ 0.13) across CBP categories. Of normotensive and prehypertensive participants, 7.5% and 29.3% had masked hypertension (daytime ABP ≥135/≥85 mm Hg). Compared with true normotension (P ≤ 0.01), HRs for stroke were 3.02 in normotension and 2.97 in prehypertension associated with masked hypertension with no difference between the latter two conditions (P = 0.93). CONCLUSION ABP refines risk stratification in normotension and prehypertension mainly by enabling the diagnosis of masked hypertension.

Strategies for Classifying Patients Based on Office, Home, and Ambulatory Blood Pressure Measurement

Hypertension guidelines propose home or ambulatory blood pressure monitoring as indispensable after office measurement. However, whether preference should be given to home or ambulatory monitoring remains undetermined. In 831 untreated outpatients (mean age, 50.6 years; 49.8% women), we measured office (3 visits), home (7 days), and 24-h ambulatory blood pressures. We applied hypertension guidelines for cross-classification of patients into normotension or white-coat, masked, or sustained hypertension. Based on office and home blood pressures, the prevalence of white-coat, masked, and sustained hypertension was 61 (10.3%), 166 (20.0%), and 162 (19.5%), respectively. Using daytime (from 8 AM to 6 PM) instead of home blood pressure confirmed the cross-classification in 575 patients (69.2%), downgraded risk from masked hypertension to normotension (n=24) or from sustained to white-coat hypertension (n=9) in 33 (4.0%), but upgraded risk from normotension to masked hypertension (n=179) or from white-coat to sustained hypertension (n=44) in 223 (26.8%). Analyses based on 24-h ambulatory blood pressure were confirmatory. In adjusted analyses, both the urinary albumin-to-creatinine ratio (+20.6%; confidence interval, 4.4–39.3) and aortic pulse wave velocity (+0.30 m/s; confidence interval, 0.09–0.51) were higher in patients who moved up to a higher risk category. Both indexes of target organ damage and central augmentation index were positively associated (P⩽0.048) with the odds of being reclassified. In conclusion, for reliably diagnosing hypertension and starting treatment, office measurement should be followed by ambulatory blood pressure monitoring. Using home instead of ambulatory monitoring misses the high-risk diagnoses of masked or sustained hypertension in over 25% of patients.

Association of Target Organ Damage With 24-Hour Systolic and Diastolic Blood Pressure Levels and Hypertension Subtypes in Untreated Chinese

The association of target organ damage with 24-hour systolic and diastolic blood pressure levels and ambulatory hypertension subtypes has not yet been examined in untreated Chinese patients. We measured left ventricular mass index by echocardiography (n=619), the urinary albumin:creatinine ratio (n=1047), and aortic pulse wave velocity by tonometry (n=1013) in 1047 untreated subjects (mean age, 50.6 years; 48.9% women). Normotension was a 24-hour systolic/diastolic blood pressure <130/<80 mm Hg. Hypertension subtypes were isolated diastolic hypertension and mixed systolic plus diastolic hypertension. We assessed associations of interest by multivariable-adjusted linear models. Using normotension as reference, mixed hypertension was associated with higher (P⩽0.003) left ventricular mass index (+4.31 g/m2), urinary albumin:creatinine ratio (+1.63 mg/mmol), and pulse wave velocity (+0.76 m/s); and isolated diastolic hypertension was associated with similar left ventricular mass index and pulse wave velocity (P≥0.39), but higher urinary albumin:creatinine ratio (+1.24 mg/mmol; P=0.002). In younger participants (<55 years), the mutually independent effect sizes associated with 1 SD increases in 24-hour systolic/diastolic blood pressure were +3.31/–0.36 g/m2 (P=0.009/0.79) for left ventricular mass index, +1.15/+1.14 mg/mmol (P=0.02/0.04) for the urinary albumin:creatinine ratio, and +0.54/–0.05 m/s (P<0.001/0.54) for pulse wave velocity. In older participants, these estimates were +3.58/+0.30 g/m2 (P=0.045/0.88), +1.23/+1.05 mg/mmol (P=0.002/0.54), and +0.76/–0.49 m/s (P<0.001/<0.001), respectively. In conclusion, 24-hour systolic blood pressure and mixed hypertension are major determinants of target organ damage irrespective of age and target organ, whereas 24-hour diastolic blood pressure and isolated diastolic hypertension only relate to the urinary albumin:creatinine ratio below middle age.

Vitamin K Dependent Protection of Renal Function in Multi-ethnic Population Studies

Background Following activation by vitamin K (VK), matrix Gla protein (MGP) inhibits arterial calcification, but its role in preserving renal function remains unknown. Methods In 1166 white Flemish (mean age, 38.2 years) and 714 South Africans (49.2% black; 40.6 years), we correlated estimated glomerular filtration (eGFR [CKD-EPI formula]) and stage of chronic kidney disease (CKD [KDOQI stages 2–3]) with inactive desphospho-uncarboxylated MGP (dp-ucMGP), using multivariable linear and logistic regression. Results Among Flemish and white and black Africans, between-group differences in eGFR (90, 100 and 122 mL/min/1.73 m2), dp-ucMGP (3.7, 6.5 and 3.2 μg/L), and CKD prevalence (53.5, 28.7 and 10.5%) were significant, but associations of eGFR with dp-ucMGP did not differ among ethnicities (P ≥ 0.075). For a doubling of dp-ucMGP, eGFR decreased by 1.5 (P = 0.023), 1.0 (P = 0.56), 2.8 (P = 0.0012) and 2.1 (P < 0.0001) mL/min/1.73 m2 in Flemish, white Africans, black Africans and all participants combined; the odds ratios for moving up one CKD stage were 1.17 (P = 0.033), 1.03 (P = 0.87), 1.29 (P = 0.12) and 1.17 (P = 0.011), respectively. Interpretation In the general population, eGFR decreases and CKD risk increases with higher dp-ucMGP, a marker of VK deficiency. These findings highlight the possibility that VK supplementation might promote renal health.