Sante D. Pierdomenico

Prognostic Effect of the Nocturnal Blood Pressure Fall in Hypertensive Patients: The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) Meta-Analysis.

The prognostic importance of the nocturnal systolic blood pressure (SBP) fall, adjusted for average 24-hour SBP levels, is unclear. The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) examined this issue in a meta-analysis of 17 312 hypertensives from 3 continents. Risks were computed for the systolic night-to-day ratio and for different dipping patterns (extreme, reduced, and reverse dippers) relative to normal dippers. ABC-H investigators provided multivariate adjusted hazard ratios (HRs), with and without adjustment for 24-hour SBP, for total cardiovascular events (CVEs), coronary events, strokes, cardiovascular mortality, and total mortality. Average 24-hour SBP varied from 131 to 140 mm Hg and systolic night-to-day ratio from 0.88 to 0.93. There were 1769 total CVEs, 916 coronary events, 698 strokes, 450 cardiovascular deaths, and 903 total deaths. After adjustment for 24-hour SBP, the systolic night-to-day ratio predicted all outcomes: from a 1-SD increase, summary HRs were 1.12 to 1.23. Reverse dipping also predicted all end points: HRs were 1.57 to 1.89. Reduced dippers, relative to normal dippers, had a significant 27% higher risk for total CVEs. Risks for extreme dippers were significantly influenced by antihypertensive treatment ( P <0.001): untreated patients had increased risk of total CVEs (HR, 1.92), whereas treated patients had borderline lower risk (HR, 0.72) than normal dippers. For CVEs, heterogeneity was low for systolic night-to-day ratio and reverse/reduced dipping and moderate for extreme dippers. Quality of included studies was moderate to high, and publication bias was undetectable. In conclusion, in this largest meta-analysis of hypertensive patients, the nocturnal BP fall provided substantial prognostic information, independent of 24-hour SBP levels.nn# Novelty and Significance {#article-title-42}The prognostic importance of the nocturnal systolic blood pressure (SBP) fall, adjusted for average 24-hour SBP levels, is unclear. The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) examined this issue in a meta-analysis of 17 312 hypertensives from 3 continents. Risks were computed for the systolic night-to-day ratio and for different dipping patterns (extreme, reduced, and reverse dippers) relative to normal dippers. ABC-H investigators provided multivariate adjusted hazard ratios (HRs), with and without adjustment for 24-hour SBP, for total cardiovascular events (CVEs), coronary events, strokes, cardiovascular mortality, and total mortality. Average 24-hour SBP varied from 131 to 140 mm Hg and systolic night-to-day ratio from 0.88 to 0.93. There were 1769 total CVEs, 916 coronary events, 698 strokes, 450 cardiovascular deaths, and 903 total deaths. After adjustment for 24-hour SBP, the systolic night-to-day ratio predicted all outcomes: from a 1-SD increase, summary HRs were 1.12 to 1.23. Reverse dipping also predicted all end points: HRs were 1.57 to 1.89. Reduced dippers, relative to normal dippers, had a significant 27% higher risk for total CVEs. Risks for extreme dippers were significantly influenced by antihypertensive treatment (P<0.001): untreated patients had increased risk of total CVEs (HR, 1.92), whereas treated patients had borderline lower risk (HR, 0.72) than normal dippers. For CVEs, heterogeneity was low for systolic night-to-day ratio and reverse/reduced dipping and moderate for extreme dippers. Quality of included studies was moderate to high, and publication bias was undetectable. In conclusion, in this largest meta-analysis of hypertensive patients, the nocturnal BP fall provided substantial prognostic information, independent of 24-hour SBP levels.

Prognostic impact from clinic, daytime, and night-time systolic blood pressure in nine cohorts of 13,844 patients with hypertension.

Background and method: To determine which SBP measure best predicts cardiovascular events (CVEs) independently, a systematic review was conducted for cohorts with all patients diagnosed with hypertension, 1+ years follow-up, and coronary artery disease and stroke outcomes. Lead investigators provided ad hoc analyses for each cohort. Meta-analyses gave hazard ratios from clinic SBP (CSBP), daytime SBP (DSBP), and night-time SBP (NSBP). Coefficients of variation of SBP measured dispersion. Nine cohorts (nu200a=u200a13u200a844) were from Europe, Brazil, and Japan. For sleep–wake SBP classification, seven cohorts used patient-specific information. Results: Overall, NSBPs dispersion exceeded DSBPs dispersion by 22.6% with nonoverlapping confidence limits. Within all nine cohorts, dispersion for NSBP exceeded that for CSBP and DSBP. For each comparison, Pu200a=u200a0.004 that this occurred by chance. Considered individually, increases in NSBP, DSBP, and CSBP each predicted CVEs: hazard ratios (95% confidence intervals)u200a=u200a1.25 (1.22–1.29), 1.20 (1.15–1.26), and 1.11 (1.06–1.16), respectively. However, after simultaneous adjustment for all three SBPs, hazard ratios were 1.26 (1.20–1.31), 1.01 (0.94–1.08), and 1.00 (0.95–1.05), respectively. Cohorts with baseline antihypertensive treatment and cohorts with patient-specific information for night–day BP classification gave similar results. Within most cohorts, simultaneously adjusted hazard ratios were greater for NSBP than for DSBP and CSBP: Pu200a=u200a0.023 and 0.012, respectively, that this occurred by chance. Conclusion: In hypertensive patients, NSBP had greater dispersion than DSBP and CSBP in all cohorts. On simultaneous adjustment, compared with DSBP and CSBP, increased NSBP independently predicted higher CVEs in most cohorts, and, overall, NSBP independently predicted CVEs, whereas CSBP and DSBP lost their predictive ability entirely.

Added predictive value of night-time blood pressure variability for cardiovascular events and mortality: The ambulatory blood pressure-international study

The association of ambulatory blood pressure (BP) variability with mortality and cardiovascular events is controversial. To investigate whether BP variability predicts cardiovascular events and mortality in hypertension, we analyzed 7112 untreated hypertensive participants (3996 men) aged 52±15 years enrolled in 6 prospective studies. Median follow-up was 5.5 years. SD of night-time BP was positively associated with age, body mass index, smoking, diabetes mellitus, and average night-time BP (all P<0.001). In a multivariable Cox model, night-time BP variability was an independent predictor of all-cause mortality (systolic, P<0.001/diastolic, P<0.0001), cardiovascular mortality (P=0.008/<0.0001), and cardiovascular events (P<0.001/<0.0001). In contrast, daytime BP variability was not an independent predictor of outcomes in any model. In fully adjusted models, a night-time systolic BP SD of ≥12.2 mm Hg was associated with a 41% greater risk of cardiovascular events, a 55% greater risk of cardiovascular death, and a 59% increased risk of all-cause mortality compared with an SD of <12.2 mm Hg. The corresponding values for a diastolic BP SD of ≥7.9 mm Hg were 48%, 132%, and 77%. The addition of night-time BP variability to fully adjusted models had a significant impact on risk reclassification and integrated discrimination for all outcomes (relative integrated discrimination improvement for systolic BP variability: 9% cardiovascular events, 14.5% all-cause death, 8.5% cardiovascular death, and for diastolic BP variability: 10% cardiovascular events, 19.1% all-cause death, 23% cardiovascular death, all P<0.01). Thus, addition of BP variability to models of long-term outcomes improved the ability to stratify appropriately patients with hypertension among risk categories defined by standard clinical and laboratory variables.

Predictive value of night-time heart rate for cardiovascular events in hypertension. The ABP-International study

BACKGROUNDnData from prospective cohort studies regarding the association between ambulatory heart rate (HR) and cardiovascular events (CVE) are conflicting.nnnMETHODSnTo investigate whether ambulatory HR predicts CVE in hypertension, we performed 24-hour ambulatory blood pressure and HR monitoring in 7600 hypertensive patients aged 52 ± 16 years from Italy, U.S.A., Japan, and Australia, included in the ABP-International registry. All were untreated at baseline examination. Standardized hazard ratios for ambulatory HRs were computed, stratifying for cohort, and adjusting for age, gender, blood pressure, smoking, diabetes, serum total cholesterol and serum creatinine.nnnRESULTSnDuring a median follow-up of 5.0 years there were 639 fatal and nonfatal CVE. In a multivariable Cox model, night-time HR predicted fatal combined with nonfatal CVE more closely than 24h HR (p=0.007 and =0.03, respectively). Daytime HR and the night:day HR ratio were not associated with CVE (p=0.07 and =0.18, respectively). The hazard ratio of the fatal combined with nonfatal CVE for a 10-beats/min increment of the night-time HR was 1.13 (95% CI, 1.04-1.22). This relationship remained significant when subjects taking beta-blockers during the follow-up (hazard ratio, 1.15; 95% CI, 1.05-1.25) or subjects who had an event within 5 years after enrollment (hazard ratio, 1.23; 95% CI, 1.05-1.45) were excluded from analysis.nnnCONCLUSIONSnAt variance with previous data obtained from general populations, ambulatory HR added to the risk stratification for fatal combined with nonfatal CVE in the hypertensive patients from the ABP-International study. Night-time HR was a better predictor of CVE than daytime HR.

Prediction of strokes versus cardiac events by ambulatory monitoring of blood pressure: results from an international database

We performed this study to elucidate the role of nighttime versus daytime ambulatory blood pressure in predicting stroke and cardiac events. The International Collaborative Study of the Prognostic Utility of ABPM, which includes prospective cohort studies of ambulatory blood pressure monitoring (ABPM) from seven sites, was analyzed in this study. The incidence of stroke and cardiac events were evaluated for an average of 5.8 years. A cox proportional hazards model of adjusting for site, age, sex, BMI, total cholesterol, smoking, and history of antihypertensive medications was used for the analysis. Dipping was defined as the percentage decline in nighttime systolic blood pressure (SBP) relative to daytime SBP. Three hundred and eleven cardiac events and 318 strokes were seen during the follow up periods. Awake and sleep SBP were both significantly associated with both cardiac and stroke events. When the awake and sleep SBP were entered together in the model, awake SBP was more strongly associated with cardiac events than sleep SBP (χ2=12.4, d.f.=1, P=0.0004); conversely, sleep SBP (χ2=13.5, d.f.=1, P<0.0002) was more predictive for stroke events than awake SBP, although awake SBP also remained a significant predictor (χ2=7.03, d.f.=1, P=0.008). The amount of dipping was a significant inverse predictor of stroke [hazards ratio (HR) 0.81 per 10% increase in dipping, confidence interval (CI) 0.70–0.94, χ2=7.70, d.f.=1, P=0.006] but not of cardiac events. It should not be assumed that one summary measure of ambulatory blood pressure would be the best predictor of different clinical outcomes.

Added Predictive Value of Night-Time Blood Pressure Variability for Cardiovascular Events and Mortality

The association of ambulatory blood pressure (BP) variability with mortality and cardiovascular events is controversial. To investigate whether BP variability predicts cardiovascular events and mortality in hypertension, we analyzed 7112 untreated hypertensive participants (3996 men) aged 52±15 years enrolled in 6 prospective studies. Median follow-up was 5.5 years. SD of night-time BP was positively associated with age, body mass index, smoking, diabetes mellitus, and average night-time BP (all P<0.001). In a multivariable Cox model, night-time BP variability was an independent predictor of all-cause mortality (systolic, P<0.001/diastolic, P<0.0001), cardiovascular mortality (P=0.008/<0.0001), and cardiovascular events (P<0.001/<0.0001). In contrast, daytime BP variability was not an independent predictor of outcomes in any model. In fully adjusted models, a night-time systolic BP SD of ≥12.2 mm Hg was associated with a 41% greater risk of cardiovascular events, a 55% greater risk of cardiovascular death, and a 59% increased risk of all-cause mortality compared with an SD of <12.2 mm Hg. The corresponding values for a diastolic BP SD of ≥7.9 mm Hg were 48%, 132%, and 77%. The addition of night-time BP variability to fully adjusted models had a significant impact on risk reclassification and integrated discrimination for all outcomes (relative integrated discrimination improvement for systolic BP variability: 9% cardiovascular events, 14.5% all-cause death, 8.5% cardiovascular death, and for diastolic BP variability: 10% cardiovascular events, 19.1% all-cause death, 23% cardiovascular death, all P<0.01). Thus, addition of BP variability to models of long-term outcomes improved the ability to stratify appropriately patients with hypertension among risk categories defined by standard clinical and laboratory variables.

Masked tachycardia. A predictor of adverse outcome in hypertension

Objective: The relative role of office heart rate (HR) and ambulatory HR for predicting major adverse cardiovascular events (MACEs) and mortality is not well known. Aim of this study was to investigate the association of white-coat tachycardia and masked tachycardia with MACE and mortality in hypertensive patients. Methods: We performed 24-h ambulatory blood pressure and HR monitoring in 7602 hypertensive patients (4165 men) aged 52u200a±u200a16 years enrolled in six prospective studies in Italy, Japan, and Australia. Participants were divided into four groups: normal office and normal night-time HRs (Nu200a=u200a5238), white-coat tachycardia (Nu200a=u200a998), masked tachycardia (Nu200a=u200a796), and sustained tachycardia (Nu200a=u200a570). Median follow-up was 5.0 years. Results: In age-and-sex-adjusted Cox model, using the normal HRs group as a reference, white-coat tachycardia was not a significant predictor of excess MACEs or all-cause death. In contrast, both masked tachycardia [hazard ratio, 95% confidence interval (CI); 1.40, 1.11–1.77] and sustained tachycardia (1.86, 1.44–2.40) were associated with risk of excess MACE. In addition, masked tachycardia (hazard ratio, 95% CI; 1.62, 1.14–2.29) but not sustained tachycardia (1.35, 0.83–2.19) was a significant predictor of excess mortality. These relationships held true in multivariable parsimonious Cox models including major risk factors. In these models, masked tachycardia remained an independent predictor of excess MACE (hazard ratio, 95% CI; 1.34, 1.06–1.71) and all-cause mortality (1.68, 1.18–2.41). Conclusion: The current study confirms that measurement of HR adds to the risk stratification for MACE and mortality and shows that an elevated night-time HR confers an increased mortality risk to hypertensive patients who have normal office HR.

Prognostic Value of Ambulatory Blood Pressure in the Obese: The Ambulatory Blood Pressure-International Study

The purpose of this study was to compare the predictive value of ambulatory blood pressure (BP) vs office BP for cardiovascular events during a 5.8‐year follow‐up period in the obese and nonobese participants of the Ambulatory Blood Pressure‐International Study (n=10,817). Both ambulatory BP and office BP considered separately were predictive of cardiovascular events. However, in Cox models including both pressures, only ambulatory BP was associated with outcome. Among obese patients, the hazard ratios for a 10‐mm Hg increase in 24‐hour and office systolic BPs were 1.37 (95% confidence interval, 1.20–1.53) and 0.91 (95% confidence interval, 0.76–1.07), respectively. Among nonobese patients, the corresponding hazard ratios were 1.39 (95% confidence interval, 1.31–1.47) and 0.94 (95% confidence interval, 0.88–1.00) (P=not significant vs obese). Similar results were obtained for diastolic BP and for daytime and nighttime BPs. Ambulatory BP has similar predictive capacity in obese and nonobese patients, suggesting that ambulatory BP monitoring is a useful diagnostic tool for the assessment of obese individuals.

Glomerular hyperfiltration is a predictor of adverse cardiovascular outcomes

The association between glomerular hyperfiltration and cardiovascular events is not well known. To investigate whether glomerular hyperfiltration is independently associated with risk of adverse outcome we analyzed 8794 participants, average age 52 years enrolled in 8 prospective studies. Of these, 89% had hypertension. Using the 5th and 95th percentiles of the age- and sex-specific quintiles of CKD-EPI-calculated estimated glomerular filtration rate (eGFR), we identified three participant groups with low, high and normal eGFR. The ambulatory pulse pressure interval was wider and nighttime blood pressure fall was smaller in both the low and high than in the normal eGFR participants. During a mean follow-up of 6.2 years, there were 722 cardiovascular events. Crude event rates were significantly higher for both high (1.8 per 100-person-year) and low eGFR groups (2.1 per 100 person-year) as compared with group with normal eGFR (1.2 per 100 person-year). In multivariable Cox models including age, sex, average 24-hour blood pressure, smoking, diabetes, and cholesterol, both high eGFR (hazard ratio 1.5 (95% confidence interval 1.2-2.1) and low eGFR (2.0 [1.5-2.6]) participants had a significantly higher risk of cardiovascular events as compared to those with normal eGFR. Addition of body mass index to the multivariable survival model did not change the magnitude of hazard estimates. Thus, glomerular hyperfiltration is a strong and independent predictor of cardiovascular events in a large multiethnic population of predominantly hypertensive individuals. Our findings support a U-shaped relationship between eGFR and adverse outcome.

7A.01: INCREASED RISK OF MORTALITY IN OBESE PATIENTS WITH HIGH NOCTURNAL BLOOD PRESSURE VARIABILITY. RESULTS FROM THE ABP-INTERNATIONAL STUDY.

Objective: The association between obesity and all-cause mortality is controversial and may differ according to subjects’ characteristics. Blood pressure variability (BPV) may be increased in obese individuals and thus impair prognosis. The purpose of this study was to evaluate whether the relationship between obesity and mortality is influenced by short-term ambulatory BPV. Design and method: The analysis was performed in 8724 participants (54% men) aged 51u200a±u200a15 years enrolled in 8 prospective studies in Australia, Italy, Japan, and U.S.A. The predictive power of obesity (BMI >=30u200akg/m2) for mortality was evaluated from multivariable Cox models in the subjects stratified by high or low nocturnal BPV (above or below the median). Results: Obese participants (Nu200a=u200a1286) had higher age-and-sex adjusted systolic and diastolic BPV than the non-obese participants (pu200a=u200a0.002/<0.001). Obese subjects with high systolic or diastolic BPV had higher nocturnal heart rate (pu200a=u200a0.01/<0.001) than obese subjects with low BPV and were more frequently diabetic (p<0.001) and heavy alcohol drinkers (pu200a<u200a0.001). During a median follow-up of 6.4 years there were 361 deaths, 4.7% in the obese and 4.0% in the non-obese individuals (Pu200a=u200aNS). However, the risk of mortality among the obese subjects greatly differed according to BPV level. In Cox models including age, sex, mean ambulatory BP, smoking, alcohol use, diabetes, cholesterol, creatinine, and nocturnal heart rate, the obese group with high systolic BPV had a doubled risk of mortality compared to the non-obese group (HR,2.0, 95%CI,1.4–2.9, pu200a<u200a0.001), whereas the risk was not increased in the obese group with low BPV (Pu200a=u200a0.81). Similar results were found for diastolic BPV, with a HR of 1.7 (1.2–2.5, pu200a=u200a0.002) in the high BPV group and no association at all with mortality (pu200a=u200a0.87) in the low BPV group. Inclusion of night-time BP dipping in the regressions did not change the strength of the associations. Conclusions: These data show that high nocturnal BPV greatly increases the risk of mortality related to obesity. High BPV is accompanied by increased heart rate and may reflect the influence of transient BP elevations related to sleep apnea and/or baroreflex dysfunction.