Risk of heart failure in ambulatory resistant hypertension: a meta-analysis of observational studies.

The impact of ambulatory resistant hypertension (ARH) on the occurrence of heart failure (HF) is not yet completely known. We performed for the first time a meta-analysis, by using published data or available data from published databases, on the risk of HF in ARH. Patients with ARH (24-h BP ≥ 130/80 mmHg during treatment with ≥3 drugs) were compared with those with controlled hypertension (CH, clinic BP < 140/90 mmHg and 24-h BP < 130/80 mmHg regardless of the number of drugs used), white coat uncontrolled resistant hypertension (WCURH, clinic BP ≥ 140/90 mmHg and 24-h BP < 130/80 mmHg in treated patients) and ambulatory nonresistant hypertension (ANRH, 24-h BP ≥ 130/80 mmHg during therapy with ≤2 drugs). We identified six studies/databases including 21,365 patients who experienced 692 HF events. When ARH was compared with CH, WCURH, or ANRH, the overall adjusted hazard ratio for HF was 2.32 (95% confidence interval (CI) 1.45-3.72), 1.72 (95% CI 1.36-2.17), and 2.11 (95% CI 1.40-3.17), respectively, (all P < 0.001). For some comparisons a moderate heterogeneity was found. Though we did not find variables that could explain the heterogeneity, sensitivity analyses demonstrated that none of the studies had a significant influential effect on the overall estimate. When we evaluated the potential presence of publication bias and small-study effect and adjusted for missing studies identified by Duval and Tweedie's method the estimates were slightly lower but remained significant. This meta-analysis shows that treated hypertensive patients with ARH are at approximately twice the risk of developing HF than other ambulatory BP phenotypes.

Prognostic impact of short-term ambulatory blood pressure variability for microvascular and macrovascular outcomes in patients with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study.

OBJECTIVE: To evaluate the prognostic importance of short-term blood pressure variability (BPV) for the occurrence of macrovascular and microvascular complications in individuals with type 2 diabetes. METHODS: Six hundred and forty patients had 24-h ambulatory BP monitoring performed at baseline and were followed-up over a median of 11.2 years. Daytime, night-time and 24-h SBP and DBPV parameters (standard deviations and variation coefficients) were calculated. Multivariate Cox analysis, adjusted for risk factors and mean BPs, examined the associations between BPV and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications [total cardiovascular events (CVEs), major adverse CVEs [MACEs]), and cardiovascular and all-cause mortalities. Improvements in risk discrimination were assessed by the C-statistic and Integrated Discrimination Improvement (IDI) index. RESULTS: During follow-up, 186 patients had a CVE (150 MACEs), and 237 patients died (107 from cardiovascular diseases); 155 newly developed or worsened diabetic retinopathy, 200 achieved the renal composite outcome (124 newly developed microalbuminuria and 102 deteriorated renal function), and 170 newly developed or worsened peripheral neuropathy. Daytime DBPV was the best predictor for all cardiovascular outcomes and mortality, with hazard ratios (for increments of 1SD) ranging from 1.27 (95% CI 1.09-1.48) for all-cause mortality to 1.55 (1.29-1.85) for MACEs, and it improved cardiovascular risk discrimination (with increases in C-statistic of up to 0.026, and IDIs of up to 22.8%). No BPV parameter predicted any microvascular outcome. CONCLUSION: Short-term BPV, particularly daytime DBPV, predicts future development of macrovascular complications and mortality and improves cardiovascular risk discrimination in patients with diabetes.

Prognostic Importance of On-Treatment Clinic and Ambulatory Blood Pressures in Resistant Hypertension: A Cohort Study.

The prognostic importances of on-treatment clinic and ambulatory blood pressure (BP) levels have never been investigated in individuals with resistant hypertension. We aimed to evaluate them for the occurrence of incident cardiovascular and mortality outcomes in a prospective cohort of 1726 patients with resistant hypertension. Clinic and ambulatory BPs were measured at baseline and serially during follow-up (analyzed as time-varying and as mean cumulative BPs) and also categorized as controlled/uncontrolled as defined by the traditional and new 2017 American College of Cardiology/American Heart Association criteria. Multivariate Cox analyses examined the associations between BP parameters and the occurrence of total cardiovascular events, major adverse cardiovascular events, and cardiovascular and all-cause mortalities. C statistics and the integrated discrimination improvement indexes evaluated the improvement in risk discrimination. Over a median follow-up of 8.3 years, 417 total cardiovascular events occurred (358 major adverse cardiovascular events) and 391 individuals died (233 cardiovascular deaths). All single systolic BP (SBP) parameters significantly predicted all outcomes, but the associations were stronger for ambulatory SBPs than for clinic SBPs and for on-treatment SBPs (particularly for mean cumulative) than for baseline SBPs, and both improved risk discrimination (with increases in C statistic of up to 0.021 and integrated discrimination improvements of up to 19.7%). These findings were consistent for diastolic BPs. Uncontrolled ambulatory BPs were associated with higher risks for all outcomes, whereas uncontrolled clinic BPs were not. In conclusion, mean cumulative ambulatory BPs during follow-up were the best prognostic markers of adverse cardiovascular outcomes and mortality in patients with resistant hypertension. Serial ambulatory BP monitoring shall be more widely used in resistant hypertension management.

Prognostic Impact of Aortic Stiffness in Patients With Resistant Hypertension.

The prognostic importance of aortic stiffness in patients with resistant hypertension has never been investigated. We aimed to evaluate it for the occurrence of adverse cardiovascular outcomes and mortality in a prospective cohort of resistant hypertensive patients. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (cf-PWV) at baseline in 891 resistant hypertensive patients who were followed-up for a median of 7.8 years. Multivariate Cox analysis examined the associations between cf-PWV and the occurrence of total cardiovascular events (CVE), major adverse CVEs, and cardiovascular and all-cause mortalities. The improvement in risk stratification was assessed by C statistics and the integrated discrimination improvement index. During follow-up, 138 patients had a CVE (123 major adverse CVE) and 142 patients died (91 from cardiovascular causes). The cf-PWV, analyzed either as a continuous or as a categorical variable, predicted all cardiovascular and mortality outcomes. Patients with increased aortic stiffness (cf-PWV ≥10 m/s after correction for the white-coat effect, or uncorrected directly measured ≥11 m/s) had a significant 2.2- to 2.6-fold increased risk of CVEs and mortality, after adjustments for other risk factors, including 24-hour ambulatory blood pressures and dipping patterns. Aortic stiffness significantly improved cardiovascular risk stratification, with integrated discrimination improvement indices ranging from 13% (for total CVEs) to 18% (for major adverse CVE). In conclusion, increased aortic stiffness predicts adverse cardiovascular outcomes and mortality and improves cardiovascular risk stratification in resistant hypertensive patients. cf-PWV measurement should be included into the routine clinical management of resistant hypertension.

Prognostic impact of carotid intima-media thickness and carotid plaques on the development of micro- and macrovascular complications in individuals with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study.

BACKGROUND: The prognostic importance of carotid atherosclerosis in individuals with diabetes is unsettled. We aimed to evaluate the relationships between parameters of carotid atherosclerosis and the future occurrence of micro- and cardiovascular complications in individuals with type 2 diabetes. METHODS: Ultrasonographic parameters of carotid atherosclerosis, intima-media thickness (CIMT) and plaques, were measured at baseline in 478 participants who were followed-up for a median of 10.8 years. Multivariate Cox analysis was used to examine the associations between carotid parameters and the occurrence of microvascular (retinopathy, renal, and peripheral neuropathy) and cardiovascular complications (total cardiovascular events [CVEs] and cardiovascular mortality), and all-cause mortality. The improvement in risk stratification was assessed by using the C-statistic and the integrated discrimination improvement (IDI) index. RESULTS: During follow-up, 116 individuals had a CVE and 115 individuals died (56 from cardiovascular diseases); 131 newly-developed or worsened diabetic retinopathy, 156 achieved the renal composite outcome (94 newly developed microalbuminuria and 78 deteriorated renal function), and 83 newly-developed or worsened peripheral neuropathy. CIMT, either analysed as a continuous or as a categorical variable, and presence of plaques predicted CVEs occurrence and renal outcomes, but not mortality or other microvascular complications. Individuals with an increased CIMT and plaques had a 1.5- to 1.8-fold increased risk of CVEs and a 1.6-fold higher risk of renal outcome. CIMT and plaques modestly improved cardiovascular risk discrimination over classic risk factors, with IDIs ranging from 7.8 to 8.4%; but more markedly improved renal risk discrimination, with IDIs from 14.8 to 18.5%. CONCLUSIONS: Carotid atherosclerosis parameters predicted cardiovascular and renal outcomes, and improved renal risk stratification. Ultrasonographic carotid imaging may be useful in type 2 diabetes management.

Prognostic impact of the ankle-brachial index on the development of micro- and macrovascular complications in individuals with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study.

AIMS/HYPOTHESIS: The prognostic importance of the ankle-brachial index (ABI) in individuals with diabetes is controversial. We aimed to evaluate the relationship between the ABI and the occurrence of micro- and macrovascular complications in individuals with type 2 diabetes. METHODS: The ABI was measured at baseline in 668 individuals with type 2 diabetes, and the individuals were followed-up for a median of 10 years. Multivariate Cox analysis was used to examine associations between the ABI and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration and peripheral neuropathy) and macrovascular (total cardiovascular events, major adverse cardiovascular events [MACE] and cardiovascular mortality) complications, and all-cause mortality. The improvement in risk stratification was assessed using the C statistic and the integrated discrimination improvement (IDI) index. RESULTS: During follow-up, 168 individuals had a cardiovascular event (140 MACE) and 191 individuals died (92 cardiovascular deaths); 156 individuals newly developed or experienced worsening diabetic retinopathy, 194 achieved the renal composite outcome (122 with newly developed microalbuminuria and 93 with deteriorating renal function) and 95 newly developed or experienced worsening peripheral neuropathy. The ABI, either analysed as a continuous or as a categorical variable, was significantly associated with all macrovascular and mortality outcomes, except for non-cardiovascular mortality. Individuals with a baseline ABI of ≤0.90 had a 2.1-fold increased risk of all-cause mortality (95% CI 1.3, 3.5; p = 0.004), a 2.7-fold excess risk of cardiovascular mortality (95% CI 1.4, 5.4; p = 0.004) and a 2.5-fold increased risk of MACE (95% CI 1.5, 4.4; p = 0.001). The ABI improved risk discrimination over classical risk factors, with relative IDIs ranging from 6.3% (for all-cause mortality) to 31% (for cardiovascular mortality). In addition, an ABI of ≤0.90 was associated with the development or worsening of peripheral neuropathy (2.1-fold increased risk [95% CI 1.1, 4.3]; p = 0.033), but not with retinopathy or renal outcomes. CONCLUSIONS/INTERPRETATION: A low ABI is associated with excess risk of adverse cardiovascular outcomes, mortality and peripheral neuropathy development or worsening, and improves cardiovascular risk stratification. The ABI should therefore be routinely evaluated in individuals with type 2 diabetes.

Aortic stiffness and ambulatory blood pressure as predictors of diabetic kidney disease: a competing risks analysis from the Rio de Janeiro Type 2 Diabetes Cohort Study.

AIMS/HYPOTHESIS: Diabetic kidney disease (DKD) is a microvascular complication associated with poor control of blood glucose and BP. We aimed to evaluate the predictors of development and progression of DKD in a cohort of high-risk individuals with type 2 diabetes, placing emphasis on ambulatory BP and arterial stiffness. METHODS: In a prospective study, 629 individuals without advanced renal failure had their renal function evaluated annually over a median follow-up period of 7.8 years. Ambulatory BP was monitored and aortic stiffness was assessed by carotid-femoral pulse wave velocity at baseline. Multivariate competing risks analysis with all-cause mortality, using the Fine and Gray approach, was used to examine the independent predictors of development and progression of DKD, a composite of development or progression of abnormal albuminuria and worsening of renal function (doubling of serum creatinine or progression to end-stage renal disease). RESULTS: At baseline, 197 individuals had DKD. During follow-up, DKD developed or progressed in 195 individuals, abnormal albuminuria developed or progressed in 125 individuals and renal function deteriorated in 91. After adjustments for baseline albuminuria and renal function, age, sex, diabetes duration and use of renin-angiotensin antagonists, poorer control of blood glucose (HR 1.17; 95% CI 0.98, 1.40; p = 0.09 for each 1 SD increment in mean first-year HbA1c), higher ambulatory systolic BP (HR 1.28; 95% CI 1.09, 1.50; p = 0.003, for each 1 SD increase in daytime systolic BP [SBP]) and increased aortic stiffness (HR 1.16; 95% CI 1.00, 1.34; p = 0.05) were independent predictors of development or progression of DKD. At baseline, ambulatory BP was a stronger predictor than BP measured in the clinic. Aortic stiffness predicted abnormal albuminuria development or progression (HR 1.26; 95% CI 1.02, 1.56; p = 0.036) whereas ambulatory BP was a stronger predictor of renal function deterioration (HR 1.32; 95% CI 1.09, 1.60; p = 0.005 for daytime SBP). CONCLUSIONS/INTERPRETATION: Poor blood glucose and BP control and increased aortic stiffness were the main predictors of development or progression of DKD; ambulatory SBP was a better predictor than BP measured in the clinic. Ambulatory BP monitoring and assessment of aortic stiffness should be more widely used in clinical type 2 diabetes management.