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.
The prognostic importance of obstructive sleep apnea (OSA) severity and other polysomnographic parameters in patients with resistant hypertension (RHT) has never been evaluated. We aimed to assess it ...in a prospective cohort of 422 individuals with RHT. OSA presence/severity was ascertained by complete polysomnography (PSG) at baseline. Multivariable Cox regressions assessed the risks associated with OSA severity and other PSG parameters (apnea-hypopnea index, sleep duration, nocturnal hypoxemia and periodic limb movements) for the primary (total cardiovascular events CVEs and all-cause mortality) and secondary outcomes (major CVEs). In the subgroup of patients with moderate/severe OSA, the risks associated with CPAP treatment were also estimated in relation to untreated individuals. One-hundred and eighty-six participants (44%) had no/mild OSA and 236 (56%) had moderate/severe OSA, and 67 of them were CPAP-treated. Over a mean follow-up of 5 years, there were 46 CVEs (37 major ones) and 44 all-cause deaths. Neither the presence of moderate/severe or severe OSA, nor being untreated during follow-up, was associated with significant excess risks for any outcome in relation to the subgroup with no/mild OSA. Similarly, no other PSG-derived parameter predicted any adverse outcome. Otherwise, CPAP treatment was associated with non-significant risk reductions of 37% for total CVEs, 49% for major CVEs and 63% for all-cause mortality in relation to those who remained untreated during follow-up. In conclusion, the presence/severity of OSA and its related PSG parameters were not associated with worse cardiovascular/mortality prognosis in patients with RHT. However, CPAP treatment might be protective in individuals with moderate/severe OSA.
The prognostic importance of several hematological parameters has been scarcely investigated in type 2 diabetes. So, we aimed to evaluate their prognostic importance for development of complications ...in a cohort of type 2 diabetes.
In a prospective study, 689 individuals with type 2 diabetes had blood red cell, platelet and leukocyte parameters obtained at baseline. Multivariate Cox analyses examined the associations between several hematological parameters (including neutrophyl-to-lymphocyte, lymphocyte-to-monocyte, platelet-to-lymphocyte, and monocyte-to-HDL ratios) and the occurrence of microvascular (retina, renal and peripheral neuropathy) and cardiovascular complications (total cardiovascular events CVEs, and major adverse CVEs MACEs), and all-cause and cardiovascular mortality. Improvements in risk discrimination were assessed by C-statistics and Integrated Discrimination Improvement (IDI) index.
During a median follow-up of 10.5 years, 212 patients had a CVE (174 MACEs), 264 patients died (131 cardiovascular deaths); 206 had a renal, 161 a retinopathy and 179 patients had a neuropathy outcome. In multivariate-adjusted analyses, the lymphocytes count and lymphocyte-to-monocyte ratio were protective (hazard ratios HRs: 0.77 and 0.72, respectively), whereas the neutrophyl-to-lymphocyte and platelet-to-lymphocyte ratios were associated with increased risks (HRs: 1.19 and 1.17) for all-cause mortality. For cardiovascular mortality, the monocytes count, the neutrophyl-to-lymphocyte and monocyte-to-HDL ratios were associated with increased risks and the lymphocyte-to-monocyte ratio was protective. Higher lymphocyte-to-monocyte ratio was protective for renal failure outcome. However, none of them improved risk discrimination.
Low lymphocytes count and leukocyte ratios that mainly included lymphocytes were predictors of macrovascular complications and mortality in individuals with type 2 diabetes. However, they did not improve risk prediction over traditional risk factors.
Liver stiffness measurement (LSM, which reflects fibrosis) and controlled attenuation parameter (CAP, which reflects steatosis), two parameters derived from hepatic transient elastography (TE), have ...scarcely been evaluated as predictors of cardiovascular complications and mortality in individuals with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD).
Four hundred type 2 diabetic patients with NAFLD had TE examination (by Fibroscan
) performed at baseline. Multivariate Cox analyses evaluated the associations between TE parameters and the occurrence of cardiovascular events (CVEs) and mortality. TE parameters were assessed as continuous variables and dichotomized at low/high values reflecting advanced liver fibrosis (LSM > 9.6 kPa) and severe steatosis (CAP > 296 or > 330 dB/m). Improvements in risk discrimination were assessed by C-statistic and by the relative Integrated Discrimination Improvement (IDI) index.
During a median follow-up of 5.5 years, 85 patients died (40 from cardiovascular causes), and 69 had a CVE. As continuous variables, an increasing LSM was a risk marker for total CVEs (hazard ratio HR: 1.05; 95% CI: 1.01-1.08) and all-cause mortality (HR: 1.04; 95% CI: 1.01-1.07); whereas an increasing CAP was a protective factor for both outcomes (HR: 0.93; 95% CI: 0.89-0.98; and HR: 0.92; 95% CI: 0.88-0.97; respectively). As dichotomized variables, a high LSM remained a risk marker of adverse outcomes (with HRs ranging from 2.5 to 3.0) and a high CAP was protective (with HRs from 0.3 to 0.5). The subgroup of individuals with low-LSM/high-CAP had the lowest risks while the opposite subgroup with high-LSM/low-CAP had the highest risks. Both LSM and CAP improved risk discrimination, with increases in C-statistics up to 0.037 and IDIs up to 52%.
Measured by hepatic TE, advanced liver fibrosis is a risk marker and severe steatosis is a protective factor for cardiovascular complications and mortality in individuals with type 2 diabetes and NAFLD.
The prognostic importance of changes in aortic stiffness for the occurrence of adverse cardiovascular outcomes and mortality has never been investigated in patients with resistant hypertension. We ...aimed to evaluate it in a prospective cohort of 442 resistant hypertension individuals. Changes in aortic stiffness were assessed by 2 carotid-femoral pulse wave velocity (CF-PWV) measurements performed over a median time interval of 4.7 years. Multivariate Cox analysis examined the associations between changes in CF-PWV (evaluated as continuous variables and categorized into quartiles and as increased/persistently high or reduced/persistently low) and the occurrence of total cardiovascular events (CVEs), major adverse CVEs, and cardiovascular/all-cause mortalities. During a median follow-up of 4.1 years after the second CF-PWV measurement, there were 49 total CVEs (42 major adverse CVEs) and 53 all-cause deaths (32 cardiovascular). As continuous variables, increments in absolute and relative changes in CF-PWV were associated with higher risks of CVEs and major adverse CVEs occurrence, but not of mortality. Divided into quartiles of CF-PWV changes, risks increased in the third and fourth quartile subgroups in relation to the reference first quartile subgroup (those with greatest CF-PWV reductions) for all outcomes. Patients who either increased or persisted with high CF-PWV had excess risks of cardiovascular morbidity/mortality, with hazard ratios ranging from 2.7 to 3.0, in relation to those who reduced or persisted with low CF-PWV values. In conclusion, reducing or preventing progression of aortic stiffness was associated with significant cardiovascular protection in patients with resistant hypertension, suggesting that it may be an additional clinical target of antihypertensive treatment.
The prognostic importance of an increased visit-to-visit blood pressure variability (BP-VVV) for the future development of micro- and macrovascular complications in type 2 diabetes has been scarcely ...investigated and is largely unsettled. We aimed to evaluate it in a prospective long-term follow-up study with 632 individuals with type 2 diabetes.
BP-VVV parameters (systolic and diastolic standard deviations SD and variation coefficients) were measured during the first 24-months. Multivariate Cox analysis, adjusted for risk factors and mean BP levels, examined the associations between BP-VVV and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications (total cardiovascular events CVEs, major adverse CVEs MACE and cardiovascular and all-cause mortality). Improvement in risk discrimination was assessed by the C-statistic and integrated discrimination improvement (IDI) index.
Over a median follow-up of 11.3 years, 162 patients had a CVE (132 MACE), and 212 patients died (95 from cardiovascular diseases); 153 newly-developed or worsened diabetic retinopathy, 193 achieved the renal composite outcome (121 newly-developed microalbuminuria and 95 deteriorated renal function), and 171 newly-developed or worsened peripheral neuropathy. Systolic BP-VVV was an independent predictor of MACE (hazard ratio: 1.25, 95% CI 1.03-1.51 for a 1-SD increase in 24-month SD), but not of total CVEs, cardiovascular and all-cause mortality, and of any microvascular outcome. However, no BP-VVV parameter significantly improved cardiovascular risk discrimination (increase in C-statistic 0.001, relative IDI 0.9%).
Systolic BP-VVV was an independent predictor of MACE, but it did not improve cardiovascular risk stratification. The goal of anti-hypertensive treatment in patients with type 2 diabetes shall remain in controlling mean BP levels, not on decreasing their visit-to-visit variability.
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.
Diabetic retinopathy (DR) is a chronic microvascular complication associated a worse prognosis. We aimed to evaluate the predictors of development/progression of DR in a cohort of 544 high-risk ...patients with type 2 diabetes who had annual ophthalmologic examinations over a median follow-up of 6 years. Ambulatory blood pressure (BP) monitoring and aortic stiffness by carotid-femoral pulse wave velocity were performed. Multivariate Cox survival analysis examined the independent predictors of development or progression of DR. During follow-up, 156 patients either newly-developed or worsened DR. Patients who developed/progressed DR had longer diabetes duration, higher ambulatory and clinic BP levels, higher aortic stiffness, and poorer glycemic control than patients who did not developed/progressed DR. After adjustments for baseline retinopathy prevalence, age and sex, a longer diabetes duration (p < 0.001), higher baseline ambulatory BPs (p = 0.013, for 24-hour diastolic BP), and higher mean cumulative exposure of HbA
(p < 0.001), clinic diastolic BP (p < 0.001) and LDL-cholesterol (p = 0.05) during follow-up were the independent predictors of development/progression of DR. BP parameters were only predictors of DR development. In conclusion, a longer diabetes duration, poorer glycemic and lipid control, and higher BPs were the main predictors of development/progression of DR. Mean cumulative clinic diastolic BP was the strongest BP-related predictor.
To evaluate the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) and Fibrosis-4 score (FIB4) as predictors of complications development and mortality in a cohort of type 2 diabetes.
554 ...type 2 diabetic subjects had NFS and FIB4 calculated at baseline. Multivariate Cox and Poisson analyses evaluated the associations between fibrosis scores and the occurrence of microvascular and cardiovascular complications, and all-cause mortality.
According to recommended cut-offs of NFS, 12.8% had advanced fibrosis and 45.9% had absence of advanced fibrosis and of FIB4, 3.8% and 86.1%, respectively. During a median follow-up of 11 years, 217subjects died, 172 had cardiovascular events (CVEs), 184 had renal events, and 139 had retinopathy and 185 neuropathy events. As continuous variables, both scores predicted all-cause mortality: NFS, HR: 1.30 (p = 0.032) and FIB4, HR: 1.24 (p = 0.021); an increased NFS implied in a significant 90% excess risk of mortality, whereas a higher FIB4 in a borderline 69% higher risk. The scores were mainly predictors of mortality in women and for non-cardiovascular deaths. The NFS was a predictor of renal events, mainly for renal function deterioration.
The NFS and FIB4 predicted all-cause mortality, particularly in women and for non-cardiovascular causes. The NFS predicted adverse renal outcomes. These liver fibrosis scores may improve stratification risk in individuals with diabetes and NAFLD.
•The importance of NFS and FIB4, has not been investigated in type 2 diabetes.•The NFS and FIB4 predicted all-cause mortality in type 2 diabetes.•This association was particularly evident in women and for non-cardiovascular causes.•The NFS was a predictor of renal events: mainly of renal function decline.•The NFS and FIB-4 may improve risk stratification in diabetic individuals with NAFLD.
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