Aerobic exercise improves central blood pressure and blood pressure variability among patients with resistant hypertension: results of the EnRicH trial.

Central blood pressure (BP) and BP variability are associated with cardiovascular disease risk. However, the influence of exercise on these hemodynamic parameters is unknown among patients with resistant hypertension. The EnRicH (The Exercise Training in the Treatment of Resistant Hypertension) was a prospective, single-blinded randomized clinical trial (NCT03090529). Sixty patients were randomized to a 12-week aerobic exercise program or usual care. The outcome measures include central BP, BP variability, heart rate variability, carotid-femoral pulse wave velocity, and circulating cardiovascular disease risk biomarkers including high-sensitivity C-reactive protein, angiotensin II, superoxide dismutase, interferon gamma, nitric oxide, and endothelial progenitor cells. Central systolic BP decreased by 12.22 mm Hg (95% CI, -1.88 to -22.57, P = 0.022) as did BP variability by 2.85 mm Hg (95% CI, -4.91 to -0.78, P = 0.008), in the exercise (n = 26) compared to the control group (n = 27). Interferon gamma -4.3 pg/mL (95%CI, -7.1 to -1.5, P = 0.003), angiotensin II -157.0 pg/mL (95%CI, -288.1 to -25.9, P = 0.020), and superoxide dismutase 0.4 pg/mL (95%CI, 0.1-0.6, P = 0.009) improved in the exercise compared to the control group. Carotid-femoral pulse wave velocity, heart rate variability, high-sensitivity C-reactive protein, nitric oxide, and endothelial progenitor cells were not different between groups (P > 0.05). In conclusion, a 12-week exercise training program improved central BP and BP variability, and cardiovascular disease risk biomarkers in patients with resistant hypertension. These markers are clinically relevant as they are associated with target organ damage and increased cardiovascular disease risk and mortality.

Effect of Exercise Training on Ambulatory Blood Pressure Among Patients With Resistant Hypertension: A Randomized Clinical Trial.

Importance: Limited evidence suggests exercise reduces blood pressure (BP) in individuals with resistant hypertension, a clinical population with low responsiveness to drug therapy. Objective: To determine whether an aerobic exercise training intervention reduces ambulatory BP among patients with resistant hypertension. Design, Settings, and Participants: The Exercise Training in the Treatment of Resistant Hypertension (EnRicH) trial is a prospective, 2-center, single-blinded randomized clinical trial performed at 2 hospital centers in Portugal from March 2017 to December 2019. A total of 60 patients with a diagnosis of resistant hypertension aged 40 to 75 years were prospectively enrolled and observed at the hospitals' hypertension outpatient clinic. Interventions: Patients were randomly assigned in a 1:1 ratio to a 12-week moderate-intensity aerobic exercise training program (exercise group) or a usual care control group. The exercise group performed three 40-minute supervised sessions per week in addition to usual care. Main Outcomes and Measures: The powered primary efficacy measure was 24-hour ambulatory systolic BP change from baseline. Secondary outcomes included daytime and nighttime ambulatory BP, office BP, and cardiorespiratory fitness. Results: A total of 53 patients completed the study, including 26 in the exercise group and 27 in the control group. Of these, 24 (45%) were women, and the mean (SD) age was 60.1 (8.7) years. Compared with the control group, among those in the exercise group, 24-hour ambulatory systolic BP was reduced by 7.1 mm Hg (95% CI, -12.8 to -1.4; P = .02). Additionally, 24-hour ambulatory diastolic BP (-5.1 mm Hg; 95% CI, -7.9 to -2.3; P = .001), daytime systolic BP (-8.4 mm Hg; 95% CI, -14.3 to -2.5; P = .006), and daytime diastolic BP (-5.7 mm Hg; 95% CI, -9.0 to -2.4; P = .001) were reduced in the exercise group compared with the control group. Office systolic BP (-10.0 mm Hg; 95% CI, -17.6 to -2.5; P = .01) and cardiorespiratory fitness (5.05 mL/kg per minute of oxygen consumption; 95% CI, 3.5 to 6.6; P < .001) also improved in the exercise group compared with the control group. Conclusions and Relevance: A 12-week aerobic exercise program reduced 24-hour and daytime ambulatory BP as well as office systolic BP in patients with resistant hypertension. These findings provide clinicians with evidence to embrace moderate-intensity aerobic exercise as a standard coadjutant therapy targeting this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT03090529.

Physical Activity is Associated With Lower Arterial Stiffness in Patients With Resistant Hypertension.

BACKGROUND: Physical activity is associated with reduced arterial stiffness, although such a relationship has not been reported in those with resistant hypertension. Therefore, this study aimed to determine the association between daily physical activity and arterial stiffness in patients with resistant hypertension. METHODS: Fifty-seven (57) patients with resistant hypertension (50.9% men), aged 58.8±9.4 years, were consecutively recruited. Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). Daily physical activity was objectively assessed with accelerometers during 7 consecutive days. RESULTS: Patients had a body mass index of 29.0±4.0 kg/m2 (84.3% overweight/obese) and were taking an average 4.5 antihypertensive medications. Overall, the cf-PWV was 9.2±2.4 m/s and the majority of participants (n=41, 71.9%) presented a cf-PWV <10 m/s. The cf-PWV showed an inverse correlation with light-intensity physical activity (r = -0.290, p=0.029) and total daily physical activity (r = -0.287, p=0.030). The correlation between light physical activity and cf-PWV remained significant after adjustment for systolic and diastolic blood pressure, but lost significance when further adjusted for age. CONCLUSIONS: Higher daily levels of light-intensity and total physical activity were associated with lower arterial stiffness. Nonetheless, this association is weak and attenuated or abolished when adjusted for blood pressure and age. These results suggest that physical activity may play an important role as a lifestyle intervention for patients with resistant hypertension. Future studies with larger samples sizes are necessary to confirm this preliminary data.

Long-Term Risk of Progression to Sustained Hypertension in White-Coat Hypertension with Normal Night-Time Blood Pressure Values.

BACKGROUND: The long-term prognosis and transition towards sustained ambulatory hypertension (SHT) of white-coat hypertension (WCHT) remain uncertain particularly in those with both normal nighttime and daytime blood pressure (BP) values. Different classification criteria and the use of antihypertensive drugs may contribute to conflicting results. Patients and Methods. We prospectively evaluated for a 7.1 year transition to SHT in 899 nondiabetic subjects free from cardiovascular (CV) events: normotensive (NT) (n = 344; 52, 9% female; ageing 48 ± 14 years); untreated WCHT (UnWCHT n = 399; 50, 1% female; ageing 51 ± 14 years); and treated WCHT with antihypertensive drugs after baseline (TxWCHT n = 156; 54, 4% female; ageing 51 ± 15 years). All underwent 24 h ambulatory BP monitoring (24 h-ABPM) at baseline, at 30 to 60 months, and at 70 to 120 months thereafter. WCHT was at baseline (with no treatment) as office BP ≥ 140/or 90 mm·Hg, daytime BP < 135/85 mm·Hg, and nighttime BP < 120/70 mm·Hg. Development of SHT was considered if daytime BP ≥ 135/or 85 mm Hg and/or nighttime BP ≥ 120/or 70 mm·Hg. RESULTS: Baseline metabolic parameters did not differ among groups. At 30-60 months and at the end of follow-up, development of SHT occurred, respectively, in NT (3.8% (n = 13) and 9.6% (n = 33)) and in UnWCHT (10.1% (n = 40) and 16.5% (n = 66)) (p < 0.009). The mean annual increase of average 24 h-systolic BP was 0.48 + 0.93 in NT and 0.73 + 1.06 in UnWCHT, whereas annual SBP in office increased in NT by 1.2 + 0.95 but decreased in UnWCHT by 1.36 + 1.35 mm Hg (p < 0.01). CONCLUSION: Untreated WCHT patients exhibit a faster and a higher risk of developing SHT compared to NT with TxWCHT assuming an intermediate position between them.

Long-term cardiovascular risk of white-coat hypertension with normal night-time blood pressure values.

BACKGROUND: The prognostic impact of white-coat hypertension (WCHT) is still a matter of debate and controversy. Night-time blood pressure (NBP) is related strongly to cardiovascular (CV) prognosis, but this has not been considered currently in the definition of WCHT. PATIENTS AND METHODS: We investigated the long-term CV prognosis of 2659 patients submitted at admission to 24 h-ambulatory blood pressure (BP) monitoring divided into three groups: normotension (NT) (n=812; 59% female; ageing 49±13 years), sustained hypertension (SHT) (n=1230; 56% female; ageing 51±13 years) and WCHT (n=617; 55% female; ageing 50±3 years) defined as office BP of at least 140/90 mmHg, daytime BP less than 135/85 mmHg and NBP less than 120/70 mmHg. RESULTS: The median follow-up was 7.6 years (range: 0.4-24.4), during which a total of 257 CV events (36 fatal) occurred (46% strokes, 32% coronary and 22% others), 38 in NT, 31 in WCHT and 188 in SHT. The event rate per 100 patient-years was 0.60 in the WCHT group, 0.66 in the NT group and 2.09 in the SHT group. Cox's regression analysis adjusted for covariables showed a higher risk of CV events in patients with SHT than WCHT [hazard ratio (HR)=2.230, 95% confidence interval: 1.339-3.716, P=0.002], whereas there was no difference between WCHT and NT groups. Event-free survival was significantly different from SH versus WCHT and NT groups. Within the group of WCHT, 29% of patients received sustained antihypertensive medication during the follow-up, but the HR of CV events between WCHT either treated or not treated did not differ: HR=0.76 (95% confidence interval: 0.37-1.51, P=0.42). CONCLUSION: In patients with WCHT defined by normal daytime and NBP values, the risk of CV events was significantly lower than that of SHT and similar to that of NT patients, suggesting that NBP should be included in the WCHT definition and in its prognostic stratification.

Annual deterioration of renal function in hypertensive patients with and without diabetes.

BACKGROUND: Chronic kidney disease (CKD) complicates hypertension and diabetes. Knowledge of the deterioration rate of CKD may anticipate adjustment of therapies with renal elimination. This study evaluates the rate of annual deterioration of renal function in hypertensive patients either with type 2 diabetes (DM2) or without it (non-DM) followed for 5 years and relates it with blood pressure (BP) and glycemic control. MATERIALS AND METHODS: Out of a total of 1924 patients, 1023 patients (594 non-DM and 429 DM2, 53% female, aged 62.1±10.2 years) were evaluated over 5 years for the annual evolution of renal function (estimated glomerular filtration rate [eGFR], Modification of Diet in Renal Disease) ambulatory 24-hour blood pressure and metabolic parameters, corresponding to the analysis of 2378 patient-years. RESULTS: DM2 and non-DM did not differ for age, mean 24-hour BP levels, nighttime BP, albuminuria, and body mass index. DM2 versus non-DM showed a higher (p<0.02) prevalence of stage 3 CKD (24.0% vs 18.0%, eGFR 30-59), stage 4 (5.4% vs 2.7%, eGFR 15-29), and stage 5 (0.8% vs 0.5%, eGFR <15). Average annual decline of eGFR was 3.3±8.2 in DM2 versus 2.4±7.7 in non-DM (p=0.12, nonsignificant). Annual changes of eGFR and of albuminuria correlated (r=0.578, p<0.001). In multivariate analysis, age, nighttime BP, double inhibition of renin angiotensin system, albuminuria, and HbA1c >8.0% in DM2 predicted the decline in eGFR. On average, 16.2% of DM2 and 13.1% of non-DM moved each year toward a more severe stage of CKD. For initial eGFR <90 mL/min/1.73 m2, 26.4% of DM2 and 18.1% of non-DM patients showed a reduction per year >10% from the previous eGFR value (p=0.042). CONCLUSION: Progressive deterioration of renal function each year is frequent in hypertensive diabetic and non-diabetic patients. Beyond aging, this is particularly dependent on BP control particularly at nighttime, on drug therapy, and on highly abnormal glucose control.

Central pressures and central hemodynamic values in white coat hypertensives are closer to those of normotensives than to those of controlled hypertensives for similar age, gender, and 24-h and nocturnal blood pressures. / Os valores da pressão arterial aórtica e índice de aumentação central em indivíduos com hipertensão da bata branca são mais próximos dos indivíduos normotensos do que dos hipertensos tratados para idênticas idades, género e pressão noturna.

INTRODUCTION: There is disagreement whether white coat hypertensives (WCH) have different hemodynamic and structural characteristics compared to normotensives (NT) and hypertensives (HT). METHODS: We compared cardiovascular prognostic markers (pulse wave velocity [PWV] and aortic stiffness index [ASI]) and data on central hemodynamics and central pressures (augmentation index [AIx], augmentation pressure [AugP] and pulse pressure amplification [PPA]) from aortic pulse wave analysis between NT (n=175), WCH (n=315) and treated HT (n=691), all with 24-h blood pressure (BP) <130/80 and nocturnal BP <120/70 mmHg after matching for age, gender, body mass index (BMI) and and nocturnal BP. The groups were also compared separately in terms of 24-h systolic BP <120 mmHg and 120-129 mmHg. RESULTS: The percentage of non-dippers was 40.1% in NT, 34.5% in WCH and 38.3 in HT. For similar 24-h and nocturnal systolic BP (NT 109/64±7/5, WCH 110/66±7/6, HT 109/64±7/5 mmHg), aortic stiffness was greater in HT (n=691, PWV 10.8±2.6 m/s and ASI 0.33±0.16, p<0.01) than in WCH (n=316, PWV 9.7±2.4 m/s and ASI 0.28±0.17) and NT (n=175, PWV 9.5±2.0 m/s and ASI 0.29±0.15); AugP and AIx were higher (p<0.01) in HT (13.9±8.2 and 29.6±12.6 mmHg) than in WCH (11.5±8.5 mmHg and 24.9±15.2) and NT (11.0±6.4 mmHg and 26.6±11.5). PPA was lower (p<0.01) in HT (11.3±5.5 mmHg) than in WCH (13.2±7.1 mmHg) and in NT (12.4±4.9 mmHg). The findings were similar when the 24-h systolic BP <120 mmHg and 120-129 mmHg subgroups were analyzed separately. CONCLUSION: Our data suggest that for similar age, gender distribution, BMI, and 24-h and nocturnal BP, aortic stiffness, central aortic pressures and wave reflection in WCH are closer to those of NT than to those with treated HT. This supports the idea that white coat hypertension may be a more benign condition than treated hypertension for similar 24-h and particularly nocturnal BP levels.

High salt intake is associated with a higher risk of cardiovascular events: a 7.2-year evaluation of a cohort of hypertensive patients.

BACKGROUND: It is controversial whether high salt intake is directly associated with cardiovascular (CV) events and how far this relation is independent of blood pressure (BP). As Portugal has higher salt consumption and higher mortality by stroke than other European countries, we examined whether salt intake could predict the development of stroke and CV events in a hypertensive population. METHODS: In a longitudinal retrospective study of a cohort of 608 adult treated hypertensive patients 54.1±14.3 years of age, BMI 29.3±8.3 kg/m, 56.3% women and 17.1% diabetics, we evaluate the long-term prognostic significance of urinary sodium (UNa) excretion measured in 24 h valid samples within the first 3 months after admission along with 24 h ambulatory blood pressure monitoring and pulse wave velocity [(PWV), complior)] measurements. RESULTS: The mean follow-up duration was 7.2 years (0.5-11.1 years), during which 122 CV events occurred including 80 strokes and 36 coronary events. In 608 patients (group A=507 without events and group B=101 with events: 69 strokes, 26 coronary events, six others), the mean 24 h UNa was 208±79 mmol/day, corresponding to a salt intake of 12.1±4.6 g/day. Twenty-four hours UNa correlated positively with BMI, PWV and systolic blood pressure (SBP) particularly with night-time SBP. Group B versus A showed higher UNa (260+98 vs. 198+71 mmol/day, P<0.001) and higher PWV, BP office, 24 h, daytime and night-time SBP. Logistic regression analysis identified age, night-time SBP and 24 h UNa+ [HR=1.09 (95% CI, 1.06-1.12, P<0.001)] for each 10 mmol increase of UNa+ as the only independent predictors of CV events. UNa+ above the median (189 mmol sodium/day) predicted CV events with HR=2.99 (95% CI, 1.75-5.13, P<0.001) with worse CV event-free survival rates (log rank statistics of 17.44, P<0.001). CONCLUSION: In a cohort of hypertensive patients, high salt intake independently predicts the occurrence of CV events, particularly of stroke.

Diagnostic value and cost-benefit analysis of 24 hours ambulatory blood pressure monitoring in primary care in Portugal.

BACKGROUND: Hypertensive patients (HTs) are usually attended in primary care (PC). We aimed to assess the diagnostic accuracy and cost-benefit ratio of 24-hour ambulatory blood pressure monitoring (ABPM) in all newly diagnosed hypertensive patients (HTs) attended in PC. METHODS: In a cross-sectional study ABPM was recorded in all 336 never treated HTs (Office BP ≥140 and/or ≥ 90 mm Hg) that were admitted during 16 months. Since benefits from drug treatment in white-coat hypertension (WCH) remain unproven, a cost benefit estimation of a general use of ABPM (vs absence of ABPM) in HTs was calculated comparing the cost of usual medical assistance of HTs only diagnosed in office with that based both on refraining from drug treatment all subjects identified as WCH and on the reduction by half of the frequency of biochemical exams and doctor visits. RESULTS: Women were 56%, age 51 ± 14 years and BMI 27 ± 4 Kg/m2. Out of these, 206 were considered as true HTs, daytime ABPM ≥ 135 and/or ≥85 mm Hg and 130 (38,7%) were identified as having white coat hypertension (WCH), daytime ABPM <135/85 mm Hg. Versus HTs, WCH group showed higher percentage of women (68% vs 51%) and lower values of an index composed by the association of cardiovascular risk factors. We estimated that with ABPM total medical expenses can be reduced by 23% (157.500 euros) with a strategy based on ABPM for 1000 patients followed for 2 years. CONCLUSIONS: In PC, the widespread use of ABPM in newly diagnosed HTs increases diagnostic accuracy of hypertension, improves cardiovascular risk stratification, reduces health expenses showing a highly favourable benefit-cost ratio vs a strategy without ABPM.

Prognostic significance of ambulatory arterial stiffness index in hypertensives followed for 8.2 years: its relation with new events and cardiovascular risk estimation.

INTRODUCTION: The ambulatory arterial stiff ness index (AASI) is a new method for estimating arterial stiffness, which is associated with cardiovascular (CV) prognosis. Our aim was to evaluate the prognostic significance of AASI for new CV events. METHODS: Casual and ambulatory blood pressure (BP) measurements were obtained in 1200 hypertensive patients (645 female, age 51 +/- 12 years, BMI 27 +/- 5 kg/m2), 53% under stabilized therapy, 47% untreated, all without previous CV events. The occurrence of CV events was determined for 9833 patient-years and analyzed by a Cox proportional hazard model adjusted for confounding variables. AASI was calculated from 24h ABPM data and all patients were classified from very high to average CV risk. RESULTS: There were 62 deaths and 152 new fatal and non-fatal CV events (79 strokes, 51 coronary events, 22 other CV events) during the 15.2 years of follow-up (mean 8.2 +/- 3.0 years). AASI correlated significantly (p < 0.001) with pulse wave velocity (PWV), casual and 24h ambulatory BP, age and BMI. In subjects with very high or high CV risk (n = 401), AASI was 0.338 +/- 0.178, while in those with low or moderate CV risk (n = 715), it was 0.291 +/- 0.173 and in those with average CV risk (n = 84), it was 0.219 +/- 0.170) (p < 0.002, ANOVA). The probability of event-free and stroke-free survival (Kaplan-Meier) was better for AASI values below vs. above the median. The adjusted relative risk (HR 95% CI) for CV events, stroke and coronary events associated with a 1-SD increment in AASI values was respectively 1.27 (1.01-1.59), 1.36 (95% CI 1.02-1.89) (p < 0.02) and 0.99 (95% CI 0.67-1.48) (NS), similar to that of 24h pulse pressure (PP) and PWV. AASI hazard ratios were no longer significant after additional adjustment for 24h PP, whereas the converse did not occur. However, AASI above the median increases the predictive value of 24h PP for CV events and stroke. CONCLUSIONS: AASI correlates with PWV, stratifies CV risk and predicts total cardiovascular events and stroke but not coronary events. AASI may add predictive value to 24h PP for CV events and stroke.

Prognostic value of subdivisions of nighttime blood pressure fall in hypertensives followed up for 8.2 years. Does nondipping classification need to be redefined?

To evaluate the long-term prognostic significance of different ranges of the percentage fall in nighttime blood pressure (BP) of the nondipping pattern, 1200 hypertensive patients (645 women, age 51+/-12 years) underwent ambulatory BP monitoring under stabilized therapy. The occurrence of cardiovascular (CV) events was followed for 9833 patient-years and analyzed by the Cox hazard model. There were 152 CV fatal/nonfatal events (79 strokes, 51 coronary events, 22 others) during the 15.2 years of follow-up. According to nighttime BP fall (%) the authors noted: <0% (reverse-dippers [RD], n=83); 0%-4.9% (nondippers 1 [ND1], n=207); 5%-9.9% (nondippers 2 [ND2], n=311), 10%-19.9% (dippers [D], n=523); and > or =20% (extreme dippers [ED], n=76). After adjustment for confounding variables, hazard ratios (95% confidence interval) of CV event and stroke in RD vs D were 2.29 (1.31-3.99) and 2.46 (1.11-5.49); of ND1 vs D were 1.42 (1.12-1.79) and 1.62 (1.17-2.23); and of ND1 vs ND2 were 2.24 (1.33-3.75) and 2.30 (1.15-4.58). No differences were found in RD vs ND1 and ND2 vs D. Nondippers have a higher CV risk than dippers but only for a nighttime BP fall <5% suggesting that the limits for nondipping should be redefined for a stratification of CV risk.

Cardiovascular prognostic value of ambulatory blood pressure monitoring in a Portuguese hypertensive population followed up for 8.2 years.

AIM: We investigated the cardiovascular (CV) prognostic value of 24-h ambulatory blood pressure (ABP) and blood pressure (BP) during the six 4-h periods of the 24-h ABP length in a cohort of 1200 Portuguese hypertensive patients (aged 51±12 years) without earlier CV events. METHOD: The presence of CV events were followed for 9.833 patient years and analyzed using a cox hazard model. RESULTS: During the 15.2 (mean 8.2) years follow-up, there were 152 CV events (11% fatal) including 79 strokes and 52 coronary events. After adjustment for risk factors and office BP (OBP), a 1-standard deviation increment of 24-h, daytime and night-time systolic BP (SBP) significantly predicted any CV event with hazard ratios (HR) 1.41, 1.33 and 1.57, respectively, and stroke with HR 1.67, 1.58, 1.67, respectively (all P<0.01), but not coronary events. Prognostic significance of these SBP values and of night-time ABP persisted after adjustment for diastolic BP and daytime ABP, respectively, whereas the opposite did not occur. SBP night-time fall (%) inversely predicted total CV events after adjustment for diastolic BP night-time fall. Among all six 4-h periods of 24-h, increment of SBP during the first 4 h of night-time was the most powerful predictor of any CV event (HR 1.64) and stroke (HR 2.02) (both P<0.01) even after adjustment for daytime and 24-h BP. CONCLUSION: In predicting CV events and stroke, ABP is superior to office BP, ABP systolic is superior to ABP diastolic, and night-time BP is superior to daytime BP particularly during the first 4 h of sleep.

Different patterns of peripheral versus central blood pressure in hypertensive patients treated with ß-blockers either with or without vasodilator properties or with angiotensin receptor blockers.

BACKGROUND: It is unclear whether the assumed inferiority of atenolol to reduce central (aortic) blood pressure (BP) extends to other ß-blockers with vasodilating properties and, within that scope, how these drugs differ from the angiotensin receptor blockers (ARBs). METHODS: In a retrospective study, we compared three groups of hypertensive patients (aged 35-65 years) chronically treated with either ARBs (n=83, group 1), carvedilol/nebivolol (n=75, 25+25 mg/day/5 mg/day, group 2) or atenolol (n=84, 50-100 mg/day, group 3), matched for age (mean 52 years), sex (61% female), brachial BP and concomitant use of diuretics (75-81%)and dihydropyridine calcium antagonists (27-33%). We measured aortic stiffness by pulse wave velocity (Complior), and central BP, central-peripheral pulse pressure amplification, wave reflection [augmentation index (AIx) corrected for heart rate] and augmentation pressure (Sphygmocor). RESULTS: For similar age, sex distribution, brachial BP levels (145/85±11/10 mmHg) and pulse wave velocity (10±2 m/s), the atenolol group showed significantly (P<0.03 analysis of variance) higher central systolic BP (139±9 mmHg) versus group 2 (135±10 mmHg) and group 1 (132±11 mmHg), higher AIx (34±12%) versus group 2 (27±7%) and group 1 (23.0±9%), lower pulse pressure amplification (1.16±0.09) versus group 2 (1.22±0.10) and group 1 (1.31±0.11) and lower heart rate beats/min (61±9) versus group 2 (69±11) and group 1 (82±11). The differences on these values, between group 2 and group 1, were also significant (P<0.04). After adjustment for the heart rate, AIx became similar in groups 2 and 1, but still lower (P<0.04) than the atenolol group. CONCLUSION: These findings suggest that, for similar brachial BP and aortic stiffness, treatment with either vasodilating ß-blockers or angiotensin receptor blockers associates with lower central systolic BP and wave reflections than treatment with atenolol. These findings may suggest that the vasodilating ß-blockers may exert more favourable central haemodynamic effects, compared with atenolol, which are more alike, although not completely equal, to those of the ARBs.

Global cardiovascular risk stratification of hypertensive patients followed in Portugal in primary care or in hospital care according to the 2007 ESH/ESC guidelines.

INTRODUCTION: Hypertension is one of the major risk factors for cardiovascular (CV) disease. Our aim was to assess and stratify the CV risk of two cohorts of hypertensive patients in Portugal attended in primary care (PC) or in outpatient hospital care (HC) using the global CV risk stratification model of the 2007 ESH/ESC guidelines. METHODS: We retrospectively analyzed the clinical data of hypertensive patients (aged 18-75 years) enrolled in other population studies and attended in PC (n = 2299, 66 +/- 11 years, 64% women) or in HC (n = 2028, 51 +/- 14 years, 54.7% women). Global risk stratification was performed according to the 2007 ESH/ESC guidelines. RESULTS: In patients attended in PC (67% treated with antihypertensive drugs, 31% with BP < 140/90 mmHg, 22% with dyslipidemia and 16% with diabetes), added global CV risk was average or low in 26%, moderate in 31%, high in 27% and very high in 16%; in patients attended in HC (77% treated with antihypertensive drugs, 16% with BP <140/90 mmHg, 47% with dyslipidemia and 26% with diabetes), added global CV risk was average or low in 16%, moderate in 30%, high in 28% and very high in 26%. CONCLUSIONS: The majority of hypertensiv patients attended in PC or HC have a high or very high global CV risk according to the 2007 ESH/ECS guidelines. Thus, global CV risk stratification should be undertaken in all hypertensive patients, as well as the implementation and reinforcement of strategies aimed at adequate control of hypertension and of all other modifiable CV risk factors.

Relationship of circadian blood pressure and morning blood pressure surge with the severity of metabolic syndrome in newly diagnosed hypertensives.

OBJECTIVES: Twenty-four-hour ambulatory blood pressure (BP) data and the presence of metabolic syndrome (MS) are both good discriminators of cardiovascular risk. We examined the relationship between metabolic syndrome scores as defined by the International Diabetes Federation 2005 report (IDF-2005) and 24h ambulatory BP data in newly diagnosed hypertensives. METHODS: We evaluated 352 non-diabetic subjects (male/female: 167/185, aged 49+/-13). Based on IDF-2005 criteria, 212 subjects fulfilled 0, 1 or 2 criteria (no metabolic syndrome) and 140 fulfilled 3, 4 or 5 criteria (metabolic syndrome). Patients were divided into two groups (MS and non-MS), matched for age and casual BP All underwent 24h ambulatory blood pressure monitoring. RESULTS: No significant differences were found between non-MS and MS for casual BP (153/92+/-17/8 vs. 154/92+/-16/8 mmHg), age (48+/-14 vs. 50+/-12 years), 24h ambulatory BP (131/82+/-14/10 vs. 133/82+/-14/9 mmHg), daytime BP (135/86+/-14/11 vs. 137/85+/-14/9 mmHg), nighttime BP (122/74+/-15/11 vs. 124/74+/-15/10 mmHg), nighttime fall (9+/-6 vs. 9+/-6 %), BP on arising (131/82+/-20/15 vs. 135/82+/-21/15 mmHg), evening surge (7+/-14 vs. 10+/-15 mmHg), percentage of dippers (42.5 vs. 37.1%) or percentage of non-dippers (50.9 vs. 50.7%). However, significant differences between non-MS and MS were found for morning BP surge (25+/-12 vs. 28+/-15 mmHg, p<0.03). Also, when patients were divided into four groups according to MS scores (0/1, 2, 3 or 4/5), significant differences between groups were observed only for BP on arising (group 2 vs. 4/5, 132/79+/-21/15 vs. 140/84+/-10/15 mmHg, p<0.05; group 3 vs. 4/5, 131/81+/-20/15 vs. 140/84+/-20/15, p<0.005) and for morning BP surge (group 0/1 vs. 4/5, 24+/-11 vs. 29+/-15 mmHg, p<0.003). CONCLUSIONS: We conclude that in newly diagnosed hypertensive subjects there is no significant relationship between the severity of metabolic syndrome and ambulatory blood pressure data or circadian variations. The only exception found was a greater morning BP surge in patients with MS, whose importance as a determinant of cardiovascular risk needs to be clarified by further studies.

Estimation of salt intake by urinary sodium excretion in a Portuguese adult population and its relationship to arterial stiffness.

BACKGROUND: Portugal has one of the highest mortality rates from stroke, a high prevalence of hypertension and probably a high salt intake level. AIM: To evaluate Portuguese salt intake levels and their relationship to blood pressure and arterial stiffness in a sample of four different adult populations living in northern Portugal. METHODS: A cross-sectional study evaluating 24-hour urinary excretion of sodium (24 h UNa+), potassium and creatinine, blood pressure (BP), and pulse wave velocity (PWV) as an index of aortic stiffness in adult populations of sustained hypertensives (HT), relatives of patients with previous stroke (Fam), university students (US) and factory workers (FW), in the context of their usual dietary habits. RESULTS: We evaluated a total of 426 subjects, mean age 50 +/- 22 years, 56% female, BMI 27.9+/-5.1, BP 159/92 mmHg, PWV 10.4+/-2.2 m/s, who showed mean 24h UNa+ of 202 +/- 64 mmol/d, corresponding to a daily salt intake of 12.3 g (ranging from 5.2 to 24.8). The four groups were: HT: n = 245, 49 +/- 18 years, 92% of those selected, 69% treated, BP 163/94 mmHg, PWV 11.9 m/s, 24 h UNa+ 212 mmol/d, i.e. 12.4 g/d of salt); Fam: n = 38, 64 +/- 20 years, 57 % of those selected, BP 144/88 mmHg, PWV 10.5 m/s, 24 h UNa+ 194 mmol/d, i.e. 11.1 g/d of salt; US: n = 82, 22 +/- 3 years, 57% of those selected, BP 124/77 mmHg, PWV 8.7 m/s, 24h UNa+ 199 mmol/d, i.e. 11.3 g/d of salt; FW: n = 61, 39 9 years, 47% of those selected, BP 129/79 mmHg, PWV 9.5 m/s, 24 h UNa+ 221 mmol/d, i.e. 12.9 g/d of salt. The ratio of urinary sodium/potassium excretion (1.9 (0.4) was significantly higher in HT than the other three groups. In the 426 subjects, 24h UNa+ correlated significantly (p < 0.01) with systolic BP (r = 0.209) and with PWV (r=0.256) after adjustment for age and BP. Multivariate analysis showed that BP, age and 24h UNa+ correlated independently with PWV taken as a dependent variable. CONCLUSIONS: Four different Portuguese populations showed similarly high mean daily salt intake levels, almost double those recommended by the WHO. Overall, high urinary sodium excretion correlated consistently with high BP levels and appeared to be an independent determining factor of arterial stiffness. These findings suggest that Portugal in general has a high salt intake diet, and urgent measures are required to restrict salt consumption in order to prevent and treat hypertensive disease and to reduce overall cardiovascular risk and events.

Relationship between ambulatory blood pressure monitoring values and future occurrence of ischemic cerebrovascular and coronary events in hypertensive patients.

OBJECTIVES: To evaluate in a prospective study the relationship between 24-hour ambulatory blood pressure monitoring (ABPM) values and the occurrence of nonfatal ischemic cerebrovascular and coronary events in treated hypertensive patients. METHODS: Out of 8780 ABPM recordings we identified 79 hypertensive patients (both genders) who suffered a first nonfatal ischemic event, either cerebrovascular (stroke or transient ischemic attack) (STR/TIA, n = 48) or coronary (myocardial infarction, angina or coronary bypass/PTCA) (COR, n = 31) and 223 control-hypertensive patients (CTR) without any events during the same period who were fully matched (at the time of ABPM) for age, gender, antihypertensive therapy, presence of dyslipidemia or diabetes, and casual blood pressure (BP), in the proportion of 1 STR/TIA to 3 CTR and 1 COR to 6 CTR. Matched groups were compared for various ABPM parameters. RESULTS: On average, the time between ABPM and the occurrence of STR/TIA and COR events was respectively 32.4 (1 to 88) and 28.0 (1 to 73) months. For similar values of matched variables significant differences (p < 0.05) were observed between STR/TIA vs. CTR in 24-hour systolic BP (147.4 +/- 20.6 vs. 140.1 +/- 14.9 mmHg), daytime systolic BP (151.6 +/- 21.8 vs. 144.6 +/- 15.2 mmHg) and nighttime systolic BP (138.5 +/- 21.2 vs. 130.9 +/- 16.0 mmHg), and between COR vs. CTR in 24-hour systolic BP (143.5 +/- 19.5 vs. 135.2 +/- 15.6 mmHg), daytime systolic BP (146.3 +/- 20.5 vs. 139.6 +/- 15.9 mmHg) and nighttime systolic BP (138.1 +/- 19.7 vs. 126.2 +/- 16.4 mmHg), BP on rising (146.2 +/- 31.7 vs. 133.6 +/- 19.9 mmHg) and blunted nighttime BP dipping (5.3 +/- 7.4 vs. 9.60 +/- 6.0%). Versus CTR, STR/TIA showed a lower percentage of dippers (27.7 vs. 44.4%) and a higher percentage of extreme dippers (10.6 vs. 6.3%), nondippers (48.9 vs. 41.7%) and inverted dippers (12.8 vs. 7.6%). Versus CTR, the COR group showed (p < 0.02) a lower percentage of dippers (21.9 vs. 46.8%) and extreme dippers (3.1 vs. 4.3%) and a higher percentage of nondippers (56.3 vs. 43.0%) and inverted dippers (18.8 vs. 5.9%). CONCLUSIONS: This prospective study in treated hypertensive patients shows that both high ABPM values and abnormal daytime/nighttime BP profiles are associated with later occurrence of ischemic cerebrovascular and coronary events independently of casual BP values and other cardiovascular risk factors. This reinforces the idea that ABPM is a powerful predictor of future cardiovascular events.

Attenuation of heart rate recovery after exercise in hypertensive patients with blunting of the nighttime blood pressure fall.

OBJECTIVES: To evaluate whether hypertensive patients with attenuation of nighttime blood pressure (BP) fall exhibit a delay of the recovery of heart rate (HR) after exercise as an index of a general decrease in the vagal tone. METHODS: Mild-moderate hypertensive patients (n = 219, age 55 +/- 3, 77% men) underwent a maximal exercise test (Bruce > 85% heart rate limited) in whom we calculated the recovery of HR as the percent decrease of HR from peak to 1 min after stopping exercise (%HR fall-1 min), a 24-h ambulatory BP monitoring, calculating the percent decrease of nighttime vs. daytime BP (% night SBP fall). Left ventricular mass index (LVMI) was measured by echo and aortic stiffness by pulse wave velocity (PWV). Sixty percent were on antihypertensive drugs (not on beta-blockers nor on non-dihydropiridine calcium blockers); 12 subjects were type 2 diabetics. RESULTS: The "% night SBP fall" ranged from - 6.3% to 38.9% and the "%HR fall-1 min" ranged from 3.3% to 43.7%. There was a significant positive correlation between these two variables (r = 0.594, p < 0.001). Population was divided into five groups according to quintiles of values for the "% night SBP fall". For similar daytime BP and age, the lowest quintile for % night SBP fall (- 6.3% to 7.2%) showed the lower "%HR fall-1 min" (3.1 +/- 0.5%), and the higher LVMI (92 +/- 3 g/m(2)) and PWV (12.1 +/- 0.4 m/s) values comparing to the other quintiles (p < 0.02). CONCLUSIONS: In hypertensives, blunting of the nocturnal fall of BP is associated with a delayed recovery in heart rate after graded maximal exercise and with greater aortic stiffness and ventricular mass. This may indicate that in non-dipper subjects a relative general decrease of parasympathetic reactivation after exercise is linked to the failure of nighttime fall of BP, both of which might contribute to target-organs deterioration.

Sequential follow-up clinic and ambulatory blood pressure evaluation in a low risk population of white-coat hypertensive patients and in normotensives.

BACKGROUND: In subjects with white-coat hypertension (WCH) it is unclear how ambulatory blood pressure (ABPM) progresses over time and whether they exhibit an increased cardiovascular risk. METHODS: We prospectively evaluated the transition of clinic and ABPM values in 39 clinic and ABPM normotensive subjects (NT) (clinic BP<140/90 mmHg and awake BP<130/85 mmHg, ages 43.4+/-2.6 y) and in 79 untreated subjects (47.2+/-2.4 y) with WCH (clinic BP>140/90, awake ABP<130/85 mmHg) with no other major cardiovascular risk factors. Ambulatory blood pressure was evaluated at baseline and on at least two further occasions during follow-up. RESULTS: At baseline all subjects were untreated and groups did not differ on values of metabolic parameters, BMI, left ventricular mass index, and ABPM values. Subjects were revaluated for ABPM half way through and at the end of follow-up, 35+/-3 and 86+/-4 months in NT and 49+/-4 and 90+/-4 months in WCH. Thirty-six WCH were on antihypertensive treatment (AH) after baseline until the end of follow-up (WCH-tr), whereas 43 WCH (WCH-untr) were free from AH throughout the study. In a similar way all groups showed a significant (p<0.01) progressive increase in 24-h ABPM systolic blood pressure (SBP)/diastolic blood pressure (DBP) from baseline throughout the follow-up in NT (+4.9/2.1+/-0.8/0.9 mmHg), average annual increase of 0.72/0.37 mmHg/y, in WCH-tr (+ 5.0/1.2+/-1.1/1.5 mmHg), average annual increase of 0.66/0.31 mmHg/y and in WCH-untr (+5.4/3.2+/-0.9/1.1 mmHg), average annual increase of 0.74/0.39 mmHg/y. During the follow-up office SBP/DBP (mmHg) significantly rose in NT (+5.7/3.9) but was reduced in WCH-tr (-7.8/5.2) and in WCH-untr (-4.7/1.1). Development of ambulatory hypertension (daytime BP >130 and/or >85 mmHg) occurred in 15.4% (6/39) of NT, in 22.7% (8/36) of WCH-tr and in 26.1% (11/43) of WCH-untr (NS). First cardiovascular events recorded were three in subjects with WCH and none in NT. CONCLUSIONS: After 7.4 years of follow-up, both the progressive increase in ABPM and the rate of transition to ambulatory hypertension in subjects with WCH (either treated or untreated), who were selected under strict criteria were similar to that of normotensive subjects. Also there was no evidence that WCH exhibited a clear higher risk of development cardiovascular events.

Morning rise, morning surge and daytime variability of blood pressure and cardiovascular target organ damage. A cross-sectional study in 743 subjects.

OBJECTIVE: To evaluate in a large population the relationship between cardiovascular target organ damage and values of the night-to-morning rise of systolic blood pressure (MR-BP), the morning surge of BP at the moment of rising (BP surge) and daytime BP variability (standard deviation [SD] of daytime BP). METHODS: This was a cross-sectional study, evaluating 743 subjects, aged 30-75 years, 416 female, with normal renal function and no previous cardiovascular events. The population included: I-174 patients with type 2 diabetes, II-317 hypertensive patients with ongoing treatment over at least the previous 6 months, III-127 hypertensive patients untreated in the last 6 months, IV-125 healthy normotensive subjects. All underwent 24-hour ambulatory BP monitoring to calculate MR-BP, BP surge and SD of daytime BP. Target organ evaluation included: pulse wave velocity (PWV) (an indicator of aortic stiffness) in 711 subjects, left ventricular mass index (LVMI) in 185 subjects and 24-hour albuminuria in 239 subjects. RESULTS: In the population as a whole, BP surge, MR-BP and SD of daytime BP correlated significantly with PWV (r = 0.434, p < 0.0001; r = 0.126, p < 0.001; 0.337, p < 0.001, respectively), with LVMI (r = 0.447, p < 0.0001; r = 0.307, p < 0.001; 0.162, p < 0.05, respectively) and to a lesser degree with albuminuria (r = 0.126, p < 0.05; r = 0.083, NS; 0.082, NS, respectively). In the upper quintile of distribution of BP surge, the percentage of cases with abnormal PWV (>12 m/s) (21%), cardiac hypertrophy (53 %) and microalbuminuria (47 %) was significantly greater (p < 0.03) than that observed in the lower quintile (1%, 14% and 27%, respectively). BP surge correlated more strongly with indices of target organ damage than did MR-BP or SD of daytime BP, independently of night-time BP and nocturnal BP fall. CONCLUSIONS: In this large population, MR-BP, BP surge and daytime BP variability are strongly correlated with target organ damage severity, and are probably related to organ deterioration. Of the three, morning surge of BP at the moment of rising is more strongly related to organ damage than MR-BP, perhaps because unlike MR-BP, BP surge is independent of night-time BP values.