Laura Settimi

Relationship Between Short-Term Blood Pressure Variability and Large-Artery Stiffness in Human Hypertension: Findings From 2 Large Databases

Short-term blood pressure (BP) variability predicts cardiovascular complications in hypertension, but its association with large-artery stiffness is poorly understood and confounded by methodologic issues related to the assessment of BP variations over 24 hours. Carotid-femoral pulse wave velocity (cfPWV) and 24-hour ambulatory BP were measured in 911 untreated, nondiabetic patients with uncomplicated hypertension (learning population) and in 2089 mostly treated hypertensive patients (83% treated, 25% diabetics; test population). Short-term systolic BP (SBP) variability was calculated as the following: (1) SD of 24-hour, daytime, or nighttime SBP; (2) weighted SD of 24-hour SBP; and (3) average real variability (ARV), that is, the average of the absolute differences between consecutive SBP measurements over 24 hours. In the learning population, all of the measures of SBP variability showed a direct correlation with cfPWV (SD of 24-hour, daytime, and nighttime SBP, r=0.17/0.19/0.13; weighted SD of 24-hour SBP, r=0.21; ARV, r=0.26; all P<0.001). The relationship between cfPWV and ARV was stronger than that with 24-hour, daytime, or nighttime SBP (all P<0.05) and similar to that with weighted SD of 24-hour SBP. In the test population, ARV and weighted SD of 24-hour SBP had stronger relationships with cfPWV than SD of 24-hour, daytime, or nighttime SBP. In both populations, SBP variability indices independently predicted cfPWV along with age, 24-hour SBP, and other factors. We conclude that short-term variability of 24-hour SBP shows an independent, although moderate, relation to aortic stiffness in hypertension. This relationship is stronger with measures of BP variability focusing on short-term changes, such as ARV and weighted 24-hour SD.

Combined effects of office and 24-h blood pressure on aortic stiffness in human hypertension.

Objective Aortic stiffness, a prognostically adverse marker of arteriosclerosis, is critically dependent on blood pressure (BP). Office BP may not always reflect BP behaviour away from the medical environment, and it is uncertain whether office or out-of-office BP values are stronger determinants of arterial stiffness. Methods Twenty-four-hour BP and carotid-to-femoral pulse wave velocity (PWV) – a direct measure of aortic stiffness – were measured in 539 never-treated hypertensive patients and in 71 normotensive individuals. Results Sustained hypertensive patients had a higher age and heart-rate-adjusted aortic PWV than normotensive individuals (9.7 ± 2 vs. 8.5 ± 2 m/s, P < 0.001), even after further adjustment for office mean pressure as a measure of distending pressure (P = 0.018). The higher aortic PWV in white-coat hypertensive patients as compared with normotensive individuals (9.3 ± 2 vs. 8.5 ± 2 m/s, P = 0.026) did not hold after adjustment for office mean pressure (P = 0.16). To examine the independent effect of office BP on aortic PWV beyond the influence of 24-h BP, patients were classified according to the difference between observed and predicted office systolic BP (the latter determined by regressing 24-h BP on office BP). Despite having comparable 24-h BP values (131/82 vs. 131/84 mmHg), the patients with higher-than-predicted office BP had higher aortic PWV than those with lower-than-predicted office BP (10.1 ± 2 vs. 9.2 ± 2 m/s, P < 0.001). Similarly, after regressing office BP on 24-h BP, the group with higher-than-predicted 24-h BP also had higher aortic PWV (9.9 ± 2 vs. 9.5 ± 2 m/s, P < 0.05) despite having identical office BP (152/95 vs. 152/96 mmHg). In a multivariate regression model, both 24-h and office mean BP independently predicted aortic PWV. Conclusions Both office and out-of-office BP are independent predictors of aortic PWV in hypertension. Elevated BP values over the 24 h are associated with increased isobaric aortic stiffness.

Cardio-ankle vascular index and subclinical heart disease

The relationship between arterial stiffness, measured as pulse wave velocity (PWV), and the left ventricle is confounded by the effects of blood pressure. We evaluated the relationship between carotid–femoral PWV and cardio-ankle vascular index (CAVI), a less pressure-dependent measurement of the stiffness constant (β) of the aorta and the iliac, femoral and tibial arteries, and obtained prognostically relevant measurements of left ventricular structure and systolic function. CAVI, carotid–femoral PWV and echocardiographic left ventricular mass and systolic function were determined in 133 subjects with either hypertension or high–normal blood pressure (33% treated; 56±16 years, blood pressure 145/89±21/12u2009mmu2009Hg). Carotid–femoral PWV exhibited a direct relationship with systolic and diastolic blood pressure (r=0.33/0.26, P<0.001/0.014), whereas CAVI demonstrated no such relationship (r=0.12/−0.05, both P>0.1). Both CAVI and PWV correlated significantly with left ventricular mass index (r=0.31, P<0.001; r=0.21, P=0.014). Subjects with inappropriately high left ventricular masses for a given cardiac workload (n=44) had higher CAVI values (9.1±2.0 vs. 7.9±1.6, P<0.001), but not higher PWV values (8.5±2.5 vs. 8.7±2.4, P>0.1). In a multivariate regression model, CAVI was independently associated with inappropriate left ventricular mass (β=0.40, P<0.001), along with body mass index. CAVI also demonstrated a negative relationship with left ventricular midwall fractional shortening (r=−0.41, P=0.001) that was independent of age, sex, blood pressure and left ventricular mass in a multivariate analysis. In conclusion, a high CAVI is associated with inappropriately high left ventricular mass and low midwall systolic function. As a marker of arterial diastolic-to-systolic stiffening, CAVI may have a relationship with left ventricular structure and function that is independent of blood pressure levels.

Aortic stiffness is increased in polymyalgia rheumatica and improves after steroid treatment

Background Inflammatory rheumatic diseases have been associated with increased cardiovascular risk and arterial stiffness. Polymyalgia rheumatica (PMR), a disease which affects primarily older people, is characterised by a systemic inflammatory response but little is known about aortic involvement in PMR. A study was undertaken to investigate whether aortic stiffness is increased in PMR and whether it improves after steroid treatment. Methods Thirty-nine patients with PMR (age 72±8 years, 44% men, blood pressure (BP) 134/75±16/9 mm Hg) and 39 age-, sex- and BP-matched control subjects underwent aortic pulse wave velocity (PWV) determination. Aortic augmentation as a measure of the impact of the reflection wave on central haemodynamics was also measured and corrected for heart rate. Twenty-nine of the patients were re-examined after 4 weeks of treatment with prednisone at a dose of 15 mg/day. Results Aortic PWV was higher in patients with PMR than in control subjects (12.4±4 vs 10.2±2 m/s, p<0.01). Treatment was followed by a reduction in heart rate (from 78±12 to 70±10 beats/min, p<0.001) and no significant change in BP. Aortic PWV decreased after prednisone treatment (from 11.8±3 to 10.5±3 m/s, p=0.015), and the difference was independent of BP and heart rate changes. The change in aortic PWV had a direct correlation with percentage change in plasma C reactive protein (r=0.40, p=0.037). Treatment was also associated with a significant reduction in aortic augmentation index (from 34±7% to 29±8%, p=0.012). Conclusions Polymyalgia rheumatica is associated with increased aortic stiffness which may improve upon reduction of systemic inflammation induced by treatment with glucocorticoids.

Antihypertensive Drug Treatment and Circadian Blood Pressure Rhythm: A Review of the Role of Chronotherapy in Hypertension

Elevated nighttime blood pressure (BP) and a reduced day-night BP fall (nondipping condition) are strong predictors of cardiovascular complications, both in hypertension and in the general population. A reduced or inverted nocturnal BP fall might also be theoretically used to define the most appropriate timing for drug administration. In a systematic review of the available evidence, we show that bedtime dosing of antihypertensive medication reduces nocturnal BP and increases day-night BP fall more than standard morning dosing. The effects of such an approach on average 24-hour BP are more modest and less univocal, with a considerable between-center heterogeneity. Admittedly, the mechanisms underlying non-dipping condition have not been fully understood yet, and it is still a matter of debate whether restorating a dipping pattern may reduce the cardiovascular risk associated with non-dipping independently from the effects on 24-hour BP. Under this regard, evidence from a single trial strongly suggests that bedtime dosing of antihypertensive medications may greatly reduce cardiovascular morbidity in hypertensive patients. The provocative results of that trial deserve to be explored further in larger intervention trials.

Relationship Between Short-Term Blood Pressure Variability and Large-Artery Stiffness in Human Hypertension

Short-term blood pressure (BP) variability predicts cardiovascular complications in hypertension, but its association with large-artery stiffness is poorly understood and confounded by methodologic issues related to the assessment of BP variations over 24 hours. Carotid-femoral pulse wave velocity (cfPWV) and 24-hour ambulatory BP were measured in 911 untreated, nondiabetic patients with uncomplicated hypertension (learning population) and in 2089 mostly treated hypertensive patients (83% treated, 25% diabetics; test population). Short-term systolic BP (SBP) variability was calculated as the following: (1) SD of 24-hour, daytime, or nighttime SBP; (2) weighted SD of 24-hour SBP; and (3) average real variability (ARV), that is, the average of the absolute differences between consecutive SBP measurements over 24 hours. In the learning population, all of the measures of SBP variability showed a direct correlation with cfPWV (SD of 24-hour, daytime, and nighttime SBP, r=0.17/0.19/0.13; weighted SD of 24-hour SBP, r=0.21; ARV, r=0.26; all P<0.001). The relationship between cfPWV and ARV was stronger than that with 24-hour, daytime, or nighttime SBP (all P<0.05) and similar to that with weighted SD of 24-hour SBP. In the test population, ARV and weighted SD of 24-hour SBP had stronger relationships with cfPWV than SD of 24-hour, daytime, or nighttime SBP. In both populations, SBP variability indices independently predicted cfPWV along with age, 24-hour SBP, and other factors. We conclude that short-term variability of 24-hour SBP shows an independent, although moderate, relation to aortic stiffness in hypertension. This relationship is stronger with measures of BP variability focusing on short-term changes, such as ARV and weighted 24-hour SD.

Relationship Between Short-Term Blood Pressure Variability and Large-Artery Stiffness in Human HypertensionNovelty and Significance

Short-term blood pressure (BP) variability predicts cardiovascular complications in hypertension, but its association with large-artery stiffness is poorly understood and confounded by methodologic issues related to the assessment of BP variations over 24 hours. Carotid-femoral pulse wave velocity (cfPWV) and 24-hour ambulatory BP were measured in 911 untreated, nondiabetic patients with uncomplicated hypertension (learning population) and in 2089 mostly treated hypertensive patients (83% treated, 25% diabetics; test population). Short-term systolic BP (SBP) variability was calculated as the following: (1) SD of 24-hour, daytime, or nighttime SBP; (2) weighted SD of 24-hour SBP; and (3) average real variability (ARV), that is, the average of the absolute differences between consecutive SBP measurements over 24 hours. In the learning population, all of the measures of SBP variability showed a direct correlation with cfPWV (SD of 24-hour, daytime, and nighttime SBP, r=0.17/0.19/0.13; weighted SD of 24-hour SBP, r=0.21; ARV, r=0.26; all P<0.001). The relationship between cfPWV and ARV was stronger than that with 24-hour, daytime, or nighttime SBP (all P<0.05) and similar to that with weighted SD of 24-hour SBP. In the test population, ARV and weighted SD of 24-hour SBP had stronger relationships with cfPWV than SD of 24-hour, daytime, or nighttime SBP. In both populations, SBP variability indices independently predicted cfPWV along with age, 24-hour SBP, and other factors. We conclude that short-term variability of 24-hour SBP shows an independent, although moderate, relation to aortic stiffness in hypertension. This relationship is stronger with measures of BP variability focusing on short-term changes, such as ARV and weighted 24-hour SD.

Relationship Between Short-Term Blood Pressure Variability and Large-Artery Stiffness in Human HypertensionNovelty and Significance: Findings From 2 Large Databases

Short-term blood pressure (BP) variability predicts cardiovascular complications in hypertension, but its association with large-artery stiffness is poorly understood and confounded by methodologic issues related to the assessment of BP variations over 24 hours. Carotid-femoral pulse wave velocity (cfPWV) and 24-hour ambulatory BP were measured in 911 untreated, nondiabetic patients with uncomplicated hypertension (learning population) and in 2089 mostly treated hypertensive patients (83% treated, 25% diabetics; test population). Short-term systolic BP (SBP) variability was calculated as the following: (1) SD of 24-hour, daytime, or nighttime SBP; (2) weighted SD of 24-hour SBP; and (3) average real variability (ARV), that is, the average of the absolute differences between consecutive SBP measurements over 24 hours. In the learning population, all of the measures of SBP variability showed a direct correlation with cfPWV (SD of 24-hour, daytime, and nighttime SBP, r=0.17/0.19/0.13; weighted SD of 24-hour SBP, r=0.21; ARV, r=0.26; all P<0.001). The relationship between cfPWV and ARV was stronger than that with 24-hour, daytime, or nighttime SBP (all P<0.05) and similar to that with weighted SD of 24-hour SBP. In the test population, ARV and weighted SD of 24-hour SBP had stronger relationships with cfPWV than SD of 24-hour, daytime, or nighttime SBP. In both populations, SBP variability indices independently predicted cfPWV along with age, 24-hour SBP, and other factors. We conclude that short-term variability of 24-hour SBP shows an independent, although moderate, relation to aortic stiffness in hypertension. This relationship is stronger with measures of BP variability focusing on short-term changes, such as ARV and weighted 24-hour SD.

BRACHIAL SYSTOLIC AND DIASTOLIC BLOOD PRESSURE AT DIFFERENT ARM HEIGHTS: A NOVEL INDEX OF ARTERIAL FUNCTION: PP.10.386

Background: The dynamic behaviour of systolic and diastolic blood pressure (BP) over different mean pressure levels has been used to generate the (ambulatory) arterial stiffness index (ASI), and may reflect functional arterial properties. According to Stevins law, hydrostatic pressure depends linearly on the height of the liquid column. Methods: In 25 healthy subjects (36% men, age 40 ± 18 years, BP 118/68 ± 16/9 mmHg), we measured brachial BP and carotid-radial pulse wave velocity (PWV). Twelve BP measurements were obtained with the arm in 4 different positions (at the heart level, and at +25, +15 and -10 cm, respectively), 3 measurements per position. Subjects remained sitting with arm supported during the procedure. ASI was defined as 1 – (1/BPVR), where BPVR (BP variability ratio) is the SBP-on-DBP slope, estimated by the ratio of their standard deviations (SBP-SD/DBP-SD). Recent model expresses BPVR as the systolic-to-diastolic stiffness ratio. According to the Bramwell-Hill formula, diastolic stiffness was expressed by PWV2. Results: In comparison with the values obtained at the heart level, mean arterial pressure changed as predicted on the basis of the arm-heart vertical distance (-14 mmHg, -8 mmHg, and +6 mmHg, respectively, at +25, +15 and -10 cm). The BP variability generated by the arm height changes showed high SBP-DBP correlation (r = 0.90 ± 0.07). No relation was found between BPVR or ASI and PWV2 (r = -0.18 and r = -0.23, respectively, both p = n.s.). As expected, diastolic PWV2 had a linear relationship with DBP (r = 0.43, p = 0.05). Also, calculated systolic stiffness (BPVR × diastolic PWV2) correlated with SBP (r = 0.51, p < 0.05), and the slope of the line was similar to that of diastolic PWV2 vs DBP (2.07 vs 2.10 m2/s2/mmHg). Conclusions: The dynamic changes of SBP and DBP at different arm heights may provide a novel and simple measure of arterial function. The resulting SBP-on-DBP slope had no correlation with diastolic arterial stiffness, and increased with increasing SBP. Results support the theoretical expression of the SBP-on-DBP slope as the ratio between systolic ad diastolic stiffnesses.

AORTIC STIFFNESS IS INCREASED IN POLYMYALGIA RHEUMATICA, AND IMPROVES AFTER STEROID TREATMENT: PP.31.229

Background: Increased arterial stiffness and cardiovascular risk have been observed in diseases inflammatory diseases. Polymyalgia rheumatica (PMR) is a disease which affects primarily the elderly and exhibits evidence of a systemic inflammatory response, but little is known about aortic involvement in PMR. We investigated whether aortic stiffness, an early marker of arteriosclerosis, is increased in PMR, and whether it improves after steroid treatment. Methods: Thirty-one patients with PMR (age 71 ± 8 years, men 45%, blood pressure 132/74 ± 14/8 mmHg) and 31 age-, sex- and blood pressure-matched control subjects underwent aortic pulse wave velocity (PWV) determination with an applanation tonometry device (Sphygmocor). Twenty-one of the PMR patients were reexamined after 4-week treatment with prednisone (starting dose, 12.5–50 mg/day). Results: Aortic PWV was significantly higher in PMR patients than in control subjects (12.5 ± 3 vs 10.5 ± 2 m/s, p = 0.002). Treatment was followed by a reduction in heart rate (from 79 ± 13 to 71 ± 10 bpm, p < 0.001), and no significant change in BP (from 132/75 ± 13/8 to 134/75 ± 15/9 mmHg, both p = n.s.). As shown in the Figure, aortic PWV decreased significantly after steroid treatment (from 11.8 ± 3 to 10.6 ± 3 m/s, p < 0.05), and the difference was independent from changes in blood pressure and heart rate. Figure 1. No caption available. Conclusions: Polymyalgia rheumatica is associated with increased aortic stiffness, which may improve upon reduction of systemic inflammation determined by treatment with corticosteroids.