Jerzy Gasowski

Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials

BACKGROUND Previous meta-analysis of outcome trials in hypertension have not specifically focused on isolated systolic hypertension or they have explained treatment benefit mainly in function of the achieved diastolic blood pressure reduction. We therefore undertook a quantitative overview of the trials to further evaluate the risks associated with systolic blood pressure in treated and untreated older patients with isolated systolic hypertension METHODS Patients were 60 years old or more. Systolic blood pressure was 160 mm Hg or greater and diastolic blood pressure was less than 95 mm Hg. We used non-parametric methods and Cox regression to model the risks associated with blood pressure and to correct for regression dilution bias. We calculated pooled effects of treatment from stratified 2 x 2 contingency tables after application of Zelens test of heterogeneity. FINDINGS In eight trials 15 693 patients with isolated systolic hypertension were followed up for 3.8 years (median). After correction for regression dilution bias, sex, age, and diastolic blood pressure, the relative hazard rates associated with a 10 mm Hg higher initial systolic blood pressure were 1.26 (p=0.0001) for total mortality, 1.22 (p=0.02) for stroke, but only 1.07 (p=0.37) for coronary events. Independent of systolic blood pressure, diastolic blood pressure was inversely correlated with total mortality, highlighting the role of pulse pressure as risk factor. Active treatment reduced total mortality by 13% (95% CI 2-22, p=0.02), cardiovascular mortality by 18%, all cardiovascular complications by 26%, stroke by 30%, and coronary events by 23%. The number of patients to treat for 5 years to prevent one major cardiovascular event was lower in men (18 vs 38), at or above age 70 (19 vs 39), and in patients with previous cardiovascular complications (16 vs 37). INTERPRETATION Drug treatment is justified in older patients with isolated systolic hypertension whose systolic blood pressure is 160 mm Hg or higher. Absolute benefit is larger in men, in patients aged 70 or more and in those with previous cardiovascular complications or wider pulse pressure. Treatment prevented stroke more effectively than coronary events. However, the absence of a relation between coronary events and systolic blood pressure in untreated patients suggests that the coronary protection may have been underestimated.

Response to Antihypertensive Therapy in Older Patients With Sustained and Nonsustained Systolic Hypertension

BackgroundThe goal of the present study was to assess the effect of antihypertensive therapy on clinic (CBP) and ambulatory (ABP) blood pressures, on ECG voltages, and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension. Methods and ResultsPatients who were ≥60 years old, with systolic CBP of 160 to 219 mm Hg and diastolic CBP of <95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both. Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups: nonsustained hypertension (<140 mm Hg), mild sustained hypertension (140 to 159 mm Hg), and moderate sustained hypertension (≥160 mm Hg). At baseline, patients with nonsustained hypertension had smaller ECG voltages (P <0.001) and, during follow-up, a lower incidence of stroke (P <0.05) and of cardiovascular complications (P =0.01) than other groups. Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension (P <0.001). The influence of active treatment on ECG voltages (P <0.05) and on the incidence of stroke (P <0.05) and cardiovascular events (P =0.06) was more favorable than that of placebo only in patients with moderate sustained hypertension. ConclusionsPatients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension. The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension.

Reference Values in White Europeans for the Arterial Pulse Wave Recorded by Means of the SphygmoCor Device

Measurement of blood pressure together with applanation tonometry at the radial artery allows the reproducible assessment of various indexes of arterial stiffness, including the peripheral (PPp) and central pulse pressures (PPc) and the peripheral (AIp) and central augmentation indexes (AIc). We defined preliminary diagnostic thresholds, using the distributional characteristics of these hemodynamic measurements in a reference population. We randomly recruited 870 subjects from 3 European populations. PPp was the average difference between systolic and diastolic blood pressure measured five times at one home visit. For measurement of PPc, AIp and AIc, we used the SphygmoCor device. We selected subjects without hypertension, diabetes, dyslipidemia in need of medical treatment or previous or concomitant cardiovascular disease. The study population included 228 men and 306 women (mean age 34.9 years). All hemodynamic measurements were curvilinearly related to age, and AIp and AIc were lower in men than in women. In men at age 40, the upper 95% prediction bands of the relations of the hemodynamic measurements with age approximated 60 mmHg for PPp, 40 mmHg for PPc, 90% for AIp, and 30% for AIc. For PPc, AIp and AIc, these thresholds must be adjusted for age, leading to lower and higher thresholds at younger and older age, respectively. In addition, in women of any age, the AIp and AIc thresholds must be increased by 10% and 7%, respectively. Pending validation in prospective outcome studies, distributional characteristics of arterial stiffness indexes in a reference population can be used to generate operational thresholds for use in clinical practice.

Is blood flow in the middle cerebral artery determined by systemic arterial stiffness

Abstract Background and purpose. The relationship between systemic arterial stiffness and parameters of cerebral circulation is poorly understood. We aimed to assess the relation between pulsatility (PI) and resistance (RI) indexes of the middle cerebral artery (MCA) and aortic pulse wave velocity (PWV) and brachial pulse pressure (PP). Methods. Bilateral transcranial Doppler ultrasound (TCD) examination of the MCAs was performed using the GE Vivid 3 Ultrasound, equipped with a 2.5-MHz probe and PI and RI were calculated. Aortic PWV was obtained with the Complior device (Colson France). Conventional blood pressures were measured at the time of TCD. Data regarding risk-profile constituents, habits and medication use were recorded. Subjects with occlusion or significant stenosis of carotid arteries or MCA, previous or acute stroke, temporary ischaemic attack, bilaterally absent transtemporal sonographic windows, dysrhythmia, haematocrit value <30% or >48% were excluded. Results. Of the 165 included subjects (mean age, 56.70±11.80 years, range 22–86 years), 50.3% were men, 20.9% smokers, 20.7% diabetic and 63.4% hypertensive. PWV correlated to both PI (r=0.45, p<0.001) and RI (r=0.36, p<0.001) of MCA. A similar relation was found for PP and PI (r=0.32, p<0.001) or RI (r=0.30, p<0.001). Age, diabetes and hypertension, but not chronic tobacco smoking, interfered with MCA flow parameters. In multivariate adjusted regression analysis, PP was related to both PI and RI of MCA (p<0.001). In similar models, increased PWV was related to PI (p=0.007), but not RI (p=0.08) of MCA. Conclusions. Increased PI and RI of MCA are closely related to measures of increased aortic stiffness.

Twenty-four-hour and conventional blood pressure components and risk of preterm delivery or neonatal complications in gestational hypertension.

Gestational hypertension is a recognized risk factor for the development of complications during pregnancy. The present study retrospectively assessed the respective values of blood pressure components derived from conventional and 24‐h recordings (ABPM) as predictors of premature delivery in women with gestational hypertension based on office readings from 26th week of gestation onwards. Blood pressures were measured conventionally and over 24 h. Standard medical and obstetric history, and standard laboratory work‐up were taken into account. The mean (± standard deviation, SD) age of 123 women was 29 ± 6 years. Current pregnancy was, on average, the second. The conventional systolic (SBP)/diastolic (DBP) blood pressure averaged 140 ± 19/92 ± 14 mmHg, and pulse pressure (PP) and mean arterial pressure (MBP) averaged 48 ± 10 and 108 ± 15 mmHg. The corresponding values derived from ABPM were 135 ± 16/90 ± 11, 47 ± 9 and 105 ± 12 mmHg. The 24‐h blood pressures had better prognostic value than the conventional blood pressures. The 24‐h SBP predicted risk of premature delivery and was inversely related to the duration of pregnancy and birth weight. After the exclusion of 41 women with white‐coat hypertension, the highest predictive value was associated with PP. PP wider by 1SD was associated with 66% higher risk of premature delivery, and was associated with shortening of pregnancy by 2 weeks and 400 g lower birth weight, even after adjustment for SBP. In conclusion, ABPM is superior to conventional blood pressure measurements in predicting adverse outcome of pregnancy. Twenty‐four‐hour PP, of all classic indices, seems to be most closely related to increase of that risk.

Pulse wave velocity in patients with coronary artery disease or type 2 diabetes mellitus.

Objective — To check whether the presence of coronary artery disease (CAD) or type 2 diabetes mellitus (DM) has a differentiating effect on arterial stiffness assessed with pulse wave velocity (PWV) - a simple, reproducible and clinically feasible measure of arterial stiffening. Methods and results — The mean age of 101 participants was 63.5±19.7years. Fifty-one % of them had CAD, 31.0% had DM and 52.5% were hypertensive subjects.The aortic PWV ranged from 3.40 to 27.50m/s, with an average of 11.73±4.69m/s. PWV was significantly higher (P<0.01) in both CAD and DM positive groups as compared with CAD and DM negatives, respectively. After adjustment for established co-variables, patients with CAD had significantly higher PWV when compared to CAD negatives (13.0 vs. 10.5m/s, P<0.01). After adjustment, DM did not seem to affect PWV. Conclusions — CAD patients had higher values of PWV when compared to those without the disease. DM, a metabolic equivalent of arterial damage, after adjustment for possible confounders, did not seem to contribute per se to arterial stiffening. The presence of high PWV values in that group of patients should be viewed as an indicator of established widespread atherosclerosis possibly affecting the coronary arteries.

The relation between ACE D/I and CYP11B2 C-344T polymorphisms and parameters of arterial stiffness in the context of renal sodium handling

Abstract Background. Sodium overload is related to the development of primary hypertension and its complications. Methods. In 131 (65 female) treated hypertensives (average blood pressure 144/82 mmHg and duration of hypertension 11.7 years), we measured peripheral and central arterial pressures, peripheral (AIxP) and central (AIxC1, AIxC2) augmentation indices, pulse-wave velocity (PWV) and daily urinary sodium excretion, and conducted genetic studies of ACE D/I and CYP11B2 C-344T polymorphisms. Proximal (FELi) and distal (FDRNa) sodium reabsorption measurements were performed using endogenous lithium clearance. Results. We found statistically significant interactions between FELi and ACE D/I polymorphism with respect to AIxC2 (PINT = 0.05) and between FELi and CYP11B2 C-344T polymorphism with respect to AIxC1 (PINT = 0.01), AIxC2 (PINT = 0.04) and AIxP (PINT = 0.01). In the group of ACE I allele carriers compared with DD homozygotes, the AIxC1 (154.1 vs 140.6%; p = 0.02), AIxC2 (33.3 vs 26.9%; p = 0.02) and AIxP (94.6 vs 85.2%; p = 0.01) were higher in the subgroup with FELi below the median value (FELi1), but not in the subgroup with FELi above the median value (FELi2). In the group of CYP11B2 TT homozygotes compared with C allele carriers, we observed higher values of AIxC1 (158.5 vs 146.4%; p = 0.03), AIxC2 (36.0 vs 29.4%; p = 0.01) and AIxP (99.0 vs 88.7%; p = 0.005) in the FELi1 but not the FELi2 subgroup. Conclusions. In the population with assumed high dietary sodium intake and long-standing history of hypertension, the relation between proximal sodium reabsorption and the development of arterial stiffness depends on the genetic context of the selected genetic polymorphisms of the renin—angiotensin—aldosterone system, independent of blood pressure.

Pharmacological Management of Hypertension in the Elderly - Certitudes and Controversies

This paper summarizes the evidence supporting the pharmacological treatment of hypertension in the elderly as well as some the remaining controversies. The world is becoming progressively older and with that, the prevalence of hypertension is increasing. A peculiar form of hypertension, most prevalent among the elderly, is isolated systolic hypertension (ISH). Hypertension in the elderly, especially when systolic blood pressure (SBP) exceeds 160 mm Hg should be treated. Lowering the SBP to less than 150 mm Hg confers substantial cardiovascular protection. This has been demonstrated in both older and newer drugs for ISH and systolo-diastolic hypertension and is beneficial in both younger individuals (60-79 years) and uncomplicated elderly (80+ years) individuals suffering from hypertension. However, a number of issues remain controversial. Firstly, the 140 mm Hg cut-off for SBP cannot be applied to all age groups. It is conceivable that lowering the SBP below 140mm Hg in some patients, particularly in the elderly may not be beneficial. Hence, the generalizations made in clinical trials should be approached with caution. Additionally some drugs, such as beta-blockers, thiazide diuretics may be associated with significantly less benefit in the elderly patients. More research is needed, especially in the areas where we lack data: the first stage of uncomplicated ISH or hypertension in the elderly with associated co-morbidities.

Systolic Swing of the Pendulum: Relation Between Hypertension and Heart Failure Revisited

Heart failure (HF) is a dreadful condition, a common final pathway of varied heart diseases. The lifetime risk of developing HF is 20%.1 Once diagnosed, HF carries a substantial risk of mortality. More than 70% of men and women at the age ≤65 years die within 8 years of the diagnosis.1 It has been estimated that, in 2009, the total direct and indirect costs of HF in the United States alone will exceed

Pulse Pressure Not Mean Pressure Determines Cardiovascular Risk in Older Hypertensive Patients

37 billion1 despite the advances in therapeutic approaches that took place in the past 30 years. Clearly, a lot of effort still needs to be directed to fighting the modifiable risk factors. Among these, hypertension (HT) has long been recognized as a crucial one, predating development of HF in 75% of cases. Thus, virtually all recent expert recommendations place prevention, early detection, and treatment of HT high on the priority list of actions with high potential to avert the constant trend toward increased incidence of HF. However, HT is a disorder with many faces. For instance, for most of the past 20 years it has been far from decided whether it is systolic blood pressure (SBP) or diastolic blood pressure (DBP) that carries most of the blood pressure-associated risk. Nineteen years ago, a seminal meta-analysis was published that, based on the collection of a large number of data, proved the relation between DBP and cardiovascular risk but disregarded SBP altogether.2 This was in line with the approach at that time, which based decisions regarding diagnosis and treatment of HT primarily on DBP. However, with time it became evident that SBP plays a great role. An analysis of data from the …