José Alfie

Contribution of stroke volume to the change in pulse pressure pattern with age.

This study investigated the effect of age on pulse pressure and its underlying mechanisms in unmedicated hypertensive men with the same level of mean arterial pressure. We included 77 men 17 to 76 years old with daytime mean arterial pressure between 95 and 114 mm Hg. In the supine position, pulse pressure showed a significant widening in young (<30 years) and older (>/=60 years) patients. Pulse pressure decreased in parallel with stroke index from age >30 to 40 to 49 years. Upright posture, however, eliminated this difference through a larger orthostatic fall in stroke index and pulse pressure in the youngest patients. After age 50 years, pulse pressure exhibited a progressive widening despite the further age-related decrease in stroke index. Supine, upright, and 24-hour pulse pressure fitted a curvilinear correlation with age (r=0.55, 0.56, and 0.68, respectively, P<0.001), with a transition at age 50 years. Before age 50 years, 24-hour pulse pressure correlated positively with stroke volume (r=0.5, P<0.001) and negatively with arterial compliance (SV/PP ratio, r=-0.37, P<0.01). In contrast, in men >/=50 years old, 24-hour pulse pressure correlated negatively with the SV/PP ratio (r=-0.5; P<0.01), without significant influence of stroke volume. Thus, in hypertensive men, the age-related change in stroke volume significantly accounted for the change in clinic and ambulatory pulse pressure during young adulthood, but its contribution decreased after the fifth decade.

Diastolic Pressure Underestimates Age-Related Hemodynamic Impairment

It has been hypothesized that as large arteries become more rigid with age, the pattern of hypertension changes from diastolic to systolic. Thus, diastolic blood pressure (DBP) may lose its ability to reflect the increase in vascular resistance with age. To assess this, we studied the age-related changes in blood pressure pattern and its steady-state and pulsatile determinants. We performed an epidemiological analysis based on a national survey of 10,462 subjects from Argentina. A hemodynamic analysis (impedance cardiography) was then carried out in 636 consecutive hypertensive patients (age, 25 to 74 years). Whereas the rate of increment in the prevalence of mild to moderate hypertension (MMH) reached a plateau after the sixth decade, isolated and borderline systolic forms of hypertension began a steep and sustained rise. Among patients with MMH, DBP remained stable from the third to the seventh decade, whereas SBP maintained a sustained increase. Despite similar DBP, the systemic vascular resistance index increased 47% (P<.01) and the cardiac index decreased 27% (P<.01), whereas the ratio of stroke volume to pulse pressure, an index of arterial compliance, decreased 45% (P<.01). However, there were no significant differences between older patients with MMH and those with isolated systolic hypertension in the level of SBP, vascular resistance, stroke volume, and cardiac index. Compared with age-matched normotensive control subjects, the ratio of stroke volume to pulse pressure was much more reduced in isolated systolic hypertension (48%) than in MMH (30%). In summary, the present study, carried out in a large sample of hypertensive subjects with a wide age range, showed a simultaneous impairment in vascular resistance and arterial compliance associated with aging in different patterns of hypertension. The magnitude of these changes, with opposite effects on DBP but additive effects on SBP, suggests that a hemodynamic mechanism could determine the transition in the prevalence of diastolic hypertension toward a systolic pattern of hypertension with aging. Also, the results suggest that SBP, but not DBP, is a reliable indicator of the underlying hemodynamic abnormalities (high resistance and low arterial compliance) in the elderly.

Parallel Decrease in Arterial Distensibility and in Endothelium-Dependent Dilatation in Young Women with a History of Pre-Eclampsia

Pre-eclampsia not only complicates 5 to 8% of pregnancies but also increases the risk of maternal cardiovascular disease and mortality later in life. We analyzed three different aspects of arterial function (pulse wave velocity, augmentation index, and flow-mediated dilatation), in 55 nonpregnant, normotensive women (18–33 years old) according to their gestational history: 15 nulliparous, 20 with a previous normotensive, and 20 formerly pre-eclamptic pregnancy. Former pre-eclamptic women showed a significantly higher augmentation index and pulse wave velocity (P < 0.001 and P < 0.05, respectively) and lower flow-mediated dilatation (p = 0.01) compared to control groups. In contrast, sublingual nitroglycerine elicited a comparable vasodilatory response in the three groups. The augmentation index correlated significantly with pulse wave velocity and flow-mediated dilatation (R = 0.28 and R = −0.32, respectively, P < 0.05 for both). No significant correlations were observed between augmentation index or flow-mediated dilatation with age, body mass index (BMI), brachial blood pressure, heart rate, or metabolic parameters (plasma cholesterol, glucose, insulin, or insulin resistance). Birth weight maintained a significantly inverse correlation with the augmentation index (R = − 0.51, p < 0.002) but not with flow-mediated dilatation. Our findings revealed a parallel decrease in arterial distensibility and endothelium-dependent dilatation in women with a history of pre-eclampsia compared to nulliparous women and women with a previous normal pregnancy. A high augmentation index was the most consistent alteration associated with a history of pre-eclampsia. The study supports the current view that the generalized arterial dysfunction associated with pre-eclampsia persists subclinically after delivery.

Predictors of Masked Hypertension Among Treated Hypertensive Patients: An Interesting Association With Orthostatic Hypertension

BACKGROUND Masked hypertension (MH) entails an increased cardiovascular risk. Therefore, it is important to identify those individuals who would benefit the most from out-of-office blood pressure (BP) measurement. We sought to determine the prevalence and identify predictors of MH among adult hypertensive patients under treatment. METHODS Treated hypertensive patients aged ≥ 18 years underwent office (duplicate sitting and standing BP in 1 visit) and home BP measurements (duplicate measurements for 4 days in the morning, afternoon, and evening; at least 16 measurements) and completed a questionnaire regarding risk factors and history of cardiovascular disease. MH was defined as normal office BP (<140/90mm Hg) with elevated home BP (≥135/85mm Hg, average of all readings discarding first day measurements). Patients with a systolic BP rise upon standing ≥5mm Hg were considered to have orthostatic hypertension (OHT). Variables indentified as relevant predictors of MH were entered into a multivariable logistic regression analysis model. RESULTS Three hundred and four patients were included (mean age = 66.7 ±13.8; 67.4% women). The prevalence of MH in the whole population was 12.4% and was 20.9% among patients with office-controlled hypertension. Factors independently associated with MH were age (odds ratio (OR) = 1.08, 95% confidence interval (CI) = 1.03-1.14), high-normal office systolic BP (OR = 5.61, 95% CI = 1.39-22.57), history of peripheral artery disease (PAD) (OR = 8.83, 95% CI = 1.5-51.84), moderate alcohol consumption (OR = 0.08, 95% CI = 0.01-0.73), and OHT (OR = 3.65, 95% CI = 1.27 to 10.51). CONCLUSIONS Easily measurable parameters such as age, office systolic BP, history of PAD, and OHT may help to detect a population at risk of MH that would benefit from home BP monitoring.

Lack of effective blood pressure control among an elder hypertensive population in Buenos Aires.

Our purpose was to determine the level of awareness, treatment, and control of hypertension in a population of subjects aged 65 or more. We studied a random sample from the national health care program in Buenos Aires. Letters were mailed to 1000 selected individuals. Among those eligible, 41.4% (n = 414) were enrolled. The mean age was 73.8 years and 68% were women. Prevalence of hypertension in our sample was 77.5% (n = 321). Awareness of hypertension was 60.7% (n = 195). Fifty-four percent (n = 173) of the hypertensive subjects were receiving pharmacologic treatment and only 18.5% (n = 32) of them were controlled. These results show that there is a low level of awareness, pharmacologic treatment, and control of hypertension in the studied elderly subjects.

Defining Thresholds for Home Blood Pressure Monitoring in Octogenarians

To generate outcome-driven thresholds for home blood pressure (BP) in the elderly, we analyzed 375 octogenarians (60.3% women; 83.0 years [mean]) enrolled in the International Database on home BP in relation to cardiovascular outcome. Over 5.5 years (median), 155 participants died, 76 from cardiovascular causes, whereas 104, 55, 36, and 51 experienced a cardiovascular, cardiac, coronary, or cerebrovascular event, respectively. In 202 untreated participants, home diastolic in the lowest fifth of the distribution (⩽65.1 mm Hg) compared with the multivariable-adjusted average risk was associated with increased risk of cardiovascular mortality and morbidity (hazard ratios [HRs], ≥1.96; P⩽0.022), whereas the HR for cardiovascular mortality in the top fifth (≥82.0 mm Hg) was 0.37 (P=0.034). Among 173 participants treated for hypertension, the HR for total mortality in the lowest fifth of systolic home BP (<126.9 mm Hg) was 2.09 (P=0.020). In further analyses of home BP as continuous variable (per 1-SD increment), higher diastolic BP predicted lower cardiovascular mortality and morbidity and cardiac and coronary risk (HR⩽0.65; P⩽0.039) in untreated participants. In those treated, cardiovascular morbidity was curvilinearly associated with systolic home BP with nadir at 148.6 mm Hg and with a 1.45 HR (P=0.046) for a 1-SD decrease below this threshold. In conclusion, in untreated octogenarians, systolic home BP ≥152.4 and diastolic BP ⩽65.1 mm Hg entails increased cardiovascular risk, whereas diastolic home BP ≥82 mm Hg minimizes risk. In those treated, systolic home BP <126.9 mm Hg was associated with increased total mortality with lowest risk at 148.6 mm Hg.

Postprandial hypotension detected through home blood pressure monitoring: a frequent phenomenon in elderly hypertensive patients

Postprandial hypotension (PPH) is a frequently under-recognized entity associated with increased morbidity and mortality. The prevalence of PPH detected through home blood pressure monitoring (HBPM) is unknown. To determine the prevalence and clinical predictors of PPH in hypertensive patients assessed through HBPM. Hypertensive patients of 18 years or older underwent home blood pressure (BP) measurements (duplicate measurements for 4 days: in the morning, 1 h before and 1 h after their usual lunch, and in the evening; OMRON 705 CP). PPH was defined as a meal-induced systolic BP decrease of ⩾20 mm Hg. Variables identified as relevant predictors of PPH were entered into a multivariate logistic regression analysis. In total, 230 patients were included in the analysis, with a median age of 73.6 (interquartile range 16.9) years, and 65.2% were female. The prevalence of PPH (at least one episode) was 27.4%. Four variables were independently associated with PPH: age of 80 years or older (odds ratio (OR) 3.45, 95% confidence interval (CI) 1.35–8.82), body mass index (BMI) (OR 0.88, 95%CI 0.81–0.96), office systolic BP (OR 1.03, 95%CI 1.01–1.05) and a history of cerebrovascular disease (OR 3.29, 95%CI 1.03–10.53). PPH after a typical meal is a frequent phenomenon that can be detected through HBPM. Easily measurable parameters in the office such as older age, higher systolic BP, lower BMI and a history of cerebrovascular disease may help to detect patients at risk of PPH who would benefit from HBPM.

Hemodynamic effects of transdermal estradiol alone and combined with norethisterone acetate

A 24 weeks, randomized, two-period, placebo controlled study was conducted to compare the effects of continuous transdermal 17 beta-estradiol replacement therapy (0.05 mg/day once a week) with placebo on systemic hemodynamics and blood pressure in postmenopausal women. Twenty-nine postmenopausal women (47-62 years) free of hormone replacement therapy were randomized in two groups; group 1 received estradiol patches for the first 12 weeks and placebo patches for the second, and group 2 received the same treatments in the reverse order. The effect of combined estradiol plus oral norethisterone acetate (NETA) 1 mg was also evaluated in the subset of women with intact uteri (n = 24). Crossover analysis showed that stroke volume and cardiac output were significantly higher (P < 0.05) and blood pressure was significantly lower (P < 0.05) with estradiol, irrespective of the order in which the treatments were administered. Although correlations between plasma estradiol levels during active treatment and hemodynamic changes were not significant, hemodynamic changes were significantly greater above 63 pg/ml than below this level (P < 0.05). Oral norethisterone acetate administration either during transdermal placebo or estradiol arms tended to modify systemic hemodynamics in the same direction than estradiol but the changes did not attained statistical significance. In summary compared with placebo, transdermal 17 beta-estradiol, replacement to postmenopausal women, increased cardiac output and decreased blood pressure. Although the average magnitude of changes was small, the results suggest that plasma estradiol levels could be a source of individual variability in the hemodynamic response. Oral NETA administration tended to enhance rather than reverse the estradiol-induced changes.

Relationship Between Systemic Hemodynamics and Ambulatory Blood Pressure Level Are Sex Dependent

Sex-related differences in systemic hemodynamics were analyzed by means of cardiac index and systemic vascular resistance according to the level of daytime ambulatory blood pressure. In addition, we assessed the relations between ambulatory blood pressure measurements and systemic hemodynamics in male and female patients. We prospectively included 52 women and 53 men referred to our unit for evaluation of arterial hypertension. Women and men were grouped according to the level of daytime mean arterial pressure: < 110 or > or = 110 mm Hg. Patients underwent noninvasive evaluation of resting hemodynamics (impedance cardiography) and 24-hour ambulatory blood pressure monitoring. Compared with women men with lower daytime blood pressure had a 12% higher systemic vascular resistance index (P = NS) and a 14% lower cardiac index (P < .02), whereas men with higher daytime blood pressure had a 25% higher vascular resistance (P < .003) and a 21% lower cardiac index (P < .0004). Furthermore, in men systemic vascular resistance correlated positively with both daytime and nighttime systolic and diastolic blood pressures, whereas cardiac index correlated negatively only with daytime diastolic blood pressure. In contrast, women did not exhibit any significant correlation between hemodynamic parameters and ambulatory blood pressure measurements. In conclusion, sex-related differences in systemic hemodynamics were more pronounced in the group with higher daytime hypertension. The relations between systemic hemodynamics and ambulatory blood pressure level depended on the sex of the patient. In men a progressive circulatory impairment underlies the increasing level of ambulatory blood pressure, but this was not observed in women.

Hemodynamic Significance of High Brachial Pulse Pressure in Young Men

This study investigates whether an increased brachial pulse pressure (PP) in young healthy men constitutes a representative measure of the central hemodynamic forces, or the mere expression of an exaggerated upper limb amplification. Thirty two healthy men between 17 and 28 years old underwent noninvasive evaluation of systemic hemodynamics (impedance cardiography) and pulse wave analysis (SphygmoCor). Subjects were divided into 3 predefined groups of brachial PP: < 50, 50–64, and ≥ 65 mmHg. The brachial–central PP difference increased with increasing brachial PP (17 ± 4, 22 ± 4, and 29 ± 4 mmHg, respectively P < 0.001). In contrast, peripheral amplification (as measured by the brachial:central PP ratio) remained constant among the tree groups, at the expense of a concomitant widening of aortic PP (P < 0.001) without difference in augmentation index. In the entire sample, central and brachial PP, and the difference between the two measures, correlated positively with cardiac output (P < 0.001) and stroke volume (P < 0.01), and negatively with systemic vascular resistance (P < 0.001), without significant relationship with heart rate. In conclusion, despite the different amplitude, central and brachial PP shared common hemodynamic determinants. A high PP among young men underlied a high output‐low resistance circulatory pattern, independently of the site of measurement