Carlos A. Feldstein

Orthostatic hypotension: a common, serious and underrecognized problem in hospitalized patients

Orthostatic hypotension (OH) is strongly age-dependent, with a prevalence ranging from 5% to 11% in middle age to 30% or higher in the elderly. It is also closely associated with other common chronic diseases, including hypertension, congestive heart failure, diabetes mellitus, and Parkinsons disease. Most studies of OH have been performed in population cohorts or elderly residents of extended care facilities, but in this review, we draw attention to a problem little studied to date: OH in hospitalized patients. The prevalence of OH in all hospitalized patients is not known because most studies have included only older individuals with multiple comorbid diseases, but in some settings as many as 60% of hospitalized adults have postural hypotension. Hospitalized patients are particularly vulnerable to the consequences of OH, particularly falls, because postural blood pressure (BP) regulation may be disturbed by many common acute illnesses as well as by bed rest and drug treatment. The temporal course of OH in hospitalized patients is uncertain, both because the reproducibility of OH is poor and because conditions affecting postural BP regulation may vary during hospitalization. Finally, OH during hospitalization often persists after discharge, where, in addition to creating an ongoing risk of falls and syncope, it is strongly associated with risk of incident cardiovascular complications, including myocardial infarction, heart failure, stroke, and all-cause mortality. Because OH is a common, easily diagnosable, remediable condition with important clinical implications, we encourage caregivers to monitor postural BP change in patients throughout hospitalization.

Long-Term Effects of Parathyroidectomy on Hypertension Prevalence and Circadian Blood Pressure Profile in Primary Hyperparathyroidism

Our aims were to evaluate the prevalence and outcome of hypertension in patients with primary hyperparathyroidism (PHPT), previously and after follow-up of parathyroidectomy. A group of 46 consecutive patients with sporadic PHPT due to adenoma undergoing surgery were followed an average of 3.5 years (range 36 to 53 months). In 16 nonselected, consecutive parathyroidectomized patients, with normalized biochemical measurements, circadian rhythm of blood pressure was evaluated with ambulatory blood pressure monitoring (ABPM). Prevalence of hypertension in PHPT was 54.35%, and there was no significant association of PTH, total and ionic calcium levels with SBP and DBP. During follow-up, none of the patients with presurgical hypertension became normotensive and five of the normotensive patients developed clinical hypertension. In ABPM, 6/11 hypertensive and 3/5 normotensive subjects showed nondipper behavior. Serum total calcium was significantly related to night-time systolic blood pressure (SBP) (r = 0.620, P < 0.02), and night-time diastolic blood pressure (DBP) (r = 0.758, P < 0.002). In dippers, creatinine clearance was significantly higher (91.3 ± 18.5 vs. 64.3 ± 11.5 ml/min, P < 0.01), while serum total calcium was lower (2.42 ± 0.13 vs. 2.23 ± 0.17 mmol/L, P < 0.04) than in nondippers. In conclusion, our results suggest that parathyroidectomy has little effect on hypertension prevalence. Renal impairment, a condition that did not improve after parathyroidectomy, may be a causal factor of hypertension in PHPT. Also, the high prevalence of nondipper behavior in hypertensive and normotensive subjects after parathyroidectomy, suggests that target organ risk persists. We hypothesized that slight elevations of serum total calcium even in the normal range could be involved in the alteration of the circadian rhythm of blood pressure.

Nocturia in arterial hypertension: a prevalent, underreported, and sometimes underestimated association

Nocturia is a risk factor for morbidity and mortality but is frequently overlooked and underreported by patients and unrecognized by physicians. Epidemiologic studies reported that nocturnal voiding is associated not only with aging and benign prostatic hyperplasia, but also with many other clinical conditions. The majority of epidemiologic studies reported a significant relationship between nocturia and hypertension. However, the cause-and-effect relationship between them has not been established. Some physiopathological changes in hypertension are conducive to result in nocturia. These include the effects of hypertension on glomerular filtration and tubular transport, resetting of the kidney pressure-natriuresis relationship, atrial stretch and release of atrial natriuretic peptide when congestive heart failure complicates hypertension, and peripheral edema. Another link between hypertension and nocturia is obstructive sleep apnea. Furthermore, some evidence supports the relationship between nondipping behavior of blood pressure and an increased prevalence of nocturia. The use of some classes of antihypertensive agents may result in nocturia. The present review aims to provide a comprehensive evaluation of the epidemiologic evidence and physiopathological links that correlate hypertension and nocturia. Emphasis is placed on the need to take a pro-active attitude to detect and treat this hazardous condition.

The complex interaction between overweight, hypertension, and sympathetic overactivity

There is ample evidence in the epidemiological and clinical literature that hypertension and overweight are closely and causally interrelated. Sympathetic nervous system (SNS) overactivity has been well documented in both hypertension and overweight, but it is not clear whether this is a coincidental finding or whether the association reflects a mechanistic role of SNS in these two interrelated clinical conditions. Whereas in this review we focus on the evidence for a primary role of SNS in the development of hypertension and overweight, it is clear that the process can be initiated from other starting points such as primary overeating or sleep apnea. After overweight evolves, hormones secreted by fat cells further accelerate SNS overactivity, weight gain, and blood pressure increase. The main thesis of this article is that regardless of where the process started, the same clinical picture of hypertension, overweight, and SNS overactivity will emerge. There is good evidence that in genetically prone individuals, prolonged SNS stimulation elicits a down regulation of beta-adrenergic receptors. This in turn decreases the ability to dissipate calories and diminishes the beta-adrenoceptor-mediated vasodilatation. We hypothesize that beta-adrenoceptor downregulation is the linchpin in the association of SNS with overweight and hypertension.

Association between Chronic Blood Pressure Changes and Development of Alzheimer's Disease

Epidemiological studies suggest an association between chronic blood pressure (BP) changes and Alzheimers disease (AD). In particular, there is growing evidence that hypertensive people that do not have their BP adequately treated and controlled in midlife are more likely to develop AD in late-life. It has been hypothesized that cerebrovascular disease is a common pathway which connects hypertension and AD in individuals with apolipoprotein E genotype through brain hypoperfusion and hypoxia. This could accelerate amyloid-β aggregation that disrupts cell-to-cell connectivity and leads to eventual brain neuron loss. Also, high BP contributes to worsen AD by raising oxidative stress and inflammatory response. Aging-related structural and functional disturbances appear to exacerbate the deleterious effect of chronic hypertension on cerebral blood flow autoregulation. There is evidence suggesting that some antihypertensive drug classes reduce the risk and progression of AD more than others. Further prospective randomized studies comparing different classes of antihypertensive drugs are needed to provide more evidence regarding their effects on AD risk. Hypotension could be a consequence of the incident dementia and conversely deteriorate the outcome of AD by worsening brain hypoperfusion. Frequent home BP monitoring should be carried out in AD patients to detect harmful orthostatic hypotension.

Association between nondipper behavior and serum calcium in hypertensive patients with mild-to-moderate chronic renal dysfunction.

A nondipping BP pattern has been shown to be predictive of end-organ damage, cardiovascular events, and mortality. The mechanisms of blunted nocturnal BP fall are multifactorial. We assessed whether total corrected serum calcium and ionic calcium (iCa) are associated with a blunted nocturnal BP fall in both treated and untreated hypertensive patients with stages 1–3 of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI). Clinical data and 24-hour ambulatory blood pressure monitoring were obtained in a cohort of 231 essential hypertensive patients. Among the entire cohort, 107 were nondippers and 124 were dippers. Only in nondippers, we found significant correlations between iCa and 24-hour systolic blood pressure (SBP; r = 0.21, P < .03), diurnal SBP (r = 0.21, P < .03), and 24-hour pulse pressure (PP; r = 0.23, P < .02). The ambulatory arterial stiffness index (AASI) was significantly related with 24-hour PP in both dippers and nondippers after adjusting for age. Both AASI and 24-hour PP were higher in nondippers than in dippers. In addition, in nondippers, the prevalence of estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2 was higher than in dippers (50% vs. 33.7%, P < .02). Logistic regression showed that patients with eGFR ≥60 mL/minute/1.73 m2 had lower risk of nondipper status than patients with eGFR <60 mL/minute/1.73 m2 (odds ratio = 2.445; 95% confidence interval = 1.398–4.277, P < .002). In conclusion, serum iCa could participate in the pathogenesis of nondipping pattern. Increased large artery stiffness may be a mechanism of the deleterious influence of nondipping on cardiovascular outcome. Hypertensive subjects with stage 3 of NKF KDOQI had a greater loss of circadian BP rhythm than those in stages 1 and 2.

Blood pressure effects of CPAP in nonresistant and resistant hypertension associated with OSA: A systematic review of randomized clinical trials

ABSTRACT Obstructive sleep apnea (OSA) is a rather common chronic disorder, associated with increased prevalence of hypertension. The pathophysiological mechanisms for hypertension in OSA are at least in part linked to intermittent hypoxia developed during nightly hypopneas and apneas. Hypoxemia stimulates sympathetic overactivity, systemic inflammation, oxidative stress, and endothelial dysfunction. However, it appears that intermittent hypoxemia is not the only factor in the development of hypertension in OSA. Supplemental oxygen therapy that improved oxyhemoglobin saturation to similar levels to those achieved with CPAP treatment did not reduce BP. In this scenario, it could be proposed that hypoxemia acts as a trigger of sympathetic overdrive, which when set is the main factor in the development of hypertension in OSA. This review appraises evidence provided by randomized controlled trials on the BP-lowering effectiveness of continuous positive airway pressure (CPAP) treatment of OSA patients with nonresistant and resistant hypertension. It suggests that CPAP treatment is more effective in treating resistant hypertension than nonresistant hypertension. A possible explanation is that sympathetic overactivity and altered vascular reactivity in OSA could be more severe in resistant hypertension than in nonresistant hypertension. An intricate interaction among compliance, adherence, and their interaction with demographic characteristics, genetic factors, and comorbidities of the population included might explain the differences found between trials on their influence over the antihypertensive effectiveness of CPAP. Further long-term trials are needed in hypertensive OSA patients to assess whether CPAP treatment in OSA patients consistently restores physiological nocturnal BP fall and adjusts resting and circadian heart rate.

Relationship between Hyperinsulinemia and Ambulatory Blood Pressure Monitoring of Lean and Overweight Male Hypertensives

Objective To elucidate the role of hypertension as part of a state of insulin resistance. Methods Thirty-one uncomplicated hypertensive men not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period and 10 lean normotensive controls were compared. Hypertensive men were divided according to their body mass index into three groups. All subjects came to the clinic for measurements of height, weight, hip and waist circumferences, and sitting blood pressure, and to begin 24 h ambulatory blood pressure monitoring. Plasma glucose and insulin levels were measured during a 2 h oral glucose (75 g)-tolerance test. For the hypertensive population as a whole, behaviors of studied variables among dippers (n= 18) and nondippers (n= 13) were determined. Results During oral glucose-tolerance testing blood glucose levels after 60 min and 120 min were significantly higher (P < 0.05) in members of the high body mass index group than they were in members of the low body mass index group. insulin levels of members of the high and middle body mass index groups were higher than those of members of the low body mass index group after 60 min (P < 0.05 for both comparisons) and 120 min (P < 0.05 for both comparisons). The mean serum insulin level in members of the low body mass index group was significantly higher than that in normotensives after 30 min, 60 min and 120 min (P < 0.05 for all three comparisons). The mean serum insulin: Plasma glucose ratio for men in the low BMI group was significantly higher than that for normotensives after 60 min and 120 min (P < 0.05 for both comparisons). Correlations of blood pressure and insulin levels were not significant. Levels of high-density lipoprotein cholesterol and triglycerides were lower in members of the group with high body mass index than they were in members of the group with low body mass index. Total cholesterol: High-density lipoprotein cholesterol ratio was higher for members of the high body mass index group than it was for members of the middle body mass index group. Weight, body mass index, casual systolic blood pressure, 24 h average systolic blood pressure and diastolic blood pressure, 0700-2300 h systolic blood pressure, and 24 h average heart rate-systolic blood pressure product of dippers were significantly lower than those of nondippers. Conclusions These results suggest that hypertension and being overweight have additive effects increasing insulinemia and that being overweight is associated with a significantly lower nocturnal fall in blood pressure. J Cardiovasc Risk 5: 25-30

Effects of blood pressure changes on Alzheimer's disease.

Alzheimer’s disease is the most frequent cause of dementia. Whereas other major causes of death have been decreasing, the number of deaths due to Alzheimer’s disease is rising. As there is no cure for this type of dementia at present, preventive measures have assumed great importance. By analyzing data from available longitudinal studies, the current review presents evidence supporting a link between Alzheimer’s disease and blood pressure changes.

Hipertensión arterial resistente

Resistant hypertension, defined as a persistent blood pressure over 140/90 mmHg despite the use of three antihypertensive drugs including a diuretic, is unusual. The diagnosis requires ruling out initially pseudoresistance and a lack of compliance with treatment. Ambulatory blood pressure recording allow the recognition of white coat hypertension. When there is a clinical or laboratory suspicion, secondary causes of hypertension should be discarded. Excessive salt intake, the presence of concomitant diseases such as diabetes mellitus, chronic renal disease, obesity, and psychiatric conditions such as panic attacks, anxiety and depression, should also be sought. The presence of target organ damage requires a more aggressive treatment of hypertension. Recent clinical studies indicate that the administration of aldosterone antagonists as a fourth therapeutic line provides significant additional blood pressure reduction, when added to previous antihypertensive regimens in subjects with resistant hypertension. The possible blood pressure lowering effects of prolonged electrical activation of carotid baroreceptors is under investigation