Michael Bursztyn

Predictors of All-Cause Mortality in Clinical Ambulatory Monitoring: Unique Aspects of Blood Pressure During Sleep

The prognostic value of sleep blood pressure reported by recent studies is variable. Our aim was to examine the relationship of sleep blood pressure, measured by 24-hour ambulatory blood pressure monitoring, with all-cause mortality. We studied a cohort of 3957 patients aged 55±16 (58% treated) referred for ambulatory monitoring (1991–2005). Sleep, including daytime sleep, was recorded by diary. Linkage with the national population register identified 303 deaths during 27 750 person-years of follow-up. Hazard ratios (HRs) for mortality in Cox proportional hazards models that included age, sex, hypertension, and diabetes treatment were 1.32 (95% CI: 0.99 to 1.76) for awake hypertension (≥135/85 mm Hg), and 1.67 (95% CI: 1.25 to 2.23) for sleep hypertension (≥120/70 mm Hg). By quintile analysis, the upper fifths of systolic and diastolic dipping during sleep were associated with adjusted HRs of 0.58 (95% CI: 0.41 to 0.82) and 0.68 (95% CI: 0.48 to 0.96), respectively. In a model controlling for awake systolic blood pressure, hazards associated with reduced systolic dipping increased from dippers (>10%; HR: 1.0), through nondippers (0% to 9.9%; HR: 1.30; 95% CI: 1.00 to 1.69) to risers (<0%; HR: 1.96; 95% CI: 1.43 to 2.96). Thus, in practice, ambulatory blood pressure predicts mortality significantly better than clinic blood pressure. The availability of blood pressure measures during sleep and, in particular, the pattern of dipping add clinically predictive information and provide further justification for the use of ambulatory monitoring in patient management.

Role of vasopressin in essential hypertension: racial differences.

Background Arginine vasopressin (AVP), in addition to being an antidiuretic hormone, might also have pressor effects relevant to the maintenance of hypertension. Results from several experimental and clinical studies suggested that the pressor function of AVP is more important in low-renin hypertension and in the salt-loaded state and that it might be further maximized under sympathetic suppression. Objective To assess whether selective vasopressin receptor inhibition lowers the blood pressure in a racially diverse group of low-renin hypertensive subjects. Methods Thirty-nine hypertensive subjects (16 Caucasian, 23 African-American) eating a 200 mmol/day sodium diet were administered a single intravenous dose of a selective vasopressin receptor antagonist and their blood pressure was monitored constantly for the ensuing 3 h. The protocol was repeated 3 days later after treatment with a single oral dose of 0.4 mg clonidine. Results Of these patients, 54% had their blood sampled for determination of hormone profiles. African-Americans with hypertension had higher baseline plasma AVP levels than did Caucasians (1.13 ± 0.05 versus 0.37 ± 0.06 pg/ml, respectively, P < 0.05), and lower plasma renin activity (0.34 ± 0.07 versus 1.03 ± 0.08 ng/ml per h, respectively, P < 0.05). Selective vasopressin receptor inhibition lowered the mean arterial pressure in African-Americans but not that in Caucasians (lowering by 28 ± 4 mmHg in African-Americans versus lowering by 5 ± 3 mmHg in Caucasians, P < 0.05). Moreover, vasopressin receptor blockade further reduced the arterial pressure in African-Americans but not that in Caucasians after pretreatment with clonidine. Conclusion AVP seems to play a more important role as a pressor hormone in maintaining the elevation of arterial pressure in African-American hypertensives than it does in Caucasian hypertensives.

Linear relationship between systolic and diastolic blood pressure monitored over 24 h: assessment and correlates.

Objectives Systolic blood pressure (SBP) and diastolic blood pressure (DBP) frequently display a linear relationship characterized by the systolic-versus-diastolic slope (‘Slope’) or the ‘ambulatory arterial stiffness index’ [AASI = 1 – (diastolic-versus-systolic Slope)] and the correlation coefficient r. We evaluated the effect of using symmetric regression on the AASI and its dependence on clinical characteristics using 24-h ambulatory monitoring. Methods Ambulatory monitoring data of 140 patients (age 56 ± 17 years, 45% men) were retrieved from a service database. Slope and the AASI were evaluated using symmetric regression procedures, and the AASI also by standard regression. Results Correlation between SBP and DBP was r = 0.74 ± 0.14 (r > 0.5 in 95% of patients). Low r-values (when SBP correlates poorly with DBP) were tightly linked with nondipping (P < 0.00001). Use of symmetric rather than standard regression eliminated the bias in slope-related parameters and unmasked their dependence on clinical characteristics. Both symmetric Slope and the AASI were independent of mean arterial pressure and r, increased with pulse pressure (P < 0.01 and P < 0.0001, respectively), with the greater effect of wider pulse pressure in older age (P < 0.005 for both). The symmetric slope was 1.29 ± 0.28, showing bivariate dependence (r = 0.82) on age (exponential, with P < 0.00001) and pulse pressure dipping (P < 0.00001), increased for antihypertensive drug treatment (0.07 ± 0.03, P < 0.05) and diabetes mellitus (0.18 ± 0.06, P < 0.005). Conclusions Application of symmetrical regression provides a more valid estimate of the systolic-on-diastolic slope and the AASI, less influenced by goodness of fit and nocturnal dipping and more sensitive to age and disease states such as hypertension and diabetes, thus providing an improved index of arterial stiffening.

Changing Profile of Health and Function from Age 70 to 85 Years

Background: Old age has traditionally been considered to begin at age 65. The improving health and functional status observed among older people may necessitate reevaluation of this cut-off point. Objective: To present the changing prevalence of common geriatric syndromes, functional parameters, common disease status and health care utilization, at ages 70, 78 and 85, in order to help address the question of when does contemporary aging actually begin. Methods: Medical, psychosocial, cognitive, and functional status, and health service utilization at age 70, 78 and 85 were assessed through the Jerusalem Longitudinal Cohort Study (1990–2010), which prospectively followed a representative sample (born 1920–1921), of 1,861 people, all of whom underwent home-based comprehensive assessment. Results: At age 70, the cohort had good health, low comorbidity, preserved cognition, mobility and independence in basic and instrumental activities of daily activities (ADL). Rising comorbidity, declining cognitive status, increasing depression, and difficulty in ADLs were seen at 78. By age 85, compared to age 70, comorbidity had tripled, depression, hearing and visual impairment, falls, dizziness and mobility problems had doubled; 23% of subjects had cognitive impairment, 42.5% suffered urinary incontinence, and dependence in basic and instrumental ADLs was common (37.8 and 51.7%, respectively). Home care was 4.5, 10.1, and 24.6%, and hospitalization in the previous year occurred among 12.3, 18.8 and 27.8% at ages 70, 78 and 85, respectively. Conclusions: At age 70, the overall health profile was favorable, prevalence of geriatric syndromes was low, cognitive and functional status was preserved, and health service utilization was low. The progressive deterioration seen at ages 78 and more profoundly so at age 85, suggest that a cut-off point beyond age 70 years may serve to better define entry into old age.

Salt Sensitivity of Blood Pressure A Scientific Statement From the American Heart Association

Salt-sensitivity of blood pressure is an abnormal phenotype that confers increased cardiovascular morbidity. We discuss its underlying renal mechanisms, including the role of systems that regulate renal salt handling. We review knockout and congenic strains that have unraveled participation of several genes in rodents inbred to produce pure salt-sensitive and salt-resistant substrains. In humans, salt-sensitivity is a continuous variable, hence, defined with arbitrary cutoffs for blood pressure responses to salt-loading or deprivation. Nonetheless, clustering of phenotypic characteristics in salt-sensitive subjects suggests an inherited component for this trait. This is supported by relationships between salt-sensitivity and gene polymorphisms in renal transporters, vasoactive substances and oxidative systems. Identification of biochemical or genetic markers of salt-sensitivity for use in the clinic would improve risk stratification of hypertensive and prehypertensive subjects. Understanding of its pivotal mechanisms may lead to specific therapies to decrease the cardiovascular risk associated with this trait in humans.

Normal Body Mass Index Rather than Obesity Predicts Greater Mortality in Elderly People: The Jerusalem Longitudinal Study

OBJECTIVES: To examine the association between body mass index (BMI) and mortality in older people.

Cohort Profile: the Jerusalem longitudinal cohort study

Whilst it has been suggested that about 25% of the variability in human longevity is attributed to genetic influences, the remaining 75% is consequent upon a complex interplay of biological, environmental, social and culturally determined factors. In rising to the challenge of understanding the complexities of human ageing, a valuable tool to emerge in ageing research has been the longitudinal study, and early pioneering works in North America and Europe were instrumental in defining the emergence of modern geriatrics and gerontology. Undertaking such studies among diverse populations in different cultures is of value in furthering the understanding of universal ageing processes. Furthermore in many societies the oldest old are among the fastest growing sector of the population, and the need for basic definitions and descriptions of their patterns of need is a matter of pressing urgency for health care planners, ageing researchers and policy makers alike. After fruitful collaboration in the late 1980s with Alvar Svanborg, the leader of the Gottenberg Longitudinal Study of 70 year olds, we decided to initiate a long-term longitudinal study of ageing among Jerusalem residents, who are a uniquely heterogeneous elderly population, including immigrants from the America, Europe, Africa and Asia. The study, which was designed to follow a birth cohort from age 70 at baseline as they advanced with age, still remains the only such study of its kind both in scope and magnitude in the geographical region. Funding was provided in part by the Ministry of Health, the Ministry of Labor and Social Affairs, the National Insurance Institute (the Israeli Social Security administration), Eshel—the Association for the Planning and Development of Services for the Aged in Israel, as well as several private and charitable funds. Following a pilot feasibility study in 1989, with subsequent refinement of the study protocols and questionnaires, the Jerusalem Longitudinal Cohort study was established in 1990, with follow-up continuing up until the present time.

Dipping Status May Be Determined by Nocturnal Urination

Nondipping, ie, failure to reduce blood pressure by ≥10% during the night, is considered an important prognostic variable of 24-hour ambulatory blood pressure monitoring. However, some people wake up at night to urinate. Usually, 24-hour ambulatory blood pressure monitoring–derived blood pressure includes these rises in the nighttime blood pressure mean. We identified 97 subjects undergoing 24-hour ambulatory blood pressure monitoring who reported waking up at night to urinate. We assessed the 24-hour ambulatory blood pressure monitoring first using total daytime and total nighttime means and then using actual daytime awake and nighttime asleep (as reported by the patient) means. Nocturnal decline in blood pressure was 14.4±8.5/11.8±6.1 mm Hg with the first method and 17.1±8.3/13.8±5.9 mm Hg with the second one (P <0.00001). Although the absolute difference between the nocturnal blood pressure declines calculated by the 2 methods was small, the effect on nocturnal dip was profound. Average systolic blood pressure dipping was 10.1% by the total day–total night method and 12.0% by the actual day awake–night asleep method (P ≤0.00001), and that of diastolic blood pressure was 14.2% and 16.7%, respectively (P ≤0.00001). The prevalence of systolic blood pressure nondipping decreased from 42.2% by the first method to 31.9% by the second method (P ≤0.0056), and that of diastolic blood pressure nondipping decreased from 22.6% to 11.3% (P ≤0.00001). Inclusion of awake blood pressure measurements during the night obscured the normal dipping pattern in people who woke up to urinate. Thus, taking into account people’s actual behavior increases the accuracy of the results.

Holocaust Survivors in Old Age: The Jerusalem Longitudinal Study

OBJECTIVES: To examine the hypothesis that Holocaust exposure during young adulthood negatively affects physical aging, causing greater morbidity, faster deterioration in health parameters, and shorter survival.

Hypertension and 5-Year Mortality among 85-Year-Olds: The Jerusalem Longitudinal Study

OBJECTIVE Hypertension is among the most common chronic complaints of older people. Among very old people with common co morbidities, it remains uncertain whether the benefits of long-term treatment seen among younger people, are also observed. Our objective was to assess the relationship of blood pressure (BP) at age 85 with 5-year all-cause mortality. DESIGN A longitudinal prospective cohort study, of an age-homogenous, representative sample born 1920-1921. SETTING Community-based home assessments. PARTICIPANTS West Jerusalem residents (1159) born 1920-1921, all aged age 85 during 2005-2006, currently enrolled in the Jerusalem Longitudinal Study. INTERVENTION None. MEASUREMENTS Comprehensive geriatric assessment of numerous health variables. BP was determined as the average of 6 measurements, from 2 separate home visits. Hypertension (HTN) defined as either treatment with antihypertensive medications, or blood pressure >140 mm Hg systolic, or >90 mm Hg. The study outcome was all-cause 5-year mortality. Mortality data were collected from the National Ministry of Interior. RESULTS One hundred and nine (9.4%) were normotensive, 152 (13.1%) untreated, and 898 (77.5%) treated hypertensives. Treatment rate was 78%, and controlled hypertension rate 38%. During 5 years 328 (28.3%) patients died. Kaplan-Meier survival curves and log rank analysis showed no difference in mortality between normotensive, untreated and treated hypertensive subjects according to sex. Treated subjects with controlled Systolic Blood Pressure (SBP) had lowest survival rate of 67%, P = .029. Continuous SBP yielded a hazard ratio (HR) for mortality of 1.00, (95% CI 0.95-1.01), after adjusting in Cox proportional hazard models for sex, heart failure, physical activity, self-rated health, diabetes, coronary and cerebrovascular diseases, smoking and antihypertensive therapy. Results were unaffected after excluding 114 deaths within the first 2-years of follow-up. Similar results were found when examining BP either as a dichotomous variable, according to treatment, or pulse pressure. CONCLUSIONS Raised SBP was not associated with increased 5-year mortality among a representative cohort of community-dwelling 85-year-olds. Indeed, before adjustment for co morbidities, subjects with controlled SBP tended to have a worse survival.