Rosalinde K. E. Poortvliet

High Blood Pressure and Resilience to Physical and Cognitive Decline in the Oldest Old: The Leiden 85-Plus Study

To evaluate the association between various blood pressure (BP) measures at age 85 and future decline in physical and cognitive function the oldest old.

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism

BACKGROUND The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS We conducted a double‐blind, randomized, placebo‐controlled, parallel‐group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 μg daily, or 25 μg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid‐related quality‐of‐life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 μg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between‐group difference, 0.0; 95% confidence interval [CI], ‐2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between‐group difference, 0.4; 95% CI, ‐2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary‐outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126.)

Blood Pressure Variability and Cardiovascular Risk in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects.

Low blood pressure predicts increased mortality in very old age even without heart failure: the Leiden 85-plus Study

To investigate whether low systolic blood pressure is predictive for increased mortality risk in 90‐year‐old subjects without heart failure, defined by low levels of NT‐proBNP, as well as in 90‐year‐old subjects with high levels of NT‐proBNP.

Homocysteine Levels and Treatment Effect in the Prospective Study of Pravastatin in the Elderly at Risk

To assess the effect of preventive pravastatin treatment on coronary heart disease (CHD) morbidity and mortality in older persons at risk for cardiovascular disease (CVD), stratified according to plasma levels of homocysteine.

Deprescribing Potentially Inappropriate Preventive Cardiovascular Medication Barriers and Enablers for Patients and General Practitioners

Background: The use of preventive cardiovascular medication by patients with low cardiovascular disease (CVD) risk is potentially inappropriate. Objective: The aim of this study was to identify barriers to and enablers of deprescribing potentially inappropriate preventive cardiovascular medication experienced by patients and general practitioners (GPs). Methods: A total of 10 GPs participating in the ECSTATIC trial (Evaluating Cessation of STatins and Antihypertensive Treatment In primary Care) audiotaped deprescribing consultations with low-CVD-risk patients. After initial conventional content analysis, 2 researchers separately coded all barriers to and enablers of deprescribing medication using framework analysis. We performed a within-case and cross-case analysis to explore barriers and enablers among both patients and GPs. Results: Patients (n = 49) and GPs (n = 10) expressed barriers and enablers with regard to the appropriateness of the medication and the deprescribing process. A family history for CVD was identified as a barrier to deprescribing medication for both patients and GPs. Patients feared possible consequences of deprescribing and were influenced by the opinion of their GP. Additionally, a presumed disapproving opinion from specialists influenced the GPs’ willingness to deprescribe medication. Conclusions: Patients appreciated discussing their doubts regarding deprescribing potentially inappropriate preventive cardiovascular medication. Furthermore, they acknowledged their GP’s expertise and took their opinion toward deprescribing into consideration. The GPs’ decisions to deprescribe were influenced by the low CVD risk of the patients, additional risk factors, and the alleged specialist’s opinion toward deprescribing. We recommend deprescribing consultations to be patient centered, with GPs addressing relevant themes and probable consequences of deprescribing preventive cardiovascular medication.

NT-proBNP, blood pressure, and cognitive decline in the oldest old: The Leiden 85-plus Study

Objective: To study the relation between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, used as a marker of heart failure in clinical practice, blood pressure (BP), and cognitive decline in the oldest old. Methods: In 560 participants of the Leiden 85-plus Study, we measured NT-proBNP levels and BP at age 85 years, at baseline, and global cognitive function (Mini-Mental State Examination [MMSE]) annually during the follow-up of 5 years. Results: Subjects in the highest tertile of NT-proBNP levels scored 1.7 points lower on the MMSE at age 85 years than subjects in the lowest tertile (p = 0.004), and had a 0.24-point-steeper decline in MMSE score per year (p = 0.021). The longitudinal association disappeared after full adjustment for possible confounders (0.14-point-steeper decline, p = 0.187). Subjects in the category “highest tertile of NT-proBNP and the lowest tertile of systolic BP” had a 3.7-point-lower MMSE score at baseline (p < 0.001) and a 0.49-point-steeper decline in MMSE score per year (p < 0.001) compared with subjects in the other categories. Conclusions: In the oldest old, high NT-proBNP levels are associated with lower MMSE scores. The combination of high NT-proBNP levels and low systolic BP is associated with worst global cognitive function and the steepest cognitive decline. Possibly, a failing pump function of the heart results in lower BP and lower brain perfusion with resultant brain dysfunction.

N-terminal pro-brain natriuretic peptide and cognitive decline in older adults at high cardiovascular risk.

Elevated levels of N‐terminal pro–brain natriuretic peptide (NT‐proBNP) are associated with cognitive impairment, which might be explained by cardiovascular diseases or risk factors. The aim of this study was to investigate the association of NT‐proBNP with cognitive function and decline in older adults at high risk of cardiovascular disease.

Biological correlates of blood pressure variability in elderly at high risk of cardiovascular disease.

BACKGROUND Visit-to-visit variability in blood pressure is an independent predictor of cardiovascular disease. This study investigates biological correlates of intra-individual variability in blood pressure in older persons. METHODS Nested observational study within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) among 3,794 male and female participants (range 70-82 years) with a history of, or risk factors for cardiovascular disease. Individual visit-to-visit variability in systolic and diastolic blood pressure and pulse pressure (expressed as 1 SD in mm Hg) was assessed using nine measurements over 2 years. Correlates of higher visit-to-visit variability were examined at baseline, including markers of inflammation, endothelial function, renal function and glucose homeostasis. RESULTS Over the first 2 years, the mean intra-individual variability (1 SD) was 14.4mm Hg for systolic blood pressure, 7.7mm Hg for diastolic blood pressure, and 12.6mm Hg for pulse pressure. After multivariate adjustment a higher level of interleukin-6 at baseline was consistently associated with higher intra-individual variability of blood pressure, including systolic, diastolic, and pulse pressure. Markers of endothelial function (Von Willebrand factor, tissue plasminogen activator), renal function (glomerular filtration rate) and glucose homeostasis (blood glucose, homeostatic model assessment index) were not or to a minor extent associated with blood pressure variability. CONCLUSION In an elderly population at risk of cardiovascular disease, inflammation (as evidenced by higher levels of interleukin-6) is associated with higher intra-individual variability in systolic, diastolic, and pulse pressure.

Increase in N-terminal pro-brain natriuretic peptide levels, renal function and cardiac disease in the oldest old

BACKGROUND the impact of renal function and its changes and the occurrence of cardiovascular events on changes in N-terminal pro-brain natriuretic peptide levels (NT-proBNP) is unknown in very old age. OBJECTIVE to assess whether increase in NT-proBNP levels over time is still associated with cardiac disease and mortality in very old age, independent of renal function. METHODS changes in NT-proBNP levels between age 85 and 90 years and their associations with incident cardiac disease, (cardiovascular) mortality and renal function were assessed in 252 nonagenarian participants from a population-based sample of the Leiden 85-plus Study. RESULTS median NT-proBNP increase over 5 years was 154 pg/ml (inter-quartile range: 29-549), while in the same period estimated glomerular filtration rate (eGFR) decreased by 5.8 ml/min/1.73 m(2) (standard deviation 7.5). Participants with increasing NT-proBNP levels more frequently developed heart failure and atrial fibrillation (odds ratio 2.79, 95% confidence interval (CI) 1.11-7.02 and 2.63, 95% CI 1.02-6.79, respectively, adjusted for eGFR at age 85 and change in eGFR) between age 85 and 90 years. Increasing NT-proBNP levels between age 85 and 90 years were associated with an increased cardiovascular mortality risk after age 90 years compared with not-increasing NT-proBNP levels (hazard ratio 1.62, 95% CI 1.04-2.51, adjusted for eGFR at age 90 years and change in eGFR). CONCLUSION in the oldest old, increase in NT-proBNP is associated with incident heart failure and atrial fibrillation and risk for cardiovascular mortality, independent of decreasing renal function.