Predictive Importance of Blood Pressure Characteristics With Increasing Age in Healthy Men and Women: The MORGAM Project.

[Figure: see text].

Sex- and age-related differences in the predictive capability of circulating biomarkers: from the MONICA 10 cohort.

OBJECTIVES: The purpose of this study was to assess whether high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble urokinase plasminogen activator receptor (suPAR) differed in their ability to predict cardiovascular outcomes beyond traditional risk factors in younger and older men and women without known cardiovascular disease. Design. Prospective population-based cohort study of 1951 individuals from the MONItoring of trends and determinants in Cardiovascular disease (MONICA) study, examined 1993-1994. Participants were stratified into four groups based on sex and age. Subjects aged 41 or 51 years were classified as younger; those aged 61 or 71 years were classified as older. The principal endpoint was death from cardiovascular causes. Predictive capabilities of biomarkers were tested using Cox proportional-hazards regression, Harrell's concordance-index, net reclassification improvement, and classification and regression tree (CART) analysis. Results. Median follow-up was 18.5 years, during which 19/597 younger men, 100/380 older men, 12/607 younger women, and 46/367 older women had died from a cardiovascular cause. NT-proBNP was independently associated with death from cardiovascular causes among all participants (p ≤ .02) except younger women (p = .70), whereas hs-CRP was associated with this endpoint in men (p ≤ .007), and suPAR in older men only (p < .001). None of the biomarkers improved discrimination ability beyond traditional risk factors (p ≥ .07). However, NT-proBNP enhanced reclassification in men and older women. CART-analysis showed that NT-proBNP was generally of greater value among men, and suPAR among women. Conclusions. Hs-CRP, NT-proBNP, and suPAR displayed different associations with cardiovascular death among apparently healthy younger and older men and women.

A pragmatic real-life study of flash glucose monitoring versus self-monitoring of blood glucose.

INTRODUCTION: The aim of this study was to investigate if the flash glucose level monitoring system (FGM) is better than traditional self-monitoring of blood glucose level (SMBG) in helping patients in the outpatient clinic control their blood glucose and improve glycaemic control measured by the concentration of glycated haemoglobin (HbA1c). METHODS: This was an observational real-life study based on data retrieved from a regional diabetes database and conducted in patients with Type 1 diabetes. HbA1c levels at baseline, and at six, nine and 12 months were compared in and between two groups counting 128 patients each. One group included patients who had recently started using the FGM system; the other patients who were using SMBG and otherwise following the routine protocol of the outpatient clinic. RESULTS: We found no difference between the FGM group and the SMBG group with respect to age, sex, weight, diabetes duration or HbA1c at baseline. After six months, HbA1c had been reduced from 64 to 60 mmol/mol (p = 0.00) in the FGM group, whereas it remained unchanged in the SMBG group (from 63 to 63 mmol/mol, p = 0.66). According to the ANOVA repeated measures test, HbA1c measures showed a significant trend of reduction from 65 to 60 mmol/mol (p = 0.002) over 12 months in the FGM group and no trend of reduction in the SMBG group (from 63 to 64 mmol/mol, p = 0.386) Conclusions: Changing the blood glucose measuring method from SMBG to FGM helped patients with Type 1 diabetes in an outpatient clinic reduce their HbA1c. FUNDING: none. TRIAL REGISTRATION: not relevant.

Does Estimated Pulse Wave Velocity Add Prognostic Information?: MORGAM Prospective Cohort Project.

The Reference Values for Arterial Stiffness Collaboration has derived an equation using age and mean blood pressure to estimated pulse wave velocity (ePWV), which predicted cardiovascular events independently of Systematic COoronary Risk Evaluation (SCORE) and Framingham Risk Score. The study aim was to investigate the independent association between ePWV and clinical outcomes in 107 599 apparently healthy subjects (53% men) aged 19 to 97 years from the MORGAM Project who were included between 1982 and 2002 in 38 cohorts from 11 countries. Using multiple Cox-regression analyses, the predictive value of ePWV was calculated adjusting for country of inclusion and either SCORE, Framingham Risk Score, or traditional cardiovascular risk factors (age, sex, smoking, systolic blood pressure, body mass index [BMI], total and high-density lipoprotein cholesterol). Cardiovascular mortality consisted of fatal stroke, fatal myocardial infarction, or coronary death, and the composite cardiovascular end point consisted of stroke, myocardial infarction, or coronary death. Model discrimination was assessed using Harrell's C-statistic. Adjusting for country and logSCORE or Framingham Risk Score, ePWV was associated with all-cause mortality (hazard ratio, 1.23 [95% CI 1.20-1.25] per m/s or 1.32 [1.29-1.34]), cardiovascular mortality (1.26 [1.21-1.32] or 1.35 [1.31-1.40]), and composite cardiovascular end point (1.19 [1.16-1.22] or 1.23 [1.20-1.25]; all P<0.001). However, after adjusting for traditional cardiovascular risk factors, ePWV was only associated with all-cause mortality (1.15 [1.08-1.22], P<0.001) and not with cardiovascular mortality (0.97 [0.91-1.03]) nor composite cardiovascular end point (1.10 [0.97-1.26]). The areas under the last 3 receiver operator characteristic curves remained unchanged when adding ePWV. Elevated ePWV was associated with subsequent mortality and cardiovascular morbidity independently of systematic coronary risk evaluation and Framingham Risk Score but not independently of traditional cardiovascular risk factors.

The exaggerated natriuresis of essential hypertension occurs independently of changes in renal medullary blood flow.

AIMS: In patients with essential hypertension, abnormal renal sodium handling includes exaggerated natriuresis in response to extracellular volume expansion. We tested the hypothesis that exaggerated natriuresis is associated with increases in medullary and/or cortical renal blood flow. METHODS: Patients with mild essential hypertension, but no signs of end organ damage, and control subjects were studied after 4 days of dietary standardization (<60 mmol Na+  day-1 ) preceded in patients by a 14-day drug washout period. On the study day, subjects received a 4-hour intravenous volume expansion with saline (2.1% of body mass). Renal medullary and cortical blood flows were measured by PET scanning using H215 O as tracer; anatomical regions of interest were defined by contrast-enhanced CT scanning. RESULTS: In patients, arterial blood pressure increased during volume expansion (107 ± 2-114 ± 3 mm Hg, P < 0.05) in contrast to the control group (92 ± 2-92 ± 2 mm Hg). Renal sodium excretion increased more in patients than in controls (+133 ± 31 µmol min-1 vs +61 ± 14 µmol min-1 , respectively, P < 0.05) confirming exaggerated natriuresis. During volume expansion, renal medullary blood flow did not change significantly in patients (2.8 ± 0.4-2.5 ± 0.5 mL (g tissue)-1  min-1 ) or in controls (3.2 ± 0.3-3.1 ± 0.2 mL (g tissue)-1 min-1 ). In control subjects, renal cortical blood flow fell during volume expansion (4.1 ± 0.3-3.7 ± 0.2 mL (g tissue)-1  min-1 , P < 0.05) in contrast to patients in which deviations remained insignificant. CONCLUSION: Exaggerated natriuresis, a hallmark of essential hypertension, is not mediated by increases in regional, renal blood flow.

Estimated Pulse Wave Velocity Calculated from Age and Mean Arterial Blood Pressure.

In a recently published paper, Greve et al [J Hypertens 2016;34:1279-1289] investigate whether the estimated carotid-femoral pulse wave velocity (ePWV), calculated using an equation derived from the relationship between carotid-femoral pulse wave velocity (cfPWV), age, and blood pressure, predicts cardiovascular disease (CVD) as good as the measured cfPWV. Because ePWV predicts CVD as good as cfPWV, some might wonder whether ePWV could be replaced by cfPWV, which is a time-consuming measurement requiring an expensive apparatus. This question is addressed in this mini-review.

Elevated estimated arterial age is associated with metabolic syndrome and low-grade inflammation.

BACKGROUND: Arterial age can be estimated from equations relating arterial stiffness to age and blood pressure in large cohorts. We investigated whether estimated arterial age (eAA) was elevated in patients with the metabolic syndrome and/or known cardiovascular disease (CVD), which factors were associated with eAA and whether eAA added prognostic information. METHODS: In 1993, 2366 study participants, 41, 51, 61, and 71 years old, had traditional cardiovascular risk factors and carotid-femoral pulse wave velocity (cfPWV) measured. Risk groups were identified based on known CVD and components of metabolic syndrome, Systematic COronary Risk Evaluation, or Framingham risk score. From age, mean blood pressure, and cfPWV, eAA and estimated cfPWV (ePWV) were calculated. In 2006, the combined cardiovascular endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for ischemic heart disease was registered. RESULTS: cfPWV and ePWV increased with ageing and cardiovascular risk (all P < 0.001), but ePWV increased more with ageing than cfPWV. The difference between eAA and chronological age was associated with male sex (ß = 0.14), higher heart rate (ß = 0.16 both P < 0.001), fasting glucose (ß = 0.08) soluble urokinase plasminogen activator receptor (ß = 0.06, both P < 0.01), and known CVD (ß = 0.06, P < 0.05) independently of age, SBP, and heart rate. Independently of Systematic COronary Risk Evaluation, eAA (hazard ratio = 1.20, P < 0.01) predicted CEP, but not as accurately as ePWV (hazard ratio = 1.58, P < 0.001) and cfPWV (hazard ratio = 1.32, P < 0.001) among apparently healthy study participants. CONCLUSION: Elevated eAA was associated with male sex, higher plasma glucose, and soluble urokinase plasminogen activator receptor and known CVD independently of age, SBP, and heart rate.

Estimated carotid-femoral pulse wave velocity has similar predictive value as measured carotid-femoral pulse wave velocity.

BACKGROUND: Carotid-femoral pulse wave velocity (cfPWV) adds significantly to traditional cardiovascular risk prediction, but is not widely available. Therefore, it would be helpful if cfPWV could be replaced by an estimated carotid-femoral pulse wave velocity (ePWV) using age and mean blood pressure, and previously published equations. The aim of this study was to investigate whether ePWV could predict cardiovascular events independently of traditional cardiovascular risk factors and/or cfPWV. METHOD: cfPWV was measured and ePWV was calculated in 2366 patients from four age groups of the Danish MONICA10 cohort. Additionally, the patients were divided into four cardiovascular risk groups based on Systematic COronary Risk Evaluation (SCORE) or Framingham risk score (FRS). In 2006, the combined cardiovascular endpoint of cardiovascular death, nonfatal myocardial infarction, stroke and hospitalization for ischemic heart disease was registered. RESULTS: Most results were retested in 1045 hypertensive patients from a Paris cohort. Bland-Altman plot demonstrated a relative difference of -0.3% [95% confidence interval (CI) -15 to 17%] between ePWV and cfPWV. In Cox regression models in apparently healthy patients, ePWV and cfPWV (per SD) added independently to SCORE in prediction of combined endpoint [hazard ratio (95%CI) = 1.38(1.09-1.76) and hazard ratio (95%CI) = 1.18(1.01-1.38)] and to FRS [hazard ratio (95%CI) = 1.33(1.06-1.66) and hazard ratio (95%CI) = 1.16(0.99-1.37)]. If healthy patients with ePWV and/or cfPWV at least 10 m/s were reclassified to a higher SCORE risk category, net reclassification index was 10.8%, P less than 0.01. These results were reproduced in the Paris cohort. CONCLUSION: ePWV predicted major cardiovascular events independently of SCORE, FRS and cfPWV indicating that these traditional risk scores have underestimated the complicated impact of age and blood pressure on arterial stiffness and cardiovascular risk.

Effective risk stratification in patients with moderate cardiovascular risk using albuminuria and atherosclerotic plaques in the carotid arteries.

OBJECTIVES: The aim of this study was to investigate whether subclinical vascular damage improved traditional risk prediction, reclassifying individuals with regard to primary prevention. METHODS: Two thousand and fifty-nine healthy individuals aged 41, 51, 61, and 71 years were divided into age, Systematic COronary Risk Evaluation (SCORE), and Framingham risk score (FRS) groups. Subclinical vascular damage was defined as carotid-femoral pulse wave velocity at least 12 m/s, and carotid atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 90th percentile of 0.73/1.06 mg/mmol in men/women. The composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for ischemic heart disease was recorded (n = 229). RESULTS: Both elevated UACR (P = 0.002) and atherosclerotic plaques (P < 0.0001) identified a subgroup of moderate SCORE risk patients and high-intermediate FRS risk patients with high risk (P = 0.04 and P = 0.001, respectively), whereas elevated carotid-femoral pulse wave velocity did not. Elevated UACR or presence of atherosclerotic plaques reclassified patients from moderate to high SCORE risk [net reclassification improvement of 6.4%; P = 0.025), or from high intermediate to high FRS risk (net reclassification improvement 8.8%; P = 0.002). Assuming primary prevention could reduce the relative cardiovascular risk by 24-27%, on the basis of actual levels of blood pressure and cholesterol, one composite endpoint could be avoided by giving primary prevention to 19 or 24 reclassified patients found by screening 52 or 104 patients with high-intermediate FRS or moderate SCORE risk, respectively. CONCLUSION: Elevated UACR and presence of atherosclerotic plaques could in a potentially cost-effective manner identify patients with moderate SCORE risk or high-intermediate FRS with actual high cardiovascular risk who will benefit from primary prevention.

Association between albuminuria, atherosclerotic plaques, elevated pulse wave velocity, age, risk category and prognosis in apparently healthy individuals.

METHOD: Two thousand and fifty-nine healthy individuals aged 41, 51, 61 and 71 years examined in 1993, were divided in age, SCORE and Framingham risk score (FRS) groups. Subclinical vascular damage (SVD) was defined as carotid-femoral pulse wave velocity (cfPWV) at least 12 m/s, carotid atherosclerotic plaques or albuminuria defined as urine albumin/creatinine ratio at least 90th percentile of 0.73/1.06 mg/mmol men/women. In 2006, the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and hospitalization for ischemic heart disease was recorded (n = 229). RESULTS: With increasing age, SCORE or FRS risk group, prevalence of cfPWV at least 12 m/s (5.2, 14.5, 35.3, 53.5% or 4.4, 15.6, 50.9, 66.1% or 4.0, 9.5, 32.1, 56.1%), atherosclerotic plaque (4.0, 19.0, 35.3, 53.5% or 3.5, 16.8, 43.7, 55.9%, or 6.6, 7.6, 9.8, 20.0%) and albuminuria (7.9, 8.7, 11.4, 20.6% or 7.9, 8.2, 16.6, 19.5% or 6.6, 7.6, 9.8, 20.0%) increased, all P < 0.001.CEP was associated with albuminuria in individuals aged 61 or 71 years, with moderate or very high SCORE or intermediate or high FRS (all P < 0.05), with atherosclerotic plaques in individuals aged 41, 51 or 61 years, with moderate SCORE or with high-intermediate or high FRS (all P < 0.01), and with cfPWV at least 12 m/s in individuals aged 51 years (P < 0.001) or high FRS (P < 0.05). Presence of at least one SVD was significantly associated with an increased risk in individuals aged 51 [hazard ratio 2.7 (1.6-4.8)] and 61 years [hazard ratio 2.7 (1.5-4.7)], moderate [hazard ratio 2.4 (1.6-3.7)] or high SCORE risk group [hazard ratio 2.3 (1.2-4.7)] and low-intermediate [hazard ratio 3.3 (1.5-7.0)], high-intermediate [hazard ratio 2.3 (1.5-3.5)] and high FRS risk group [hazard ratio 2.0 (1.4-3.0)]. CONCLUSION: SVD and especially atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 0.73/1.06 mg/mmol (men/women) added prognostic information in individuals aged 51 or 61 years or with moderate or intermediate risk.