EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study.

AIMS: To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement. METHODS AND RESULTS: An 18 country, cross-sectional, observational study of patients prescribed LLT for primary or secondary prevention in primary or secondary care across Europe. Between June 2017 and November 2018, data were collected at a single visit, including LLT in the preceding 12 months and most recent LDL-C. Primary outcome was the achievement of risk-based 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) LDL-C goal while receiving stabilized LLT; 2019 goal achievement was also assessed. Overall, 5888 patients (3000 primary and 2888 secondary prevention patients) were enrolled; 54% [95% confidence interval (CI) 52-56] achieved their risk-based 2016 goal and 33% (95% CI 32-35) achieved their risk-based 2019 goal. High-intensity statin monotherapy was used in 20% and 38% of very high-risk primary and secondary prevention patients, respectively. Corresponding 2016 goal attainment was 22% and 45% (17% and 22% for 2019 goals) for very high-risk primary and secondary prevention patients, respectively. Use of moderate-high-intensity statins in combination with ezetimibe (9%), or any LLT with PCSK9 inhibitors (1%), was low; corresponding 2016 and 2019 goal attainment was 53% and 20% (ezetimibe combination), and 67% and 58% (PCSK9i combination). CONCLUSION: Gaps between clinical guidelines and clinical practice for lipid management across Europe persist, which will be exacerbated by the 2019 guidelines. Even with optimized statins, greater utilization of non-statin LLT is likely needed to reduce these gaps for patients at highest risk.

Proportion of High-Risk/Very High-Risk Patients in Europe with Low-Density Lipoprotein Cholesterol at Target According to European Guidelines: A Systematic Review.

OBJECTIVE: Assess achievement of low-density lipoprotein cholesterol (LDL-C) targets in European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines. DESIGN: Systematic literature review. DATA SOURCES: Medline, EMBASE, Cumulated Index to Nursing and Allied Health Literature. ELIGIBILITY CRITERIA: Observational studies reporting LDL-C levels/target attainment, measured between 1 August 2006 to 31 August 2017, in European adults with established cardiovascular disease (CVD), diabetes with target organ damage, familial hypercholesterolaemia (FH) or 10-year risk of fatal CVD ≥ 5% (assessed by Systematic Coronary Risk Evaluation [SCORE]). DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted relevant studies and assessed study quality using the Risk of Bias for Non-Randomised Studies-Interventions (ROBINS-I) tool. Primary outcome was the proportion of patients achieving LDL-C targets in the 2011/2016 ESC/EAS guidelines. Where available, patient characteristics were presented as means weighted by sample size. The proportions of patients achieving LDL-C targets in the 5 years before and after publication of the 2011 guidelines were compared using a chi-square test. RESULTS: Across 81 eligible studies (303,534 patients), achievement of LDL-C < 1.8 mmol/L was poor among patients with established CVD (16%; range 9-56%) and at very high risk of CVD (SCORE ≥ 10% [18%; 14-25%]). In individuals with FH, SCORE 5-10%, or diabetes and target organ damage, LDL-C < 2.5 mmol/L was achieved by 15% (9-22%), 46% (21-55%) and 13% (6-34%), respectively. Comparing the 5 years before/after publication of the 2011 guidelines, target achievement increased significantly over time but remained suboptimal (LDL-C < 1.8, 22% versus 15%; LDL-C < 2.5, 68% versus 61%; both p < 0.001; established CVD group only). CONCLUSIONS: These data show suboptimal LDL-C control among European patients at high risk of CVD. Those at greatest overall risk (clinically established CVD or at least a 10% 10-year risk of fatal CVD) had the lowest achievement of 2011/2016 EAS/ESC LDL-C targets. With lower LDL-C targets advocated in 2019 ESC/EAS guidelines, this unmet need will increase. PROTOCOL REGISTRATION: PROSPERO registration number; CRD77844.

Morbidity and mortality associated with atherosclerotic peripheral artery disease: A systematic review.

BACKGROUND AND AIMS: It is unclear whether improvements in the detection/treatment of peripheral artery disease (PAD) affect overall survival and morbidity. We undertook a systematic review to describe survival and morbidity in contemporary PAD cohorts. METHODS: Electronic databases were searched for randomised and observational studies reporting mortality/morbidity events between 1 May 2003 and 31 December, 2017 in patients with PAD, diagnosed by intermittent claudication (IC), critical limb ischaemia (CLI), or an ankle brachial index (ABI) < 0.9. Pooled event rates for all-cause and cardiovascular (CV) mortality, non-fatal myocardial infarction (MI), non-fatal stroke, major CV events (MACE; non-fatal MI/stroke, CV death), and major amputation were calculated per 1000 person-years. RESULTS: 124 eligible studies were identified (570,856 patients; 855,894 person-years of follow-up). Statin use was reported in 67% of the overall cohort and antiplatelet use in 79%. Pooled event rates for all-cause and CV mortality, MI, stroke, MACE, and major amputation were 113, 39, 20, 12, 71, and 70 per 1000 person-years, respectively. Compared with patients with an ABI <0.9, the presence of CLI was associated with increased rates of all-cause and CV mortality, MI, MACE, and major amputation. Event rates for stroke were similar between patients with an ABI <0.9 and CLI. CONCLUSIONS: Our data show PAD patients have a high risk of all-cause and CV mortality, and imply the risk of stroke or MI is at least equivalent to the risk in patients with coronary artery disease. Moreover, our data underline the need for improved treatments to attenuate CV risk in PAD patients.

Combining cholesterol-lowering strategies with imaging data: a visible benefit?

Coronary artery disease is characterised by the development of atherosclerotic plaques and is associated with significant morbidity and mortality on a global level. However, many patients with atherosclerosis are asymptomatic and the prediction of acute coronary events is challenging. The role of imaging studies in characterising plaque morphology and stability is emerging as a valuable prognostic tool, while providing evidence for the beneficial effects of cholesterol-lowering therapy on plaque burden. This review provides an overview of contemporary studies describing the value of imaging strategies for atherosclerotic plaques. Coronary angiography is commonly used in the clinical setting, but requires a significant radiation dose (similar to computed tomography). Magnetic resonance imaging evaluation of coronary vessels would avoid exposure to ionising radiation, but is not yet feasible due to motion artefacts. The roles of alternative imaging techniques, including grey-scale intravascular ultrasound, optical coherence tomography and near-infrared spectroscopy have emerged in recent years. In particular, grey-scale intravascular ultrasound has been effectively applied to detect changes in plaque burden and features of plaques predictive of rupture, as well as plaque characteristics during cholesterol-lowering therapy, providing novel insights into factors that may contribute to treatment effectiveness. Challenges and limitations to the use of imaging techniques are considered in this context, along with future imaging strategies.

Relationship of home blood pressure with target-organ damage in children and adolescents.

The objective of this study was to compare home blood pressure (HBP) vs. ambulatory (ABP) and clinic (CBP) measurements in terms of their association with target-organ damage in children and adolescents. A total of 81 children and adolescents (mean age 13 ± 3 years, 53 boys) referred for elevated CBP had measurements of CBP (1 visit), HBP (6 days) and ABP (24-h). Seventy-six participants were also assessed with carotid-femoral pulse wave velocity (PWV) and 54 with echocardiography. Average CBP was 122.1 ± 15.1/71 ± 12.9 mm Hg (systolic/diastolic), HBP 121.3 ± 11.5/69.4 ± 6.6 mm Hg and 24-h ABP 118.9 ± 12/66.6 ± 6.1 mm Hg. Left ventricular mass (LVM) was correlated with systolic blood pressure (BP) (coefficient r = 0.55/0.54/0.45 for 24-h/daytime/nighttime ABP, 0.53 for HBP and 0.41 for CBP; all P< 0.01). No significant correlations were found for diastolic BP. PWV was also significantly correlated with systolic BP (r = 0.52/0.50/0.48 for 24-h/daytime/nighttime ABP, 0.50 for HBP and 0.47 for CBP; all P < 0.01). Only diastolic ABP and HBP were significantly correlated with PWV (r = 0.30 and 0.28, respectively, P<0.05). In multivariate stepwise regression analysis (with age, gender, body mass index [BMI], clinic, home and 24-h ambulatory systolic/diastolic BP and pulse pressure, clinic, home and 24-h heart rate as independent variables), PWV was best predicted by systolic HBP (R(2) = 0.22, beta ± s.e. = 0.06 ± 0.01), whereas LVM was determined (R(2) = 0.67) by 24-h pulse pressure (beta = 1.21 ± 0.41), age (beta = 2.93 ± 1.32), 24-h heart rate (beta = -1.27 ± 0.41) and BMI (beta = 1.78 ± 0.70). These data suggest that, in children and adolescents, ABP as well as HBP measurements appear to be superior to the conventional CBP measurements in predicting the presence of subclinical end-organ damage.

Ambulatory arterial stiffness index, pulse pressure and pulse wave velocity in children and adolescents.

Arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV) or indirectly by pulse pressure (PP) or ambulatory arterial stiffness index (AASI), is an independent predictor of cardiovascular disease in adults. However, in children limited evidence is available. This study investigated the usefulness of AASI and PP as indices of arterial stiffness in children and adolescents, by taking PWV as the reference method. Eighty-two children and adolescents (mean age 13.1±2.9 years) had 24-h ambulatory blood pressure (ABP) monitoring, PWV measurement and echocardiography. Compared with normotensives, subjects with hypertension (n=16) had higher 24-h ABP, 24-h PP and PWV, but not AASI. 24-h, PP was strongly correlated with age, weight, height, 24-h systolic ABP, PWV, left ventricular mass (LVM), LVM index, stroke volume and inversely with 24-h heart rate. AASI was also correlated with weight, height, systolic ABP and LVM, yet these associations were weaker than those of PP, and no significant correlations were found with PWV or LVM index. Moreover, closer agreement of PWV was observed with 24-h PP (71%, kappa 0.21) than with 24-h AASI (61%, kappa -0.06) in detecting subjects at the top quartile of the respective distributions. In children and adolescents, 24-h PP compared with AASI appears to be more closely associated with: (i) arterial stiffness assessed by PWV; (ii) target organ damage assessed by LVM index; and (iii) the presence of essential hypertension. These data suggest that the usefulness of AASI as an index of arterial stiffness in the pediatric population is questionable.

Long-term reproducibility of home vs. office blood pressure in children and adolescents: the Arsakeion school study.

This study compared the long-term reproducibility of home blood pressure (BP) in comparison with office BP in children and adolescents. Forty-eight subjects (27 boys, mean age 11.3+/-3.1 (s.d.) years) recruited from the Arsakeion school study because of elevated office and/or home BP were assessed with office (1 visit, mercury sphygmomanometer) and home BP measurements (3 days, electronic devices) in two assessments 17+/-4.9 months apart (range 10-26 months). Home and office BP were compared on the basis of the following criteria: (a) s.d. of mean BP; (b) s.d. of differences; (c) variation coefficient (CV); (d) concordance correlation coefficient (CCC); (e) test-retest correlations; (f) correlation with ambulatory BP. (a) The s.d. of mean home BP was lower than that of office BP in both the initial (home BP 9.1/7.1 mm Hg, systolic/diastolic; office BP 13.1/8.0 mm Hg) and the second assessment (9.2/6.0 and 14.9/11.5 respectively). (b) The s.d. of differences was lower for home BP (8.3/6.5 mm Hg, systolic/diastolic) than for office BP (13.9/10.7 mm Hg). (c) The CV of home BP (5.3/6.6, systolic/diastolic) was lower than that of office BP (8.2/10.9). (d) The CCC of home BP (0.54/0.50, systolic/diastolic) was higher than that of office BP (0.51/0.41). (e) Test-retest correlations were closer for home BP (r=0.58/0.52, systolic/diastolic) than for office BP (0.51/0.44). (f) Awake ambulatory BP was more closely associated with home (r=0.77/0.40, systolic/diastolic) than with office BP (0.65/0.24). These data suggest that in children and adolescents the long-term reproducibility of home BP is superior to that of office measurements.

Diagnosis of hypertension in children and adolescents based on home versus ambulatory blood pressure monitoring.

OBJECTIVE: To investigate the usefulness of home blood pressure measurements in comparison with ambulatory monitoring in the diagnosis of sustained, white-coat hypertension and masked hypertension in children and adolescents. SUBJECTS AND METHODS: One hundred and two subjects, referred for elevated blood pressure, were assessed with clinic (two visits), home (6 days) and awake ambulatory blood pressure measurements [64 boys, mean age 12.8 +/- 2.9 (SD) years, range 6-18 years]. RESULTS: Office hypertension was diagnosed in 38 subjects, ambulatory hypertension in 31 and home hypertension in 23 (P = 0.07). On the basis of clinic and ambulatory blood pressure, 52% of subjects were normotensive, 20% hypertensive, 18% had white-coat hypertension and 11% masked hypertension, whereas on the basis of clinic and home blood pressure, 55, 15, 23 and 8%, respectively. There was an agreement between ambulatory and home blood pressure in the diagnosis of hypertension in 82 cases (80%). When a 5-mmHg gray zone of diagnostic uncertainty was applied above and below the diagnostic thresholds, there were only eight cases with clinically important disagreement. By taking ambulatory blood pressure as the reference method for the diagnosis of hypertension, the sensitivity, specificity and positive and negative predictive values of home blood pressure were 55, 92, 74 and 82%, respectively, for the diagnosis of white-coat hypertension 89, 92, 70 and 98%, respectively, and for masked hypertension 36, 96, 50 and 93%, respectively. CONCLUSION: In children and adolescents, there is a reasonable agreement between home and ambulatory blood pressure measurements as diagnostic methods in hypertension. Home blood pressure appears to be a useful diagnostic test in this population, particularly for the detection of white-coat hypertension.

Can validated wrist devices with position sensors replace arm devices for self-home blood pressure monitoring? A randomized crossover trial using ambulatory monitoring as reference.

BACKGROUND: Electronic devices that measure blood pressure (BP) at the arm level are regarded as more accurate than wrist devices and are preferred for home BP (HBP) monitoring. Recently, wrist devices with position sensors have been successfully validated using established protocols. This study assessed whether HBP values measured with validated wrist devices are sufficiently reliable to be used for making patient-related decisions in clinical practice. METHODS: This randomized crossover study compared HBP measurements taken using validated wrist devices (wrist-HBP, Omron R7 with position sensor) with those taken using arm devices (arm-HBP, Omron 705IT), and also with measurements of awake ambulatory BP (ABP, SpaceLabs), in 79 subjects (36 men and 43 women) with hypertension. The mean age of the study population was 56.7 +/- 11.8 years, and 33 of the subjects were not under treatment for hypertension. RESULTS: The average arm-HBP was higher than the average wrist-HBP (mean difference, systolic 5.2 +/- 9.1 mm Hg, P < 0.001, and diastolic 2.2 +/- 6.7, P < 0.01). Twenty-seven subjects (34%) had a > or =10 mm Hg difference between systolic wrist-HBP and arm-HBP and twelve subjects (15%) showed similar levels of disparity in diastolic HBP readings. Strong correlations were found between arm-HBP and wrist-HBP (r 0.74/0.74, systolic/diastolic, P < 0.0001). However, ABP was more strongly correlated with arm-HBP (r 0.73/0.76) than with wrist-HBP (0.55/0.69). The wrist-arm HBP difference was associated with systolic ABP (r 0.34) and pulse pressure (r 0.29), but not with diastolic ABP, sex, age, arm circumference, and wrist circumference. CONCLUSIONS: There might be important differences in HBP measured using validated wrist devices with position sensor vs. arm devices, and these could impact decisions relating to the patient in clinical practice. Measurements taken using arm devices are more closely related to ABP values than those recorded by wrist devices. More research is needed before recommending the widespread use of wrist monitors in clinical practice. American Journal of Hypertension doi:10.1038/ajh.2008.176American Journal of Hypertension (2008); 21, 7, 753-758. doi:10.1038/ajh.2008.176.

Home blood pressure monitoring in children: how many measurements are needed?

OBJECTIVE: To investigate the minimum schedule of blood pressure (BP) measurements necessary to provide a reliable assessment of home BP (HBP) in children and adolescents. METHODS: Subjects aged 6-18 years referred for elevated BP were assessed with HBP monitoring (6 workdays, duplicate morning and evening measurements) and 24-h ambulatory BP monitoring (ABP). Criteria for HBP reliability were its reproducibility (test-retest correlations and SD of differences (SDDs) between repeated measurements), its stability (average home BP of an increasing number of readings and its SD), and its relationship with ABP. RESULTS: Data from 100 subjects were analyzed (mean age 13 +/- 2.8 (SD) years, 61 boys). The reproducibility of 3-day HBP (r 0.88/0.79, SDDs 5.1/4.9, systolic/diastolic) was superior to that of a single (r 0.79/0.65, SDDs 7.6/7.1) or 2-day HBP (r 0.85/0.72, SDDs 6.1/5.4). By averaging up to 12 readings (3 days), there was a progressive decline in average HBP, with no further decline thereafter. The SD of average HBP was also progressively reduced, with little change after day 3. The association of HBP with ABP was improved by averaging more readings up to 12, with no further improvement when more readings were averaged. The exclusion of first-day measurements slightly increased the SD of average HBP and weakened the correlation with ABP, probably due to reduced number of readings. CONCLUSIONS: In children and adolescents, 3-day monitoring with duplicate morning and evening measurements appears to be the minimum schedule for the reliable assessment of HBP.

Validation of the A&D UM-101 professional hybrid device for office blood pressure measurement according to the International Protocol.

OBJECTIVE: Assessment of the accuracy of the A&D UM-101 mercury-free professional device for auscultatory blood pressure (BP) measurement according to the European Society of Hypertension International Protocol. Further to auscultation, the device has a button to mark readings during deflation. METHODS: Fifteen adults were included in phase 1 and another 18 in phase 2. Simultaneous BP measurements were taken by two observers (connected mercury sphygmomanometers) four times, sequentially with three measurements using the tested device (two connected tested devices, one used with and the other without the mark button). RESULTS: In phase 1, the device produced 44/45/45 measurements within 5/10/15 mmHg, respectively, for systolic BP (SBP) and 39/43/45 for diastolic (DBP). In phase 2.1, 87/97/99 measurements within 5/10/15 mmHg, respectively, for SBP, and 91/97/99 for DBP (using the mark button 65/93/98 for SBP and 76/96/99 for DBP). In phase 2.2, 29 participants had at least two of their SBP differences within 5 mmHg and none had any differences within 5 mmHg, whereas 32 and none, respectively, for DBP (with mark 24/4 participants for SBP; 29/1 for DBP). Mean SBP differences were -1.5+/-3.5 mmHg and DBP -1.3+/-3.0 (with mark -3.6+/-4.2 and -2.8+/-3.7). The difference in SBP measured by the tested device with versus without using the mark button was 3.0+/-3.3 mmHg (P<0.001) and DBP 1.9+/-2.5 mmHg (P<0.001). CONCLUSION: The device comfortably passed the validation protocol requirements. Using the mark button, the device, however, failed to meet the validation criteria. Therefore, it is recommended for clinical use without using the mark button.

Validation of the Microlife WatchBP Home device for self home blood pressure measurement according to the International Protocol.

OBJECTIVE: Current guidelines recommend that self monitoring of blood pressure at home should only be performed using validated devices. This study assessed the accuracy of the Microlife WatchBP Home device for self home blood pressure measurement according to the European Society of Hypertension International Protocol. METHODS: Thirty-three participants were included (15 in phase 1 and an additional 18 in phase 2). Simultaneous blood pressure measurements were taken by two observers (Y-tube-connected mercury sphygmomanometers) four times sequentially, with three measurements taken using the tested device. Absolute differences between observer and device measurements were classified into three zones (within 5, 10 and 15 mmHg). The number of measurements with a difference within 5 mmHg was calculated for each individual. RESULTS: In phase 1, the device produced 38, 43 and 43 measurements within 5, 10 and 15 mmHg, respectively, for systolic blood pressure and 35, 45 and 45 for diastolic blood pressure. In phase 2.1, the device produced 75, 91 and 97 measurements within 5, 10 and 15 mmHg for systolic, and 74, 93 and 99 for diastolic blood pressure. In phase 2.2, 30 participants had at least two of their differences within 5 mmHg and two participants had no differences within 5 mmHg for systolic blood pressure, whereas for diastolic blood pressure the number of participants were 27 and three, respectively. Mean difference for systolic blood pressure was -0.3+/-5.6 mmHg and for diastolic -2.4+/-4.8 mmHg. CONCLUSIONS: The Microlife WatchBP Home device for self home blood pressure measurement fulfills all the validation criteria of the International Protocol and can, therefore, be recommended for clinical use in the adult population.

A tool for reliable self-home blood pressure monitoring designed according to the European Society of Hypertension recommendations: the Microlife WatchBP Home monitor.

BACKGROUND: Self-blood pressure monitoring by patients at home (HBPM) is being increasingly used in clinical practice and has been endorsed by hypertension societies as an important adjunct to the conventional office blood pressure measurements. Several problems, however, exist regarding the application of HBPM in practice, such as device inaccuracy, observer bias and misreporting, variable monitoring schedule and variable method for summarizing measurements. The European Society of Hypertension Working Group (ESH-WG) on Blood Pressure Monitoring has published detailed recommendations on how to apply HBPM in clinical practice. OBJECTIVE: The Microlife WatchBP Home monitor is designed to provide reliable and unbiased self-blood pressure monitoring by patients at home, strictly according to the ESH-WG recommendations. DESIGN: Dual-function automated oscillometric monitor for HBPM in the arm, with memory, PC link capacity and embedded monitoring schedule. The device has a Usual mode for casual HBPM and a Diag (diagnostic) mode for HBPM strictly according to the ESH-WG proposed schedule (duplicate morning and evening measurements for 7 days). Readings are averaged by the device after exclusion of the initial day according to ESH-WG recommendations and can be transferred to PC for storing or printing. A pilot study in hypertensive patients with previous experience in HBPM suggested that the device is user-friendly and well accepted. CONCLUSION: The Microlife WatchBP Home monitor is a novel device that provides a reliable and unbiased assessment of home blood pressure strictly according to the ESH recommendations.

Validation of the Microlife BPA100 Plus device for self-home blood pressure measurement according to the International Protocol.

OBJECTIVE: Current guidelines recommend that only validated devices for blood pressure measurement should be used. This study presents the validation results of the Microlife BPA100 Plus monitor for self-home blood pressure measurement, according to the European Society of Hypertension International Protocol. METHODS: Fifteen study participants were included in phase 1 and an additional 18 in phase 2 (total 33). Simultaneous blood pressure measurements were taken by two trained observers (Y tube connected mercury sphygmomanometers) four times, sequentially with three measurements taken using the tested device. Absolute differences between observer and device blood pressure were classified into three zones (within 5, 10 and 15 mmHg). The number of readings with a difference within 5 mmHg was calculated for each individual. RESULTS: In phase 1, the device produced 32, 42 and 43 measurements within 5, 10 and 15 mmHg, respectively, for systolic blood pressure and 31, 45 and 45 for diastolic blood pressure. In phase 2.1, the device produced 71, 87 and 96 measurements within 5, 10 and 15 mmHg, respectively, for systolic blood pressure, and 71, 98 and 99 measurements for diastolic blood pressure. In phase 2.2, 26 participants had at least two of their differences within 5 mmHg and three participants had no differences within 5 mmHg for systolic blood pressure, whereas for diastolic blood pressure 24 and three participants, respectively. Mean systolic blood pressure differences were -2.0+/-6.0 mmHg and diastolic blood pressure differences were -3.1+/-4.1 mmHg. CONCLUSIONS: The Microlife BPA100 Plus device for self-home blood pressure measurement comfortably passes the validation requirements of the International Protocol and therefore can be recommended for clinical use in the adult population.