Intensity of and adherence to lipid-lowering therapy as predictors of goal attainment and major adverse cardiovascular events in primary prevention.

BACKGROUND: The effectiveness of lipid-lowering therapy (LLT) for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in routine care may depend on treatment intensity and adherence. METHODS: Observational study of adults with newly initiated LLT for primary prevention of ASCVD in Stockholm, Sweden, during 2017-2021. Study exposures were LLT adherence [proportion of days covered (PDC)], LLT intensity (expected reduction of LDL cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity were calculated during the previous 12 months, and the patients estimated ASCVD risk was categorized. Study outcomes were major adverse cardiovascular events (MACE) and LDL-C goal attainment. RESULTS: Thirty-six thousand two hundred eighty-three individuals (mean age 63 years, 47% women, median follow-up 2 years), with a baseline low-moderate (40%), high (49%), and very-high (11%) ASCVD risk started LLT. Increases in LLT adherence, intensity, or adherence-adjusted intensity of 10% over 1 year were associated with lower risks of MACE (with hazard ratios of 0.95 [95% CI, 0.93-0.98]; 0.93 [0.86-1.00]; and 0.90 [0.85-0.95], respectively) and higher odds of attaining LDL goals. Patients with good adherence (≥80%) had similar risks of MACE and similar odds ratios for LDL-C goal attainment with low-moderate and high-intensity LLT. Treatment discontinuation was associated with increased MACE risk. The relative and absolute benefits of good adherence were greatest in patients with very high ASCVD risk. CONCLUSION: In routine-care primary prevention, better adherence to LLT was associated with a lower risk of MACE across all treatment intensities. Improving adherence is especially important among patients with very high ASCVD risk.

Management of patients with hypertension and chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. On behalf of the European Society of Hypertension Working Group on Hypertension and the Kidney.

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

What is the context? Hypertension is a strong independent risk factor for development of chronic kidney disease (CKD) and progression of CKD to ESKD. Improved adherence to the guidelines in the treatment of CKD is believed to provide further reduction of cardiorenal events. European Society of Hypertension Excellence Centres (ESH-ECs) have been developed in Europe to provide excellency regarding management of patients with hypertension and implement guidelines. Numerous deficits regarding general practitioner CKD screening, use of nephroprotective drugs and referral to nephrologists prior to referral to ESH-ECs have been reported. In contrast, real-life management of these patients among ESH-ECs is unknown. Before implementation of strategies to improve guideline adherence in Europe, we aimed to investigate how patients with CKD are managed among the ESH-ECs.What is the study about? In this study, a survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-ECs. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed among their centres.What are the results? RAAS blockers are initiated in 90% of ESH-ECs in CKD patients, but the initiation of MRA and SGLT2i is less frequently done. Hyperkalemia is the main barrier for initiation or adequate dosing of RAAS blockade, and its most reported management was RAAS blockers dosage reduction. These findings will be crucial to implement strategies in order to improve management of patients with CKD and guideline adherence among ESH-ECs.

Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Since the publication of the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines for the Management of Arterial Hypertension, several high-quality studies, including randomised, sham-controlled trials on catheter-based renal denervation (RDN) were published, confirming both the blood pressure (BP)-lowering efficacy and safety of radiofrequency and ultrasound RDN in a broad range of patients with hypertension, including resistant hypertension. A clinical consensus document by the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on RDN in the management of hypertension was considered necessary to inform clinical practice. This expert group proposes that RDN is an adjunct treatment option in uncontrolled resistant hypertension, confirmed by ambulatory BP measurements, despite best efforts at lifestyle and pharmacological interventions. RDN may also be used in patients who are unable to tolerate antihypertensive medications in the long term. A shared decision-making process is a key feature and preferably includes a patient who is well informed on the benefits and limitations of the procedure. The decision-making process should take (i) the patient's global cardiovascular (CV) risk and/or (ii) the presence of hypertension-mediated organ damage or CV complications into account. Multidisciplinary hypertension teams involving hypertension experts and interventionalists evaluate the indication and facilitate the RDN procedure. Interventionalists require expertise in renal interventions and specific training in RDN procedures. Centres performing these procedures require the skills and resources to deal with potential complications. Future research is needed to address open questions and investigate the impact of BP-lowering with RDN on clinical outcomes and potential clinical indications beyond hypertension.

Sex differences in arterial hypertension.

There is strong evidence that sex chromosomes and sex hormones influence blood pressure (BP) regulation, distribution of cardiovascular (CV) risk factors and co-morbidities differentially in females and males with essential arterial hypertension. The risk for CV disease increases at a lower BP level in females than in males, suggesting that sex-specific thresholds for diagnosis of hypertension may be reasonable. However, due to paucity of data, in particularly from specifically designed clinical trials, it is not yet known whether hypertension should be differently managed in females and males, including treatment goals and choice and dosages of antihypertensive drugs. Accordingly, this consensus document was conceived to provide a comprehensive overview of current knowledge on sex differences in essential hypertension including BP development over the life course, development of hypertension, pathophysiologic mechanisms regulating BP, interaction of BP with CV risk factors and co-morbidities, hypertension-mediated organ damage in the heart and the arteries, impact on incident CV disease, and differences in the effect of antihypertensive treatment. The consensus document also highlights areas where focused research is needed to advance sex-specific prevention and management of hypertension.

Skin microvascular reactivity and subendocardial viability ratio in relation to dyslipidemia and signs of insulin resistance in non-diabetic hypertensive patients.

OBJECTIVE: The aim of this study was to evaluate the influence of dyslipidemia and insulin resistance for the development of microvascular dysfunction in non-diabetic primary hypertension. METHODS: Seventy-one patients with untreated primary hypertension were included. Skin microvascular reactivity was evaluated by laser Doppler fluxmetry with iontophoresis (acetylcholine, ACh and sodium nitroprusside, SNP) and heat-induced hyperemia. Myocardial microvascular function was estimated by the subendocardial viability ratio (SEVR) calculated from pulse wave analysis and applanation tonometry. Triglyceride x glucose (TyG index) and triglyceride/HDL cholesterol ratio were used as measurements of insulin resistance. RESULTS: Skin microvascular dysfunction was associated with low HDL cholesterol, where Ach-mediated peak flux (r = .27, p = .025) and heat-induced peak flux (r = .29, p = .017) related to HDL cholesterol levels. ACh peak flux was inversely related to TG/HDL ratio (r = -.29, p = .016), while responses to local heating and SNP did not. SEVR did not relate to HDL and was unrelated to markers of insulin resistance. These findings were confirmed by multivariable analyses, including potential confounders. CONCLUSIONS: Early microvascular dysfunction can be detected in non-diabetic hypertensive patients and is related to dyslipidemia and to signs of insulin resistance, thus predicting future cardiovascular risk.

Prediabetes and incident heart failure in hypertensive patients: Results from the Swedish Primary Care Cardiovascular Database.

BACKGROUNDS AND AIMS: The cardiovascular risk conferred by concomitant prediabetes in hypertension is unclear. We aimed to examine the impact of prediabetes on incident heart failure (HF) and all-cause mortality, and to describe time in therapeutic blood pressure range (TTR) in a hypertensive real-world primary care population. METHODS AND RESULTS: In this retrospective cohort study, 9628 hypertensive individuals with a fasting plasma glucose (FPG) in 2006-2010 but no diabetes, cardiovascular or renal disease were followed to 2016; median follow-up was 9 years. Prediabetes was defined as FPG 5.6-6.9 mmol/L, and in a secondary analysis as 6.1-6.9 mmol/L. Study outcomes were HF and all-cause mortality. Hazard ratios (HR) were compared for prediabetes with normoglycemia using Cox regression. All blood pressure values from 2001 to the index date (first FPG in 2006-2010) were used to calculate TTR. At baseline, 51.4% had prediabetes. The multivariable-adjusted HR (95% confidence intervals) was 0.86 (0.67-1.09) for HF and 1.06 (0.90-1.26) for all-cause mortality. For FPG defined as 6.1-6.9 mmol/L, the multivariable-adjusted HR were 1.05 (0.80-1.39) and 1.42 (1.19-1.70), respectively. The prediabetic group had a lower TTR (p < 0.05). CONCLUSIONS: Prediabetes was not independently associated with incident HF in hypertensive patients without diabetes, cardiovascular or renal disease. However, prediabetes was associated with all-cause mortality when defined as FPG 6.1-6.9 mmol/L (but not as 5.6-6.9 mmol/L). TTR was lower in the prediabetic group, suggesting room for improved blood pressure to reduce incident heart failure in prediabetes.

User experience of self-reported computerized medical history taking for acute chest pain: The Clinical Expert Operating System Chest Pain Danderyd Study.

BACKGROUND AND OBJECTIVE: Chest pain is one of the most common complaints in emergency departments (EDs). Self-reported computerized history taking (CHT) programmes can be used for interpretation of the clinical significance of medical information coming directly from patients. The adoption of CHT in clinical practice depends on reactions and attitudes to the technology from patients and their belief that the technology will have benefits for their medical care. The study objective was to explore the user experience of the self-reported CHT programme Clinical Expert Operating System (CLEOS) in the setting of patients visiting an ED for acute chest pain. METHODS: This qualitative interview study is part of the ongoing CLEOS-Chest Pain Danderyd Study. A subset (n = 84) of the larger sample who had taken part in self-reported history taking during waiting times at the ED were contacted by telephone and n = 54 (64%) accepted participation. An interview guide with open-ended questions was used and the text was analysed using directed content analysis. RESULTS: The patients' experiences of the CLEOS programme were overall positive although some perceived it as extensive. The programme was well accepted and despite the busy environment, patients were highly motivated and deemed it helpful to make a diagnosis. Six categories of user experience emerged: The clinical context, The individual context, Time aspect, Acceptability of the programme, Usability of the programme and Perceptions of usefulness in a clinical setting. CONCLUSIONS: The programme was well accepted by most patients in the stressful environment at ED although some found it difficult to answer all the questions. Adjustments to the extent of an interview to better suit the context of the clinical use should be a future development of the programme. The findings suggest that CHT programmes can be integrated as a standard process for collecting self-reported medical history data in the ED setting.

Aortic stiffness and aortic-brachial stiffness mismatch as markers of renal dysfunction in hypertension.

PURPOSE: The dismal combination of hypertension and chronic kidney disease potentiates both cardiovascular disease and loss of renal function. Research points to the importance of arterial and left ventricular stiffening in this process but few studies have compared aspects of central and peripheral hemodynamics in relation to renal function in hypertension. MATERIALS AND METHODS: We investigated 107 hypertensive individuals with renal function ranging from normal to severe dysfunction with pulse wave analysis to obtain central blood pressures (BP), augmentation index, carotid-femoral and carotid-radial pulse wave velocity (cfPWV, crPWV), aortic-to-brachial stiffness mismatch (cfPWV/crPWV), endothelial function by forearm flow-mediated vasodilation and myocardial microvascular function by subendocardial viability ratio, and indices of left ventricular structure (left ventricular mass index and relative wall thickness, RWT) and diastolic function (left atrial volume index, E/A, and E/é). RESULTS: Mean age was 58 years, BP 149/87 mm Hg, 9% had cardiovascular disease, and 31% were on antihypertensive treatment. Mean estimated glomerular filtration rate (eGFR) was 74 (range 130-21) ml/min × 1.73 m2. Whereas cfPWV and cfPWV/crPWV were independently related to eGFR (r = -0.20, p = 0.002, r = -0.16, p = 0.01), central diastolic BP (r = 0.21, p = 0.04), RWT (r = -0.34, p = 0.001), E/é (r = -0.39, p < 0.001) and E/A (r = 0.27, p = 0.01) were related to eGFR in bivariate correlations, but these findings were not retained in multivariate analyses. Remaining markers of hypertensive heart disease and measures of microvascular function were not related to eGFR. CONCLUSION: Increased aortic stiffness and aortic-to-brachial stiffness mismatch are independently related to reduced eGFR in hypertensive patients, suggesting an important role for aortic stiffness in the evolution of hypertension-mediated renal dysfunction. Aortic stiffness and aortic-brachial stiffness mismatch may be useful early markers to find hypertensive patients at risk for decline in renal function.

Covid-19 associated reduction in hypertension-related diagnostic and therapeutic procedures in Excellence Centers of the European Society of Hypertension.

BACKGROUND: The Covid-19 pandemic necessitated a decrease in non-Covid-19 related diagnostic and therapeutic procedures in many countries. We explored the impact on tertiary hypertension care. METHODS: We conducted an electronic survey regarding 6 key procedures in hypertension care within the Excellence Center network of the European Society of Hypertension. RESULTS: Overall, 54 Excellence Centers from 18 European and 3 non-European countries participated. From 2019 to 2020, there were significant decreases in the median number per centre of ambulatory blood pressure monitorings (ABPM: 544/289 for 2019/2020), duplex ultrasound of renal arteries (Duplex RA: 88.5/55), computed tomographic/magnetic resonance imaging angiography of renal arteries (CT/MRI RA: 66/19.5), percutaneous angioplasties of renal arteries (PTA RA: 5/1), laboratory tests for catecholamines (116/67.5) and for renin/aldosterone (146/83.5) (p < 0.001 for all comparisons, respectively). While reductions in all assessed diagnostic and therapeutic procedures were observed in all annual 3-months periods in the comparisons between 2019 and 2020, the most pronounced reduction occurred between April and June 2020, which was the period of the first wave and the first lockdown in most affected countries. In this period, the median reductions in 2020, as compared to 2019, were 50.7% (ABPM), 47.1% (Duplex RA), 50% (CT/MRI RA), 57.1% (PTA RA), 46.9% (catecholamines) and 41.0% (renin/aldosterone), respectively. Overall differences in reduction between 3-month time intervals were statistically highly significant. CONCLUSION: Diagnostic and therapeutic procedures related to hypertension were dramatically reduced during the first year of the Covid-19 pandemic, with the largest reduction during the first lockdown. The long-term consequences regarding blood pressure control and, ultimately, cardiovascular events remain to be investigated.

Effects of exenatide on microvascular reactivity in patients with type 2 diabetes and coronary artery disease: A randomized controlled study.

OBJECTIVE: We studied the effect of the GLP-1RA exenatide on skin microvascular function in patients with T2DM and CAD. METHODS: Thirty-five patients with T2DM, CAD, and HbA1C 42-86 mmol/mol were randomized to treatment with exenatide or conventional non-GLP-1-based therapy for 12 weeks. Skin microvascular function was examined in the forearm by LDF and iontophoretic application of acetyl choline and SNP, and by PORH at baseline and after 12 weeks. Blood samples for fasting plasma glucose, HbA1C, and lipid profile were collected. RESULTS: At 12 weeks, patients on exenatide showed reductions in HbA1C (from 63.5 ± 13 to 60.7 ± 14 mmol/mol, p = .065), body weight (from 92.6 ± 16 to 89 ± 16 kg, p < .001), and systolic blood pressure (from 141 ± 13 to 134 ± 16 mm Hg, p < .05) as compared to the conventionally treated group. There were no significant changes in skin microvascular function between or within the two groups at follow-up. CONCLUSIONS: Three months' daily treatment with the GLP-1RA exenatide in T2DM patients with CAD showed no significant effects on skin microvascular function or blood glucose control, while this study confirms a reduction in body weight and blood pressure by exenatide, as compared to conventional antidiabetic drug treatment.

Altered Vascular Reactivity to Circulating Angiotensin II in Familial Hypercholesterolemia.

ABSTRACT: We have previously shown increased vascular reactivity to angiotensin (Ang) II in familial combined hyperlipidemia. However, this has not been well studied in familial hypercholesterolemia (FH), a condition with incipient endothelial dysfunction. This study aimed to examine microvascular and macrovascular responses to Ang II in FH. Therefore, we investigated the effects of a 3-hour infusion of Ang II on blood pressure and forearm skin microvascular function in 16 otherwise healthy patients with FH and matched healthy controls. Skin microvascular hyperemia was studied by laser Doppler fluxmetry during local heating. Microvascular resistance was determined by the ratio of mean arterial pressure to microvascular hyperemia. Macrovascular reactivity was assessed by changes in brachial blood pressure. Compared with the controls, the FH group had increased baseline systolic blood pressure (127 ± 14 vs. 115 ± 12 mm Hg; P = 0.02), while systolic blood pressure responses were similar (+24 ± 9 vs. +21 ± 7 mm Hg; P = 0.26) after 3 hours of Ang II infusion. At baseline, there were no group differences in microvascular hyperemia or resistance. However, after 3 hours of Ang II infusion, heat-induced microvascular hyperemia was less pronounced in FH (126 ± 95 vs. 184 ± 102 arbitrary units; P = 0.01), while microvascular resistance during heat-induced hyperemia was increased (1.9 ± 0.9 vs. 0.9 ± 0.8, P = 0.01), as compared to controls. Both these responses were further pronounced 1 hour after stopping Ang II. In conclusion, despite similar blood pressure responses to Ang II in the FH group and controls, microvascular dilatation capacity was impaired in the FH group, indicating endothelial dysfunction. These findings and increased microvascular resistance may lead to hypertension and microvascular complications in FH.

Socioeconomic status affects achievement of blood pressure target in hypertension: contemporary results from the Swedish primary care cardiovascular database.

OBJECTIVE: To assess the relation between socioeconomic status and achievement of target blood pressure in hypertension. DESIGN: Retrospective longitudinal cohort study between 2001 and 2014. SETTING: Primary health care in Skaraborg, Sweden. SUBJECTS: 48,254 patients all older than 30 years, and 53.3% women, with diagnosed hypertension. MAIN OUTCOME MEASURES: Proportion of patients who achieved a blood pressure target <140/90 mmHg in relation to the country of birth, personal disposable income, and educational level. RESULTS: Patients had a lower likelihood of achieving the blood pressure target if they were born in a Nordic country outside Sweden [risk ratio 0.92; 95% confidence interval (CI) 0.88-0.97], or born in Europe outside the Nordic countries (risk ratio 0.87; 95% CI 0.82-0.92), compared to those born in Sweden. Patients in the lowest income quantile had a lower likelihood to achieve blood pressure target, as compared to the highest quantile (risk ratio 0.93; 95% CI 0.90-0.96). Educational level was not associated with outcome. Women but not men in the lowest income quantile were less likely to achieve the blood pressure target. There was no sex difference in achieved blood pressure target with respect to the country of birth or educational level. CONCLUSION: In this real-world population of primary care patients with hypertension in Sweden, being born in a foreign European country and having a lower income were factors associated with poorer blood pressure control.KEY POINTSThe association between socioeconomic status and achieving blood pressure targets in hypertension has been ambiguous.•In this study of 48,254 patients with hypertension, lower income was associated with a reduced likelihood to achieve blood pressure control.•Being born in a foreign European country is associated with a lower likelihood to achieve blood pressure control.•We found no association between educational level and achieved blood pressure control.

Use of Self-Reported Computerized Medical History Taking for Acute Chest Pain in the Emergency Department - the Clinical Expert Operating System Chest Pain Danderyd Study (CLEOS-CPDS): Prospective Cohort Study.

BACKGROUND: Chest pain is one of the most common chief complaints in emergency departments (EDs). Collecting an adequate medical history is challenging but essential in order to use recommended risk scores such as the HEART score (based on history, electrocardiogram, age, risk factors, and troponin). Self-reported computerized history taking (CHT) is a novel method to collect structured medical history data directly from the patient through a digital device. CHT is rarely used in clinical practice, and there is a lack of evidence for utility in an acute setting. OBJECTIVE: This substudy of the Clinical Expert Operating System Chest Pain Danderyd Study (CLEOS-CPDS) aimed to evaluate whether patients with acute chest pain can interact effectively with CHT in the ED. METHODS: Prospective cohort study on self-reported medical histories collected from acute chest pain patients using a CHT program on a tablet. Clinically stable patients aged 18 years and older with a chief complaint of chest pain, fluency in Swedish, and a nondiagnostic electrocardiogram or serum markers for acute coronary syndrome were eligible for inclusion. Patients unable to carry out an interview with CHT (eg, inadequate eyesight, confusion or agitation) were excluded. Effectiveness was assessed as the proportion of patients completing the interview and the time required in order to collect a medical history sufficient for cardiovascular risk stratification according to HEART score. RESULTS: During 2017-2018, 500 participants were consecutively enrolled. The age and sex distribution (mean 54.3, SD 17.0 years; 213/500, 42.6% women) was similar to that of the general chest pain population (mean 57.5, SD 19.2 years; 49.6% women). Common reasons for noninclusion were language issues (182/1000, 18.2%), fatigue (158/1000, 15.8%), and inability to use a tablet (152/1000, 15.2%). Sufficient data to calculate HEART score were collected in 70.4% (352/500) of the patients. Key modules for chief complaint, cardiovascular history, and respiratory history were completed by 408 (81.6%), 339 (67.8%), and 291 (58.2%) of the 500 participants, respectively, while 148 (29.6%) completed the entire interview (in all 14 modules). Factors associated with completeness were age 18-69 years (all key modules: Ps<.001), male sex (cardiovascular: P=.04), active workers (all key modules: Ps<.005), not arriving by ambulance (chief complaint: P=.03; cardiovascular: P=.045), and ongoing chest pain (complete interview: P=.002). The median time to collect HEART score data was 23 (IQR 18-31) minutes and to complete an interview was 64 (IQR 53-77) minutes. The main reasons for discontinuing the interview prior to completion (n=352) were discharge from the ED (101, 28.7%) and tiredness (95, 27.0%). CONCLUSIONS: A majority of patients with acute chest pain can interact effectively with CHT on a tablet in the ED to provide sufficient data for risk stratification with a well-established risk score. The utility was somewhat lower in patients 70 years and older, in patients arriving by ambulance, and in patients without ongoing chest pain. Further studies are warranted to assess whether CHT can contribute to improved management and prognosis in this large patient group. TRIAL REGISTRATION: ClinicalTrials.gov NCT03439449; https://clinicaltrials.gov/ct2/show/NCT03439449. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-031871.

Lipid-lowering and anti-thrombotic therapy in patients with peripheral arterial disease.

Patients with peripheral arterial disease (PAD) are at very high risk of cardiovascular events, but risk factor management is usually suboptimal. This Joint Task Force from the European Atherosclerosis Society and the European Society of Vascular Medicine has updated evidence on the management on dyslipidaemia and thrombotic factors in patients with PAD. Guidelines recommend a low-density lipoprotein cholesterol (LDLC) goal of more than 50% reduction from baseline and <1.4 mmol/L (<55 mg/dL) in PAD patients. As demonstrated by randomized controlled trials, lowering LDL-C not only reduces cardiovascular events but also major adverse limb events (MALE), including amputations, of the order of 25%. Addition of ezetimibe or a PCSK9 inhibitor further decreases the risk of cardiovascular events, and PCSK9 inhibition has also been associated with reduction in the risk of MALE by up to 40%. Furthermore, statin- based treatment improved walking performance, including maximum walking distance, and pain-free walking distance and duration. This Task Force recommends strategies for managing statin-associated muscle symptoms to ensure that PAD patients benefit from lipid-lowering therapy. Antiplatelet therapy, either daily clopidogrel 75 mg or the combination of aspirin 100 mg and rivaroxaban (2×2.5 mg) is also indicated to prevent cardiovascular events. Dual pathway inhibition (aspirin and rivaroxaban) may be considered following revascularization, taking into account bleeding risk. This Joint Task Force believes that adherence with these recommendations for lipid-lowering and antithrombotic therapy will improve the morbidity and mortality in patients with PAD.

Current antihypertensive drug therapy in 12,436 Swedish patients, 90 years and above, in relation to sex and comorbidity.

Purpose: To describe current antihypertensive treatment in very old hypertensive patients according to sex and comorbidity.Materials and methods: We used the Stockholm regional healthcare data warehouse (Vårdanalysdatabasen) providing information on all healthcare consultations, diagnoses, hospitalizations, dispensed prescription drugs, sex and age in 2.1 million people living in the greater Stockholm region, Sweden. This cross-sectional analysis identified 12,436 individuals with a diagnosis of hypertension, who were 90 years or older.Results: Mean age was 92.6 ± 2.6 years, 75% were women; and 34% of women and 24% of men had no diagnoses of concomitant diabetes or cardiovascular disease. The number of dispensed drug classes was similar (2.1 ± 1.4) in women and in men. Women more often used angiotensin receptor blockers and beta-blockers, while men more frequently used ACE inhibitors and calcium channel blockers (all p < .05). Compared to men, women with concomitant diabetes or heart failure used less ACE inhibitors or angiotensin receptor blockers (52 vs. 60% and 49 vs. 55%, respectively; all p < .01and adjusted for age and comorbidity), which is contrary to current recommendations.Conclusion: Our findings suggest that antihypertensive treatment is common also in very old patients. Given the rapidly ageing population and circumstantial evidence in favour of maintaining well-tolerated antihypertensive therapy in very old patients, prospective well-designed outcome studies are warranted.

The interrelation of endothelial function and microvascular reactivity in different vascular beds, and risk assessment in hypertension: results from the Doxazosin-ramipril study.

There are several non-invasive methods to study endothelial function, but their interrelation and association to cardiovascular risk have not been well evaluated. We studied macrovascular and microvascular endothelial function simultaneously in different vascular beds in relation to cardiovascular mortality risk (Systematic Coronary Risk Evaluation, SCORE) and hypertension induced cardiac organ damage, and their interrelationship. The study investigated 71 hypertensive patients by forearm post-ischemic flow-mediated vasodilation, pulse wave analysis (applanation tonometry) and beta 2-adrenoceptor agonist stimulation for changes in reflection index, skin microvascular reactivity by laser Doppler fluxmetry with iontophoresis and heat-induced hyperaemia, and coronary microvascular function by subendocardial viability ratio (derived from pulse wave analysis). Flow mediated vasodilation related inversely to SCORE (r = 0.34, P = 0.011). Adding microalbuminuria and pulse wave velocity strengthened the associations. Pulse wave reflection changes did not relate to SCORE. Skin microvascular reactivity related inversely to SCORE (peak flux change to sodium nitroprusside r = 0.29, P = 0.033, and to heating r = 0.31, P = 0.018). Subendocardial viability ratio did not relate to SCORE. Endothelial function indices showed no consistent relation to cardiac target organ damage. The agreement between the different methods for evaluating indices of macrovascular and microvascular endothelial function was weak. In conclusion, indices of macrovascular and microvascular endothelial function relate to cardiovascular mortality risk. Their use may improve cardiovascular risk prediction in hypertension. However, methods representing different vascular beds show little interrelationship and are not interchangeable, which may depend on different pathogenetic mechanisms representing different aspects of future cardiovascular risk.Trial registry: NCT02901977.

Medication persistence to antihypertensive drug treatment - a cross-sectional study of attitudes towards hypertension and medication in persistent and non-persistent patients.

Purpose: To study the differences in attitudes towards hypertension and drug treatment between patients persistent and non-persistent to antihypertensive drug treatment. Materials and methods: Cross-sectional study on patients with hypertension treated at 25 primary healthcare centres in Stockholm, Sweden. Questionnaires were sent to the patients 3-12 months after initiation of antihypertensive drug treatment. Persistent medication users, defined as patients with less than 30 days without tablet supply between prescription refills, were compared with non-persistent users by scores from Likert scales: Brief-Illness Perception Questionnaire (Brief IPQ, 0-10) and Beliefs about Medicines Questionnaire (BMQ General, 4-20 and BMQ Specific, 5-25). Results: A total of 711 patients were included in the final analyses (mean age: 62 years; 50% women), of whom 609 (86%) were classified as persistent and 102 (14%) as non-persistent by analyses of their filled prescriptions. Likert scales from the Brief-IPQ showed (all p < 0.02) that persistent patients believed that hypertension was a chronic condition (median 6 vs. 4), that hypertension had less consequences on their life (median 2 vs. 3) and that they can prevent cardiovascular disease by taking antihypertensive treatment (median 7 vs. 5). Likert scales from the BMQ General showed (all p < 0.02) that persistent patients believed that there are potential benefits from taking the treatment (median 16 vs. 16), and they did not believe that the doctors put too much trust in drugs (median 12 vs. 13). Further, results from the BMQ Specific showed that they believed that the antihypertensive drugs are necessary for them in order to maintain or improve their own health (median 17 vs. 16). Conclusions: Primary healthcare providers should further emphasize the chronicity of hypertension diagnosis and the benefits of treatment, to improve the patients' medication persistence to antihypertensive treatment.

Effects of Angiotensin-Converting Enzyme Inhibition and Alpha 1-Adrenergic Receptor Blockade on Inflammation and Hemostasis in Human Hypertension.

Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We examined the contribution of the angiotensin-converting enzyme inhibitor ramipril and the alpha 1-adrenergic receptor blocker doxazosin on blood pressure and on markers of inflammation and hemostasis in 59 individuals with mild-to-moderate hypertension randomized to receive double-blind ramipril 10 mg od or doxazosin 8 mg od for 12 weeks. Inflammatory markers (interleukin-6, soluble interleukin-6 receptor, interleukin-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and C-reactive protein) and hemostasis (plasminogen activator inhibitor-1 activity, tissue plasminogen activator antigen, thrombin-antithrombin complex, and thrombin generation by calibrated automated thrombogram) were assessed. The treatment reduced blood pressure in both groups. Thrombin-antithrombin complex decreased by treatment, and this was dependent on a reduction in thrombin-antithrombin complex in the ramipril group alone. There were no changes in plasminogen activator inhibitor-1 activity, whereas tissue plasminogen activator antigen increased by ramipril and decreased by doxazosin. Only minor changes were observed in systemic inflammation by treatment. Treatment with ramipril seems to reduce thrombin generation beyond effects on reducing blood pressure. Drugs blocking the renin-angiotensin-aldosterone system may reduce atherothrombotic complications beyond their effects to reduce blood pressure.

Drug adherence in treatment resistant and in controlled hypertension-Results from the Swedish Primary Care Cardiovascular Database (SPCCD).

PURPOSE: To assess drug adherence in patients treated with ≥3 antihypertensive drug classes, with both controlled and uncontrolled blood pressure and describe associated factors for nonadherence. METHODS: Patients with hypertension, without cardiovascular comorbidity, aged >30 years treated with ≥3 antihypertensive drug classes were followed for 2 years. Both patients with treatment resistant hypertension (TRH) and patients with controlled hypertension were included. Clinical data were derived from a primary care database. Pharmacy refill data from the Swedish Prescribed drug registry was used to calculate proportion of days covered (PDC). Patients with a PDC level ≥ 80% were included. RESULTS: We found 5846 patients treated ≥3 antihypertensive drug classes, 3508 with TRH (blood pressure ≥ 140/90), and 2338 with controlled blood pressure (<140/90 mm Hg). TRH patients were older (69.1 vs 65.8 years, P < .0001) but had less diabetes (28.5 vs 31.7%, P < .009) compared with patients with controlled blood pressure. The proportion of patients with PDC ≥ 80% declined with 11% during the first year in both groups. Having diabetes was associated with staying adherent at 1 year (RR 0.82; 95% CI, 0.68-0.98) whilst being born outside Europe was associated with nonadherence at one and (RR 2.05; 95% CI, 1.49-2.82). CONCLUSIONS: Patients with multiple antihypertensive drug therapy had similar decline in adherence over time regardless of initial blood pressure control. Diabetes was associated with better adherence, which may imply that the structured caregiving of these patients enhances antihypertensive drug treatment.