Systolic murmur in disguise: subclavian artery stenosis as an overlooked cause of missed case of hypertension.

In this report we present a case of missed hypertension due to subclavian artery stenosis. A 77 year-old female patient, initially thought as being normotensive, was referred to us due to newly discovered systolic heart murmur suspicious for aortic stenosis. We noted inter-arm blood pressure difference of 30 mmHg, with higher, hypertensive values on right arm. Further workup and medical imaging excluded aortic stenosis and revealed an asymptomatic, hemodynamically significant, stenosis of left subclavian artery. Due to absence of symptoms, the patient has been managed with conservative therapy for subclavian stenosis and hypertension, and she is currently in good conditions and followed up for any signs of disease progression. This case clearly shows importance of measuring blood pressure on both arms when initially diagnosing hypertension as this is often overlooked and is key to properly diagnose hypertension and possible subclavian stenosis.

Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial: rational and protocol.

BACKGROUND: Hypertension and diabetes cause chronic kidney disease (CKD) and diastolic left ventricular dysfunction (DVD) as forerunners of disability and death. Home blood pressure telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling prevention. METHODS: UPRIGHT-HTM (Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform [NCT04299529]) is an investigator-initiated 5-year clinical trial with patient-centred design, which will randomise 1148 patients to be recruited in Europe, sub-Saharan Africa and South America. During the whole study, HTM data will be collected and freely accessible for patients and caregivers. The UPP, measured at enrolment only, will be communicated early during follow-up to 50% of patients and their caregivers (intervention), but only at trial closure in 50% (control). The hypothesis is that early knowledge of the UPP risk profile will lead to more rigorous risk factor management and result in benefit. Eligible patients, aged 55-75 years old, are asymptomatic, but have ≥5 CKD- or DVD-related risk factors, preferably including hypertension, type-2 diabetes, or both. The primary endpoint is a composite of new-onset intermediate and hard cardiovascular and renal outcomes. Demonstrating that combining UPP with HTM is feasible in a multicultural context and defining the molecular signatures of early CKD and DVD are secondary endpoints. EXPECTED OUTCOMES: The expected outcome is that application of UPP on top of HTM will be superior to HTM alone in the prevention of CKD and DVD and associated complications and that UPP allows shifting emphasis from treating to preventing disease, thereby empowering patients.

May Measurement Month 2019: an analysis of blood pressure screening results from Slovenia.

Accounting for an estimated 10.4 million deaths each year, arterial hypertension is a worldwide epidemic. However, it is a treatable condition that can be readily recognized with cost-effective blood pressure (BP) measurements. Alongside continuous improvements in BP control and treatment, worldwide strategies aim to achieve a high level of hypertension awareness. May Measurement Month (MMM) is a global campaign initiated by the International Society of Hypertension to raise awareness of high BP. Slovenia began with yearly cost-free BP measurements and awareness campaigns in 2005 when World Hypertension Day was announced by the World Hypertension League and in 2017, we joined the MMM initiative. In May 2019, we performed a cross-sectional survey following the standardized MMM protocol. Healthcare personnel obtained BP measurements in a sample of adult subjects (≥18 years) across all regions of the country, mostly in healthcare facilities and pharmacies. In total, 4974 individuals (61.1% female), with a mean age of 59.6 years, were screened. After multiple imputation for missing data, 3037 (61.1%) participants had hypertension. Of individuals not receiving antihypertensive medication, 973 (33.4%) were hypertensive. Of those who reported receiving antihypertensives, 1110 (53.8%) had uncontrolled BP. MMM19 was the largest BP screening campaign undertaken in Slovenia so far. We again identified a substantial number of participants with possible hypertension and uncontrolled BP despite taking antihypertensive medication, which were then referred to their general practitioners or dedicated hypertension centres for further evaluation and management. Taken together, our findings underline the importance of opportunistic screening programmes.

May Measurement Month 2018: an analysis of blood pressure screening results from Slovenia.

Elevated blood pressure (BP) is a growing burden worldwide, contributing to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative organized by the International Society of Hypertension aimed to raise awareness of high BP. In May 2018, we carried out an opportunistic cross-sectional survey of volunteers from different parts of the country aged ≥18 years. Blood pressure measurement followed the standard MMM protocol and statistical analysis mean of the last 2 of 3 readings was used, where these were unavailable additional imputations were performed. In total, 4883 individuals (61.0% female) were screened during the whole month of May in 91 primary and secondary health facilities, pharmacies and through an online survey. After multiple imputation, 2841 (58.2%) had HTN. Of individuals not receiving antihypertensive medication, 850 (29.4%) were hypertensive. Of those receiving antihypertensive medication, 1025 (51.5%) had uncontrolled BP. MMM18 was the largest BP screening campaign undertaken in Slovenia. A substantial number of people with possible HTN were identified and referred to general practitioners for further management. The high number of individuals with HTN, with newly diagnosed HTN and with uncontrolled BP despite medication, confirms a real need for such screening programmes in our country.

Hypertension and cardiac arrhythmias: a consensus document from the European Heart Rhythm Association (EHRA) and ESC Council on Hypertension, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE).

Hypertension is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease, stroke, peripheral artery disease and chronic renal insufficiency. Hypertensive heart disease can manifest as many cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both supraventricular and ventricular arrhythmias may occur in hypertensive patients, especially in those with left ventricular hypertrophy (LVH) or HF. Also, some of the antihypertensive drugs commonly used to reduce blood pressure, such as thiazide diuretics, may result in electrolyte abnormalities (e.g. hypokalaemia, hypomagnesemia), further contributing to arrhythmias, whereas effective control of blood pressure may prevent the development of the arrhythmias such as AF. In recognizing this close relationship between hypertension and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society of Cardiology (ESC) Council on Hypertension convened a Task Force, with representation from the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit to comprehensively review the available evidence to publish a joint consensus document on hypertension and cardiac arrhythmias, and to provide up-to-date consensus recommendations for use in clinical practice. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and the patient in light of all of the circumstances presented by that patient.

Risk stratification by self-measured home blood pressure across categories of conventional blood pressure: a participant-level meta-analysis.

BACKGROUND: The Global Burden of Diseases Study 2010 reported that hypertension is worldwide the leading risk factor for cardiovascular disease, causing 9.4 million deaths annually. We examined to what extent self-measurement of home blood pressure (HBP) refines risk stratification across increasing categories of conventional blood pressure (CBP). METHODS AND FINDINGS: This meta-analysis included 5,008 individuals randomly recruited from five populations (56.6% women; mean age, 57.1 y). All were not treated with antihypertensive drugs. In multivariable analyses, hazard ratios (HRs) associated with 10-mm Hg increases in systolic HBP were computed across CBP categories, using the following systolic/diastolic CBP thresholds (in mm Hg): optimal, <120/<80; normal, 120-129/80-84; high-normal, 130-139/85-89; mild hypertension, 140-159/90-99; and severe hypertension, ≥160/≥100. Over 8.3 y, 522 participants died, and 414, 225, and 194 had cardiovascular, cardiac, and cerebrovascular events, respectively. In participants with optimal or normal CBP, HRs for a composite cardiovascular end point associated with a 10-mm Hg higher systolic HBP were 1.28 (1.01-1.62) and 1.22 (1.00-1.49), respectively. At high-normal CBP and in mild hypertension, the HRs were 1.24 (1.03-1.49) and 1.20 (1.06-1.37), respectively, for all cardiovascular events and 1.33 (1.07-1.65) and 1.30 (1.09-1.56), respectively, for stroke. In severe hypertension, the HRs were not significant (p≥0.20). Among people with optimal, normal, and high-normal CBP, 67 (5.0%), 187 (18.4%), and 315 (30.3%), respectively, had masked hypertension (HBP≥130 mm Hg systolic or ≥85 mm Hg diastolic). Compared to true optimal CBP, masked hypertension was associated with a 2.3-fold (1.5-3.5) higher cardiovascular risk. A limitation was few data from low- and middle-income countries. CONCLUSIONS: HBP substantially refines risk stratification at CBP levels assumed to carry no or only mildly increased risk, in particular in the presence of masked hypertension. Randomized trials could help determine the best use of CBP vs. HBP in guiding BP management. Our study identified a novel indication for HBP, which, in view of its low cost and the increased availability of electronic communication, might be globally applicable, even in remote areas or in low-resource settings.

Out-of-office blood pressure improves risk stratification in normotension and prehypertension people.

This review addresses to what extent out-of-office blood pressure, the ambulatory blood pressure monitoring and the self-measured home blood pressure, refines conventional blood pressure-based risk stratification across increasing blood pressure categories, in particular individuals assumed to be associated with no or only mildly increased risk. Compared with sustained normotension, individuals with prehypertension as well as masked hypertension tend to be developed to true hypertension. Ambulatory blood pressure measurement refines risk stratification among prehypertensive people. Home blood pressure is more useful for the prediction of cerebrovascular diseases than conventional blood pressure, by replacing information from conventional to home blood pressure in risk stratification system. Furthermore, the two participant-level meta-analyses demonstrated that the out-of-office blood pressure substantially refines risk stratification in normotension and prehypertension, particularly among participants with masked hypertension. Properly organized randomized clinical trials are required to demonstrate that identification and treatment of masked hypertension, compared with the current standard care based on conventional pressure, lead to the reduction of cardiovascular diseases in population and are cost-effective.

What did we learn from the International Databases on Ambulatory and Home Blood Pressure in Relation to Cardiovascular Outcome?

To assess in individual-person meta-analyses how out-of-office blood pressure (BP) contributes to risk stratification and the management of hypertension, an international consortium set up the International Databases on Ambulatory (IDACO) and Home (IDHOCO) Blood Pressure in Relation to Cardiovascular Outcome. This review summarizes key findings of recent IDACO/IDHOCO articles. Among various BP indexes derived from office and ambulatory BP recordings, the 24-h and nighttime BP level were the best predictors of adverse health outcomes. Second, using the 10-year cardiovascular risk associated with guideline-endorsed office BP thresholds as reference, corresponding thresholds were derived for home and ambulatory BP. Stratified by the underlying cardiovascular risk, the rate of cardiovascular events in white-coat hypertensive patients and matched normotensive controls were not substantially different. The observation that masked hypertension carries a high cardiovascular risk was replicated in Nigerian Blacks, using home BP monitoring. The thresholds for 24-h mean arterial pressure, i.e., the BP component measured by oscillometric devices, delineating normotension, elevated BP and hypertension were <90, 90 to 92 and ≥92 mmHg. At young age, the absolute risk associated with out-of-office BP was low, but the relative risk was high, whereas with advancing age, the relative risk decreased and the absolute risk increased. Using pulse pressure as an exemplary case, the relative risks of death, cardiovascular endpoints and stroke decreased over 3-fold from 55 to 75 years of age, whereas in contrast absolute risk rose 3-fold. In conclusion, IDACO/IDHOCO forcefully support the notion that the pressing need to curb the hypertension pandemic cannot be met without out-of-the-office BP monitoring.

Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial-First progress report.

High blood pressure (BP) and type-2 diabetes (T2DM) are forerunners of chronic kidney disease and left ventricular dysfunction. Home BP telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling risk stratification and personalized prevention. UPRIGHT-HTM (NCT04299529) is an investigator-initiated, multicenter, open-label, randomized trial with blinded endpoint evaluation designed to assess the efficacy of HTM plus UPP (experimental group) over HTM alone (control group) in guiding treatment in asymptomatic patients, aged 55-75 years, with ≥5 cardiovascular risk factors. From screening onwards, HTM data can be freely accessed by all patients and their caregivers; UPP results are communicated early during follow-up to patients and caregivers in the intervention group, but at trial closure in the control group. From May 2021 until January 2023, 235 patients were screened, of whom 53 were still progressing through the run-in period and 144 were randomized. Both groups had similar characteristics, including average age (62.0 years) and the proportions of African Blacks (81.9%), White Europeans (16.7%), women 56.2%, home (31.2%), and office (50.0%) hypertension, T2DM (36.4%), micro-albuminuria (29.4%), and ECG (9.7%) and echocardiographic (11.5%) left ventricular hypertrophy. Home and office BP were 128.8/79.2 mm Hg and 137.1/82.7 mm Hg, respectively, resulting in a prevalence of white-coat, masked and sustained hypertension of 40.3%, 11.1%, and 25.7%. HTM persisted after randomization (48 681 readings up to 15 January 2023). In conclusion, results predominantly from low-resource sub-Saharan centers proved the feasibility of this multi-ethnic trial. The COVID-19 pandemic caused delays and differential recruitment rates across centers.

Management of patients with combined arterial hypertension and aortic valve stenosis: a consensus document from the Council on Hypertension and Council on Valvular Heart Disease of the European Society of Cardiology, the European Association of Cardiovascular Imaging (EACVI), and the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Aortic valve stenosis (AS) is the third most common cardiovascular disease. The prevalence of both AS and arterial hypertension increases with age, and the conditions therefore often co-exist. Co-existence of AS and arterial hypertension is associated with higher global left ventricular (LV) pressure overload, more abnormal LV geometry and function, and more adverse cardiovascular outcome. Arterial hypertension may also influence grading of AS, leading to underestimation of the true AS severity. Current guidelines suggest re-assessing patients once arterial hypertension is controlled. Management of arterial hypertension in AS has historically been associated with prudence and concerns, mainly related to potential adverse consequences of drug-induced peripheral vasodilatation combined with reduced stroke volume due to the fixed LV outflow obstruction. Current evidence suggests that patients should be treated with antihypertensive drugs blocking the renin-angiotensin-aldosterone system, adding further drug classes when required, to achieve similar target blood pressure (BP) values as in hypertensive patients without AS. The introduction of transcatheter aortic valve implantation has revolutionized the management of patients with AS, but requires proper BP management during and following valve replacement. The purpose of this document is to review the recent evidence and provide practical expert advice on management of hypertension in patients with AS.

ESC Council on hypertension position document on the management of hypertensive emergencies.

Hypertensive emergencies are those situations where very high blood pressure (BP) values are associated with acute organ damage, and therefore, require immediate, but careful, BP reduction. The type of acute organ damage is the principal determinant of: (i) the drug of choice, (ii) the target BP, and (iii) the timeframe in which BP should be lowered. Key target organs are the heart, retina, brain, kidneys, and large arteries. Patients who lack acute hypertension-mediated end organ damage do not have a hypertensive emergency and can usually be treated with oral BP-lowering agents and usually discharged after a brief period of observation.

Correlation Between Mitochondrial DNA Content Measured in Myocardium and Peripheral Blood of Patients with Non-Ischemic Heart Failure.

BACKGROUND/OBJECTIVES: Heart failure (HF) is associated with disturbances in mitochondrial energy production. This mitochondrial dysfunction is reflected by depletion of mitochondrial DNA (mtDNA) in different tissues. Our aims were to determine if there was a correlation between mtDNA content measured in myocardial tissue and the easily accessible peripheral blood cells of patients with non-ischemic HF; and to determine if there was a correlation between myocardial mtDNA and left ventricular (LV) ejection fraction. METHODS: We prospectively collected paired myocardial tissue and peripheral blood samples from 13 consecutive end-stage non-ischemic HF patients undergoing cardiac transplantation. mtDNA content was assessed with real-time quantitative PCR by calculating the relative ratio of two specific mitochondrial sequences and one nuclear control gene sequence. RESULTS: HF patients with lower myocardial mtDNA content had a significantly lower LV ejection fraction (r = 0.65, p = 0.016). Peripheral blood mtDNA content correlated positively with right ventricular myocardial mtDNA content (r = 0.63, p = 0.021). We also observed that averaged myocardial DNA content tended to correlate with peripheral blood mtDNA content (r = 0.53, p = 0.061). CONCLUSIONS: In non-ischemic HF patients, myocardial mtDNA content is positively correlated with peripheral blood mtDNA content and LV function as assessed by echocardiography.

Peripheral blood mitochondrial DNA content in relation to circulating metabolites and inflammatory markers: A population study.

Mitochondrial DNA (mtDNA) content might undergo significant changes caused by metabolic derangements, oxidative stress and inflammation that lead to development and progression of cardiovascular diseases. We, therefore, investigated in a general population the association of peripheral blood mtDNA content with circulating metabolites and inflammatory markers. We examined 310 subjects (50.6% women; mean age, 53.3 years) randomly selected from a Flemish population. Relative mtDNA content was measured by quantitative real-time PCR in peripheral blood cells. Peak circulating metabolites were quantified using nuclear magnetic resonance spectroscopy. The level of inflammation was assessed via established inflammatory markers. Using Partial Least Squares analysis, we constructed 3 latent factors from the 44 measured metabolites that explained 62.5% and 8.5% of the variance in the contributing metabolites and the mtDNA content, respectively. With adjustments applied, mtDNA content was positively associated with the first latent factor (P = 0.002). We identified 6 metabolites with a major impact on the construction of this latent factor including HDL3 apolipoproteins, tyrosine, fatty acid with αCH2, creatinine, ß-glucose and valine. We summarized them into a single composite metabolite score. We observed a negative association between the composite metabolic score and mtDNA content (P = 0.001). We also found that mtDNA content was inversely associated with inflammatory markers including hs-CRP, hs-IL6, white blood cell and neutrophil counts as well as neutrophil-to-lymphocyte ratio (P≤0.0024). We demonstrated that in a general population relative peripheral blood mtDNA content was associated with circulating metabolites indicative of perturbed lipid metabolism and with inflammatory biomarkers.

Association of left ventricular structure and function with peripheral blood mitochondrial DNA content in a general population.

BACKGROUND/OBJECTIVES: mtDNA content might be an important biomarker in heart disease prediction and to date no population studies are available on the association of mtDNA content with cardiac structure and function. We, therefore, investigated in a general population in cross-sectional and longitudinal studies whether echocardiographic indexes of LV structure and function are associated with mtDNA content measured in peripheral blood cells. METHODS: At baseline we performed echocardiography in 701 randomly selected individuals (50.9% women, mean age, 53.2years) from a Flemish population. Relative mtDNA copy number compared to nuclear DNA was measured by quantitative real-time PCR in peripheral blood cells. RESULTS: With adjustments applied, we observed significant inverse association of LV diastolic and systolic diameters (P≤0.028) and volumes (P=0.013) with mtDNA content. Moreover, for a 1-SD increment in mtDNA (0.37), we found an increase in Tissue Doppler s' velocity by 0.093cm/s (P=0.019) and a decrease in E/e' ratio by 0.18 (P=0.008). In 223 subjects with available echocardiography and mtDNA content at baseline and follow-up, we observed that higher baseline mtDNA content was associated with less increase in 2D LV diastolic volume (P=0.0003), M-mode LV diameter (P=0.046) and LV mass (P=0.003) during the follow-up period. CONCLUSIONS: In the general population, higher mtDNA content was associated with smaller LV diastolic and systolic diameters and volumes and better LV systolic and diastolic function. Moreover, we observed that baseline mtDNA content was a significant predictor of longitudinal changes of LV diastolic volume and dimension, and LV mass.

Risk stratification by ambulatory blood pressure monitoring across JNC classes of conventional blood pressure.

BACKGROUND: Guidelines propose classification of conventional blood pressure (CBP) into normotension (<120/<80 mm Hg), prehypertension (120-139/80-89 mm Hg), and hypertension (≥140/≥90 mm Hg). METHODS: To assess the potential differential contribution of ambulatory blood pressure (ABP) in predicting risk across CBP strata, we analyzed outcomes in 7,826 untreated people recruited from 11 populations. RESULTS: During an 11.3-year period, 809 participants died (276 cardiovascular deaths) and 639, 383, and 225 experienced a cardiovascular, cardiac, or cerebrovascular event. Compared with normotension (n = 2,639), prehypertension (n = 3,076) carried higher risk (P ≤ 0.015) of cardiovascular (+41%) and cerebrovascular (+92%) endpoints; compared with hypertension (n = 2,111) prehypertension entailed lower risk (P ≤ 0.005) of total mortality (-14%) and cardiovascular mortality (-29%) and of cardiovascular (-34%), cardiac (-33%), or cerebrovascular (-47%) events. Multivariable-adjusted hazard ratios (HRs) for stroke associated with 24-hour and daytime diastolic ABP (+5 mm Hg) were higher (P ≤ 0.045) in normotension than in prehypertension and hypertension (1.98 vs.1.19 vs.1.28 and 1.73 vs.1.09 vs. 1.24, respectively) with similar trends (0.03 ≤ P ≤ 0.11) for systolic ABP (+10 mm Hg). However, HRs for fatal endpoints and cardiac events associated with ABP did not differ significantly (P ≥ 0.13) across CBP categories. Of normotensive and prehypertensive participants, 7.5% and 29.3% had masked hypertension (daytime ABP ≥135/≥85 mm Hg). Compared with true normotension (P ≤ 0.01), HRs for stroke were 3.02 in normotension and 2.97 in prehypertension associated with masked hypertension with no difference between the latter two conditions (P = 0.93). CONCLUSION: ABP refines risk stratification in normotension and prehypertension mainly by enabling the diagnosis of masked hypertension.