Antihypertensive Use Research Articles

Relationship between antihypertensive drug use and number of people with high blood pressure in FY 2018: a descriptive epidemiological study based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan open data

BackgroundIn most countries barring Japan, antihypertensive drug use has been reported using the defined daily doses/1000 inhabitants/day (DID). Although DID has been shown to allow for the assessment of the number of patients treated with a particular drug, the relationship between DID and the number of patients with hypertension has not been clarified. This study aimed to clarify the relationship between antihypertensive drug use and the number of people with high blood pressure based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) open data.MethodsDID was calculated by extracting the use of oral antihypertensive drugs from outpatient prescriptions in the NDB Open Data in FY 2018. The number of people with high blood pressure was calculated using the number of enrollees in each sex–age group for systolic and diastolic blood pressure in the 40–74 years age group. The correlation between the DID of antihypertensive drugs and the number of people with high blood pressure by sex and age class was evaluated using Spearman’s rank correlation coefficient.ResultsThe use of antihypertensive drugs increased with age in both men and women. Furthermore, in both sexes, dihydropyridine derivatives, calcium antagonists, and angiotensin II receptor blockers were the main drugs used from the age of 20 years onward. In addition, a very strong positive correlation was found between the number of people with high systolic blood pressure and DID in both sexes (men: r = 1, P < 0.05; women: r = 1, P < 0.05). In contrast, there was no significant correlation between the number of people with high diastolic blood pressure and DID in both sexes (men: r = − 0.214, P > 0.05; women: r = 0.393, P > 0.05).ConclusionsTo our knowledge, this study is the first to investigate the use of oral antihypertensive drugs in outpatient settings in Japan. In addition, the DID of antihypertensive drugs can be used as an alternative indicator of the number of people with high systolic blood pressure.

Abstract B136: Hypertension, anti-hypertensive drug use, and breast cancer survival among Black women

Abstract Introduction: In the United States (US), Black women are 59% more likely to have hypertension than White women. US Black women are also 40% more likely to die from breast cancer when compared to US White women, yet the associations between hypertension, use of anti-hypertensive medications, and breast cancer survival are not well-established in this population. Methods: The prospective Black Women’s Health Study includes 1,757 women with invasive breast cancer diagnosed at stages 1, 2 or 3. Data on physician-diagnosed hypertension and use of anti-hypertensive medications (i.e., angiotensin II receptor blockers [ARBs], angiotensin-converting enzyme [ACE] inhibitors, beta blockers, and diuretics) are collected every two years. We used Cox proportional hazards models adjusted for age and stage at breast cancer diagnosis to estimate hazard ratios (HR) and 95% confidence intervals for associations of untreated and treated hypertension around the time of breast cancer diagnosis with breast cancer survival. Results: The HR for breast cancer mortality was 1.60 (1.10, 2.34) for women with untreated hypertension relative to women without hypertension. The association was especially strong among Stage 2/3 cases (HR=1.89 [1.25, 2.87]) and estrogen receptor negative cases (HR=1.96 [1.11, 3.48]). Women with treated hypertension did not have a higher risk of breast cancer-specific death relative to women without hypertension (HR=0.96 [0.73, 1.27]), although there was some evidence of variation by type of anti-hypertensive used. HRs were 0.86 (0.54, 1.37), 1.04 (0.68, 1.57), 1.26 (0.85, 1.87), and 1.25 (0.85, 1.86) for hypertensive women who used ARBs, ACE inhibitors, beta blockers, and diuretics, respectively. Conclusions: Among Black women with hypertension, breast cancer-specific survival is better if the hypertension is treated. Data from our study and others suggest that treatment with ARBs or ACE inhibitors may be especially beneficial when a key concern is breast cancer-specific survival. Citation Format: Mollie E. Barnard, Nuo N. Xu, Dennis Jones, Julie R. Palmer. Hypertension, anti-hypertensive drug use, and breast cancer survival among Black women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B136.

What do we still need to know about antihypertensives and dementia prevention?

AbstractThere is a substantial evidence base linking higher blood pressures to an increased risk of cognitive decline and dementia and an increasingly strong evidence base showing reduced dementia risk with blood pressure lowering. Several clinical trials including SPRINT‐MIND have strongly suggested that antihypertensive treatment to lower blood pressure reduces dementia risk. Furthermore, a recent individual participant data meta‐analysis combining data from 5 large double‐blind placebo‐controlled trials of antihypertensives in a late‐mid to early‐late life population (N = 28008) found a 13% reduction in incident dementia cases (OR0.87 (95%CI: 0.75,0.99))(1). The blood pressure difference between the two combined trial arms was ∼10mmHg in systolic blood pressure and there was no clear U shape indicating no increase in risk at lower pressures. This is supported by numerous earlier meta‐analyses of published trial and epidemiological data. Blood pressure lowering is acknowledged as one of the most promising ways in which we might reduce the risk of dementia and cognitive decline.Despite this substantial progress and although we are arguably closer than ever before to answering the question of whether blood pressure lowering reduces dementia risk, there have been no double‐blind placebo‐controlled trials that have definitively shown dementia risk reduction with antihypertensive use. In the absence of strong results, recommendations for antihypertensive use inevitably remain cautious. Furthermore, not only do we still lack a definitive blood pressure dementia risk reduction trial, such a trial would need to be large and complex. Uncertainties also exist about how to deliver treatment against the backdrop of widespread antihypertensive use to reduce cardiovascular risks such as stroke or heart attack. Research is also still progressing on key practical questions. For example, whether we should have a goal blood pressure for brain health, how far we should lower blood pressure to reduce dementia risk, what is the ideal treatment package and how much do factors such as age and frailty matter? We present the key evidence so far and an ongoing pilot trial designed to answer the leading questions in the field.(1)Peters et al Eur Heart J 2022

Enlarged Perivascular Spaces in a Diverse Community‐based Sample. The Multi‐Ethnic Study of Atherosclerosis

AbstractBackgroundEnlarged perivascular spaces (ePVS) have been associated with small vessel disease of the brain (SVD). Nevertheless, the burden, correlates and significance of ePVS have been studied predominantly in White individuals, so the generalizability of these findings to other racial/ethnic groups remains uncertain. Herein, we present an investigation of ePVS in a large, multi‐ethnic, community‐based cohort.MethodePVS volumes were quantified in 1,026 participants (median age 71 years; 47% men) from the Multi‐Ethnic Study of Atherosclerosis, using a fully‐automated deep learning model with 82% lesion‐wise sensitivity. Based on previously‐described clinical rating systems, ePVS were grouped in four brain regions: basal ganglia, thalamus, frontoparietal region, and temporal region, and were normalized to the respective regional volumes. Cognition was assessed with the Cognitive Abilities Screening Instrument, the Digit Symbol Coding, and the Digit Span test. APOE‐ε4 isoforms were estimated from single nucleotide polymorphisms (rs429358,rs7412). The relationships of normalized regional ePVS volumes with demographic and vascular risk factors, neuroimaging indices, cognition, and APOE genotype were explored using generalized linear models.ResultBasal ganglia was the anatomic region with the largest ePVS burden (median[IQR] = 1.9[1.4] % of total regional volume), followed by the frontoparietal region (0.6[0.5]), temporal region (0.4[0.4]), and thalamus (0.3[0.3]) – Figure 1,Table 1. Basal ganglia ePVS volume was positively associated with age, systolic blood pressure (SBP), use of antihypertensives, white matter hyperintensity volume (WMHV), and microbleeds (MBs), and negatively associated with white matter fractional anisotropy (FA) and Black race (Tables 1,2). Thalamic ePVS volume was positively associated with age, use of antihypertensives, WMHV, and MBs, and negatively associated with FA. Frontoparietal ePVS volume was positively associated with SBP, and negatively associated with age. Temporal region ePVS volume was negatively associated with age, Chinese and Hispanic ethnicity. No significant associations were observed between regional ePVS volumes and cognition or APOE genotype.ConclusionIncreased ePVS burden in the basal ganglia and thalamus was associated with hypertension and imaging biomarkers of vascular brain damage in a multi‐ethnic population of older adults, likely reflecting underlying SVD. Compared to other racial/ethnic groups, White race was associated with higher ePVS burden in the basal ganglia and temporal regions.

Antemortem visit‐to‐visit blood pressure variability and postmortem cerebrovascular disease lesion burden in older adults without dementia

AbstractBackgroundBlood pressure management is an accessible therapeutic target for dementia prevention. Beyond the current focus of managing mean levels, there is a burgeoning interest in understanding the variability in blood pressure levels. Emerging research suggests elevated blood pressure variability is associated with increased risk for Alzheimer’s dementia and cerebrovascular disease, including white matter hyperintensities on MRI (e.g., Fazekas score), but relationships with white matter lesions and overall cerebrovascular pathology at autopsy remain understudied. The aim of the current study was to determine whether antemortem blood pressure variability predicts cerebrovascular pathology in older adults without clinical dementia.Method1866 older adults from the National Alzheimer’s Coordinating Center study underwent repeated approximately annual blood pressure measurement and autopsy and were free of clinical dementia at study baseline. Visit‐to‐visit blood pressure variability was calculated as variability independent of mean using at least 3 (median 5, range 3 ‐ 15) annual blood pressure measurements. White matter rarefaction was scored as none vs mild/moderate vs severe. An index of overall cerebrovascular lesion burden (range 0‐7) was calculated as the sum of severity (0‐2) of atherosclerosis in the Circle of Willis and arteriolosclerosis, and the presence/absence (0‐1) of microinfarcts, infarcts and lacunes, and microbleeds and hemorrhages. Linear and multinomial logistic regression models examined relationships between blood pressure variability, white matter rarefaction severity, and overall cerebrovascular lesion burden, controlling for age, sex, mean blood pressure, antihypertensive use, and Hachinski Ischemic Score, among other variables.ResultElevated blood pressure variability predicted increased severity of white matter rarefaction (OR of mild/moderate [vs none] = 1.21 [1.06, 1.33], p = .004; OR of severe [vs none] = 1.30 [1.07, 1.46], p = .008), and greater overall cerebrovascular lesion burden (ß = .12 [.11, .42]; p &lt; .0001).ConclusionElevated blood pressure variability is related to postmortem cerebrovascular lesion burden, including increased severity of white matter rarefaction, in older adults without clinical dementia, independent of mean blood pressure. Findings are consistent with studies using MRI‐based markers of cerebrovascular disease and may help improve blood pressure as a risk indicator for dementia and cerebrovascular disease.

Community Pharmacy-Based Blood Pressure Screening in Newfoundland and Labrador, Canada for World Hypertension Day 2022: A Cross-Sectional Study

BackgroundHigh blood pressure (BP) is a leading cause of cardiovascular and stroke-related events. Office-based BP measurement has declined in recent years due to the COVID-19 pandemic, which may have resulted in higher rates of undetected and uncontrolled hypertension. To gain a better idea of adult BP levels in Newfoundland and Labrador, we engaged community pharmacists in BP screening on World Hypertension Day. MethodsData collection and BP screening occurred on May 17, 2022. Pharmacists and pharmacy students collected 3 seated BP readings from participants, using an automated device. The average of readings 2 and 3 was used to estimate BP, with elevated BP defined as ≥ 140/90 mm Hg, or ≥ 130/80 mm Hg for individuals with diabetes. Data on participant demographics, access to primary care, medical history, and antihypertensive use were also collected. Data analysis included descriptive statistics and logistic regression techniques. ResultsA total of 460 participants were included in the analysis. The mean age was 56.3 years (standard deviation: 16.95); 63.3% (n = 291) were female; and 43.7% (n = 201) reported having hypertension. Elevated BP was identified in 27% (n = 123). Of those with elevated BP, 41.5% (n = 51) had no history of diagnosed hypertension. Age, sex, and diabetes were statistically significant predictors of elevated BP in the multivariable model. ConclusionsA large proportion of participants in our study had elevated BP. Targeted measures are needed to improve the detection, treatment, and control of high BP in Newfoundland and Labrador. Community pharmacists can support BP care.

Visit‐to‐visit blood pressure variability and medial temporal perfusion in APOE e4 homozygotes

AbstractBackgroundBlood pressure variability (BPV), independent of traditionally studied/targeted average blood pressure levels, is an emerging risk factor for cognitive impairment and Alzheimer’s dementia, possibly through links with cerebrovascular disease. Recent studies suggest vulnerability of the medial temporal lobes to tau accumulation and atrophy among individuals with elevated BPV, especially older APOE e4 carriers. Increased BPV has also been linked with lower cerebral blood flow (CBF) and perfusion decline in medial temporal regions, but it remains unclear how BPV and APOE e4 may interact to influence CBF. The aim of the current study was to determine whether the relationship between BPV and medial temporal lobe CBF varies by APOE e4 dose in older adults without dementia.Method105 older adults without dementia from the Alzheimer’s Disease Neuroimaging Initiative underwent 3‐4 blood pressure measurements between study baseline and 12‐months follow‐up and arterial spin labeling (ASL)‐MRI at 12‐months follow‐up or later (range: 0 – 84 months). Visit‐to‐visit BPV was calculated as variability independent of mean. CBF was determined for medial temporal regions (residualized by precentral [reference region] CBF), including hippocampus, parahippocampal gyrus, and entorhinal cortex. Venipuncture determined APOE e4 allele count (0 alleles: n = 71; 1 allele: n = 28; 2 alleles: n = 6). Multiple linear regression examined the interaction of BPV x APOE e4 dose on medial temporal CBF, controlling for age, sex, race/ethnicity, antihypertensive use, mean blood pressure, and cerebral metabolism (FDG‐PET).ResultElevated BPV was associated with lower CBF in entorhinal cortex (ß = ‐.96 [‐1.62, ‐.31]; p = .005) and parahippocampal gyrus (ß = ‐.63 [‐1.26, ‐.0002]; p = .049) in individuals with 2 APOE e4 alleles, whereas BPV was not significantly associated with CBF in these regions in individuals with 0 or 1 APOE e4 alleles (p’s &gt; = .08). There was no significant interaction of BPV x APOE e4 dose on hippocampal CBF.ConclusionHigher BPV is associated with lower medial temporal CBF in APOE e4/e4 carriers, suggesting BPV may be an understudied vascular risk factor for those at greatest genetic risk for Alzheimer’s disease, with potential therapeutic implications.

Long-term risk-factor control and secondary prevention are insufficient after first TIA: Results from QregPV.

Long-term risk-factor control and secondary prevention are not well characterized in patients with a first transient ischemic attack (TIA). With baseline levels as reference, we compared primary-care data on blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), smoking, and use of antihypertensives, statins and antiplatelet treatment/oral anticoagulation (APT/OAC) during 5 years after a first TIA. Patients in QregPV, a Swedish primary-care register for the Region of Västra Götaland, with a first TIA discharge diagnosis from wards proficient in stroke care 2010 to 2012 were identified and followed up to 5 years. BP, LDL-C, smoking, use of antihypertensives, statins, APT/OAC, and achievement of target levels were calculated. We used logistic mixed-effect models to analyze the effect of follow-up over time on risk-factor control and secondary prevention treatment. We identified 942 patients without prior cerebrovascular disease who had a first TIA. Compared to baseline, the first year of follow-up was associated with improvements in concomitant attainment of BP <140/90 mmHg, LDL-C < 2.6 mmol/L and non-smoking, which rose from 20% to 33% (OR 2.08, 95% CI 1.38-3.13), but then stagnated in years 2-5. In the first year of follow-up, 47% of patients had complete secondary prevention treatment (antihypertensives, APT/OAC and statin), but continued follow-up was associated with a yearly decrease in secondary prevention treatment (OR 0.94, 95% CI 0.94-0.98). Risk-factor control was inadequate, leaving considerable potential for improved secondary prevention treatment after a first TIA in Swedish patients followed up to 5 years.

Endocan as a Potential Marker for Predicting All-Cause Mortality in Hemodialysis Patients

Endocan, a pro-inflammatory cytokine and pro-angiogenic factor, is a marker of endothelial dysfunction and has been proven to correlate with cardiovascular disease. In hemodialysis (HD) patients, cardiovascular disease is the major cause of mortality. Our study aimed to investigate the relationship between serum endocan and all causes of mortality in HD patients. A total of 103 patients, aged over 20 years old and undergoing HD for more than 3 months, were included and followed for 36 months. Mortality events, serum endocan, biochemical data, body mass index, systolic and diastolic blood pressure, baseline characteristics, and the use of antihypertensive and lipid-lowering drugs were recorded. In our study, a total of 26 deaths (25.2%) occurred. Hemodialysis patients with diabetes mellitus, older age, higher serum endocan, and lower creatinine and albumin levels had a higher risk of mortality. Adjusting for prognostic variables, HD patients with higher serum endocan (p = 0.010) and lower serum creatinine (p = 0.034) demonstrated significantly higher all-cause mortality. In our study, increased endocan and lower creatinine are associated with all-cause mortality in HD patients. Serum endocan levels could serve as a biomarker for a high mortality risk in HD patients.

Factors for achieving target serum uric acid levels after initiating urate-lowering therapy in patients with gout: results from the ULTRA registry

Achieving target serum uric acid (SUA) levels is important in gout management. Guidelines recommend lowering SUA levels to < 6 mg/dL; however, many patients fail to reach this target, even with uric acid-lowering therapy (ULT). This study investigated clinical characteristics of target SUA achievers among Korean patients with gout. This study used data from the ULTRA registry, a nationwide inception cohort established in September 2021 that enrolls patients with gout who initiate ULT. Demographic, clinical, and laboratory data were collected at baseline; the 6-month follow-up. Patients were divided into two groups: target achievers (SUA level < 6 mg/dL at 6 months) and non-achievers. The mean participant (N = 117) age was 56.1 years, and 88.0% were male. At 6 months, 83 patients (70.9%) reached target SUA levels. Target achievers had better drug adherence (≥ 80%) to ULT (97.6% vs. 76.5%; p < 0.01) than non-achievers. Target non-achievers had a higher percentage of a family history of gout (32.4% vs. 10.8%; p < 0.01) and less antihypertensive agent use (38.2% vs. 59.0%; p = 0.03) than target achievers. Multivariate regression analysis revealed that good adherence to ULT, the absence of a family history of gout, and antihypertensive agent use were key factors associated with achieving target SUA levels at 6 months.

Trends of Antihypertensive, Antidiabetic, and Nonsteroidal Anti-Inflammatory Drugs Use among the Health Workers Cohort Study, Mexico 2004 to 2018.

Hypertension and type 2 diabetes (T2D) are the most prevalent noncommunicable diseases in Mexico and worldwide. According to international practice management guidelines, the principal chronic management therapy is daily oral medication. We aim to describe the trends of antihypertensive, antidiabetic, and nonsteroidal anti-inflammatory (NSAID) drugs use among the Mexican adult population from 2004-2018. We analyzed data from the Health Workers Cohort Study (HWCS) for males and females aged >18 years. We calculated the prevalence of chronic diseases and utilization for every kind of antihypertensive, antidiabetic, and NSAIDs (measured by self-reported utilization) at baseline and two follow-ups (2004, 2010, and 2017). Trends were analyzed using Fisher's exact test. Hypertension prevalence increased from 19.8 to 30.3%, higher than T2D prevalence from 7.0 to 12.8% through fourteen years of follow-up. Like the self-reported dual therapy, the proportion of patients using beta-blockers and angiotensin II receptor blockers increased. Regarding T2D, the prevalence of metformin utilization increased to 83.9%. The utilization of common NSAIDs, mainly for muscular pain, remained around 13 to 16%. Our findings showed a changing prevalence of drug utilization for hypertension and T2D between 2004 and 2018 and consistent use of NSAIDs in the adult Mexican population.

The 18-year risk of cancer, angioedema, insomnia, depression, and erectile dysfunction in association with antihypertensive drugs: post-trial analyses from ALLHAT-Medicare linked data.

This study aimed to determine the 18-year risk of cancer, angioedema, insomnia, depression, and erectile dysfunction in association with antihypertensive drug use. This is a post-trial passive follow-up study of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants between 1994 and 1998 that was conducted by linking their follow-up data with Medicare claims data until 2017 of subjects who were free of outcomes at baseline on 1 January 1999. The main outcomes were the occurrence of cancer (among n = 17,332), angioedema (among n = 17,340), insomnia (among n = 17,340), depression (among n = 17,330), and erectile dysfunction (among n = 7,444 men) over 18 years of follow-up. The 18-year cumulative incidence rate of cancer other than non-melanoma skin cancer from Medicare inpatient claims was 23.9% for chlorthalidone, 23.4% for amlodipine, and 25.3% for lisinopril. There were no statistically significant differences in the 18-year risk of cancer, depression, and erectile dysfunction among the three drugs based on the adjusted hazard ratios. The adjusted 18-year risk of angioedema was elevated in those receiving lisinopril than in those receiving amlodipine (hazard ratio: 1.63, 95% CI: 1.14-2.33) or in those receiving chlorthalidone (1.33, 1.00-1.79), whereas the adjusted 18-year risk of insomnia was statistically significantly decreased in those receiving lisinopril than in those receiving amlodipine (0.90, 0.81-1.00). The 18-year risk of angioedema was significantly higher in patients receiving lisinopril than in those receiving amlodipine or chlorthalidone; the risk of insomnia was significantly lower in patients receiving lisinopril than in those receiving amlodipine; and the risk of cancer, depression, and erectile dysfunction (in men) was not statistically significantly different among the three drug groups.

A Rationality Study of Antihypertensive Drugs Usage in Preeclampsia Patients in the Private Hospital

Preeclampsia is a hypertension that happens in pregnancy of ≥ 20 weeks and occurs with proteinuria. Preeclampsia is also the highest cause of mother’s death second place in Indonesia. According to that, a study of rationality is needed concerning medicine usage as one of the efforts to determine which medicine is accepted by the rational patient so that the expected therapeutic effect is achieved and does not harm the lives of the mother and baby. The purpose of this research is to determine the profile and rationality of anti-hypertension medicine usage on pregnant mothers with preeclampsia at a private hospital in Malang. This is an observational descriptive research that uses retrospective data. The sample-taking method of this research is using a total sampling method. This research data is served on a diagram or table and percentage. The result of this research is that 3 kinds of anti-hypertension medicine are used: nifedipine 78%, amlodipine 17%, and candesartan 5%. The rationality study of the use of antihypertensive drugs in this study obtained 78% correct indication, 100% correct drug, 93% correct dose, 62% correct interval of administration, and 100% correct patient. This study shows that the usage of antihypertensive drugs in preeclampsia is rational in several parameters.

Is the association between blood pressure and cognition in the oldest-old modified by physical, vascular or brain pathology markers? The EMIF-AD 90 + Study

BackgroundPrior studies suggest a changing association between blood pressure (BP) and cognition with aging, however work in the oldest-old has yielded ambiguous results. Potentially, these mixed results can be explained by modifying factors. The aim of this study was to establish whether physical, vascular or brain pathology markers that describe a state of increased vulnerability, affect the association between BP and cognition in the oldest-old. Results may influence clinicians’ decisions regarding the use of antihypertensives in this age group.MethodsWe included 122 individuals (84 without cognitive impairment and 38 with cognitive impairment) from the EMIF-AD 90 + Study (mean age 92.4 years). First, we tested cross-sectional associations of systolic and diastolic BP with a cognitive composite score. Second, we tested whether these associations were modified by physical markers (waist circumference, muscle mass, gait speed and handgrip strength), vascular markers (history of cardiac disease, carotid intima media thickness as a proxy for atherosclerosis and carotid distensibility coefficient as a proxy for arterial stiffness) or brain pathology markers (white matter hyperintensities and cortical thickness).ResultsIn the total sample, there was no association between BP and cognition, however, waist circumference modified this association (p-value for interaction with systolic BP: 0.03, with diastolic BP: 0.01). In individuals with a high waist circumference, higher systolic and diastolic BP tended to be associated with worse cognition, while in individuals with a low waist circumference, higher systolic BP was associated with better cognition. The others physical, vascular and brain pathology markers did not modify the association between BP and cognition.ConclusionsWhen examining various markers for physical, vascular and brain vulnerability, only waist circumference affected the association between BP and cognition. This warrants further research to evaluate whether waist circumference may be a marker in clinical practice influencing the use of antihypertensives in the oldest-old.

Development and Validation of the American Heart Association's PREVENT Equations.

Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equations among US adults 30 to 79 years of age without known CVD. The derivation sample included individual-level participant data from 25 data sets (N=3 281 919) between 1992 and 2017. The primary outcome was CVD (atherosclerotic CVD and heart failure). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, antihypertensive or statin use, and diabetes) and estimated glomerular filtration rate. Models were sex-specific, race-free, developed on the age scale, and adjusted for competing risk of non-CVD death. Analyses were conducted in each data set and meta-analyzed. Discrimination was assessed using the Harrell C-statistic. Calibration was calculated as the slope of the observed versus predicted risk by decile. Additional equations to predict each CVD subtype (atherosclerotic CVD and heart failure) and include optional predictors (urine albumin-to-creatinine ratio and hemoglobin A1c), and social deprivation index were also developed. External validation was performed in 3 330 085 participants from 21 additional data sets. Among 6 612 004 adults included, mean±SD age was 53±12 years, and 56% were women. Over a mean±SD follow-up of 4.8±3.1 years, there were 211 515 incident total CVD events. The median C-statistics in external validation for CVD were 0.794 (interquartile interval, 0.763-0.809) in female and 0.757 (0.727-0.778) in male participants. The calibration slopes were 1.03 (interquartile interval, 0.81-1.16) and 0.94 (0.81-1.13) among female and male participants, respectively. Similar estimates for discrimination and calibration were observed for atherosclerotic CVD- and heart failure-specific models. The improvement in discrimination was small but statistically significant when urine albumin-to-creatinine ratio, hemoglobin A1c, and social deprivation index were added together to the base model to total CVD (ΔC-statistic [interquartile interval] 0.004 [0.004-0.005] and 0.005 [0.004-0.007] among female and male participants, respectively). Calibration improved significantly when the urine albumin-to-creatinine ratio was added to the base model among those with marked albuminuria (>300 mg/g; 1.05 [0.84-1.20] versus 1.39 [1.14-1.65]; P=0.01). PREVENT equations accurately and precisely predicted risk for incident CVD and CVD subtypes in a large, diverse, and contemporary sample of US adults by using routinely available clinical variables.

Temporal trends of first time antihypertensive treatment among citizens over 75 years - a register-based, cohort study

Abstract Background Hypertension is highly prevalent, particularly among the increasingly large elderly population. There is a need for investigating the use of antihypertensive drugs in elderly patients. Data on clinicians’ first drug of choice, effectiveness, and magnitude of use are sparse, partly due to older patients often being excluded from clinical trials which in turn limits knowledge about their cardiovascular drug safety. Furthermore, drug metabolism and pharmacokinetics are known to differ with increasing age. Purpose To investigate temporal trends for first-line drug choice for first time antihypertensive treatment among elderly patients over 75 years from 2000-2021. Methods Using nationwide registers, we identified all patients over 75 years initiated on either beta blockers (BB), calcium channel blockers (CCB), renin-angiotensin system inhibitors (RASi), thiazides, or a combination between 2000-2021. Patients treated earlier in life with any antihypertensive drug were excluded, as were patients with atrial fibrillation, heart failure, chronic kidney disease, and acute coronary syndrome. Patients were included on the date of their first claimed prescription and temporal trends were reported as proportions per calendar year. We described adherence, change or discontinuation of antihypertensive medication using additionally claimed prescriptions during the first 180 days following study entry. Only patients alive 180 days after initial inclusion contributed to the latter analysis. Results A total of 187,309 patients (median age 80 years [interquartile range (IQR) :77-84], 59.1% female) were eligible for inclusion. The first drug of choice for antihypertensive treatment in patients above 75 years of age has changed markedly between 2000 (BB 12.7%, CCB 22.3%, RASi 11.6%, thiazides 61.3%, and combinations 2.6%) and 2021 (BB 12.9% CCB 28.2%, RASi 48.2%, thiazides 8.0%, and combinations 2.7%), especially for RASi and thiazides (Figure 1). Following the first 180 days, 172,756 patients (median age 80 [IQR:77:84], 59.3% female) were still alive and eligible. Adherence, discontinuation, and shift varied according to first drug of choice. Discontinuation within 180 days was highest among patients initiated on thiazides 19,544 (28.4%) whereas most patients continued the same 1-drug regimen if they started on RASi (64.6%), BB (57.8%), and CCB (59.5%). The highest proportion who had a second drug added within 180 days were patients initiated on CCB (21.1%) and RASi (21.1%) (Figure 2). Conclusion Elderly patients initiated on antihypertensive medication for the first time after the age of 75 is a substantial patient group, and from 2000–2021 a preference for thiazides has largely been replaced by RASi and CCB. It seemed that patients initiated on thiazides were more likely to discontinue or shift shortly afterwards. Further evaluation of thiazides as an equal first drug of choice for hypertension in the elderly could be warranted.

High-normal systolic blood pressure in early midlife is a stronger risk factor for incident hypertension later in life for women than men

Abstract Background We have previously found that having high-normal blood pressure (BP) in early midlife is a stronger risk factor for incident hypertension later in life for women than for men. Whether this risk is related both to high-normal systolic and diastolic BP is not known. Purpose To explore whether there is a sex difference in risk of incident hypertension related to high-normal systolic and diastolic BP in early midlife. Methods In the community-based Hordaland Health Study, 1025 women and 703 men were examined at age 42 years (baseline) and re-examined after 26 years. Patients with hypertension at baseline were excluded. Attended BP was measured in triplets, and clinic BP taken as the average of the two last measurements. High-normal systolic BP was identified as systolic BP of 130-139 mmHg and high normal diastolic BP as diastolic BP 85-89 mmHg. Incident hypertension was identified as BP ≥140/90 mmHg or patient reported use of antihypertensive drugs on the follow-up visit. The associations of systolic and diastolic BP at baseline with incident hypertension at follow-up were explored in sex specific multivariable logistic regression analyses. Multivariable analysis looking at high-normal diastolic BP was adjusted for baseline BMI, systolic BP, high-normal diastolic BP , heart rate, physical activity, daily smoker, cholesterol, triglycerides. Multivariable analysis looking at high-normal systolic BP was adjusted for baseline BMI, diastolic BP, high normal systolic BP , heart rate, physical activity, daily smoker, cholesterol, triglyceride. Results are presented as odds ratios (OR), 95% confidence intervals (CI) and p-values. Results At baseline, average BP was 119/73 mmHg in women and 126/76 mmHg in men (p&amp;lt;0.001). A high-normal systolic BP was found in 16% of women and 35% of men (p&amp;lt; 0.001). A high-normal diastolic BP was found in 7% of women and 11% of men(p=0.008). After 26 years of follow-up, 39% of women and 45% of men had developed hypertension (p&amp;lt;0.05). In multivariable logistic regression analyses, high-normal systolic and diastolic BP at baseline predicted incident hypertension at follow up in both sexes (Table 1). High-normal systolic BP was a significantly stronger predictor for incident hypertension in women (OR 2.32, CI 1.5-3.5) with p&amp;lt;0.01 for sex interaction (Table 1). In men, high-normal diastolic BP at baseline, was the strongest predictor of incident hypertension (OR 2.1, 95% CI 1.2-3.7), but no sex-interaction was found for high-normal diastolic BP, possibly due to low numbers. Conclusions Having a high-normal systolic BP in early midlife is a greater risk for developing hypertension later in life for women than men.Table 1

Mendelian randomization study of the relevance of blood pressure to vascular mortality among 150,000 participants in the mexico city prospective study

Abstract Background Mendelian randomization (MR) studies are commonly used to reduce confounding and reverse-causality when estimating the effects of risk factors on disease and provide estimates of effects over the whole life-course. However, most previous MR studies have been conducted in populations of European-ancestry. We used MR to investigate the effect of systolic blood pressure (SBP) on vascular mortality at ages 35-74 in a large prospective study of Mexican adults. Methods Between 1998 and 2004, 150,000 adults aged ≥35 years were recruited into the Mexico City Prospective Study and followed for median 19 years(1,2). Using 886 externally-selected single nucleotide polymorphisms (SNPs)(3) we created a genetic risk score for SBP (GRS-SBP). Those taking an antihypertensive drug at recruitment had their SBP adjusted by +6 mmHg(2) (adjustment by +15 mmHg rather than +6 mmHg was done in a sensitivity analysis). Cox regression and the MR ‘ratio’ method were then used to estimate the causal effect of SBP on vascular mortality at ages 35-74 years. Analyses were adjusted for age at risk, sex, residential district, education, smoking, alcohol consumption, physical activity, adiposity, diabetes mellitus and the first 7 genetic principal components. They excluded those aged ≥75 years, had incomplete data, or had prior vascular disease or any other chronic condition (except diabetes). Alternative MR approaches (inverse-variance-weighted, weighted median and MR Egger) were used for sensitivity analyses. Conventional epidemiological analyses of the association between SBP and mortality after correction for regression dilution bias were also done. Results Among 127,849 included individuals, the GRS-SBP explained 1.9% of baseline SBP variation. Those in the top fifth of the GRS-SBP distribution had 6.6 mmHg higher SBP and twice the prevalence of self-reported hypertension and antihypertensive drug use than those in the bottom fifth, but the GRS-SBP was uncorrelated with other factors. The strength of association between GRS-SBP and measured SBP was broadly similar in men and women, at different ages, and between people with different proportions of Amerindian genetic ancestry. Using the ratio method and a single estimate of the association of GRS-SBP with SBP, each 10 mmHg higher genetically predicted SBP was associated with 58% higher vascular mortality at ages 35-74 years (RR 1.58, 95% CI 1.27-1.96), including 69% higher ischaemic heart disease mortality (RR 1.69, 95% CI 1.31-2.16) and 65% higher stroke mortality (RR 1.65, 1.15-2.33). These genetic estimates were somewhat larger than conventional observational associations of usual SBP to risk. Alternative MR approaches found no evidence of pleiotropy and yielded similar conclusions. Conclusions These MR analyses confirm that blood pressure is a major cause of premature death from vascular diseases in Mexican adults.

RAAS inhibitors in patients undergoing transcatheter aortic valve implantation: insights from the EffecTAVI registry

Abstract Background Aortic Stenosis (AS) is the most common heart disease in western countries, with a prevalence that is increasing in tandem with life expectancy. Renin-angiotensin-aldosterone system (RAAS) activation participates to myocardial fibrosis and worse clinical consequences. Purpose The association between baseline treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and cardiovascular (CV) mortality was evaluated in hypertensive patients with severe AS undergoing transcatheter aortic valve implantation (TAVI). Methods We retrospectively examined hypertensive patients with AS who had undergone TAVI at 2-year follow-up. Univariable and multivariable Cox regression models were built according to baseline RAAS inhibitors (RAASi) therapy status and a second analysis was undertaken by categorizing patients in ARBs (n= 110), ACEi (n= 112) and other antihypertensive meds (n= 105). As a sensitivity analysis, survival-time data were converted to case-control data in order to conduct a case–control study nested in the observational study. Results The present analysis included 327 hypertensive patients with severe AS undergoing TAVI. During the 2-year follow-up 43 patients died for CV death. In univariable Cox regression, the rate of the 2-year CV mortality was significantly lower in patients taking RAASi at baseline (HR=0.44, 95% CI 0.23-0.81 p=0.009), however after multivariable adjustment for significant confounders baseline treatment with RAASi was no more significant. Patients were then grouped based on ARBs/ACEIs/other antihypertensive therapy (Figure 1). In the univariate regression analysis ARBs therapy was associated with 65% reduction in CV mortality (HR=0.35, 95% CI 0.15-0.78 p=0.011) significantly lower than other anti-hypertensive meds (figure 1). The results were confirmed in multivariate analysis adjusted for significant confounders (HR=0.34, 95% CI 0.14-0.85 p=0.021). To reduce the risk of bias and better evaluate the stability of the results, a case–control study nested in the observational study was performed. Based on preliminary analysis, patients exposed to ARBs were selected as the case group, those not exposed as the control group, matching controls and cases in a 1:1 manner and balancing for sex, chronic kidney disease, atrial fibrillation and type 2 diabetes mellitus. Multivariable logistic regression analyses were conducted to determine the possible risk factors for CV mortality. After adjusting for the effect of significant confounders, the use of ARBs was found to be associated with a significant reduced risk of CV mortality (OR 0.30, 95% CI 0.11 – 0.82, p=0.019) (Figure 2). Conclusion In patients with severe AS undergoing TAVI, baseline treatment with ARBs was associated with reduced risk of CV mortality over 2 years of follow-up compared to the use of other antihypertensive drugs. The results were also confirmed by the nested, balanced, case-control analysis.KM curves grouped for ACEI/ARBs/otherAdjusted odds-ratio in the nested case-c

Demonstrating the Benefits of Antihypertensive Nighttime Dosing and Indapamide Usage in Hypertension Management.

Background: Uncontrolled hypertension, specifically nocturnal hypertension, increases the risk for significant clinical outcomes. Evidence on the use of nighttime antihypertensives is scant and conflicting. In addition, hydrochlorothiazide continues to be the primary thiazide used despite being the least potent. Objective: The primary purpose of this study was to evaluate instituting nighttime dosing to control hypertension and compare the short-term effectiveness of blood pressure control with indapamide versus hydrochlorothiazide. Methods: This was a retrospective, observational study. Participant inclusion criteria consisted of patients 18 years of age or older, a current diagnosis of hypertension, and hypertension that required medical therapy. The investigator documented whether a patient was taking at least one antihypertensive at night versus all morning medications, as well as the use of indapamide versus hydrochlorothiazide. The patient's baseline and first follow-up blood pressure readings were documented. The primary outcome was to determine whether including nighttime dosing in antihypertensive regimens is more effective than all morning antihypertensive regimens. The secondary outcome was to determine whether indapamide was more effective than hydrochlorothiazide. Results: A total of 64 patients were included in the study. Twenty-eight patients were taking >1 nighttime antihypertensives versus 32 patients on all morning medications. Patients on at least one nighttime medication demonstrated greater systolic blood pressure reduction. There was no difference in blood pressure reduction between indapamide and hydrochlorothiazide. Conclusion: The study findings support the use of nighttime dosing to improve blood pressure management. The results on the effectiveness of indapamide versus hydrochlorothiazide conflict with previous research.