Issue 30.10 focus on arterial hypertension

Arterial hypertension is a major cardiovascular risk factor,1 still poorly under control in clinical practice.2 The present issue of the Journal is dedicated to a number of issues related to hypertension, ranging from hypertension epidemiology to its impact on risk stratification and to strategies for its control. Elevated systolic blood pressure (HSBP) has a greater impact on the risk of cardiovascular events than diastolic blood pressure. The main feature of hypertension in the elderly population is a significant increase in systolic blood pressure. However, despite the implementation of several preventive interventions and the usage of antihypertensive medications, the current management for HSBP is still unsatisfactory. Based on the 2019 Global Burden of Disease (GBD) data, this study analysed the current disease burden caused by HSBP in the elderly population and the trends over the past 30 year.3 Not surprisingly, the death rates caused by HSBP decreased in older adults from 1990 to 2019, while the number of deaths increased by more than half. Significant sex and regional discrepancies were also observed. Moreover, the elderly population in the middle/low income region had a heavy burden of HSBP, while it was reduced for the elderly population in the high income region. Limitations of this analysis are definition of HSBP (≥ 110–115 mmHg), and the inclusion of individuals already at the age of 60. More strict criteria would provide more definitive conclusions. Very high levels of high-density lipoprotein cholesterol (HDL-C) have been paradoxically linked to increased mortality risk.4 Here a prospective cohort study, that included 429 792 participants (244 866 with hypertension and 184 926 without) from the UK Biobank, examined the associations of HDL-C and varied sizes of the HDL particle (HDL-P) with mortality risk stratified by hypertension.5 It confirmed that, compared with individuals with normal HDL-C of 50–70 mg/dL, those with very high HDL-C levels (>90 mg/dL) had a significantly higher risk of all-cause mortality among individuals with hypertension (hazard ratio, (HR) 1.47; 95% confidence interval (CI), 1.35–1.61), but not among those without hypertension (HR 1.05, 95% CI 0.91–1.22). In individuals with hypertension, the increased risk at a high HDL-C level was attributed to a larger size of HDL-P, which was directly associated with mortality risk. This support HDL-P as a stronger predictor of cardiovascular mortality, which might better reflect the biological relation between HDL and clinical risks than conventional HDL-C. More research is needed to clarify the mechanisms of such a relation. The hypertension guidelines have lowered the pharmacological intervention threshold for blood pressure (BP) in high-risk patients, such as those with chronic coronary syndromes (CCS), with an optimal BP target of <130/80 mmHg. The European guidelines however advise against lowering BP below the so-called lower safety boundaries (i.e. 120 mmHg for systolic BP and 70 mmHg for diastolic BP), because of an increased risk, especially in patients with CCS, of impaired coronary perfusion. Here a comparison of the benefit associated with strict vs. standard control of BP was performed in CCS. Based on a study population of nearly 20 000 patients from the CLARIFY registry (Prospective Observational Longitudinal Registry of Patients with Stable Coronary Artery Disease) the benefit associated with strict BP control (BP < 130/80 mmHg) was marginal and only driven by the diastolic component, whereas having one or more uncontrolled other risk factors was associated with a gradually increasing risk, for all underlying BP levels.6 Thus, patients with CCS should be treated to achieve BP <140/80 mmHg, but optimizing the burden of other risk factors (lipid-lowering therapy, exercise, smoking cessation, diabetes control) may need to be prioritized before considering further reduction of SBP. Time to target range (TTR) is defined as the percentage of time during which the SBP is within the target range. TTR for BP could incorporate both the degree of BP variability and the mean BP level, which reflect variation over time both within and outside of the target range. Elderly hypertensive patients frequently experience wide BP fluctuations due to episodes of pseudo hypertension, postural hypotension, whitecoat or masked hypertension, and pronounced reactivity to environmental stimuli, which typically manifest as frequently increased SBP and pulse pressure. While there is evidence that short-term BP time in target range (TTR) independently predicts cardiovascular outcomes in adults, there is limited data on the prognostic value of long-term TTR for BP among elderly participants. Here in 943 elderly participants with hypertension aged over 75 years from the Chinese veteran cohort study it was observed that also in elderly patients greater long-term TTR for SBP was associated with a decreased risk of cardiovascular events, independently of mean BP, suggesting that also long-term SBP TTR might serve as a modifiable risk factor for future cardiovascular health in elderly patients with hypertension7 Global hypertension prevalence often appears to be increased in migrants from low and middle-income countries living in Europe and the USA, with prevalence rates exceeding those of the host populations.8 Longitudinal research on ethnic differences in BP levels provides the opportunity to assess the efficacy of strategies aimed at mitigating gaps in hypertension control. Here, the change in BP levels over time in a multi-ethnic population-based cohort in Amsterdam, the Netherlands, was investigated. In a study population of more than 10 000 people, compared with the Dutch population, the mean SBP increased significantly more from baseline to follow-up in Ghanaians (1.78 mmHg), Moroccans (2.06 mmHg), and the Turkish population (1.30 mmHg). However SBP differences were in part explained by differences in body mass index, implying the importance of control of CV risk factors.9 The Systematic Coronary Risk Assessment 2 (SCORE2) algorithm, as derived, calibrated, and validated in 2021, is a state-of-the-art calculator to estimate the 10-year risk of first-onset cardiovascular diseases and is currently used to guide decision-making in the primary prevention. Despite its multiple advantages, SCORE2 has several limitations. For instance, only certain common risk factors are included in risk calculation since other risk factors often are unavailable. This could lead to inaccurate estimation particularly among individuals with other relevant risk factors. Here, the SCORE2 was calculated in 4588 non-diabetic participants aged 46–68 years. The incremental value for predicting cardiovascular events of adding carotid plaque or intima-media thickness (IMT) to SCORE2 was evaluated using C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Adding presence of carotid plaque or IMT to SCORE2 significantly improved performance for predicting CVDs. The improvements in C-statistics, IDI, and NRI of adding carotid plaque to SCORE2 for events occurring during the first 10 years were 2.20%, 0.70%, and 46.1%, respectively (all P < 0.0001). More interestingly, SCORE2 over-predicted the 10-year cardiovascular risk in those without carotid plaque while under-predicted the risk in those with carotid plaque.10 Isolated diastolic hypertension (IDH), defined as SBP < 140 mmHg and diastolic BP ≥90 mmHg, is a relatively common condition, particularly in younger people. Previous studies on cardiovascular outcomes associated with IDH have shown varying results. In a retrospective analysis of the data of 71 297 individuals, it was observed that individuals with DBP <90 mmHg showed a lower risk of composite CVD events [hazard ratio (HR): 0.75, 95% confidence interval (CI): 0.67–0.83] than those with DBP of ≥90 mmHg at 1 year. A reduction in DBP per 5 mmHg during the 1-year follow-up was associated with a lower composite CVD event risk (HR: 0.92, 95% CI: 0.89–0.95). The results remained consistent across a multitude of sensitivity analyses.11 Resistant hypertension, defined as BP above goal despite the use of at least three antihypertensive medications or achieving target BP with four or more medications, has increased in recent years, due in part to reductions in goal BP targets. Numerous non- biological factors, such as medication non-adherence, white coat effect, and submaximal drug dosing, should be excluded prior to diagnosing resistant hypertension. When such conditions cannot be excluded, the term apparent treatment-resistant hypertension (aRH) is utilized, a criterion met by an estimated 12–15% of treated antihypertensive patients. Although it may be seen as a not ominous condition, here retrospective examination of medical records from over 48 000 Finnish individuals found that the risk of future adverse medical events increased with a need for greater number of blood pressure medications in middle age. Using the number of BP medications simultaneously prescribed before age 55, the risk of renal failure, heart failure and stroke increased. Individuals with very difficult to treat high BP (needing at least four medications) had greater risk of nearly all assessed clinical outcomes, including death. Consequently, there is need to start controlling BP early in life to avoid the need of multiple concomitant medications.12 The Strategy of Blood Pressure Intervention in Elderly Hypertensive Patients (STEP) trial was a multicentre, randomized, controlled trial which enrolled 8511 young-older (60–80 years) hypertensive patients without prior stroke to compare the cardiovascular prognosis of the intensive treatment (SBP target, 110 to <130 mmHg) vs. the standard treatment (130 to <150 mmHg) demonstrating the cardiovascular benefit of intensive systolic blood pressure (SBP) control. Two substudies from this trial are here presented. The first one specifically assessed the association between intensive SBP lowering and the risk of new-onset diabetes. In a cohort of 5601 participants (mean age: 66.1 years) free from diabetes with a mean baseline SBP of 145.9 mmHg, reported that intensive SBP lowering (target, 110 to <130 mmHg) was not associated with a different risk of new-onset diabetes or impaired fasting glucose in hypertensive patients. Interesting the mean highest fasting glucose concentration during the follow-up was not different between the intensive and standard groups (5.82 and 5.84 mmol/L respectively) respectively.13 A second paper assessed the association of mean achieved SBP and cardiovascular events: patients achieving a target in the intensive-treatment group have better cardiovascular outcome than patients achieving a target in the standard treatment arm, supporting the cardiovascular benefits of maintaining SBP <130 mmHg. However J-shaped relationships were observed between mean achieved SBP and cardiovascular outcomes (with the nadir around 130 mmHg), but not for stroke, suggesting the presence of severe side effects in the high intensity treated patients.14 Similar findings were observed in a sub-analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). Here, intensive BP treatment reduced the incidence of non-fatal major adverse cardiovascular event (MACE), predominantly due to a lower incidence of heart failure, but was associated with increased incidence of severe adverse events (SAE) driven by a higher incidence of hypotension, syncope, electrolyte abnormalities, and acute kidney injury. A post-hoc analysis of the SPRINT study, in the present issue of the Journal,15 evaluated whether the occurrence of an initial MACE or an SAE mediates the association of intensive BP treatment with mortality. The direct effect of intensive treatment was a lowering of total mortality [odds ratio (OR) 0.75, 95% CI: 0.60–0.94], but the MACE-mediated effect substantially attenuated mortality effect (OR 0.96, 95% CI: 0.92–0.99), while the SAE- mediated effect was associated with increased mortality (OR 1.03, 95% CI: 1.01–1.05). Similar patterns were noted for the effects of intensive BP treatment on cardiovascular and non cardiovascular mortality. SAE incidence was 3.9-fold higher than MACE incidence. The SAE to MACE and mortality preponderance was found across all age groups, with the ≥80-year age group having the highest differences. In conclusion, intensive BP treatment seemed to be associated with an attenuated mortality benefit particularly in more elderly. It has to be emphasized that the conclusions of these studies largely apply to fit elderly and not to frail elderly individuals.