Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people.
The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease.
We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371.
During 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9-63·8) compared with 46·1% (45·5-46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8-5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years.
The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them.
Medical Research Council, National Institute for Health Research, and Wellcome Trust.
Rapsomaniki E
，Timmis A
，George J
，Pujades-Rodriguez M
，Shah AD
，Denaxas S
，White IR
，Caulfield MJ
，Deanfield JE
，Smeeth L
，Williams B
，Hingorani A
，Hemingway H
... -
《-》
Higher blood pressure targets for hypertension in older adults.
This is an update of the original Cochrane review, published in 2017. Eight out of 10 major antihypertensive trials in adults, 65 years of age or older, attempted to achieve a target systolic blood pressure (BP) of < 160 mmHg. Collectively, these trials demonstrated cardiovascular benefit for treatment, compared to no treatment, for older adults with BP > 160 mmHg. However, an even lower BP target of < 140 mmHg is commonly applied to all age groups. Yet the risk and benefit of antihypertensive therapy can be expected to vary across populations, and some observational evidence suggests that older adults who are frail might have better health outcomes with less aggressive BP lowering. Current clinical practice guidelines are inconsistent in target BP recommendations for older adults, with systolic BP targets ranging from < 130 mmHg to < 150 mmHg. The 2017 review did not find compelling evidence of a reduction in any of the primary outcomes, including all-cause mortality, stroke, or total serious cardiovascular adverse events, comparing a lower BP target to a higher BP target in older adults with hypertension. It is important to update this review to explore if new evidence exists to determine whether older adults might do just as well, better, or worse with less aggressive pharmacotherapy for hypertension.
To assess the effects of a less aggressive blood pressure target (in the range of < 150 to 160/95 to 105 mmHg), compared to a conventional or more aggressive BP target (of < 140/90 mmHg or lower) in hypertensive adults, 65 years of age or older.
For this update, Cochrane Hypertension's Information Specialist searched the following databases for randomised controlled trials up to June 2024: Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE Ovid, and Embase Ovid, and the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov for ongoing trials. We also contacted authors of relevant papers requesting information on further published and unpublished work. The searches had no language restrictions.
We included randomised trials of hypertensive older adults (≥ 65 years) that spanned at least one year, and reported the effect on mortality and morbidity of a higher or lower systolic or diastolic BP treatment target. Higher BP targets ranged from systolic BP < 150 to 160 mmHg or diastolic BP < 95 to 105 mmHg; lower BP targets were 140/90 mmHg or lower, measured in an ambulatory, home, or office setting.
Two authors independently screened and selected trials for inclusion, assessed risk of bias and certainty of the evidence, and extracted data. We combined data for dichotomous outcomes using the risk ratio (RR) with 95% confidence interval (CI). For continuous outcomes, we used mean difference (MD). Primary outcomes were all-cause mortality, stroke, institutionalisation, and serious cardio-renal vascular adverse events. Secondary outcomes included cardiovascular mortality, non-cardiovascular mortality, unplanned hospitalisation, each component of cardiovascular serious adverse events separately (including cerebrovascular disease, cardiac disease, vascular disease, and renal failure), total serious adverse events, total minor adverse events, withdrawals due to adverse effects, systolic BP achieved, and diastolic BP achieved.
With the addition of one new trial, we included four trials in this updated review (16,732 older adults with a mean age of 70.3 years). Of these, one trial used a combined systolic and diastolic BP target and compared a higher target of < 150/90 mmHg to a lower target of < 140/90 mmHg, and two trials utilised a purely systolic BP target, and compared a systolic BP < 150 mmHg (1 trial) and a systolic BP < 160 mmHg (1 trial), to a systolic BP < 140 mmHg. The fourth and newest trial also utilised a systolic BP target, but also introduced a lower limit for systolic BP. It compared systolic BP in the target range of 130 to 150 mmHg to a lower target range of 110 to 130 mmHg. The evidence shows that treatment to the lower BP target over two to four years may result in little to no difference in all-cause mortality (RR 1.14, 95% CI 0.95 to 1.37; 4 studies, 16,732 participants; low-certainty evidence), but the lower BP target does reduce stroke (RR 1.33, 95% CI 1.06 to 1.67; 4 studies, 16,732 participants; high-certainty evidence), and likely reduces total serious cardiovascular adverse events (RR 1.25, 95% CI 1.09 to 1.45; 4 studies, 16,732 participants; moderate-certainty evidence). Adverse effects were not available from all trials, but the lower BP target likely does not increase withdrawals due to adverse effects (RR 0.99, 95% CI 0.74 to 1.33; 3 studies, 16,008 participants; moderate-certainty evidence).
When comparing a higher BP target, in the range of < 150 to 160/95 to 105 mmHg, to a lower BP target of 140/90 or lower, over two to four years of follow-up, there is high-certainty evidence that the lower BP target reduces stroke, and moderate-certainty evidence that the lower BP target likely reduces serious cardiovascular events. The effect on all-cause mortality is unclear (low-certainty evidence), and the lower BP target likely does not increase withdrawals due to adverse effects (moderate-certainty evidence). Although additional research is warranted in those who are 80 years of age and older, and those who are frail (in whom risks and benefits may differ), conventional BP targets may be appropriate for the majority of older adults.
Falk JM
，Froentjes L
，Kirkwood JE
，Heran BS
，Kolber MR
，Allan GM
，Korownyk CS
，Garrison SR
... -
《Cochrane Database of Systematic Reviews》
Impact of residual disease as a prognostic factor for survival in women with advanced epithelial ovarian cancer after primary surgery.
Ovarian cancer is the seventh most common cancer among women and a leading cause of death from gynaecological malignancies. Epithelial ovarian cancer is the most common type, accounting for around 90% of all ovarian cancers. This specific type of ovarian cancer starts in the surface layer covering the ovary or lining of the fallopian tube. Surgery is performed either before chemotherapy (upfront or primary debulking surgery (PDS)) or in the middle of a course of treatment with chemotherapy (neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS)), with the aim of removing all visible tumour and achieving no macroscopic residual disease (NMRD). The aim of this review is to investigate the prognostic impact of size of residual disease nodules (RD) in women who received upfront or interval cytoreductive surgery for advanced (stage III and IV) epithelial ovarian cancer (EOC).
To assess the prognostic impact of residual disease after primary surgery on survival outcomes for advanced (stage III and IV) epithelial ovarian cancer. In separate analyses, primary surgery included both upfront primary debulking surgery (PDS) followed by adjuvant chemotherapy and neoadjuvant chemotherapy followed by interval debulking surgery (IDS). Each residual disease threshold is considered as a separate prognostic factor.
We searched CENTRAL (2021, Issue 8), MEDLINE via Ovid (to 30 August 2021) and Embase via Ovid (to 30 August 2021).
We included survival data from studies of at least 100 women with advanced EOC after primary surgery. Residual disease was assessed as a prognostic factor in multivariate prognostic models. We excluded studies that reported fewer than 100 women, women with concurrent malignancies or studies that only reported unadjusted results. Women were included into two distinct groups: those who received PDS followed by platinum-based chemotherapy and those who received IDS, analysed separately. We included studies that reported all RD thresholds after surgery, but the main thresholds of interest were microscopic RD (labelled NMRD), RD 0.1 cm to 1 cm (small-volume residual disease (SVRD)) and RD > 1 cm (large-volume residual disease (LVRD)).
Two review authors independently abstracted data and assessed risk of bias. Where possible, we synthesised the data in meta-analysis. To assess the adequacy of adjustment factors used in multivariate Cox models, we used the 'adjustment for other prognostic factors' and 'statistical analysis and reporting' domains of the quality in prognosis studies (QUIPS) tool. We also made judgements about the certainty of the evidence for each outcome in the main comparisons, using GRADE. We examined differences between FIGO stages III and IV for different thresholds of RD after primary surgery. We considered factors such as age, grade, length of follow-up, type and experience of surgeon, and type of surgery in the interpretation of any heterogeneity. We also performed sensitivity analyses that distinguished between studies that included NMRD in RD categories of < 1 cm and those that did not. This was applicable to comparisons involving RD < 1 cm with the exception of RD < 1 cm versus NMRD. We evaluated women undergoing PDS and IDS in separate analyses.
We found 46 studies reporting multivariate prognostic analyses, including RD as a prognostic factor, which met our inclusion criteria: 22,376 women who underwent PDS and 3697 who underwent IDS, all with varying levels of RD. While we identified a range of different RD thresholds, we mainly report on comparisons that are the focus of a key area of clinical uncertainty (involving NMRD, SVRD and LVRD). The comparison involving any visible disease (RD > 0 cm) and NMRD was also important. SVRD versus NMRD in a PDS setting In PDS studies, most showed an increased risk of death in all RD groups when those with macroscopic RD (MRD) were compared to NMRD. Women who had SVRD after PDS had more than twice the risk of death compared to women with NMRD (hazard ratio (HR) 2.03, 95% confidence interval (CI) 1.80 to 2.29; I2 = 50%; 17 studies; 9404 participants; moderate-certainty). The analysis of progression-free survival found that women who had SVRD after PDS had nearly twice the risk of death compared to women with NMRD (HR 1.88, 95% CI 1.63 to 2.16; I2 = 63%; 10 studies; 6596 participants; moderate-certainty). LVRD versus SVRD in a PDS setting When we compared LVRD versus SVRD following surgery, the estimates were attenuated compared to NMRD comparisons. All analyses showed an overall survival benefit in women who had RD < 1 cm after surgery (HR 1.22, 95% CI 1.13 to 1.32; I2 = 0%; 5 studies; 6000 participants; moderate-certainty). The results were robust to analyses of progression-free survival. SVRD and LVRD versus NMRD in an IDS setting The one study that defined the categories as NMRD, SVRD and LVRD showed that women who had SVRD and LVRD after IDS had more than twice the risk of death compared to women who had NMRD (HR 2.09, 95% CI 1.20 to 3.66; 310 participants; I2 = 56%, and HR 2.23, 95% CI 1.49 to 3.34; 343 participants; I2 = 35%; very low-certainty, for SVRD versus NMRD and LVRD versus NMRD, respectively). LVRD versus SVRD + NMRD in an IDS setting Meta-analysis found that women who had LVRD had a greater risk of death and disease progression compared to women who had either SVRD or NMRD (HR 1.60, 95% CI 1.21 to 2.11; 6 studies; 1572 participants; I2 = 58% for overall survival and HR 1.76, 95% CI 1.23 to 2.52; 1145 participants; I2 = 60% for progression-free survival; very low-certainty). However, this result is biased as in all but one study it was not possible to distinguish NMRD within the < 1 cm thresholds. Only one study separated NMRD from SVRD; all others included NMRD in the SVRD group, which may create bias when comparing with LVRD, making interpretation challenging. MRD versus NMRD in an IDS setting Women who had any amount of MRD after IDS had more than twice the risk of death compared to women with NMRD (HR 2.11, 95% CI 1.35 to 3.29, I2 = 81%; 906 participants; very low-certainty).
In a PDS setting, there is moderate-certainty evidence that the amount of RD after primary surgery is a prognostic factor for overall and progression-free survival in women with advanced ovarian cancer. We separated our analysis into three distinct categories for the survival outcome including NMRD, SVRD and LVRD. After IDS, there may be only two categories required, although this is based on very low-certainty evidence, as all but one study included NMRD in the SVRD category. The one study that separated NMRD from SVRD showed no improved survival outcome in the SVRD category, compared to LVRD. Further low-certainty evidence also supported restricting to two categories, where women who had any amount of MRD after IDS had a significantly greater risk of death compared to women with NMRD. Therefore, the evidence presented in this review cannot conclude that using three categories applies in an IDS setting (very low-certainty evidence), as was supported for PDS (which has convincing moderate-certainty evidence).
Bryant A
，Hiu S
，Kunonga PT
，Gajjar K
，Craig D
，Vale L
，Winter-Roach BA
，Elattar A
，Naik R
... -
《Cochrane Database of Systematic Reviews》
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