Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis

Nazarzadeh, Milad; Bidel, Zeinab; Canoy, Dexter; Copland, Emma; Bennett, Derrick; Dehghan, Abbas; Smith, George Davey; Holman, Rury R.; Woodward, Mark; Gupta, Ajay; Adler, Amanda I; Wamil, Małgorzata; Sattar, Naveed; Cushman, William C.; McManus, Richard J; Teo, Koon K.; Davis, Barry R.; Chalmers, John; Pepine, Carl J.; Rahimi, Kazem; Agodoa, Lawrence; Algra, Ale; Asselbergs, Folkert W.; Beckett, Nigel; Berge, Eivind; Black, Henry R.; Brouwers, Frank P.; Brown, Morris J.; Bulpitt, Christopher J.; Byington, Bob; Cutler, Jeffrey A.; Devereaux, Richard B.; Dwyer, Jamie P.; Estacio, R.O.; Fagard, Robert; Fox, Kim; Fukui, Tsuguya; Imai, Yutaka; Ishii, Masao; Julius, Stevo; Kanno, Yoshihiko; Kjeldsen, Sverre E.; Kostis, John B.; Kuramoto, Kizuku; Lanke, Jan; Lewis, Edmund J.; Lewis, Julia B.; Lièvre, Michel; Lindholm, Lars; Lueders, Stephan; MacMahon, Stephen; Mancia, Giuseppe; Matsuzaki, Masunori; Mehlum, Maria H; Nissen, Steven; Ogawa, Hiroshi; Ogihara, Toshio; Ohkubo, Takayoshi; Palmer, C.; Patel, Anushka; Pfeffer, Marc Allan; Poulter, Neil; Rakugi, Hiromi; Reboldi, Gianpaolo; Reid, C.; Remuzzi, Giuseppe; Ruggenenti, Piero; Saruta, Takao; Schrader, Joachim; Schrier, Robert W.; Sever, Peter; Sleight, Peter; Staessen, Jan A; Suzuki, Hiromichi; Thijs, Lutgarde; Ueshima, Kenji; Umemoto, Seiji; Gilst, Wiek H. van; Verdecchia, Paolo; Wachtell, Kristian; Whelton, Paul K.; Wing, Lindon; Yui, Yoshiki; Yusuf, Salim; Zanchetti, Alberto; Zhang, Z Y; Anderson, Craig S.; Baigent, Colin; Bm, Brenner; Collins, Rory; Zeeuw, Dick de; Lubsen, Jacobus; Malacco, Ettore; Neal, Bruce; Perkovic, Vlado; Pitt, Bertram; Rodgers, Anthony; Rothwell, Peter M.; Salimi‐Khorshidi, Gholamreza; Sundström, Johan; Turnbull, Fiona; Viberti, Giancarlo; Wang, J

doi:10.1016/s2213-8587(22)00172-3

Cited by 51 publications

(18 citation statements)

References 33 publications

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“…Targeting SBP to targets even lower than the threshold used in the present study has demonstrated incremental cardiovascular benefits in individuals without T2D, 29 and of note, a recent meta-analysis of individual participant-level data in trials suggests that targets for SBP should be similar for those with and those without T2D. 30 Further research and more specific trials of blood pressure reduction in individuals with T2D may be warranted.…”

Section: Discussionmentioning

confidence: 57%

Twenty Years of Cardiovascular Complications and Risk Factors in Patients With Type 2 Diabetes: A Nationwide Swedish Cohort Study

Sattar,

McMurray,

Borén

et al. 2023

Circulation

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BACKGROUND: The goal of this work was to investigate trends (2001–2019) for cardiovascular events and cardiometabolic risk factor levels in individuals with type 2 diabetes (T2D) and matched control subjects. METHODS: This study included 679 072 individuals with T2D from the Swedish National Diabetes Register and 2 643 800 matched control subjects. Incident outcomes comprised coronary artery disease, acute myocardial infarction, cerebrovascular disease, and heart failure (HF). Trends in time to first event for each outcome were analyzed with Cox regression and standardized incidence rates. In the group with T2D, Cox regression was also used to assess risk factor levels beyond target and outcomes, as well as the relative importance of each risk factor to each model. RESULTS: Among individuals with T2D, incidence rates per 10 000 person-years in 2001 and 2019 were as follows: acute myocardial infarction, 73.9 (95% CI, 65.4–86.8) and 41.0 (95% CI, 39.5–42.6); coronary artery disease, 205.1 (95% CI, 186.8–227.5) and 80.2 (95% CI, 78.2–82.3); cerebrovascular disease, 83.9 (95% CI, 73.6–98.5) and 46.2 (95% CI, 44.9–47.6); and HF, 98.3 (95% CI, 89.4–112.0) and 75.9 (95% CI, 74.4–77.5). The incidence for HF plateaued around 2013, a trend that then persisted. In individuals with T2D, glycated hemoglobin, systolic blood pressure, estimated glomerular filtration rate, and lipids were independently associated with outcomes. Body mass index alone potentially explained >30% of HF risk in T2D. For those with T2D with no risk factor beyond target, there was no excess cardiovascular risk compared with control subjects except for HF, with increased hazard with T2D even when no risk factor was above target (hazard ratio, 1.50 [95% CI, 1.35–1.67]). Risk for coronary artery disease and cerebrovascular disease increased in a stepwise fashion for each risk factor not within target. Glycated hemoglobin was most prognostically important for incident atherosclerotic events, as was body mass index for incident of HF. CONCLUSIONS: Risk and rates for atherosclerotic complications and HF are generally decreasing among individuals with T2D, although HF incidence has notably plateaued in recent years. Modifiable risk factors within target levels were associated with lower risks for outcomes. This was particularly notable for systolic blood pressure and glycated hemoglobin for atherosclerotic outcomes and body mass index for heart failure.

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Section: Discussionmentioning

confidence: 57%

Twenty Years of Cardiovascular Complications and Risk Factors in Patients With Type 2 Diabetes: A Nationwide Swedish Cohort Study

Sattar,

McMurray,

Borén

et al. 2023

Circulation

Self Cite

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“…Hence, while our investigation on its own is insufficient for recommending revisions of hypertension guidelines, our work rather functions as independent analyses complementing the findings of the individualized patient data meta-analysis of randomized evidences. 26 Together, they support the lower the better paradigm of SBP in patients with diabetes.…”

Section: Discussionmentioning

confidence: 83%

“…First, as recently shown by trial evidence, the relative effect of BP lowering on cardiovascular outcomes was half as strong in people with diabetes as those without diabetes. 26 This might be due to the fact that part of the effect of BP lowering on CVD outcomes is mediated through prevention of diabetes; a pathway that might not be relevant to people with pre-existing diabetes. 27 Second, our cohort included patients with several comorbidities and use of several medications.…”

Section: Discussionmentioning

confidence: 99%

Systolic Blood Pressure and Cardiovascular Risk in Patients With Diabetes: A Prospective Cohort Study

Rao

Nazarzadeh

et al. 2023

Hypertension

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BACKGROUND: Whether the association between systolic blood pressure (SBP) and risk of cardiovascular disease is monotonic or whether there is a nadir of optimal blood pressure remains controversial. We investigated the association between SBP and cardiovascular events in patients with diabetes across the full spectrum of SBP. METHODS: A cohort of 49 000 individuals with diabetes aged 50 to 90 years between 1990 and 2005 was identified from linked electronic health records in the United Kingdom. Associations between SBP and cardiovascular outcomes (ischemic heart disease, heart failure, stroke, and cardiovascular death) were analyzed using a deep learning approach. RESULTS: Over a median follow-up of 7.3 years, 16 378 cardiovascular events were observed. The relationship between SBP and cardiovascular events followed a monotonic pattern, with the group with the lowest baseline SBP of <120 mm Hg exhibiting the lowest risk of cardiovascular events. In comparison to the reference group with the lowest SBP (<120 mm Hg), the adjusted risk ratio for cardiovascular disease was 1.03 (95% CI, 0.97–1.10) for SBP between 120 and 129 mm Hg, 1.05 (0.99–1.11) for SBP between 130 and 139 mm Hg, 1.08 (1.01–1.15) for SBP between 140 and 149 mm Hg, 1.12 (1.03–1.20) for SBP between 150 and 159 mm Hg, and 1.19 (1.09–1.28) for SBP ≥160 mm Hg. CONCLUSIONS: Using deep learning modeling, we found a monotonic relationship between SBP and risk of cardiovascular outcomes in patients with diabetes, without evidence of a J-shaped relationship.

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“…The absolute risk reductions were similar for persons having vs. not having diabetes at 1.54% vs 1.61% for overall major cardiovascular events, 0.58% vs. 0.56% for stroke, 0.97% vs 0.91% for ischemic heart disease, and 0.77% vs 0.39% for heart failure, although reduction in cardiovascular (CV) mortality was significant (0.48%) for those not having diabetes but not for those with diabetes (0.09%). The optimal systolic blood pressure was <120 mm Hg both for persons having and not having diabetes, leading the authors to conclude, “In people with established type 2 diabetes, the current blood pressure thresholds for initiation of blood pressure treatment do not seem to be justified.” 9 As a reminder, the current American Diabetes Association recommendations are for a target <140/90 mm Hg for individuals with diabetes and hypertension whose 10‐year CV disease risk is <15%, although “<130/80 mm Hg may be appropriate, if it can be safely attained” for those at higher CV risk. 10 …”

Section: Therapymentioning

confidence: 99%

“…The optimal systolic blood pressure was <120 mm Hg both for persons having and not having diabetes, leading the authors to conclude, "In people with established type 2 diabetes, the current blood pressure thresholds for initiation of blood pressure treatment do not seem to be justified." 9 As a reminder, the current American Diabetes Association recommendations are for a target <140/90 mm Hg for individuals with diabetes and hypertension whose 10-year CV disease risk is <15%, although "<130/80 mm Hg may be appropriate, if it can be safely attained" for those at higher CV risk. 10 In analysis of outcome among persons with diabetes in the United Kingdom Clinical Practice Research Datalink, after weighting and adjustment for baseline confounders, 31 136 initiating insulin treatment with a longacting analog vs. 26 198 users of neutral protamine Hagedorn showed an 11% reduced risk of major CV events, 18% reduction in hospitalization for heart failure, and 10% reduction in CV mortality; although the authors acknowledge the potential that there might be "residual confounding by observable and non-observable variables," they suggest this might lead to greater use of the former classes of insulin.…”

Section: Therapymentioning

confidence: 99%

Diabetes update: What's new, what's interesting

Bloomgarden

2022

Journal of Diabetes

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Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis

Cited by 51 publications

References 33 publications

Twenty Years of Cardiovascular Complications and Risk Factors in Patients With Type 2 Diabetes: A Nationwide Swedish Cohort Study

Twenty Years of Cardiovascular Complications and Risk Factors in Patients With Type 2 Diabetes: A Nationwide Swedish Cohort Study

Systolic Blood Pressure and Cardiovascular Risk in Patients With Diabetes: A Prospective Cohort Study

Diabetes update: What's new, what's interesting

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