Cost-Effectiveness of a Multicomponent Primary Care Intervention for Hypertension.

BACKGROUND: The SingHypertension primary care clinic intervention, which consisted of clinician training in hypertension management, subsidized single-pill combination medications, nurse-delivered motivational conversations and telephone follow-ups, improved blood pressure control and cardiovascular disease (CVD) risk scores relative to usual care among patients with uncontrolled hypertension in Singapore. This study quantified the incremental cost-effectiveness, in terms of incremental cost per unit reduction disability-adjusted life years, of SingHypertension relative to usual care for patients with hypertension from the health system perspective. METHODS AND RESULTS: We developed a Markov model to simulate CVD events and associated outcomes for a hypothetical cohort of patients over a 10-year period. Costs were measured in US dollars, and effectiveness was measured in disability-adjusted life years averted. We present base-case results and conducted deterministic and probabilistic sensitivity analyses. Based on a willingness-to-pay threshold of US $55 500 per DALY averted, SingHypertension was cost-effective for patients with hypertension (incremental cost-effectiveness ratio: US $24 765 per disability-adjusted life year averted) relative to usual care. This result held even if risk reduction was assumed to decline linearly to 0 over 10 years but not sooner than 7 years. Incremental cost-effectiveness ratios were most sensitive to the magnitude of the reduction in CVD risk; at least a 0.13% to 0.16% point reduction in 10-year CVD risk is required for cost-effectiveness. Probabilistic sensitivity analysis indicates that SingHypertension has a 78% chance of being cost-effective at the willingness-to-pay threshold. CONCLUSIONS: SingHypertension represents good value for the money for reducing CVD incidence, morbidity, and mortality and should be considered for wide-scale implementation in Singapore and possibly other countries. REGISTRATION INFORMATION: REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02972619.

Kidney function trajectories, associated factors, and outcomes in multiethnic Asian patients with type 2 diabetes.

BACKGROUND: We examined the trajectory of estimated glomerular filtrate rate (eGFR), associated risk factors, and its relationship with end-stage kidney disease (ESKD) among a multiethnic patient population with type 2 diabetes in Singapore. METHODS: A follow-up study included 62 080 individuals with type 2 diabetes aged ≥18 years in a multi-institutional SingHealth Diabetes Registry between 2013 and 2019. eGFR trajectories were analyzed using latent class linear mixed models. Factors associated with eGFR trajectories were evaluated using multinomial logistic regression. The association of eGFR trajectories with ESKD was assessed via competing risk models. RESULTS: Trajectory of kidney function, determined by eGFR, was nonlinear. The trajectory pattern was classified as stable initially then gradual decline (75%), progressive decline (21.9%), and rapid decline (3.1%). Younger age, female sex, Malay ethnicity, lower-income housing type, current smoking, higher glycated hemoglobin, lower low-density lipoprotein, higher triglyceride, uncontrolled blood pressure, albuminuria, cardiovascular disease, hypertension, and higher eGFR levels each were associated with progressive or rapid decline. Compared with the trajectory of stable initially then gradual eGFR decline, progressive decline increased the hazard of ESKD by 6.14-fold (95% confidence interval [CI]: 4.96-7.61)) and rapid decline by 82.55 folds (95% CI: 55.90-121.89). CONCLUSIONS: Three nonlinear trajectory classes of kidney function were identified among multiethnic individuals with type 2 diabetes in Singapore. About one in four individuals had a progressive or rapid decline in eGFR. Our results suggest that eGFR trajectories are correlated with multiple social and modifiable risk factors and inform the risk of ESKD.

Heterogeneity by age and gender in the association of kidney function with mortality among patients with diabetes - analysis of diabetes registry in Singapore.

BACKGROUND: We aimed to explore the three-way interaction among age, gender, and kidney function on the risk of all-cause mortality and cardiovascular mortality among patients with type 2 diabetes (T2D). METHODS: In a retrospective cohort study, patients aged > 40 years with T2D with serum creatinine and urine albumin measured from 2013 to 2019 were included from a multi-institutional diabetes registry. The exposure was estimated glomerular filtration rate (eGFR), outcomes were all-cause mortality (primary outcome) and cardiovascular disease (CVD) mortality (secondary outcome). We applied multivariable cox proportional hazards regression analysis to compute the association between eGFR and mortality. RESULTS: A total of 36,556 patients were followed for up to 6 years during which 2492 (6.82%) died from all causes, and 690 (1.9%) died from CVD. We observed a significant three-way interaction (p = 0.021) among age (younger, < 65; older, ≥65 years), gender and eGFR for the risk of all-cause mortality. Using age- and gender-specific eGFR of 90 ml/min/1.73m2 as the reference point, the adjusted hazard rate (HR) (95% CI) for all-cause mortality at eGFR of 40 ml/min/1.73m2 was 3.70 (2.29 to 5.99) in younger women and 1.86 (1.08 to 3.19) in younger men. The corresponding adjusted HRs in older women and older men were 2.38 (2.02 to 2.82) and 2.18 (1.85 to 2.57), respectively. Similar results were observed for CVD deaths, although the three-way interaction was not statistically significant. Sensitivity analysis yielded similar results. CONCLUSIONS: In this T2D population, younger women with reduced kidney function might be more susceptible to higher risks of all-cause mortality and CVD mortality than younger men.

Social Determinants of Health and Disparities in Hypertension and Cardiovascular Diseases.

High blood pressure causes over 10 million preventable deaths annually globally. Populations in low- and middle-income countries suffer the most, experiencing increased uncontrolled blood pressure and cardiovascular disease (CVD) deaths. Despite improvements in high-income countries, disparities persist, notably in the United States, where Black individuals face up to 4× higher CVD mortality than White individuals. Social determinants of health encompass complex, multidimensional factors linked to an individual's birthplace, upbringing, activities, residence, workplaces, socioeconomic and environmental structures, and significantly affect health outcomes, including hypertension and CVD. This review explored how social determinants of health drive disparities in hypertension and related CVD morbidity from a socioecological and life course perspective. We present evidence-based strategies, emphasizing interventions tailored to specific community needs and cross-sector collaboration to address health inequalities rooted in social factors, which are key elements toward achieving the United Nations' Sustainable Development Goal 3.4 for reducing premature CVD mortality by 30% by 2030.

Lifestyle management of hypertension: International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension.

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.

Real-World Systolic and Diastolic Blood Pressure Levels and Cardiovascular Mortality in Patients With Type 2 Diabetes-Results From a Large Registry Cohort in Asia.

BACKGROUND: Elevated blood pressure (BP) is associated with increased risk of cardiovascular mortality. However, there is ongoing debate whether intensive BP lowering may paradoxically increase the risk of cardiovascular disease (CVD), especially in patients with type 2 diabetes (T2D). We investigated the association of BP with risk of CVD mortality in patients with T2D. METHODS AND RESULTS: We used data on 83 721 patients with T2D from a multi-institutional diabetes registry in Singapore from 2013 to 2019. BP was analyzed as categories and restricted cubic splines using Cox multivariable regression analysis stratified by preexisting CVD and age (<65 years versus ≥65 years). The primary outcome was CVD mortality, determined via linkage with the national registry. Among 83 721 patients with T2D (mean age 65.3 years, 50.6% women, 78.9% taking antihypertensive medications), 7.6 per 1000 person-years experienced the primary outcome. Systolic BP had a graded relationship with a significant increase in CVD mortality at levels >120 to 129 mm Hg. Diastolic BP levels >90 mm Hg were significantly associated with CVD mortality in those aged ≥65 years. In addition, diastolic BP <70 mm Hg was associated with a significantly higher risk of CVD mortality in all patients. CONCLUSIONS: In patients with T2D, clinic systolic BP levels ≥130 mm Hg or diastolic BP levels ≥90 mm Hg are associated with higher risk of CVD mortality. Diastolic BP <70 mm Hg is also associated with the risk of adverse CVD outcomes, although reverse causality cannot be ruled out.

A meta-analysis of GFR slope as a surrogate endpoint for kidney failure.

Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min-1 per 1.73 m2 or kidney failure with replacement therapy). We used a Bayesian mixed-effects meta-regression model to relate treatment effects on GFR slope with those on the clinical endpoint across all studies and by disease groups (diabetes, glomerular diseases, CKD or cardiovascular diseases). Treatment effects on the clinical endpoint were strongly associated with treatment effects on total slope (median coefficient of determination (R2) = 0.97 (95% Bayesian credible interval (BCI) 0.82-1.00)) and moderately associated with those on chronic slope (R2 = 0.55 (95% BCI 0.25-0.77)). There was no evidence of heterogeneity across disease. Our results support the use of total slope as a primary endpoint for clinical trials of CKD progression.

Change in Albuminuria and GFR Slope as Joint Surrogate End Points for Kidney Failure: Implications for Phase 2 Clinical Trials in CKD.

SIGNIFICANCE STATEMENT: Changes in albuminuria and GFR slope are individually used as surrogate end points in clinical trials of CKD progression, and studies have demonstrated that each is associated with treatment effects on clinical end points. In this study, the authors sought to develop a conceptual framework that combines both surrogate end points to better predict treatment effects on clinical end points in Phase 2 trials. The results demonstrate that information from the combined treatment effects on albuminuria and GFR slope improves the prediction of treatment effects on the clinical end point for Phase 2 trials with sample sizes between 100 and 200 patients and duration of follow-up ranging from 1 to 2 years. These findings may help inform design of clinical trials for interventions aimed at slowing CKD progression. BACKGROUND: Changes in log urinary albumin-to-creatinine ratio (UACR) and GFR slope are individually used as surrogate end points in clinical trials of CKD progression. Whether combining these surrogate end points might strengthen inferences about clinical benefit is unknown. METHODS: Using Bayesian meta-regressions across 41 randomized trials of CKD progression, we characterized the combined relationship between the treatment effects on the clinical end point (sustained doubling of serum creatinine, GFR <15 ml/min per 1.73 m 2 , or kidney failure) and treatment effects on UACR change and chronic GFR slope after 3 months. We applied the results to the design of Phase 2 trials on the basis of UACR change and chronic GFR slope in combination. RESULTS: Treatment effects on the clinical end point were strongly associated with the combination of treatment effects on UACR change and chronic slope. The posterior median meta-regression coefficients for treatment effects were -0.41 (95% Bayesian Credible Interval, -0.64 to -0.17) per 1 ml/min per 1.73 m 2 per year for the treatment effect on GFR slope and -0.06 (95% Bayesian Credible Interval, -0.90 to 0.77) for the treatment effect on UACR change. The predicted probability of clinical benefit when considering both surrogates was determined primarily by estimated treatment effects on UACR when sample size was small (approximately 60 patients per treatment arm) and follow-up brief (approximately 1 year), with the importance of GFR slope increasing for larger sample sizes and longer follow-up. CONCLUSIONS: In Phase 2 trials of CKD with sample sizes of 100-200 patients per arm and follow-up between 1 and 2 years, combining information from treatment effects on UACR change and GFR slope improved the prediction of treatment effects on clinical end points.

It is strongly recommended to not conduct, fund, or publish research studies that use spot urine samples with estimating equations to assess individuals' sodium (salt) intake in association with health outcomes: a policy statement of the World Hypertension League, International Society of Hypertension and Resolve to Save Lives.

Spot urine samples with estimating equations have been used to assess individuals' sodium (salt) intake in association with health outcomes. There is large random and systematic error in estimating sodium intake using this method and spurious health outcome associations. Substantial controversy has resulted from false claims the method is valid. Hence, the World Hypertension League, International Society of Hypertension and Resolve to Save Lives, supported by 21 other health organizations, have issued this policy statement that strongly recommends that research using spot urine samples with estimating equations to assess individuals' sodium (salt) intake in association with health outcomes should not be conducted, funded or published. Literature reviews on the health impacts of reducing dietary sodium that include studies that have used spot and short duration timed urine samples with estimating equations need to explicitly acknowledge that the method is not recommended to be used and is associated with spurious health outcome associations.

Evaluation of Variation in the Performance of GFR Slope as a Surrogate End Point for Kidney Failure in Clinical Trials that Differ by Severity of CKD.

BACKGROUND: The GFR slope has been evaluated as a surrogate end point for kidney failure in meta-analyses on a broad collection of randomized controlled trials (RCTs) in CKD. These analyses evaluate how accurately a treatment effect on GFR slope predicts a treatment effect on kidney failure. We sought to determine whether severity of CKD in the patient population modifies the performance of GFR slope. METHODS: We performed Bayesian meta-regression analyses on 66 CKD RCTs to evaluate associations between effects on GFR slope (the chronic slope and the total slope over 3 years, expressed as mean differences in ml/min per 1.73 m2/yr) and those of the clinical end point (doubling of serum creatinine, GFR <15 ml/min per 1.73 m2, or kidney failure, expressed as a log-hazard ratio), where models allow interaction with variables defining disease severity. We evaluated three measures (baseline GFR in 10 ml/min per 1.73 m2, baseline urine albumin-to-creatinine ratio [UACR] per doubling in mg/g, and CKD progression rate defined as the control arm chronic slope, in ml/min per 1.73 m2/yr) and defined strong evidence for modification when 95% posterior credible intervals for interaction terms excluded zero. RESULTS: There was no evidence for modification by disease severity when evaluating 3-year total slope (95% credible intervals for the interaction slope: baseline GFR [-0.05 to 0.03]; baseline UACR [-0.02 to 0.04]; CKD progression rate [-0.07 to 0.02]). There was strong evidence for modification in evaluations of chronic slope (95% credible intervals: baseline GFR [0.02 to 0.11]; baseline UACR [-0.11 to -0.02]; CKD progression rate [0.01 to 0.15]). CONCLUSIONS: These analyses indicate consistency of the performance of total slope over 3 years, which provides further evidence for its validity as a surrogate end point in RCTs representing varied CKD populations.

Sex disparity in left ventricular hypertrophy in South Asians with hypertension: influence of central obesity and high blood pressure.

Women have been reported to be at greater risk of left ventricular hypertrophy (LVH) than men in South Asia, but whether the sex disparity is affected by central obesity and blood pressure has not been well studied. We examined prospectively the interaction of sex with waist circumference and systolic blood pressure at baseline on LVH measured after a median of 8-year follow-up among 539 individuals with hypertension in Karachi, Pakistan, and found that the risk of LVH for women vs men increased with higher baseline waist circumference and systolic blood pressure. Our results underscore the urgency for public health programs to prevent obesity and control hypertension in women in South Asia.

Longitudinal HbA1c trajectory modelling reveals the association of HbA1c and risk of hospitalization for heart failure for patients with type 2 diabetes mellitus.

BACKGROUND: Inconsistent conclusions in past studies on the association between poor glycaemic control and the risk of hospitalization for heart failure (HHF) have been reported largely due to the analysis of non-trajectory-based HbA1c values. Trajectory analysis can incorporate the effects of HbA1c variability across time, which may better elucidate its association with macrovascular complications. Furthermore, studies analysing the relationship between HbA1c trajectories from diabetes diagnosis and the occurrence of HHF are scarce. METHODS: This is a prospective cohort study of the SingHealth Diabetes Registry (SDR). 17,389 patients diagnosed with type 2 diabetes mellitus (T2DM) from 2013 to 2016 with clinical records extending to the end of 2019 were included in the latent class growth analysis to extract longitudinal HbA1c trajectories. Association between HbA1c trajectories and risk of first known HHF is quantified with the Cox Proportional Hazards (PH) model. RESULTS: 5 distinct HbA1c trajectories were identified as 1. low stable (36.1%), 2. elevated stable (40.4%), 3. high decreasing (3.5%), 4. high with a sharp decline (10.8%), and 5. moderate decreasing (9.2%) over the study period of 7 years. Poorly controlled HbA1c trajectories (Classes 3, 4, and 5) are associated with a higher risk of HHF. Using the diabetes diagnosis time instead of a commonly used pre-defined study start time or time from recruitment has an impact on HbA1c clustering results. CONCLUSIONS: Findings suggest that tracking the evolution of HbA1c with time has its importance in assessing the HHF risk of T2DM patients, and T2DM diagnosis time as a baseline is strongly recommended in HbA1c trajectory modelling. To the authors' knowledge, this is the first study to identify an association between HbA1c trajectories and HHF occurrence from diabetes diagnosis time.

Post-intervention acceptability of multicomponent intervention for management of hypertension in rural Bangladesh, Pakistan, and Sri Lanka- a qualitative study.

BACKGROUND: COBRA-BPS (Control of Blood Pressure and Risk Attenuation-Bangladesh, Pakistan, Sri Lanka), a multicomponent, community health-worker (CHW)-led hypertension management program, has been shown to be effective in rural communities in South Asia. This paper presents the acceptability of COBRA-BPS multicomponent intervention among the key stakeholders. METHODS: We conducted post-implementation interviews of 87 stakeholder including 23 community health workers (CHWs), 19 physicians and 45 patients in 15 rural communities randomized to COBRA-BPS multicomponent intervention in in Bangladesh, Pakistan, and Sri Lanka. We used Theoretical Framework for Acceptability framework (TFA) with a focus on affective attitude, burden, ethicality, intervention coherence, opportunity cost, perceived effectiveness and self-efficacy. RESULTS: COBRA-BPS multicomponent intervention was acceptable to most stakeholders. Despite some concerns about workload, most CHWs were enthusiastic and felt empowered. Physicians appreciated the training sessions and felt trusted by their patients. Patients were grateful to receive the intervention and valued it. However, patients in Pakistan and Bangladesh expressed the need for supplies of free medicines from the primary health facilities, while those in Sri Lanka were concerned about supplies' irregularities. All stakeholders favoured scaling-up COBRA-BPS at a national level. CONCLUSIONS: COBRA-BPS multicomponent intervention is acceptable to the key stakeholders in Bangladesh, Pakistan and Sri Lanka. Community engagement for national scale-up of COBRA-BPS is likely to be successful in all three countries.

Range and Consistency of Cardiovascular Outcomes Reported by Clinical Trials in Kidney Transplant Recipients: A Systematic Review.

Cardiovascular disease is a major cause of morbidity and mortality in kidney transplant recipients. Trial evidence to improve cardiovascular outcomes is limited by inconsistent reporting of outcomes, which may also lack patient-relevance. This study aimed to assess the range and consistency of cardiovascular outcomes reported by contemporary trials in kidney transplant recipients. Methods: A systematic review of all randomized controlled trials involving adult kidney transplant recipients that reported at least 1 cardiovascular outcome from January 2012 to December 2019 was performed, including Embase, MEDLINE, Cochrane, and ClinicalTrials.gov electronic databases. Trial characteristics were extracted and all levels of specification of the cardiovascular outcome measures reported were analyzed (the measure definition, metric' and method of aggregation). Measures assessing a similar aspect of cardiovascular disease were categorized into outcomes. Results: From 93 eligible trials involving 27 609 participants, 490 outcome measures were identified. The outcome measures were grouped into 38 outcomes. A cardiovascular composite was the most common outcome reported (40 trials, 43%) followed by cardiovascular mortality (42%) and acute coronary syndrome (31%). Cardiovascular composite was also the most heterogeneous outcome with 77 measures reported followed by cardiovascular mortality (n = 58) and inflammatory biomarkers (n = 51). The most common cardiovascular composite outcome components reported were major cardiovascular events (18 trials), stroke unspecified (11 trials), and myocardial infarction unspecified (10 trials). Conclusions: There is substantial heterogeneity in cardiovascular outcome reporting in kidney transplant trials.

Defining measures of kidney function in observational studies using routine health care data: methodological and reporting considerations.

The availability of electronic health records and access to a large number of routine measurements of serum creatinine and urinary albumin enhance the possibilities for epidemiologic research in kidney disease. However, the frequency of health care use and laboratory testing is determined by health status and indication, imposing certain challenges when identifying patients with kidney injury or disease, when using markers of kidney function as covariates, or when evaluating kidney outcomes. Depending on the specific research question, this may influence the interpretation, generalizability, and/or validity of study results. This review illustrates the heterogeneity of working definitions of kidney disease in the scientific literature and discusses advantages and limitations of the most commonly used approaches using 3 examples. We summarize ways to identify and overcome possible biases and conclude by proposing a framework for reporting definitions of exposures and outcomes in studies of kidney disease using routinely collected health care data.

Addressing global disparities in blood pressure control: perspectives of the International Society of Hypertension.

ABSTRACT: Raised blood pressure (BP) is the leading cause of preventable death in the world. Yet, its global prevalence is increasing, and it remains poorly detected, treated, and controlled in both high- and low-resource settings. From the perspective of members of the International Society of Hypertension based in all regions, we reflect on the past, present, and future of hypertension care, highlighting key challenges and opportunities, which are often region-specific. We report that most countries failed to show sufficient improvements in BP control rates over the past three decades, with greater improvements mainly seen in some high-income countries, also reflected in substantial reductions in the burden of cardiovascular disease and deaths. Globally, there are significant inequities and disparities based on resources, sociodemographic environment, and race with subsequent disproportionate hypertension-related outcomes. Additional unique challenges in specific regions include conflict, wars, migration, unemployment, rapid urbanization, extremely limited funding, pollution, COVID-19-related restrictions and inequalities, obesity, and excessive salt and alcohol intake. Immediate action is needed to address suboptimal hypertension care and related disparities on a global scale. We propose a Global Hypertension Care Taskforce including multiple stakeholders and societies to identify and implement actions in reducing inequities, addressing social, commercial, and environmental determinants, and strengthening health systems implement a well-designed customized quality-of-care improvement framework.

Impact of COVID-19 on perceived wellbeing, self-management and views of novel modalities of care among medically vulnerable patients in Singapore.

OBJECTIVES: This study aims to examine the impact of COVID-19 measures on wellbeing and self-management in medically vulnerable non-COVID patients and their views of novel modalities of care in Singapore. METHODS: Patients with cardiovascular disease (CVD), respiratory disease, chronic kidney disease, diabetes and cancer were recruited from the SingHealth cluster and national cohort of older adults. Data on demographics, chronic conditions and perceived wellbeing were collected using questionnaire. We performed multivariable regression to examine factors associated with perceived wellbeing. Qualitative interviews were conducted to elicit patient's experience and thematically analyzed. RESULTS: A total of 91 patients participated. Male patients compared with female patients perceived a lower impact of the pandemic on subjective wellbeing. Patients with CVD compared to those having conditions other than CVD perceived a lower impact. Impacts of the pandemic were primarily described in relation to emotional distress and interference in maintaining self-care. Hampering of physical activity featured prominently, but most did not seek alternative ways to maintain activity. Despite general willingness to try novel care modalities, lack of physical interaction and communication difficulties were perceived as main barriers. DISCUSSION: Findings underline the need to alleviate emotional distress and develop adaptive strategies to empower patients to maintain wellbeing and self-care.

Including measures of chronic kidney disease to improve cardiovascular risk prediction by SCORE2 and SCORE2-OP.

AIMS: The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an 'Add-on' to incorporate CKD measures into these algorithms, using a validated approach. METHODS: In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP. We validated C-statistics and net reclassification improvement (NRI), accounting for competing risk of non-CVD death, in 5,997 719 participants from 34 different datasets. RESULTS: In the target population of SCORE2 and SCORE2-OP without diabetes, the CKD Add-on (eGFR only) and CKD Add-on (eGFR + ACR) improved C-statistic by 0.006 (95%CI 0.004-0.008) and 0.016 (0.010-0.023), respectively, for SCORE2 and 0.012 (0.009-0.015) and 0.024 (0.014-0.035), respectively, for SCORE2-OP. Similar results were seen when we included individuals with diabetes and tested the CKD Add-on (eGFR + dipstick). In 57 485 European participants with CKD, SCORE2 or SCORE2-OP with a CKD Add-on showed a significant NRI [e.g. 0.100 (0.062-0.138) for SCORE2] compared to the qualitative approach in the ESC guideline. CONCLUSION: Our Add-ons with CKD measures improved CVD risk prediction beyond SCORE2 and SCORE2-OP. This approach will help clinicians and patients with CKD refine risk prediction and further personalize preventive therapies for CVD.