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Pasquale Maffia

Publications and source records attributed to Pasquale Maffia.

3 recordsLinked to original sources

Global inequalities in cardiometabolic care and achievable cardiovascular risk reduction by wealth, region, and sex: a pooled analysis of individual participant data from 76 countries.

BACKGROUND: Wealth-related inequalities affect cardiometabolic health worldwide, but their implications for cardiometabolic care and potentially preventable cardiovascular disease remain poorly understood. We aimed to quantify wealth-related inequalities in the care cascade for hypertension, diabetes, and hypercholesterolaemia by wealth quintile, region, and sex. METHODS: In this cross-sectional, individual-level analysis, we analysed harmonised, nationally representative health examination surveys conducted in five WHO regions. Adults aged 18 years or older with data on age, sex, wealth, and at least one cardiometabolic outcome were eligible. All variables in the surveys were obtained from standardised in-person examinations. We evaluated hypertension, diabetes, and hypercholesterolaemia and applied a care cascade of disease awareness, treatment, and control for each condition uniformly across all surveys. Disease status was defined from measured biomarkers, self-reported diagnosis, or current medication; awareness and treatment were based on self-reported information, and control on measured biomarkers. Each indicator was expressed as the proportion of all individuals with the corresponding condition. Socioeconomic position was assessed using household wealth indices derived within each survey, and participants were ranked within each country and categorised into country-specific quintiles (quintile 1 to quintile 5), with quintile 1 including those with the least household wealth. Inequality was quantified by the quintile 5 minus quintile 1 difference, the slope index of inequality (SII), and relative index of inequality (RII). Predicted 10-year cardiovascular risk was estimated with the Globorisk equations, and trial-derived relative risk reductions were applied to estimate achievable absolute risk reduction. The ASANDE consortium is registered with ClinicalTrials.gov (NCT07427355). FINDINGS: We analysed data from 109 surveys conducted in 76 countries between 2002 and 2024. 315 403 (65·9%) of 478 947 survey participants with available data were included in this analysis (median age 40 years [IQR 30-52], 185 209 [58·7%] women, and 130 194 [41·3%] men). Inequalities widened progressively across the care cascade in all regions and were most pronounced for disease control. Pooled across regions, the SII for control was 4·4% (95% CI 2·4-6·4) for hypertension (RII 1·1, 1·1-1·2), 4·8% (0·6-9·0) for diabetes (RII 1·1, 1·0-1·2), and 6·5% (3·8-9·2) for hypercholesterolaemia (RII 1·1, 1·0-1·1). However, regional patterns varied substantially. In the region of the Americas, disease control consistently favoured wealthier individuals (SII 9·2% for hypertension, 4·8-13·5; RII 1·2, 1·1-1·3). In the African region, coverage was uniformly low, and the largest absolute inequality favoured individuals with the least wealth, particularly for hypercholesterolaemia treatment (SII -37·6%, -49·7 to -25·5; RII 0·6, 0·5 to 0·7). Baseline cardiovascular risk was higher in individuals with the least wealth than among the wealthiest (13·6% vs 12·2%), but achievable absolute risk reduction was correlated with baseline risk rather than with treatment coverage: achievable reduction was greatest in the European Region (3·9%) and lowest in the Africa region (2·5%). Across all regions, achievable absolute risk reduction was greater in men than in women (4·6% vs 3·5% in the European region). INTERPRETATION: The populations with the largest treatment gaps are not necessarily those that could achieve the greatest absolute reduction in cardiovascular risk through treating individuals who are currently untreated. In settings where coverage is uniformly low, expanding the supply of care matters more than redistributing access to it. Moreover, because socioeconomic inequalities widen after diagnosis, screening alone is unlikely to reduce disparities unless accompanied by sustained access to treatment. Policy should prioritise overall population health over maximise equity within the population. FUNDING: None.

Journal Article

Identification of a PRDM1-regulated T cell network to regulate atherosclerotic plaque inflammation.

BACKGROUND: Inflammation is a key driver of atherosclerosis, yet the mechanisms sustaining inflammation in human plaques remain poorly understood. This study uses a network-based approach to identify immune gene programs involved in the transition from low- to high-risk (rupture-prone) human atherosclerotic plaques. METHODS: Expression data from human carotid artery plaques, both stable (low-risk, n = 16) and unstable (high-risk, n = 27), were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA). Bayesian network inference, operated on the eigengene values from the WGCNA, further extended the WGCNA analysis, and similarity to the signature of T cell subsets was validated in single-cell RNA sequencing data of human plaques, and a loss-of-function study in a mouse model of atherosclerosis. In silico drug repurposing was performed to identify potential therapeutic targets. RESULTS: Our analysis revealed a distinct gene module with a prominent T cell signature, particularly in unstable plaques. Key regulatory factors, RUNX3, IRF7 and in particular PRDM1, were significantly downregulated in plaque T cells from symptomatic versus asymptomatic patients, indicating a protective role. Additionally, as PRDM1 is downstream of IRF7, we opted for PRDM1 as a key target. T cell-specific Prdm1 deficiency in Western-type diet fed Ldlr knockout mice featured accelerated plaque progression. Finally, as PRDM1 targeting drugs are not yet available, we performed in silico drug repurposing, identifying EGFR inhibitors as promising therapeutic candidates. CONCLUSIONS: This study highlights a PRDM1-regulated T cell network that distinguishes high-risk from low-risk plaques and demonstrates the regulatory role of T cell PRDM1 in controlling atherosclerosis, positioning this pathway as a promising therapeutic target.

Plaque, Atherosclerotic