Carlos González-Carballo

Aims: Most polygenic risk scores (PRSs) for coronary heart disease (CHD) are derived from European ancestry populations. This paper evaluates the performance of CHD PRSs in a Mexican population. Methods and results: 133 207 participants aged 35–79 years from the Mexico City Prospective Study were included. Eight PRSs (comprising 44–6 472 620 polymorphisms) were selected for prediction of CHD (defined as self-reported prior heart attack or angina, or CHD death before age 80 years). Logistic regression was adjusted for age, sex, and the first seven genetic principal components, before and after adjustment for other cardiovascular risk factors. The area under the receiving operating characteristic curve (‘C-statistic’) was also estimated. Of the included participants, 67% were women, the mean (±SD) age was 51 ± 12 years, and Indigenous American ancestry averaged 67%. CHD was documented for 5163 participants (3.9%), including 1901 prevalent and 3479 fatal cases. All eight PRSs were positively and log-linearly associated with CHD, with odds ratios (ORs) per 1 SD PRS increase ranging from 1.05 (95% CI, 1.03–1.08) to 1.29 (95% CI, 1.25–1.33). Associations were consistent across strata of age and ancestry and were independent of other vascular risk factors. For six PRSs, however, associations were substantially stronger in men than women. Multi-ancestry PRSs outperformed Eurocentric-ancestry PRSs. Despite remaining predictive of risk independently of established non-genetic risk factors, inclusion of a PRS into a risk model did not increase the C-statistic noticeably. Conclusion: In this Mexican population, existing PRSs predicted CHD independently of established vascular risk factors, particularly for men. PRSs better capturing genetic variation in Latin American people may further enhance risk prediction in such populations.

BACKGROUND: Observational studies relating blood pressure in middle age to mortality may underestimate lifelong effects. Mendelian randomization can reduce the impact of confounding and reverse causality and may better estimate lifelong effects of blood pressure on mortality. METHODS: Mendelian randomization analyses used 125 895 Mexico City Prospective Study participants aged 35 to 74 years at recruitment with valid genetic and other data. Cox regression, adjusted for confounders and regression dilution bias, related blood pressure to mortality in 133 027 participants aged 35 to 74 years without prior chronic disease (other than diabetes) at recruitment. RESULTS: In the genetic analyses (40 560 [32%] men; mean age 50 years, mean body mass index 29 kg/m ² ) there were 13 153 deaths before age 75 years (3478 cardiovascular, 2053 kidney, and 7622 other). Each 10 mm Hg higher genetically predicted lifelong systolic blood pressure was associated with 73% higher cardiovascular mortality at ages 35 to 74 years (rate ratio, 1.73 [95% CI, 1.44–2.06]), 42% higher kidney death (1.42 [95% CI, 1.15–1.75]), but no clear increase in death from other causes. These lifelong rate ratios were higher than those estimated by observational analyses relating blood pressure in middle age to risk. Mendelian randomization analyses of lifelong diastolic blood pressure confirmed strong associations with cardiovascular but not kidney death. Mortality rate ratios were similar for men and women and in those with versus without diabetes, and broadly similar at different ages and at different proportions of Indigenous American ancestry. Sensitivity analyses gave consistent results. CONCLUSIONS: In this Mexican population, genetically informed lifelong differences in blood pressure were strongly related to death from cardiovascular and kidney disease.

Background: Persistent hyperglycaemia in diabetes can cause weight loss, distorting the association of adiposity with mortality. We estimated the lifelong associations of genetically predicted body mass index (BMI) with 52 causes of death among 125 003 Mexican adults, in whom persistent hyperglycaemia in diabetes was common. Methods: A trans-ancestry genetic instrument for BMI (from 724 BMI-associated single-nucleotide polymorphisms) estimated the causal relevance of BMI to mortality before age 75 years, stratified by sex and adjusted for age and underlying ancestry structure, using a one-sample Mendelian randomization (MR) approach. Two-sample MR and other sensitivity analyses were also performed. Results: The genetic instrument explained 3% of the BMI variation and predicted BMI similarly in men and women. Each 5-kg/m2 higher genetically predicted BMI was associated with nearly a doubling in the risk of all-cause mortality at ages 35–74 years [13 066 deaths; hazard ratio (HR) 1.80, 95% confidence interval (CI) 1.63–2.00]. Hazard ratios were greater for vascular-metabolic (n = 7111; HR 2.15, 95% CI 1.87–2.48) than for non-vascular-metabolic causes (n = 5955; HR 1.47, 95% CI 1.27–1.71) and particularly strong for renal (n = 2034; HR 3.59, 95% CI 2.76–4.67), acute diabetic crises (n = 557; HR 2.70, 95% CI 1.64–4.44), and infective deaths (n = 811; HR 2.61, 95% CI 1.73–3.92). For all-cause mortality, HRs were somewhat greater at younger ages compared with older ages, and slightly larger in those with a higher proportion of Indigenous American ancestry. The strength of the association with mortality was reduced by more than half after simple adjustment for genetic predisposition to diabetes. Sensitivity analyses supported the main conclusions. Conclusion: In this Mexican population, genetically predicted lifelong BMI was strongly related to mortality and mediated substantially through diabetes.

Importance: There is limited population-based evidence on the prevalence of cognitive impairment in Mexico, a country with a rapidly aging population and where key risk factors, such as diabetes and obesity, are common. Objective: To describe the distribution of cognitive impairment in a sample of adults from Mexico City. Design, Setting, and Participants: This cross-sectional population-based study included participants from the Mexico City Prospective Study which 50,000 men and 100,000 women aged ≥35 years from two districts in 1998-2004. In 2015-2019 about 10,000 survivors were resurveyed with identical information from the original survey and additional assessments including a cognitive assessment. The main analyses included those aged 50-89 years with complete cognitive assessment and covariate data at resurvey. Main outcomes and measures: Cognition was assessed using the Mini Mental State Examination (MMSE) and those with cognitive impairment (MMSE ≤24) were identified. The distribution of MMSE scores and cognitive impairment by age, sex, and major disease risk factors (diabetes, hypertension, and adiposity) was analyzed among those with complete MMSE data and some degree of self-reported formal education. Results: Of the 9,288 participants aged 50-89 years at the 2015-2019 resurvey with complete data, 8,197 reported having at least some years of formal education. Among these (mean age 66 years; 31% men), their mean MMSE score was 26.2 (SD 3.6) points, 1,941 (24%) had cognitive impairment, mean body-mass index (BMI) was 28.6 (SD 5.5) kg/m ² , 3,008 (37%) had previously-diagnosed hypertension and 2,467 (30%) had previously-diagnosed diabetes. The sex- and district-standardised prevalence of cognitive impairment increased strongly with age, from 10% in those 50-59 years to 55% in those aged 80-89. At any given age, the prevalence of cognitive impairment was higher in women than in men. After accounting for the effects of age, sex, and district there was little difference in the prevalence of cognitive impairment between participants with or without diabetes, hypertension, overweight or obesity (BMI ≥25 km/m ² ), or high levels of fat mass. Conclusion and relevance: In this population of adults aged 50-89 years from two districts of Mexico City, the prevalence of cognitive impairment was high, particularly among women. The extent to which cognitive impairment relates to health outcomes in this population needs to be investigated. KEY POINTS: Question: What is the distribution of cognitive impairment among adults in Mexico City? Findings: In this cross-sectional study of 8,197 adults aged 50-89 years, the sex- and district-standardised prevalence of cognitive impairment ranged from 10% in those 50-59 years to 55% in those aged 80-89 and at any given age was higher in women than in men. There was little difference in the prevalence of cognitive impairment between participants with or without hypertension, diabetes or excess of adiposity. Meaning: Cognitive impairment is common in adults in Mexico City. Its relevance to major morbidity and mortality deserves future research.

Introduction Although higher risks of infectious diseases among individuals with diabetes have long been recognized, the magnitude of these risks is poorly described, particularly in lower income settings. This study sought to assess the risk of death from infection associated with diabetes in Mexico. Research design and methods Between 1998 and 2004, a total of 159 755 adults ≥35 years were recruited from Mexico City and followed up until January 2021 for cause-specific mortality. Cox regression yielded adjusted rate ratios (RR) for death due to infection associated with previously diagnosed and undiagnosed (HbA1c ≥6.5%) diabetes and, among participants with previously diagnosed diabetes, with duration of diabetes and with HbA1c. Results Among 130 997 participants aged 35–74 and without other prior chronic diseases at recruitment, 12.3% had previously diagnosed diabetes, with a mean (SD) HbA1c of 9.1% (2.5%), and 4.9% had undiagnosed diabetes. During 2.1 million person-years of follow-up, 2030 deaths due to infectious causes were recorded at ages 35–74. Previously diagnosed diabetes was associated with an RR for death from infection of 4.48 (95% CI 4.05–4.95), compared with participants without diabetes, with notably strong associations with death from urinary tract (9.68 (7.07–13.3)) and skin, bone and connective tissue (9.19 (5.92–14.3)) infections and septicemia (8.37 (5.97–11.7)). In those with previously diagnosed diabetes, longer diabetes duration (1.03 (1.02–1.05) per 1 year) and higher HbA1c (1.12 (1.08–1.15) per 1.0%) were independently associated with higher risk of death due to infection. Even among participants with undiagnosed diabetes, the risk of death due to infection was nearly treble the risk of those without diabetes (2.69 (2.31–3.13)). Conclusions In this study of Mexican adults, diabetes was common, frequently poorly controlled, and associated with much higher risks of death due to infection than observed previously, accounting for approximately one-third of all premature mortality due to infection.

Background: Body‐mass index is the sum of fat mass index (FMI) and lean mass index (LMI), which vary by age, sex, and impact on disease outcomes. We investigated the separate and joint relevance of FMI and LMI with vascular‐metabolic causes of death in Mexican adults. Methods and Results: A total of 113 025 adults aged 35 to 74 years and free from diabetes or other chronic diseases when recruited into the Mexico City Prospective Study were followed for 19 years. Cox models estimated sex‐specific death rate ratios from vascular‐metabolic causes after adjustment for confounders and exclusion of the first 5 years of follow‐up. To account for the strong correlation between FMI and LMI, additional models estimated rate ratios associated with “residual FMI” and “residual LMI” (ie, the residuals from linear regression analyses of FMI on LMI, or vice versa). In both sexes, higher FMI and LMI were associated with higher risks of vascular‐metabolic mortality. For a given (ie, fixed) level of LMI, the rate ratio (95% CI) for vascular‐metabolic mortality per 1 kg/m ² higher residual FMI strengthened and was higher in women (1.52 [1.38–1.68]) than in men (1.19 [1.13–1.25]). By contrast, for a given level of FMI, higher residual LMI was inversely associated with vascular‐metabolic mortality (rate ratio per 1 kg/m ² 0.67 [0.56–0.80] in women and 0.94 [0.90–0.98] in men). Conclusions: In this study, higher residual FMI was more strongly associated with vascular‐metabolic mortality in women than in men. Conversely, higher residual LMI was inversely associated with vascular‐metabolic mortality, particularly in women.

Introduction: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop coronavirus disease 2019 (COVID-19). Risk factors associated with death vary among countries with different ethnic backgrounds. We aimed to describe the factors associated with death in Mexicans with confirmed COVID-19.Material and methods: We analysed the Mexican Ministry of Health’s official database on people tested for SARS-CoV-2 infection by real-time reverse transcriptase–polymerase chain reaction (rtRT-PCR) of nasopharyngeal fluids. Bivariate analyses were performed to select characteristics potentially associated with death, to integrate a Cox-proportional hazards model.Results: As of May 18, 2020, a total of 177,133 persons (90,586 men and 86,551 women) in Mexico received rtRT-PCR testing for SARS-CoV-2. There were 5332 deaths among the 51,633 rtRT-PCR-confirmed cases (10.33%, 95% CI: 10.07–10.59%). The median time (interquartile range, IQR) from symptoms onset to death was nine days (5–13 days), and from hospital admission to death 4 days (2–8 days). The analysis by age groups revealed that the significant risk of death started gradually at the age of 40 years. Independent death risk factors were obesity, hypertension, male sex, indigenous ethnicity, diabetes, chronic kidney disease, immunosuppression, chronic obstructive pulmonary disease, age > 40 years, and the need for invasive mechanical ventilation (IMV). Only 1959 (3.8%) cases received IVM, of whom 1893 were admitted to the intensive care unit (96.6% of those who received IMV).Conclusions: In Mexico, highly prevalent chronic diseases are risk factors for death among persons with COVID-19. Indigenous ethnicity is a poorly studied factor that needs more investigation.

Objective. During the onset of a novel epidemic, there are public health priorities that need to be estimated, such as risk factors for infection, hospitalization, and clinical severity to allocate resources and issue health policies. In this work we calculate the risk of infection and hospitalization by Covid-19 conferred by demographic, lifestyle, and co-morbidity factors. Material and methods. This is a case-control study including the tested individuals for SARS-Cov-2 by RT-PCR officially reported by the Health Secretary of Mexico from January 01 to May 8, 2020 (102,875 subjects). Demographic (sex, age, foreign and immigrant status, native speaking, place of residence), life-style (smoking), and co-morbidities [diabetes, obesity, high blood pressure (HBP), asthma, immunosuppression, chronic obstructive pulmonary disease (COPD), cardiovascular disease other than HBP, chronic kidney disease (CKD), and other not specified diseases (other diseases)] variables were included in this study. The risk of infection and hospitalization conferred by each variable was calculated with univariate (ULR) and multivariate (MLR) logistic regression models. Results. The place of residence (OR=4.91 living in Tijuana City), followed by advanced age (OR=6.71 in 61-70 years-old), suffering from diabetes (OR=1.87) or obesity (OR=1.61), being male (OR=1.55), having HBP (OR=1.52), and notoriously being indigenous (OR=1.49) conferred a higher risk of becoming infected by SARS-CoV-2 in Mexico. Unexpectedly, we found that having asthma (OR=0.63), immunosuppression (OR=0.65) or smoking (OR=0.85) are protective factors against infection, while suffering from COPD does not increase the risk for SARS-CoV-2 infection. In contrast, advanced age (OR=11.6 in ≥ 70 years-old) is the main factor for hospitalization due to Covid-19, followed by some co-morbidities, mainly diabetes (OR=3.69) and HBP (OR=2.79), being indigenous (OR=1.89), male sex (OR=1.67) and the place of residence (OR=4.22 for living in Juarez City). Unlike the protective risk against infection, immunosuppression (OR=2.69) and COPD (OR=3.63), contribute to the risk of being hospitalized, while having asthma (OR=0.7) also provides protection against hospitalization. Conclusions. In addition to confirming that older age, diabetes, HBP and obesity are the main risk of infection and hospitalization by Covid-19, we found that being indigenous, immunosuppression, smoking and asthma protect against infection, and the latter also against hospitalization.