BACKGROUND: Effective treatments are available for obesity and for hypertension and hypercholesterolaemia, which mediate the cardiovascular and renal effects of obesity. Our aim was to compare blood pressure, cholesterol...BACKGROUND: Effective treatments are available for obesity and for hypertension and hypercholesterolaemia, which mediate the cardiovascular and renal effects of obesity. Our aim was to compare blood pressure, cholesterol, and the use of antihypertensive and lipid-lowering medicines in people with obesity and normal weight and assess whether the BMI-associated excess risk has diminished. METHODS: Our primary outcomes were mean systolic blood pressure (SBP), non-HDL cholesterol and HDL cholesterol, and the proportion of the participants who used antihypertensive and lipid-lowering medicines. We used data from 110 health surveys conducted from 1990 to 2024 with 978 425 participants aged 20-79 years sampled from national populations of seven countries: Japan, South Korea, Taiwan, Thailand, Finland, England, and the USA. We used graphical presentation and trend analysis to evaluate changes over time in these outcomes in participants in the normal BMI range (20·0 to <25·0 kg/m), and changes in the difference between participants with obesity (separately for class I obesity [30·0 to <35·0 kg/m] and class II and III obesity [BMI ≥35·0 kg/m]) or overweight (25·0 to <30·0 kg/m) and those in the normal BMI range. FINDINGS: Mean non-HDL cholesterol and SBP declined over time, especially among those older than 40 years, with the notable exception of some sex-age groups in Thailand. When pooled across all countries, age groups, and obesity and overweight BMI ranges, the difference in mean non-HDL cholesterol with normal BMI became smaller by -0·05 mmol/L per decade (95% CI -0·07 to -0·03) for females and -0·07 mmol/L per decade (-0·09 to -0·05) for males. For SBP, the pooled estimate of change in the difference with normal BMI across all countries, age groups, and obesity and overweight BMI ranges was -0·7 mmHg per decade (95% CI -1·0 to -0·4) for females and -0·6 mmHg per decade (-0·9 to -0·4) for males. The declines were larger in individuals with obesity, especially class II and III obesity, than in normal BMI, leading to a convergence of these risk factors between obesity and normal BMI in people older than 40 years. As a result of these trends, in England, the USA, Thailand, South Korea, and Japan, older people with obesity often became indistinguishable from, or better off than, those with normal BMI in terms of non-HDL cholesterol and SBP. These trends accompanied a larger increase in the use of lipid-lowering and antihypertensive medicines in middle-aged and older people with obesity than in those with normal BMI. The pooled estimate for the increase in difference in lipid-lowering medicines compared with normal BMI across all countries, age groups, and obesity and overweight BMI ranges was 1·5 percentage points per decade (1·0-2·1) for females and 1·6 percentage points per decade (1·0-2·2) for males. For antihypertensive medicines, the pooled estimate was 0·7 percentage points per decade (0·3-1·0) for females and 2·0 percentage points per decade (1·3-2·8) for males. Mean HDL cholesterol increased more in people with normal BMI than those with obesity, leading to a divergence. For people younger than 40 years, there has been little change in the gap between those with obesity or overweight and those with normal BMI; young adults were rarely treated for high cholesterol or blood pressure regardless of their BMI. INTERPRETATION: In industrialised countries, blood pressure and non-HDL cholesterol in older adults with obesity are increasingly similar to those with normal BMI, with higher use of antihypertensive and lipid-lowering medicines a possible driver of this convergence. There is nonetheless heterogeneity across countries in the extent of convergence. Young adults with obesity remain metabolically at higher risk than their counterparts with normal weight. FUNDING: UK Medical Research Council and UK Research and Innovation (Innovate UK).
mRNA vaccines represent a transformative advance in vaccinology, combining rapid development timelines, scalable manufacturing, and strong immunogenicity with a favourable safety profile. Global deployment of mRNA vaccin...mRNA vaccines represent a transformative advance in vaccinology, combining rapid development timelines, scalable manufacturing, and strong immunogenicity with a favourable safety profile. Global deployment of mRNA vaccines during the COVID-19 pandemic provided an unprecedented real-world evaluation of this platform, with billions of doses administered across diverse populations. In this Review, we critically examine the safety and efficacy of mRNA vaccines from mechanistic, preclinical, clinical, and public health perspectives. We outline the biological basis of mRNA vaccines, including their transient cytoplasmic expression, lack of genomic integration, and rapid clearance, distinguishing them clearly from other gene therapies. We synthesise evidence on vaccine components, manufacturing quality controls, and regulatory standards that underpin safety, alongside data from randomised trials, post-authorisation surveillance, and active pharmacovigilance systems. We also review real-world effectiveness across age groups, pregnancy, and populations that are immunocompromised, along with the effects on transmission. Last, we address public perception and vaccine confidence, and discuss implications for next-generation mRNA vaccines, including strategies to reduce reactogenicity, improve breadth and durability of immunity, enhance global access, and support sustainable public trust. Together, the accumulated evidence affirms mRNA vaccines as a safe, effective, and adaptable platform with enduring relevance for future infectious disease prevention and public health preparedness, and for the treatment of cancer and autoimmunity.