349 research outputs found
Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
No full textBackground: empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.Methods: in the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).Findings: between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0·96 [95% CI 0·82-1·13]; p=0·64). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1·03 [95% CI 0·96-1·10]; p=0·44). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0·95 [95% CI 0·84-1·08]; p=0·44). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis.Interpretation: in adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes.Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z).Translations: for the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.</p
Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials.
No full textOBJECTIVE: To assess the effects of selective cyclo-oxygenase-2 (COX 2) inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of vascular events. DESIGN: Meta-analysis of published and unpublished tabular data from randomised trials, with indirect estimation of the effects of traditional NSAIDs. DATA SOURCES: Medline and Embase (January 1966 to April 2005); Food and Drug Administration records; and data on file from Novartis, Pfizer, and Merck. REVIEW METHODS: Eligible studies were randomised trials that included a comparison of a selective COX 2 inhibitor versus placebo or a selective COX 2 inhibitor versus a traditional NSAID, of at least four weeks' duration, with information on serious vascular events (defined as myocardial infarction, stroke, or vascular death). Individual investigators and manufacturers provided information on the number of patients randomised, numbers of vascular events, and the person time of follow-up for each randomised group. RESULTS: In placebo comparisons, allocation to a selective COX 2 inhibitor was associated with a 42% relative increase in the incidence of serious vascular events (1.2%/year v 0.9%/year; rate ratio 1.42, 95% confidence interval 1.13 to 1.78; P = 0.003), with no significant heterogeneity among the different selective COX 2 inhibitors. This was chiefly attributable to an increased risk of myocardial infarction (0.6%/year v 0.3%/year; 1.86, 1.33 to 2.59; P = 0.0003), with little apparent difference in other vascular outcomes. Among trials of at least one year's duration (mean 2.7 years), the rate ratio for vascular events was 1.45 (1.12 to 1.89; P = 0.005). Overall, the incidence of serious vascular events was similar between a selective COX 2 inhibitor and any traditional NSAID (1.0%/year v 0.9%/year; 1.16, 0.97 to 1.38; P = 0.1). However, statistical heterogeneity (P = 0.001) was found between trials of a selective COX 2 inhibitor versus naproxen (1.57, 1.21 to 2.03) and of a selective COX 2 inhibitor versus non-naproxen NSAIDs (0.88, 0.69 to 1.12). The summary rate ratio for vascular events, compared with placebo, was 0.92 (0.67 to 1.26) for naproxen, 1.51 (0.96 to 2.37) for ibuprofen, and 1.63 (1.12 to 2.37) for diclofenac. CONCLUSIONS: Selective COX 2 inhibitors are associated with a moderate increase in the risk of vascular events, as are high dose regimens of ibuprofen and diclofenac, but high dose naproxen is not associated with such an excess
The efficacy and safety of aspirin in individuals with and without diabetes: a collaborative meta-analysis of individual participant data from randomised trials
No full textBackground: Whether aspirin is of net clinical benefit for the primary prevention of vascular events in those at high risk, such as some people with diabetes, is uncertain. Methods: Individual participant data from 26 randomised trials (123,361 individuals, 760,000 person-years) assessing aspirin versus control in people with and without diabetes were included. Major outcomes included serious vascular events (SVE: myocardial infarction, stroke or vascular death) and major extracranial bleeding (MEB). Findings: In the primary prevention setting, aspirin reduced SVE (0.65% vs 0.71% per year; relative risk (RR) 0.90 [95% confidence interval (CI) 0.85-0.96]; p=0.0006) and increased MEB (0.10% vs 0.07% per year; RR 1.52 [95% CI 1.30-1.78]; p5%, may derive net clinical benefit in the primary prevention setting. At a 5-year risk level of 5-10%, for example, people without diabetes might have a 1.6% (95% CI 1.1-2.1) reduction in 5-year SVE balanced against a 0.5% (95% CI 0.3-0.8) increase in 5-year MEB. In comparison, people with diabetes and 5-year risk of 5-10% might have a 1.7% (95% CI 1.2-2.2) reduction in 5-year SVE balanced against a 0.3% (95% CI 0.1-0.4) increase in 5-year MEB. Even if an approximate halving of baseline vascular risk by modern preventative measures such as statins is factored in before aspirin therapy is considered, aspirin may still have a worthwhile net clinical benefit in such people at least at moderate vascular risk. Interpretation: Some people without previous disease but at higher vascular risk, such as people with diabetes and 5-year risk >5%, may derive net clinical benefit from aspirin. Further direct randomised evidence in these individuals will help clarify the balance of risks and benefits
Adiposity and cause-specific mortality in the Mexico City Prospective Study
No full textBackground: Previous studies have reported conflicting results about the associations of adiposity with risk of all-cause mortality in Hispanic populations. Moreover, the relevance of different markers of adiposity for cause-specific mortality may differ between Hispanic and other populations.
Methods: Between 1998 and 2004, 159 755 adults aged ≥35 years from Mexico City were enrolled into a prospective study. Follow-up for cause-specific mortality was until 1st January 2018. Cox regression was used to estimate the relative risks (RRs) of death from specific causes associated with general adiposity (total body mass [BMI] and fat mass index [FMI]) and with abdominal adiposity (waist circumference, waist-hip ratio [WHR], and waist-height ratio [WHtR]), both overall and independently of each other, after adjustment for confounders. To minimise bias from reverse causation, the main analyses excluded those with screen-detected or diagnosed diabetes, other chronic diseases, and deaths in the first 5 years of follow-up. Excess attributable mortality and survival curves were derived from the RRs combined with national mortality rates.
Results: Among those aged 35-89 years when recruited, mean (standard deviation [SD]) BMI was 29.5 (4.9) kg/m2 and 34% were obese (>30 kg/m2). Both BMI and FMI had J-shaped associations with all-cause mortality, whereas waist circumference, WHR and WHtR were all linearly and positively related to mortality throughout the ranges studied. Each 5 kg/m2 higher BMI above 25 kg/m2 was associated with 32% higher risk of death at ages 40-74 years, chiefly due to a 38% higher risk of death from vascular or metabolic diseases. Across the full ranges, 1 SD higher levels of the adiposity markers were associated with 21% higher mortality at ages 40-74 years for BMI, 22% higher mortality for FMI, 25% higher mortality for waist circumference, 17% higher mortality for WHR, and 26% higher mortality for WHtR. For deaths from a vascular or metabolic cause, these estimates were 29%, 31%, 32%, 24% and 37%, respectively. Adjustment of BMI, WHR and WHtR for other markers of adiposity resulted in only a modest attenuation of the strength of the associations of these markers with mortality. By contrast, adjustment of waist circumference for the other markers of adiposity strengthened its association with mortality. Similarly, after adjustment for lean mass index, the association of FMI with all-cause mortality was strengthened. The various adiposity markers also displayed associations with several non-vascular non-metabolic causes of death. In particular, all of the adiposity markers were strongly related to death from respiratory and infective causes, but none were strongly associated with cancer mortality. Associations were broadly similar in men and women, somewhat stronger at younger than at older ages, and consistent according to levels of other confounders. Sensitivity analyses replicated the results of the main findings. Among those with diabetes, adiposity (particularly BMI) was inversely related to mortality, reflecting a reversal of causality caused by weight loss resulting from poor glycaemic control. The excess mortality associated with BMI above 30 kg/m2 compared with BMI below 25 kg/m2 accounted for 14% of all vascular and metabolic deaths. Applying the findings to current national Mexican death rates, compared with a BMI of 25 kg/m2 life expectancy from age 40 years was reduced by about 3 years at a BMI of 30 kg/m2, but by almost 10 years at a BMI of 40 kg/m2.
Conclusions: Consistent with findings in Western populations, both general, and especially, abdominal adiposity, were strongly predictive of all-cause and cause-specific mortality in this Mexican cohort, thereby refuting the ‘Hispanic obesity paradox’. The failure of previous studies of Hispanic populations to detect such associations is likely due to their failure to account for reverse causality bias (arising from weight loss due to poorly controlled diabetes). Further studies are needed to elucidate the causal relevance of the associations with different markers of adiposity, and to determine the mechanisms underlying such associations
Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis
No full textBackground: We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1–2 inhibitor, for the treatment of patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was done, which included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936) and is ongoing. Findings: Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77–0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45–0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72–0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes. Interpretation: In patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.</p
Prediction of coronary heart disease risk using polygenic risk scores in a Mexican population
No full textBackground: Coronary heart disease (CHD) is the global leading cause of death with a high genetic heritability and polygenic predisposition. Polygenic risk scores (PRSs) have been found to enhance CHD risk prediction in populations of European ancestry but evidence in other populations is limited. Thesis aims: 1) To conduct a literature review on PRSs published for CHD risk prediction. 2) To evaluate the transferability of eight external CHD PRSs in the Mexico City Prospective Study (MCPS). 3) To construct a novel MCPS-informed CHD PRS with greater representation of admixed-American ancestry. 4) To evaluate the predictive ability of integrated scores (combining genetic and clinical risk) for CHD.Methods: The Mexico City Prospective Study (MCPS) is a blood-based prospective cohort study with over 150,000 participants recruited between 1998 and 2004, aged over 35 years at the time of recruitment. The participants have been followed up through the National Death Registry. Imputed genotype data are available for over 140,000 participants.133,207 MCPS participants aged between 35 and 79 years at recruitment and with genetic data available were included in the main analyses. CHD was defined as self-reported diagnosis at baseline or death before age 80 with CHD listed as the primary or as a contributory cause of death. Logistic regression was used to assess the strength of association between each of the eight selected external CHD PRSs (comprising 44 to 6,472,620 single nucleotide polymorphisms [SNPs]) and CHD, adjusted for age, sex and the first seven genetic principal components (PCs). Discrimination was assessed using the area under the receiver-operating-characteristic curve (AUC).The novel MCPS-informed PRS was trained on 80% of the MCPS data, using a 10-fold cross validation (CV) approach, and evaluated three PRS construction methods with thousands of hyperparameter combinations (Pruning and Thresholding [P+T], LDpred2 and PRS-CSx). Genome wide association study (GWAS) analyses on CHD were conducted using MCPS data and metaanalysed with external GWAS results to boost sample size and incorporate genetic information from other ancestries, to be used as input for PRS construction algorithms. The best-performing candidate PRS of each method was then tested on the remaining 20% of the MCPS individuals that were not included for the PRS construction, using logistic regression with no other adjustments.The best-performing external CHD PRS was combined with three guideline-recommended clinical risk scores (two variations of SCORE2 and the Pooled Cohort Equation [PCE]) into integrated risk scores (clinical risk score x PRS). Each integrated score was evaluated for its performance by comparing it to the original clinical risk score from which it was derived, using logistic regression with no other adjustments and the net reclassification index (NRI).Results: Over two-thirds of the included participants were women and the mean baseline age was 51 years (standard deviation [SD] 12 years). In the analysis of external PRSs, all eight PRSs were positively and log-linearly associated with CHD, with odds ratios (ORs) per SD ranging from 1.05 (95% confidence interval [CI], 1.03-1.08) to 1.29 (1.25-1.33). Further adjustment for conventional CHD risk factors did not attenuate these associations materially. Multi-ancestry PRSs generally outperformed Eurocentric single-ancestry PRSs. Overall, PRSs only improved model discrimination marginally. Significant sex heterogeneity was identified for six of the eight PRSs, with PRSs consistently showing stronger associations in men compared to women (e.g., OR per SD was 1.37 [95%CI, 1.32-1.43] in men and 1.23 [1.18-1.28] in women for the Patel et al. PRS, which was the PRS with the strongest overall association with CHD).During the training of the candidate PRSs, multi-ancestry PRSs showed greater association strength and predictive ability. The novel MCPS-informed PRS was constructed using the PRSCSx method, including 1,180,546 SNPs and leveraging genetic information from three ancestries (i.e., admixed-Americans, Europeans and East-Asians). The MCPS-PRS was strongly associated with CHD when tested on the other 20% of the MCPS data, with an OR per SD of 1.34 (95%CI, 1.26-1.42), which was comparable to the best-performing external CHD PRS. The novel MCPS-informed score included eight times as many admixed-American individuals during its construction as the next most representative admixed-American CHD PRS.Compared to the clinical risk scores alone, the integrated risk scores predicted a higher CHD risk for participants in the top 20% risk stratum relative to the lowest 20% group (e.g., OR=12.92 for SCORE2-diabetes-recalibrated vs OR=13.66 for SCORE2-diabetes-recalibrated x PRS). In addition, based on a 7.5% CHD risk threshold, this integrated score improved CHD reclassification significantly, with categorical NRI of 1.50% (95% CI, 0.73%-2.27%) and continuous NRI of 17.50% (14.75%-20.24%) compared to SCORE2-diabetes-recalibrated. If extrapolated to the whole of Mexico, this integrated score has the potential to reclassify correctly approximately 30,000 more CHD cases among adults in Mexico. Conclusion: The selected external PRSs have reasonable transferability among Mexicans and could predict CHD risk independently of conventional CHD risk factors. Sex heterogeneity was identified in genetic predisposition to CHD with men showing greater risk than women. A novel multi-ancestry CHD PRS was developed, leveraging genetic information from three ancestries and including the largest number of admixed-Americans to date. When combining a PRS with a clinical risk score, the integrated risk scores improved CHD risk classification and have the potential to improve early detection of CHD and hence its prevention. Further studies are needed to enhance the representation of women and admixed-Americans in genetic research, and to improve the calibration of clinical risk scores for admixed-American populations
Multiple testing correction in a meta-analysis of all adverse events recorded in large long-term randomised trials of statin therapy
No full textBackground: Randomised trials have shown that statin therapy reduces the risk of major vascular events (ie, heart attacks, strokes and coronary revascularisation procedures) without any increase in the risk of nonvascular causes of death or of site-specific cancer, but does produce a small increase in the risk of muscle pain or weakness, diabetes and, possibly, haemorrhagic stroke. Although statins are widely prescribed, there are concerns that they might have a range of other side effects. This DPhil addresses these concerns through an individual-participant-data meta-analysis of all recorded adverse events (AEs) in all large, long-term, randomised, double-blind trials of statin therapy, taking into consideration the substantial challenges related to multiple hypotheses testing (MHT).
Methods: Double-blind randomised trials of statin therapy with at least 1,000 participants and a scheduled treatment duration of at least 2 years were included. Individual participant data on all AEs reported in 19 trials of statin vs placebo (123,940 randomised participants) and 4 trials of a more intensive versus a less intensive statin regimen (30,724 randomised participants) were analysed. A literature review identified potentially relevant MHT methods and simulation studies were done to assess their expected performance (ie, control of false positive [FP] and false negative results). Adverse event data were organised and coded according to a common medical dictionary based upon the Medical Dictionary for Regulatory Activities (MedDRA). Under the selected strategy, inverse-variance-weighted meta-analyses of the effects on all AEs were performed using time-to-event analyses for the first occurrence of each outcome among participants randomly assigned into each trial.
Results: The literature review identified 6,569 eligible papers, of which 337 were included for full text review. Five MHT methods (Holm, Hochberg, Hommel, Benjamini & Hochberg and Mehrotra & Adewale) were selected as the most appropriate based on their statistical control of type I and II error rates. Simulation analyses identified the Mehrotra & Adewale method, which controls the false discovery rate (FDR), as the most suitable as it resulted in a low expected number of FP results whilst maintaining reasonable statistical power to detect any real effects of statin therapy. Blinded (ie, using a ‘shuffled’ treatment allocation) meta-analyses of the trials of statin vs placebo were first done, which confirmed that no correction for MHT resulted in 179 (4.4%) FP findings while the Mehrotra & Adewale MHT method led to zero FPs. Unblinded analyses (ie, using the actual treatment allocation) of all non-lipid-related AEs then confirmed the already known beneficial effects of statins on major vascular events. They also showed that statin therapy was FDR-significantly associated with a reduced risk of having an arteriogram or an angiogram procedure. Subsequent analyses which ignored the already known beneficial or harmful effects of statin therapy, very rare outcomes and irrelevant overlap in tests, identified two new benefits of statin therapy: reductions in the risk of peripheral embolism and thrombosis (361 [0.6%] vs 451 [0.7%], rate ratio [RR] 0.72, 95% confidence interval [CI]: 0.61−0.83, p=0.0012), and carotid endarterectomy (47 [<0.1%] vs 83 [0.1%], RR 0.57, 95% CI: 0.40−0.80, p= 0.0013). However, statins were also FDR-significantly associated with an increased risk of hepatobiliary investigations (1,349 [2.2%] vs 1,025 [1.7%], RR 1.32, 95% CI: 1.22–1.43, p<0.0001) and the extremely rare outcome parosmia (18 vs 2, p=0.00036). The meta-analyses of the 4 trials of more vs less statin revealed that more intensive statin therapy was associated with an FDR-significantly reduced risk of coronary artery disorders (3,518 [22.9%] vs 3,779 [24.6%], RR 0.92, 95% CI: 0.88−0.96, p= 0.00025), general system disorders (5,098 [33.1%] vs 5,682 [37.1%],RR 0.87, 95% CI: 0.84−0.91, p<0.0001), any surgical and medical procedures (4,067 [26.4%] vs 4,333 [28.3%],RR 0.93, 95% CI: 0.89−0.97, p= 0.00059) and the rare AE of renal therapeutic procedures (30 [0.2%] vs 57 [0.4%], RR 0.54, 95% CI: 0.35−0.82, p= 0.0038). More intensive statin regimens were also FDR-significantly associated with an increased risk of hepatobiliary investigations (502 [3.3%] vs 253 [1.6%], RR 1.95, 95% CI: 1.69–2.25, p<0.0001) and high blood creatine phosphokinase (223 [1.4%] vs 146 [1.0%], RR 1.51, 95% CI: 1.24−1.86, p<0.0001).
Conclusion: These findings highlight the importance of using appropriate statistical methods to control for multiple testing. The results confirmed the already known benefits of statin therapy while identifying some new potential benefits and harms. However, the nature and frequency of the newly detected harms confirm that the benefits of statin therapy greatly outweigh the potential harms
Within-person variation in coronary risk factors: implications for the aetiology and prevention of coronary heart disease.
No full textEpidemiological studies clearly demonstrate the importance of numerous risk factors for coronary heart disease (CHD), including blood lipids, blood pressure, cigarette smoking and physical inactivity. These factors are widely believed to account for only around 50% of CHD cases. However, "within-person" variation in coronary risk factors can affect the size and even direction of estimated aetiological relationships, and though these effects have been explored for the univariate relations of blood pressure and blood cholesterol, much uncertainty remains. In this thesis, data from the British Regional Heart Study, a prospective study of cardiovascular disease in middle-aged British men, is used to investigate the extent and effects of "within-person variation" in a range of coronary risk factors. The effects on estimated relations with CHD are examined and the combined importance of the major risk factors to CHD risk assessed. The potential effectiveness of different CHD prevention strategies, and the size and cause of social inequalities in CHD are also estimated. The findings reveal a high degree of within-person variation in both established and novel coronary risk factors. Taking within-person variation into account, CHD risk-relations for blood lipids, blood pressure, cigarette smoking and physical inactivity increase in magnitude though the estimated protective effect from moderate alcohol intake is reduced. After correction for within-person variation, blood cholesterol, blood pressure and cigarette smoking together account for at least 75 80% of CHD cases in British men. Moderate population-wide improvements in these risk factors could there fore greatly reduce population levels of CHD, while "high-risk" strategies, unless applied to a large proportion of the population, are likely to have only a limited effect. Narrow ing social inequalities in CHD would also have a comparatively modest effect on CHD compared with population-wide control of the key causal coronary risk factors
Smoking and cause-specific mortality in large prospective studies from Cuba, Mexico, and the United States
No full textBackground: Tobacco smoking caused an estimated 100 million deaths in the 20th century, and unless widespread cessation and prevention occur, it could cause one billion deaths in the 21st century. An estimated 50 million smokers live in Latin America, but there is little direct evidence of the effects of smoking in Latin American populations.
Methods: Information from three large, prospective studies of Latin American populations was used to determine the relevance of smoking and smoking cessation to mortality. In 1996-2002, 146 556 Cuban adults aged ≥30 years were recruited into the Cuba Prospective Study, of whom 8691 died at ages 30-69 during follow-up. In 1998-2004, 159 755 Mexican adults aged ≥35 years were recruited into the Mexico City Prospective Study, of whom 19 091 died at ages 35-89 during follow-up (10 773 without major chronic disease at recruitment, and 8318 with major chronic disease). Finally, in 1997-2014, 446 531 adults aged ≥30 years were recruited into the US National Health Interview Survey, of whom 48 440 died at ages 30-89 during follow-up (3242 Mexican Americans, 2177 other Hispanics, 34 482 non-Hispanic Whites, 6978 non-Hispanic Blacks, and 1561 participants of other race/ethnicity). In each prospective study, Cox regression (adjusting for age-at-risk, sex, education, area, and alcohol consumption) was used to relate smoking habits at recruitment to mortality rate ratios (RRs). Resurveys of Cuban and Mexican participants informed ‘usual’ smoking behaviours.
Results: In the Cuba Prospective Study, half of men and one-quarter of women were smokers at recruitment. One-third of current cigarette smokers reported having started smoking regularly in childhood (age <15 years). Compared with never smokers, all-cause mortality RRs at ages 30-69 for Cuban cigarette smokers (mean 15 cigarettes/day) who had started at ages 5-9, 10-14, 15-19, and ≥20 years were 2.51 (95%CI 2.21-2.85), 1.83 (1.72-1.95), 1.56 (1.46-1.65) and 1.50 (1.39-1.62), respectively (overall RR for current smokers: 1.66 [1.59-1.74]). In the Mexico City Prospective study, half of men and one-quarter of women were smokers at recruitment, and one-fifth of smokers began smoking before age 15, but consumption was low (8 cigarettes/day among daily smokers). Among Mexican adults without chronic disease at recruitment, compared with never smokers, the all-cause mortality RR at ages 35-69 for smoking ≥10 cigarettes/day was 1.52 (1.36-1.70), and was similar at ages 70-89 and among men and women (overall RR for daily smokers: 1.27 [1.19-1.35]). In the US National Health Interview Survey prospective study, one-fifth of smokers began smoking before age 15, which was associated with three times the mortality rate at ages 30-69 of never smoking, with even greater risk among those starting to smoke before age 10. Compared with never smokers, the all-cause mortality RR for daily smokers was
1.39 (1.24-1.54) among Mexican Americans, 2.45 (2.20-2.72) among other Hispanics, 2.74 (2.61-2.89) among non-Hispanic Whites, 2.29 (2.19-2.41) among non-Hispanic Blacks, and 2.08 (1.84-2.35) among participants of other races. In each of these populations, smoking cessation by age ~40 avoided most of the excess risk associated with continued smoking.
Conclusions: In Cubans, Mexicans, and Mexican Americans, the excess mortality risk associated with smoking was substantial, but was lower than the risk associated with smoking among Western populations. This may be due to a combination of intermittent
smoking patterns in each of these populations, lower levels of consumption among Mexicans and Mexican Americans, and variability in products smoked over time. This thesis provides the first reliable, direct evidence of the relationship between smoking and mortality in Cuba and Mexico, which led to estimates of smoking-attributable mortality similar to those from the Global Burden of Disease (GBD) Study. Therefore, the GBD Study may provide the best available estimates of smoking-attributable mortality in other Latin American populations in which there is not yet direct evidence
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