Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV1 (PURE): an international, community-based cohort study

Summary: Background: The associations between the extent of forced expiratory volume in 1 s (FEV1) impairment and mortality, incident cardiovascular disease, and respiratory hospitalisations are unclear, and how these associations might vary across populations is unknown. Methods: In this international, community-based cohort study, we prospectively enrolled adults aged 35–70 years who had no intention of moving residences for 4 years from rural and urban communities across 17 countries. A portable spirometer was used to assess FEV1. FEV1 values were standardised within countries for height, age, and sex, and expressed as a percentage of the country-specific predicted FEV1 value (FEV1%). FEV1% was categorised as no impairment (FEV1% ≥0 SD from country-specific mean), mild impairment (FEV1% <0 SD to −1 SD), moderate impairment (FEV1% <–1 SD to −2 SDs), and severe impairment (FEV1% <–2 SDs [ie, clinically abnormal range]). Follow-up was done every 3 years to collect information on mortality, cardiovascular disease outcomes (including myocardial infarction, stroke, sudden death, or congestive heart failure), and respiratory hospitalisations (from chronic obstructive pulmonary disease, asthma, pneumonia, tuberculosis, or other pulmonary conditions). Fully adjusted hazard ratios (HRs) were calculated by multilevel Cox regression. Findings: Among 126 359 adults with acceptable spirometry data available, during a median 7·8 years (IQR 5·6–9·5) of follow-up, 5488 (4·3%) deaths, 5734 (4·5%) cardiovascular disease events, and 1948 (1·5%) respiratory hospitalisation events occurred. Relative to the no impairment group, mild to severe FEV1% impairments were associated with graded increases in mortality (HR 1·27 [95% CI 1·18–1·36] for mild, 1·74 [1·60–1·90] for moderate, and 2·54 [2·26–2·86] for severe impairment), cardiovascular disease (1·18 [1·10–1·26], 1·39 [1·28–1·51], 2·02 [1·75–2·32]), and respiratory hospitalisation (1·39 [1·24–1·56], 2·02 [1·75–2·32], 2·97 [2·45–3·60]), and this pattern persisted in subgroup analyses considering country income level and various baseline risk factors. Population-attributable risk for mortality (adjusted for age, sex, and country income) from mildly to moderately reduced FEV1% (24·7% [22·2–27·2]) was larger than that from severely reduced FEV1% (3·7% [2·1–5·2]) and from tobacco use (19·7% [17·2–22·3]), previous cardiovascular disease (5·5% [4·5–6·5]), and hypertension (17·1% [14·6–19·6]). Population-attributable risk for cardiovascular disease from mildly to moderately reduced FEV1 was 17·3% (14·8–19·7), second only to the contribution of hypertension (30·1% [27·6–32·5]). Interpretation: FEV1 is an independent and generalisable predictor of mortality, cardiovascular disease, and respiratory hospitalisation, even across the clinically normal range (mild to moderate impairment). Funding: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Ontario Ministry of Health and Long-Term Care, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline, Novartis, and King Pharma. Additional funders are listed in the appendix

Availability and affordability of blood pressure-lowering medicines and the effect on blood pressure control in high-income, middle-income, and low-income countries: an analysis of the PURE study data

Background: Hypertension is considered the most important risk factor for cardiovascular diseases, but its control is poor worldwide. We aimed to assess the availability and affordability of blood pressure-lowering medicines, and the association with use of these medicines and blood pressure control in countries at varying levels of economic development. Methods: We analysed the availability, costs, and affordability of blood pressure-lowering medicines with data recorded from 626 communities in 20 countries participating in the Prospective Urban Rural Epidemiological (PURE) study. Medicines were considered available if they were present in the local pharmacy when surveyed, and affordable if their combined cost was less than 20% of the households' capacity to pay. We related information about availability and affordability to use of these medicines and blood pressure control with multilevel mixed-effects logistic regression models, and compared results for high-income, upper-middle-income, lower-middle-income, and low-income countries. Data for India are presented separately because it has a large generic pharmaceutical industry and a higher availability of medicines than other countries at the same economic level. Findings: The availability of two or more classes of blood pressure-lowering drugs was lower in low-income and middle-income countries (except for India) than in high-income countries. The proportion of communities with four drug classes available was 94% in high-income countries (108 of 115 communities), 76% in India (68 of 90), 71% in upper-middle-income countries (90 of 126), 47% in lower-middle-income countries (107 of 227), and 13% in low-income countries (nine of 68). The proportion of households unable to afford two blood pressure-lowering medicines was 31% in low-income countries (1069 of 3479 households), 9% in middle-income countries (5602 of 65 471), and less than 1% in high-income countries (44 of 10 880). Participants with known hypertension in communities that had all four drug classes available were more likely to use at least one blood pressure-lowering medicine (adjusted odds ratio [OR] 2·23, 95% CI 1·59–3·12); p<0·0001), combination therapy (1·53, 1·13–2·07; p=0·054), and have their blood pressure controlled (2·06, 1·69–2·50; p<0·0001) than were those in communities where blood pressure-lowering medicines were not available. Participants with known hypertension from households able to afford four blood pressure-lowering drug classes were more likely to use at least one blood pressure-lowering medicine (adjusted OR 1·42, 95% CI 1·25–1·62; p<0·0001), combination therapy (1·26, 1·08–1·47; p=0·0038), and have their blood pressure controlled (1·13, 1·00–1·28; p=0·0562) than were those unable to afford the medicines. Interpretation: A large proportion of communities in low-income and middle-income countries do not have access to more than one blood pressure-lowering medicine and, when available, they are often not affordable. These factors are associated with poor blood pressure control. Ensuring access to affordable blood pressure-lowering medicines is essential for control of hypertension in low-income and middle-income countries. Funding: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Canadian Institutes of Health Research Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, the Ontario Ministry of Health and Long-Term Care, pharmaceutical companies (with major contributions from AstraZeneca [Canada], Sanofi Aventis [France and Canada], Boehringer Ingelheim [Germany amd Canada], Servier, and GlaxoSmithKline), Novartis and King Pharma, and national or local organisations in participating countries