Journal Club

1. Journal Club Berry JD, Dyer A, Cai X, Garside DB, Ning H, Thomas A, Greenland P, Van Horn L, Tracy RP, Lloyd-Jones DM. Lifetime risks of cardiovascular disease. N Engl J Med. 2012 Jan 26;366(4):321-9. Choi HK, Soriano LC, Zhang Y, Rodríguez LA. Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study. BMJ. 2012 Jan 12;344:d8190. doi: 10.1136/bmj.d8190. 埼玉医科大学　総合医療センター　内分泌・糖尿病内科 Department of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University 松田　昌文 Matsuda, Masafumi 2012年2月9日8:30-8:55 ８階　医局

2. The University of Texas Southwestern Medical Center, Department of Medicine, Division of Cardiology, Dallas (J.D.B.); the Department of Preventive Medicine (A.D., X.C., D.B.G., H.N., P.G., L.V.H., D.M.L.-J.) and the Bluhm Cardiovascular Institute, Department of Medicine (P.G., D.M.L.-J.), Northwestern University Feinberg School of Medicine, Chicago; the Coordinating Centers for Biometric Research, Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis (A.T.); and the University of Vermont College of Medicine, Burlington (R.P.T.). N Engl J Med 2012;366:321-9.

3. Background The lifetime risks of cardiovascular disease have not been reported across the agespectrum in black adults and white adults.

4. Methods We conducted a meta-analysis at the individual level using data from 18 cohort studies involving a total of 257,384 black men and women and white men and women whose risk factors for cardiovascular disease were measured at the ages of 45, 55, 65, and 75 years. Blood pressure, cholesterol level, smoking status, and diabetes status were used to stratify participants according to risk factors into five mutually exclusive categories. The remaining lifetime risks of cardiovascular events were estimated for participants in each category at each age, with death free of cardiovascular disease treated as a competing event.

8. Figure 1. Lifetime Risk of Death from Cardiovascular Disease among Black Men and White Men at 55 Years of Age, According to the Aggregate Burden of Risk Factors and Adjusted for Competing Risks of Death. The risk-factor profile was considered optimal when a participant had a total cholesterol level of less than 180 mg per deciliter (4.7 mmol per liter) and untreated blood pressure of less than 120 mm Hg systolic and less than 80 mm Hg diastolic, was a nonsmoker, and did not have diabetes. It was considered not to be optimal for nonsmokers without diabetes who had a total cholesterol level of 180 to 199 mg per deciliter or untreated systolic blood pressure of 120 to 139 mm Hg or untreated diastolic blood pressure of 80 to 89 mm Hg. Levels of risk factors were viewed as elevated for nonsmokers without diabetes who had a total cholesterol level of 200 to 239 mg per deciliter (5.17 to 6.18 mmol per liter) or untreated systolic blood pressure of 140 to 159 mm Hg or untreated diastolic blood pressure of 90 to 99 mm Hg. Major risk factors were defined as current smoking, diabetes, treatment for hypercholesterolemia, an untreated total cholesterol level of at least 240 mg per deciliter (6.21 mmol per liter), and treatment for hypertension, untreated systolic blood pressure of at least 160 mm Hg, or untreated diastolic blood pressure of at least 100 mm Hg. The data were derived from the 17 studies in the pooled cohort; data from the Multiple Risk Factor Intervention Trial were not included.

9. Figure 2. Lifetime Risk of Death from Cardiovascular Disease among Black Women and White Women at 55 Years of Age, According to the Aggregate Burden of Risk Factors and Adjusted for Competing Risks of Death. The data were derived from the 17 studies in the pooled cohort; data from the Multiple Risk Factor Intervention Trial were not included.

10. Supplemental Figure 1a: Lifetime risk for CVD death adjusted for the competing risk of death for men according to aggregate risk factor burden at 45 years of age. Data from the pooled analysis of 17 studies (excluding MRFIT screenees).

11. Supplemental Figure 1b: Lifetime risk for CVD death adjusted for the competing risk of death for women according to aggregate riskfactor burden at 45 years of age. Data from the pooled analysis of 17 studies (excluding MRFIT screenees).

12. Supplemental Figure 2a: Lifetime risk for CVD death adjusted for the competing risk of death for white men screenees in the Multiple Risk Factor Intervention Trial according to aggregate risk factor burden measured at age 55 years.

13. Supplemental Figure 2b: Lifetime risk for CVD death adjusted for the competing risk of death for black men screenees in the Multiple Risk Factor Intervention Trial according to aggregate risk factor burden measured at age 55 years.

14. Supplemental Figure 3: 20-year risk for CVD death adjusted for the competing risk of death for men and women born prior to and after 1920 according to aggregate risk factor burden at 55 years of age; (3a) Men, 1 elevated risk factor; (3b) Men, 1 major risk factor; (3c) Men, ≥ 2 major risk factors; (3d) Women, 1 elevated risk factor; (3e) Women, 1 major risk factor; (3f) Women, ≥ 2 major risk factors. Data from the pooled analysis of 17 studies (excluding MRFIT screenees).

15. Supplemental Figure 4: 20-year risk for CVD death adjusted for the competing risk of death for men and women according to aggregate risk factor burden at 55 years of age for participants in NHANES I, II, and III; (4a) Men, 1 major risk factor; (4b) Men, ≥ 2 major risk factors; (4c) Women, 1 major risk factor; (4d) Women, ≥ 2 major risk factors.

16. Supplemental Figure 5a: Comparison of cumulative incidence of CVD death adjusted for competing risk (Lifetime Risk estimate) with cumulative incidence of CVD death unadusted for competing risk (Kaplan-Meier estimate) in men with ≥ 2 risk factors. Data from the pooled analysis of 17 studies (excluding MRFIT screenees).

17. Supplemental Figure 5b: Comparison of cumulative incidence of CVD death adjusted for competing risk (Lifetime Risk estimate) with cumulative incidence of CVD death unadusted for competing risk (Kaplan-Meier estimate) in women with ≥ 2 risk factors. Data from the pooled analysis of 17 studies (excluding MRFIT screenees).

20. Results We observed marked differences in the lifetime risks of cardiovascular disease across risk-factor strata. Among participants who were 55 years of age, those with an optimal risk-factor profile (total cholesterol level, <180 mg per deciliter [4.7 mmol per liter]; blood pressure, <120 mm Hg systolic and 80 mm Hg diastolic; nonsmoking status; and nondiabetic status) had substantially lower risks of death from cardiovascular disease through the age of 80 years than participants with two or more major risk factors (4.7% vs. 29.6% among men, 6.4% vs. 20.5% among women). Those with an optimal risk-factor profile also had lower lifetime risks of fatal coronary heart disease or nonfatal myocardial infarction (3.6% vs. 37.5% among men, <1% vs. 18.3% among women) and fatal or nonfatal stroke (2.3% vs. 8.3% among men, 5.3% vs. 10.7% among women). Similar trends within risk-factor strata were observed among blacks and whites and across diverse birth cohorts.

21. Conclusions Differences in risk-factor burden translate into marked differences in the lifetime risk of cardiovascular disease, and these differences are consistent across race and birth cohorts. (Funded by the National Heart, Lung, and Blood Institute.)

22. Message コホート研究18件の参加者約25万人のデータを対象に、心血管疾患の生涯リスクを推定。55歳時に危険因子が至適な人（総コレステロール値180mg/dL未満、収縮/拡張期血圧120/80mmHg未満など）は、危険因子2つ以上の人に比べ、80歳までの心血管死リスクが低かった（男性4.7％対29.6％、女性6.4％対20.5％）。

25. Objective To determine the independent associations of antihypertensive drugs with the risk of incident gout among people with hypertension.

26. Design Nested case-control study. SettingUK general practice database, 2000-7. Participants All incident cases of gout (n=24 768) among adults aged 20-79 and a random sample of 50,000 matched controls. Main outcome measure Relative risk of incident gout associated with use of antihypertensive drugs.

28. *Adjusted for sex, age, calendar year, number of visits to a general practitioner, body mass index, alcohol intake, ischaemic heart disease, hyperlipidaemia, diabetes, chronic renal failure and heart failure, and simultaneously for the other antihypertensive drug classes.

29. *Adjusted for sex, age, calendar year, number of visits to general practitioner, body mass index, alcohol intake, ischaemic heart disease, hyperlipidaemia, diabetes, chronic renal failure, heart failure, and simultaneously for the other antihypertensive drug classes.

30. *Adjusted for sex, age, calendar year, number of visits to general practitioner, body mass index, alcohol intake, ischaemic heart disease, hyperlipidaemia, diabetes, chronic renal failure, heart failure, and simultaneously for the other antihypertensive drug classes.

31. Results After adjusting for age, sex, body mass index, visits to the general practitioner, alcohol intake, and pertinent drugs and comorbidities, the multivariate relative risks of incident gout associated with current use of antihypertensive drugs among those with hypertension (n=29 138) were 0.87 (95% confidence interval 0.82 to 0.93) for calcium channel blockers, 0.81 (0.70 to 0.94) for losartan, 2.36 (2.21 to 2.52) for diuretics, 1.48 (1.40 to 1.57) for β blockers, 1.24 (1.17 to 1.32) for angiotensin converting enzyme inhibitors, and 1.29 (1.16 to 1.43) for non-losartan angiotensin II receptor blockers. Similar results were obtained among those without hypertension. The multivariate relative risks for the duration of use of calcium channel blockers among those with hypertension were 1.02 for less than one year, 0.88 for 1-1.9 years, and 0.75 for two or more years and for use of losartan they were 0.98, 0.87, and 0.71, respectively (both P<0.05 for trend).

32. Conclusions Compatible with their urate lowering properties, calcium channel blockers and losartan are associated with a lower risk of incident gout among people with hypertension. By contrast, diuretics, β blockers, angiotensin converting enzyme inhibitors, and non-losartan angiotensin II receptor blockers are associated with an increased risk of gout.

33. Message 英国の一般診療データベースから、降圧薬使用中の高血圧患者2万9138人を対象に、降圧薬と痛風の関連をコホート内症例対照研究で評価。年齢、性別などを調整後、痛風発症の多変量相対リスクは、カルシウム（Ca）拮抗薬0.87、ロサルタン0.81、利尿薬2.36、β遮断薬1.48、アンジオテンシン変換酵素阻害薬1.24だった。