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Table 2 Joint effects of smoking status and CKM syndrome on CVD outcomes with significant interaction

From: Cardiovascular-kidney-metabolic syndrome modifies smoking-related risk for cardiovascular diseases: findings from an observational cohort study in UK Biobank

听

Never smokers

Former smokers

Current smokers

P for trend

Multiplicative interaction

Additive interaction

Case/control

HR (95% CI)

Case/control

HR (95% CI)

Case/control

HR (95% CI)

HR

P

RERIc (95% CI)

Ischemic stroke

鈥僀KM stage 0

60/14399

Ref

39/6654

1.24 (0.83, 1.85)

15/2263

1.47 (0.84, 2.59)

鈥�< 0.001

1.03

0.594a

0.32(0.02,0.58)

鈥僀KM stage 1

56/8206

1.53 (1.06, 2.2)

31/4812

1.23 (0.79, 1.89)

10/1473

1.53 (0.78, 2.98)

听听

0.007b

听

鈥僀KM stage 2

1480/107702

1.98 (1.53, 2.57)

1316/70400

2.23 (1.71, 2.89)

447/19650

3.47 (2.65, 4.56)

听听听听

鈥僀KM stage 3

84/1009

5.66 (4.04, 7.92)

78/1312

3.82 (2.71, 5.39)

86/1054

5.74 (4.1, 8.03)

听听听听

Abdominal aortic aneurysm

鈥僀KM stage 0

4/14455

Ref

6/6687

2.67 (0.75, 9.45)

8/2270

10.39 (3.12, 34.56)

鈥�< 0.001

0.83

0.082a

2.79(1.12,5.55)

鈥僀KM stage 1

4/8258

1.58 (0.39, 6.31)

3/4840

1.46 (0.33, 6.52)

3/1480

6.26 (1.4, 27.98)

听听

0.182b

听

鈥僀KM stage 2

178/109004

2.46 (0.91, 6.62)

380/71336

5.54 (2.06, 14.87)

240/19857

19.05 (7.08, 51.27)

听听听听

鈥僀KM stage 3

10/1083

3.91 (1.22, 12.53)

36/1354

9.49 (3.36, 26.82)

45/1095

17.68 (6.33, 49.43)

听听听听

Coronary artery disease

鈥僀KM stage 0

208/14251

Ref

118/6575

1.12 (0.89, 1.4)

83/2195

2.26 (1.75, 2.91)

鈥�< 0.001

0.88

鈥�< 0.001a

0.22(0.04,0.41)

鈥僀KM stage 1

160/8102

1.26 (1.02, 1.55)

124/4719

1.45 (1.16, 1.81)

51/1432

2.11 (1.55, 2.87)

听听

鈥�< 0.001b

听

鈥僀KM stage 2

6143/103039

2.5 (2.17, 2.87)

5645/66071

2.93 (2.55, 3.37)

1807/18290

3.99 (3.45, 4.61)

听听听听

鈥僀KM stage 3

236/857

5.41 (4.48, 6.54)

306/1084

5.05 (4.22, 6.04)

217/923

4.57 (3.77, 5.54)

听听听听

Aortic valve stenosis

鈥僀KM stage 0

22/14437

Ref

13/6680

1.08 (0.55, 2.15)

7/2271

1.96 (0.84, 4.59)

鈥�< 0.001

0.86

0.038a

0.38(鈭�0.18,0.82)

鈥僀KM stage 1

19/8243

1.41 (0.76, 2.6)

16/4827

1.63 (0.86, 3.11)

7/1476

3.01 (1.28, 7.05)

听听

0.071b

听

鈥僀KM stage 2

802/108380

2.61 (1.7, 3.99)

854/70862

3.37 (2.2, 5.15)

194/19903

3.85 (2.47, 5.99)

听听听听

鈥僀KM stage 3

60/1033

8.12 (4.95, 13.32)

77/1313

7.64 (4.72, 12.36)

46/1094

6.34 (3.79, 10.6)

听听听听

Heart failure

鈥僀KM stage 0

77/14382

Ref

54/6639

1.32 (0.94, 1.88)

23/2255

1.65 (1.04, 2.64)

鈥�< 0.001

0.94

0.157a

0.31(0.004,0.58)

鈥僀KM stage 1

58/8204

1.21 (0.86, 1.71)

46/4797

1.36 (0.95, 1.96)

26/1457

2.94 (1.88, 4.58)

听听

鈥�< 0.001b

听

鈥僀KM stage 2

2104/107078

2.04 (1.62, 2.56)

2158/69558

2.59 (2.06, 3.25)

691/19406

3.78 (2.98, 4.79)

听听听听

鈥僀KM stage 3

140/953

6.27 (4.73, 8.31)

184/1206

6.01 (4.59, 7.89)

141/999

6.18 (4.66, 8.2)

听听听听

Peripheral vascular disease

鈥僀KM stage 0

27/14432

Ref

15/6678

1.05 (0.56, 1.98)

19/2259

3.59 (1.99, 6.46)

鈥�< 0.001

1.07

0.368a

1.42(0.87,2)

鈥僀KM stage 1

13/8249

0.76 (0.39, 1.48)

9/4834

0.75 (0.35, 1.59)

10/1473

3 (1.45, 6.2)

听听

0.003b

听

鈥僀KM stage 2

388/108794

1.04 (0.71, 1.54)

636/71080

2.1 (1.43, 3.1)

420/19677

6.04 (4.08, 8.94)

听听听听

鈥僀KM stage 3

34/1059

3.99 (2.39, 6.67)

63/1327

5.42 (3.42, 8.59)

91/1049

10.53 (6.79, 16.34)

听听听听

MACE

鈥僀KM stage 0

84/14375

Ref

37/6656

0.88 (0.59, 1.29)

47/2231

2.99 (2.09, 4.28)

鈥�< 0.001

0.85

鈥�< 0.001a

0.41(0.13,0.68)

鈥僀KM stage 1

57/8205

1.1 (0.78, 1.54)

40/4803

1.14 (0.78, 1.66)

28/1455

2.75 (1.79, 4.22)

听听

鈥�< 0.001b

听

鈥僀KM stage 2

2567/106615

2.49 (2, 3.09)

2341/69375

2.85 (2.29, 3.55)

1041/19056

5.25 (4.2, 6.57)

听听听听

鈥僀KM stage 3

126/967

6.44 (4.86, 8.51)

168/1222

6.07 (4.65, 7.93)

129/1011

6.1 (4.62, 8.06)

听听听听

Stroke

鈥僀KM stage 0

109/14350

Ref

61/6632

1.08 (0.79, 1.47)

23/2255

1.27 (0.81, 1.99)

鈥�< 0.001

1.05

0.279a

0.31(0.08,0.52)

鈥僀KM stage 1

76/8186

1.16 (0.86, 1.55)

46/4797

1.03 (0.73, 1.45)

14/1469

1.2 (0.69, 2.09)

听听

0.002b

听

鈥僀KM stage 2

2061/107121

1.59 (1.31, 1.92)

1803/69913

1.79 (1.47, 2.18)

597/19500

2.69 (2.19, 3.31)

听听听听

鈥僀KM stage 3

100/993

4.08 (3.09, 5.38)

93/1297

2.81 (2.12, 3.73)

97/1043

3.96 (3, 5.24)

听听听听

Coronary heart disease

鈥僀KM stage 0

253/14206

Ref

147/6546

1.15 (0.94, 1.41)

91/2187

2.03 (1.6, 2.58)

鈥�< 0.001

0.90

鈥�< 0.001a

0.16(0.001,0.33)

鈥僀KM stage 1

186/8076

1.2 (1, 1.46)

156/4687

1.51 (1.24, 1.84)

56/1427

1.91 (1.43, 2.55)

听听

鈥�< 0.001b

听

鈥僀KM stage 2

6919/102263

2.37 (2.09, 2.68)

6251/65465

2.76 (2.43, 3.13)

1969/18128

3.66 (3.21, 4.18)

听听听听

鈥僀KM stage 3

249/844

4.94 (4.14, 5.9)

328/1062

4.74 (4.01, 5.6)

235/905

4.3 (3.59, 5.14)

听听听听

All cardiovascular disease

鈥僀KM stage 0

352/14107

Ref

206/6487

1.15 (0.97, 1.37)

113/2165

1.84 (1.49, 2.28)

鈥�< 0.001

0.93

鈥�< 0.001a

0.2(0.05,0.32)

鈥僀KM stage 1

252/8010

1.18 (1, 1.38)

198/4645

1.38 (1.16, 1.64)

66/1417

1.65 (1.27, 2.14)

听听

鈥�< 0.001b

听

鈥僀KM stage 2

8619/100563

2.13 (1.91, 2.37)

7716/64000

2.47 (2.22, 2.75)

2453/17644

3.37 (3.01, 3.78)

听听听听

鈥僀KM stage 3

319/774

4.64 (3.98, 5.41)

385/1005

4.07 (3.51, 4.72)

305/835

4.14 (3.54, 4.83)

听听听听
  1. All models adjusted for age, sex, employment status, income levels, education, physical activity, diet, healthy sleep score, and alcohol consumption
  2. Abbreviations: N total sample size, Case number of cases, HR hazard ratio, CI confidence interval, P P value, RERI relative excess risk due to interaction, CVD cardiovascular disease, CKM cardiovascular-kidney-metabolic, Ref. reference group for each CVD type, MACE major adverse cardiovascular events
  3. a P value for effect modification on the multiplicative scale, evaluated by including a multiplicative interaction term between CKM syndrome stage and smoking traits (both treated as ordinal variables) in the Cox regression models
  4. b P value for effect modification on the multiplicative scale, evaluated using a likelihood ratio test comparing models with and without the cross-product term, with CKM syndrome (Stage 0 to 3) and smoking traits (never, former, current smoker) treated as categorical variables
  5. c RERI calculated by transformed smoking status (smoker vs. non-smoker) and CKM syndrome (Stage 0鈥�1 vs. Stage 2鈥�3) into binary variables
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