Table 1
Study cohort characteristics of patients diagnosed with RCC in Finland between 1995–2012.
|
Total, n
|
User of antihypertensive medication
|
Non-user of antihypertensive medication
|
Cohort
|
13,873
|
10,953 (79.0%)
|
2,920 (21.0%)
|
Men
|
7,720 (55.6 %)
|
5,899 (76.4%)
|
1,821 (23.6%)
|
Women
|
6,153 (44.4 %)
|
5,054 (82,1)
|
1,099 (17.9%)
|
Age at diagnosis, mean
|
67.2
|
69.1
|
60.2
|
Deaths overall
|
8,541 (61.6 %)
|
6,753
|
1,788
|
RCC as cause of death
|
5,179 (37.3 %)
|
3,921
|
1,258
|
Overall years of follow-up, median
|
6.20
|
6.12
|
6.49
|
Comorbidities
|
|
|
|
Dyslipidemia
|
5,033
|
4,705(43.0%)
|
328 (11.2%)
|
Diabetes
|
3,123
|
2,912 (26.6%)
|
211 (7.2%)
|
Obesity
|
265
|
247 (2,3%)
|
18 (0.6%)
|
RCC stage at diagnosis
|
|
|
|
Local/local nodular
|
6,341 (45.7 %)
|
5,117 (46.7%)
|
1,224 (41.9%)
|
Distantly metastatic
|
4,588 (33.1 %)
|
3,516 (32.1%)
|
1,072 (36.7%)
|
Unknown
|
2,944 (21.2 %)
|
2,320 (21.2%)
|
624 (21.4%)
|
Primary treatment
|
|
|
|
Surgery
|
6,624 (47.7 %)
|
5,375 (49.1%)
|
1,249 (42.8%)
|
Palliative surgery
|
1,351 (9.7 %)
|
996 (9.1%)
|
355 (12.2%)
|
Cytostatic/radiation
|
934 (6.7 %)
|
676 (6.2%)
|
258 (8.8%)
|
Other
|
154 (1.1 %)
|
129 (1.2%)
|
25 (0.9%)
|
Unknown
|
4,810 (34.7%)
|
3,777 (34.5%)
|
1,033 (35.4%)
|
Table 2
The risk of distantly metastatic RCC at the time of diagnosis. Values reaching statistical significance (p < 0.05) are marked *. A cohort of 13,873 newly diagnosed patients with RCC in Finland between 1995-2012.
|
OR (95% CI) age-adjusted
|
OR (95% CI) multivariable-adjusted
|
ACE-inhibitors
|
0.93 (0.81–1.06)
|
1.01 (0.88–1.16)
|
AR-blockers
|
1.78 (0.90–3.50)
|
1.87 (0.94–3.72)
|
Ca2-channel blockers
|
0.87 (0.77–0.98)*
|
0.92 (0.81–1.05)
|
Diuretics
|
0.99 (0.88–1.12)
|
0.95 (0.84–1.08)
|
b-blockers
|
0.92 (0.83–1.03)
|
1.02 (0.91–1.14)
|
Table 3
The overall risk of RCC specific death and different antihypertensive medication. HRs with statistical significance (p < 0.05) are marked with *. A cohort of 13,873 newly diagnosed patients with RCC in Finland between 1995-2012.
|
HR (95% CI)age-adjusted
|
HR (95% CI)multivariable-adjusted
|
ACE-inhibitors
|
1.04 (0.95–1.14)
|
1.10 (1.01–1.21)*
|
ARB
|
0.91 (0.53–1.58)
|
0.86 (0.50–1.49)
|
Ca2-channel blockers
|
0.92 (0.85–1.01)
|
1.00 (0.91–1.09)
|
Diuretics
|
1.10 (1.01–1.19)*
|
1.10 (1.01–1.19)*
|
B-blockers
|
0.99 (0.92–1.06)
|
1.06 (0.98–1.14)
|
Table 4
The overall hazard ratio (HR) between RCC specific death and antihypertensive medication in time-dependent analysis. Cohort of 13,873 newly diagnosed patients with RCC in Finland between 1995-2012.
|
HR (95% CI)age-adjusted
|
HR (95% CI)multivariable-adjusted
|
ACE-inhibitor
|
0.76 (0.71–0.82)
|
0.88 (0.82–0.95)
|
Angiotensin receptor blocker
|
0.69 (0.63–0.76)
|
0.91 (0.83–1.00)
|
Calcium channel blocker
|
0.68 (0.63–0.73)
|
0.78 (0.72–0.83)
|
b-blocker
|
0.91 (0.85–0.97)
|
1.08 (1.01–1.14)
|
Diuretics
|
1.13 (1.06–1.20)
|
1.03 (0.97–1.10)
|
Table 5
Risk of RCC specific death and antihypertensive medication use stratified by intensity of use after RCC diagnosis. A cohort of 13,873 newly diagnosed patients with RCC in Finland between 1995-2012.
|
HR (95% CI)age adjusted
|
HR (95% CI)multivariable adjusted
|
ACE-inhibitors, DDD amount
|
|
|
< 76.4
|
0.73 (0.67–0.79)
|
0.80 (0.74–0.87)
|
76.4–392.0
|
0.64 (0.58–0.73)
|
0.78 (0.69–0.88)
|
> 392.0
|
0.45 (0.37–0.54)
|
0.54 (0.45–0.66)
|
ARB, DDD amount
|
|
|
< 205.3
|
0.60 (0.54–0.67)
|
0.75 (0.68–0.84)
|
205.3–786.1
|
0.67 (0.57–0.82)
|
0.86 (0.71–1.03)
|
> 786.1
|
0.46 (0.35–0.61)
|
0.66 (0.50–0.87)
|
Ca2-channel blockers, DDD amount
|
|
|
< 61.3
|
0.71 (0.64–0.78)
|
0.76 (0.69–0.84)
|
61.3–331.0
|
0.65 (0.56–0.74)
|
0.75 (0.65–0.86)
|
> 331.0
|
0.85 (0.68–1.05)
|
1.12 (0.90–1.40)
|
b-blockers
|
|
|
< 76.0
|
0.81 (0.76–0.87)
|
0.99 (0.92–1.06)
|
76.0–331.0
|
0.77 (0.69–0.85)
|
1.00 (0.90–1.12)
|
>331.0
|
0.65 (0.56–0.77)
|
0.90 (0.77–1.06)
|
Diuretics
|
|
|
< 124.5
|
1.06 (0.98–1.13)
|
1.06 (0.99–1.14)
|
124.5–568.2
|
0.97 (0.88–1.08)
|
1.08 (0.97–1.19)
|
> 568.2
|
0.94 (0.81–1.09)
|
1.03 (0.88–1.20)
|
Table 6
Lag-time analysis of separate drug groups. Cohort of 13,873 newly diagnosed RCC patients in Finland between 1995-2012.
|
1-year lag
|
3-year lag
|
5-year lag
|
ACE-inhibitors
|
1.16 (1.08–1.24)
|
1.19 (1.10–1.27)
|
1.15 (1.07–1.24)
|
Angiotensin receptor blockers
|
1.17 (1.06–1.28)
|
1.17 (1.06–1.30)
|
1.08 (0.96–1.22)
|
Calcium channel blockers
|
0.98 (0.91–1.05)
|
0.98 (0.91–1.05)
|
0.99 (0.92–1.06)
|
b-blockers
|
1.12 (1.05–1.20)
|
1.12 (1.05–1.19)
|
1.10 (1.03–1.18)
|
Diuretics
|
1.11 (1.04–1.19)
|
0.98 (0.91–1.05)
|
1.05 (0.98–1.12)
|
Table 7
Subgroup analyses in current cohort stratified by different drug groups of antihypertensive medication. Cohort of 13,873 RCC patients diagnosed in Finland between 1995-2012. Abbreviations: CCB = calcium channel blocker; ARB = angiontensin receptor blocker
HR (95% CI) multivariable-adjusted
|
|
ACE-inhibitors
|
ARB
|
CCB
|
b-blockers
|
Diuretics
|
Gender
|
|
Male
|
0.73 (0.66–0.80)
|
0.69 (0.60–0.78)
|
0.80 (0.72–0.90)
|
0.93 (0.85–1.02)
|
1.11 (1.01–1.21)
|
Female
|
0.78 (0.70–0.87)
|
0.84 (0.74–0.96)
|
0.74 (0.66–0.84)
|
1.00 (0.91–1.11)
|
0.98 (0.89–1.08)
|
Age at diagnosis
|
|
Under 69 years
|
0.66 (0.59–0.74)
|
0.65 (0.56–0.74)
|
0.83 (0.73–0.95)
|
0.95 (0.86–1.06)
|
1.11 (1.00–1.23)
|
Over 69 years
|
0.86 (0.78–0.94)
|
0.92 (0.81–1.04)
|
0.78 (0.70–0.87)
|
1.00 (0.92–1.09)
|
0.96 (0.87–1.04)
|
Tumor extent at diagnosis
|
|
Local/local with nodular metastases
|
0.66 (0.57–0.77)
|
0.51 (0.42–0.61)
|
0.87 (0.74–1.03)
|
0.90 (0.77–1.05)
|
1.09 (0.93–1.27)
|
Distantly metastatic
|
0.83 (0.76–0.91)
|
0.99 (0.88–1.11)
|
0.83 (0.75–0.92)
|
1.10 (1.02–1.20)
|
1.01 (0.93–1.10)
|
Tumor morphology
|
|
Clear cell carcinoma
|
0.69 (0.64–0.76)
|
0.68 (0.61–0.76)
|
0.82 (0.74–0.90)
|
0.99 (0.91–1.07)
|
1.10 (1.01–1.19)
|
Chromophobic
|
0.55 (0.08–3.33)
|
n/a
|
n/a
|
0.86 (0.05–13.43)
|
4.15 (0.29–59.45)
|
Primary treatment
|
|
Radical surgery
|
0.65 (0.57–0.75)
|
0.56 (0.48–0.67)
|
0.78 (0.68–0.91)
|
0.93 (0.81–1.07)
|
1.05 (0.92–1.21)
|
Palliative surgery
|
0.77 (0.65–0.90)
|
1.02 (0.83–1.26)
|
0.88 (0.73–1.06)
|
0.99 (0.85–1.14)
|
0.94 (0.81–1.09)
|
Cytostatic/radiation
|
0.84 (0.70–1.02)
|
1.03 (0.81–1.30)
|
0.93 (0.75–1.15)
|
1.11 (0.93–1.32)
|
1.10 (0.92–1.31)
|