Cardiovascular events after elective colorectal cancer surgery in patients with stage I-III disease with no previous cardiovascular disease

Figures & data

Table 1. Distribution of demographics, lifestyle, anthropometry and gastrointestinal comorbidity for 876 colorectal cancer patients and 3508 matched controls participating in the Diet Cancer and Health study.

		Patients with colorectal cancer		Cancer-free comparisons
		N	%	N	%
Total (N = 4380)		876	(20.0)	3504	(80.0)
Demographics
Sex	Women	375	(43)	1500	(42.8)
	Men	501	(57)	2004	(57.2)
Age at diagnosis (mean, SD)		71	(5.6)	71	(5.9)
Lifestyle
Alcohol intake	No alcohol intake	66*	(7)	244	(7.0)
	Moderate	651	(74)	2763	(78.9)
	Excessive	159	(18)	486	(13.9)
	Missing	*	(<1)	11	(<1)
Smoking status	Never	274	(31)	1215**	(34.6)
	Former	297	(34)	1141	(32.6)
	Current	305	(35)	1148	(32.8)
	Missing	NA	–	**	(<1)
Physical activity (MET-score)	4th quartile (most active)	221	(25)	934	(26.7)
	3rd quartile	223	(25)	934	(26.7)
	2nd quartile	238	(27)	886	(25.3)
	1st quartile (least active)	194	(22)	744	(21.2)
Anthropometry
BMI	Normal (<25 kg/m^2)	329	(38)	1568	(44.7)
	Overweight (25–30 kg/m^2)	394	(45)	1461	(41.7)
	Obese (>30 kg/m^2)	152	(17)	473	(13.5)
	Missing	<5	(<1)	<5	(<1)
Cardiovascular comorbidity
Diabetes		92	(11)	276	(7.9)
Use of hypertensive drugs		511	(58)	1908	(54.5)
Use of lipid-lowering drugs		269	(31)	1052	(30.0)

*missing patients added to “no alcohol intake” due to micro data (<5 patients).

**missing patients added to “never smoked” due to micro data (<5 patients).

Table 2. Clinical and surgical characteristics along with treatment information for 923 persons diagnosed with stage I-III colon or rectum cancer who underwent elective surgery between 2001 and 2015.

		Cancer type
Clinical factors		Colon N = 604 (65%)		Rectum N = 319 (35%)		p-value
Stage	I	115	(19.0)	101	(31.7)	<0.001
	II	285	(47.2)	96	(30.1)
	III	204	(33.8)	122	(38.2)
ASA score	I	140	(23.2)	101	(31.7)	0.01
	II	367	(60.8)	186	(58.3)
	III + IV	81	(13.4)	27	(8.4)
	Unknown	16	(2.6)	5	(1.6)
Type of surgery	Laparotomy	239	(39.6)	170	(53.3)	<0.001
	Laparoscopy	365	(60.4)	149	(46.7)
Year of surgery	2001–2005	112	(18.5)	102	(32.0)	<0.01
	2006–2011	213	(35.3)	123	(38.6)
	2012–2016	279	(46.2)	94	(29.5)
Complications within 90 days of elective surgery
Any surgical complications*	Yes	73	(12.1)	70	(21.9)	<0.001
Anastomosis leakage	Yes	25	(4.1)	27	(8.5)	0.01
Radio- and chemotherapy
Neoadjuvant radiotherapy	Yes	0	0	68	(21.3)	<0.001
Neoadjuvant chemotherapy	Yes	<5	(0.5)	28	(8.8)	<0.001
Adjuvant chemotherapy	Yes	160	(26.5)	40	(15.4)	<0.001
Relapse and deaths
Relapse	Yes	50	(8.3)	39	(12.2)	0.07
Death	Yes	101	(16.7)	67	(21.0)	0.13

*surgical complications within 90 days of surgery including anastomosis leakage.

Figure 1. Unadjusted and multivariate-adjusted hazard ratios with 95% confidence intervals for angina pectoris, acute myocardial infarction, heart failure, transitional cerebral ischemia, and ischemic stroke for 876 patients operated for stage I-III colorectal cancer compared to 3504 cancer-free comparisons. HR: hazard ratio; CI: confidence interval. Risk time contributed by controls: 6,896,467 person-years, Risk time contributed by cases: 1,614,340 person-years, Model 1 adjusted for age, sex, time since entry into Diet, Cancer and Health study, and education, Model 2 adjusted for Model 1 + BMI, MET-score, alcohol in g/day and smoking status, Model 3 adjusted for Model 1 + Model 2 + diabetes, use of antihypertensive drugs, and use of lipid-lowering drugs.

Figure 2. Cumulative incidence functions (CIF) for angina pectoris (AP)/acute myocardial infarction (MI), heart failure (HF), transitional cerebral ischemia (TCI)/ischemic stroke (IS), and deaths in the 908 colorectal cancer patients included in the exploratory analyses of risk factors for cardiovascular events among persons with colorectal cancer.

Table 3. Identification of risk factors for cardiovascular events for 923 colorectal cancer patients within the first 90 days and beyond 90 days of elective surgery.

		Within 90 days after surgery			Beyond 90 days of surgery
		Adjusted* HR (95% CI)			Adjusted* HR (95% CI)
		Acute myocardial infarction /Angina pectoris	HF	Stroke / Transitional cerebral ischemia	Acute myocardial infarction /Angina pectoris	HF	Stroke / Transitional cerebral ischemia
Lifestyle
BMI	Normal (< 25)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	Overweight (25–30)	2.95 (0.49–17.8)	1.20 (0.20––7.21)	0.84 (0.12–5.97)	1.74 (0.77–3.92)	4.49 (1.52–13.2)	1.59 (0.72–3.48)
	Obese (>30)	2.86 (0.59–13.8)	3.18 (0.53–19.2)	NA	2.37 (0.95–5.95)	7.59 (2.42–23.9)	2.57 (1.07–6.16)
Physical activity (MET-score)	4th quartile (Most active)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	3rd quartile	0.52 (0.05–5.79)	0.70 (0.12–4.21)	NA	0.75 (0.26–2.19)	1.12 (0.42–2.99)	0.82 (0.34–1.98)
	2nd quartile	2.30 (0.45–11.9)	0.69 (0.11–4.13)	0.98 (0.06–15.6)	1.39 (0.57–3.40)	1.39 (0.56–3.48)	1.02 (0.45–2.32)
	1st quartile	2.05 (0.37–11.2)	0.35 (0.04–3.37)	2.25 (0.20–24.95)	1.49 (0.60–3.73)	1.09 (0.41–2.91)	0.57 (0.21–1.55)
Smoking	Never	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	Former	1.05 (0.23–4.72)	2.55 (0.26–24.9)	0.38 (0.20–24.9)	0.98 (0.42–2.26)	0.97 (0.43–2.20)	0.86 (0.39–1.87)
	Current	1.32 (0.24–4.80)	3.36 (0.37–30.3)	0.48 (0.04 − 4.48)	1.16 (0.51–2.65)	0.72 (0.31–1.69)	0.74 (0.32–1.71)
Alcohol consumption	Moderate consumption	1.00 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	Abstaining	NA	7.23 (1.29–40.6)	3.85 (0.39–37.8)	0.81 (0.19–3.47)	2.20 (0.74–6.56)	1.03 (0.44–2.39)
	Excessive consumption	0.36 (0.05–2.77)	1.86 (0.34–10.2)	NA	1.10 (0.49–2.45)	1.50 (0.67–3.39)	1.97 (0.67–5.80)
Clinical factors
Cancer type	Colon	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	Rectum	0.53 (0.14–1.97)	1.28 (0.30–5.40)	1.88 (0.26–13.5)	1.19 (0.61–2.31)	0.67 (0.32–1.40)	0.79 (0.40–1.55)
Stage at diagnosis	I	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	II	0.54 (0.14–2.16)	0.53 (0.07–3.78)	0.51 (0.03–8.16)	1.21 (0.48–3.01)	0.93 (0.41–2.18)	1.10 (0.46–2.62)
	III	2.04 (0.66–6.34)	1.39 (0.25–7.61)	1.40 (0.13–15.4)	2.03 (0.83–4.99)	1.08 (0.44–2.61)	1.08 (0.48–2.44)
Surgical access	Laparotomy	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	Laparoscopy	1.51 (0.39–5.80)	0.24 (0.03–2.18)	1.77 (0.22–14.3)	1.15 (0.32–4–11)	0.33 (0.04–2.89)	1.37 (0.17–10.8)
ASA-score	I	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	II	1.02 (0.18–5.63)	NA	NA	1.09 (0.51–2.33)	4.23 (1.24–14.4)	1.87 (0.76–4.59)
	III + IV	5.57 (0.99–31.4)	NA	NA	3.26 (1.13–9.43)	15.8 (4.03–61.8)	8.22 (2.87–23.5)
	Unknown	13.8 (1.92–98.8)	NA	NA	1.31 (0.17–10.3)	5.56 (0.57–54.5)	NA
Complications of surgery
Any surgical complications	No	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	Yes	1.69 (0.46–6.25)	3.23 (0.78–13.6)	NA	0.87 (0.34–2.27)	1.41 (0.43–4.65)	1.54 (0.70–3.38)
Anastomosis leakage	No	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	Yes	3.09 (0.67–14.1)	NA	NA	0.87 (0.21–3.64)	2.31 (1.10–4.84)	0.89 (0.21–3.73)
Diabetes	No	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	Yes	NA	2.47 (0.50–12.4)	2.60 (0.27–25.3)	1.09 (0.38–3.13)	3.39 (1.61–7.17)	1.61 (0.66–3.91)
Lipid-lowering drugs	No	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	Yes	8.03 (2.14–30.1)	2.97 (0.71–12.5)	2.07 (0.29–14.9)	2.38 (1.25–4.25)	2.20 (1.04–4.66)	2.39 (1.23–4.62)
Antihypertensive drugs	No	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	Yes	1.66 (0.49–5.58)	4.64 (0.57–37.9)	0.60 (0.08–4.32)	2.09 (1.06–4.13)	1.34 (0.68–2.65)	1.56 (0.78–3.11)
Treatment
Chemo-therapy**	No	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)	1 (ref)
	Yes	1.87 (0.36–9.76)	0.78 (0.09–7.15)	NA	0.32 (0.14–0.74)	0.36 (0.15–0.90)	0.78 (0.36–1.68)

HR: hazard ratio; CI: confidence interval.

*Adjusted for sex, age at diagnosis, period of diagnosis and education.

**further adjusted for the stage at diagnosis.

NA indicates not enough events to conduct an analysis.

Data availability statement

The data that support the findings of this study are available upon reasonable request from the corresponding author. The data are not publicly available as they contain information that could compromise the privacy of research participations.