We systematically searched for articles indexed in PubMed and Scopus (inception to July 15, 2025). We sought to identify all articles examining the association of AHA CVH measures and cancer outcomes. Our search strings are presented in Supplementary Table 1. The reference lists of recent reviews and included studies were screened for additional eligible studies.

Our study selection methodology was designed to identify cohort studies examining the association of AHA CVH metrics (eg, LS7, LE8) with cancer risk and cancer mortality. We included original research articles available in English. We included studies that examined cohorts of adults unselected for cancer in which CVH metrics were assessed at baseline and cancer outcomes were ascertained during follow-up. We included all published studies in the systematic review meeting these criteria. Screening was performed in Covidence. Three authors (JT, SN, KTN) jointly participated in each step of screening and full-text review. For each article, any 2 of these authors conducted screening and full-text review. Disagreements were resolved by the third author.

Data on the characteristics of each included study were extracted independently by 1 author and verified by a second author using an adapted Cochrane data extraction template ( http://cccrg.cochrane.org/author-resources ). We extracted study characteristics (year, location, cohort, data collection year range, inclusion/exclusion criteria sample size, mean age), exposure (AHA CVH metric), outcome (cancer incidence and mortality), and summary statistical measures for selected exposure-outcome associations (risk ratio or hazards ratio).

The Newcastle–Ottawa Scale was used to evaluate quality of evidence and risk of bias (JT). The Newcastle–Ottawa Scale is a scored instrument with a maximum of 9 points based on criteria related to selection, comparability, and outcomes.

We utilized specific criteria to select published studies and analyses for inclusion in the meta-analyses. We included analyses presenting low (worst), moderate, and high (best) CVH scores, with the low score group as the reference category, or where this information could be calculated from presented data, we used established methods for rereferencing relative risks based on the point estimates and confidence interval bounds of the new reference group. Where multiple publications analyzed overlapping cohorts, we included the estimate with the smallest standard error for the relevant high-versus-low score comparison (by outcome), as this provided the most statistically precise estimate and accounted for large variations in sample size relative to number of events across studies. Where a study presented data utilizing multiple models for the same outcome we selected data from the most adjusted model. We conducted cancer specific incidence meta-analyses where at least 3 unique studies reported on the same specific cancer.

We calculated the log transformed risk ratio and standard error of the risk ratio. We utilized the Stata (MP 17.0) meta function to calculate summary effect estimates and 95% confidence intervals. We a priori used the conservative random-effects model for all analyses regardless of calculated heterogeneity. The proportion of heterogeneity due to study variation was quantified using the I ² statistic per the heterogi function. We performed meta-regression using the meta regress function. The presence of small study and missing results effects were a priori planned to be evaluated if a meta-analysis included at least 10 studies. We prespecified subgroup analysis by exposure type (eg, LE8). Tests were considered statistically significant if the 2-sided P -value was <.05. KTN had full access to all the data in the study and takes responsibility for its integrity and the data analysis.

We screened 607 studies after removal of duplicates. There were 75 studies that underwent full-text review, of which 49 studies were excluded, as outlined in Figure 1 . Details of the 26 studies included in our systematic review and their characteristics are summarized in Table 1 . Sample size ranged from 785 to 342,226 individuals. Included studies analyzed 10 unique datasets examining the exposure of LS7 or LE8 scores. Outcomes examined included overall incident cancer, individual cancer risk, and overall cancer mortality. Studies included data collection from 1979-2020 and were primarily conducted in datasets from the US and Europe. Mean patient age ranged from 45-72 years across publications. The designations of low, moderate, and high CVH scores of studies included in the meta-analysis are detailed in Supplementary Table 2. Individual cancer types examined by study are detailed in Supplementary Table 3.

PRISMA flow diagram of study selection.

Table 1

Characteristics of studies included in systematic review

Publication	Location	Study	Data collection time	Publication specific exclusion criteria	Total sample size	Mean age, y *	CVH metric	Outcome
Abramov et al	USA	NHANES	2009-2018	History of CHD, angina, HA, stroke, cancer, CVD	20,215	45	LE8	Cancer mortality
Chen et al	USA	NHANES	2005-2018	< 20 y, pregnant, not having baseline CKD	3,814	47	LE8	Cancer mortality
Dinh et al	USA	NHANES	2011-2018	< 20 y, pregnant/breastfeeding	21,183	48	LE8, LC9	Cancer mortality
Greenlee et al	USA	CHS	1989-1993	History of cancer or CVD	3,491	72	LS7	Cancer mortality, incident cancer
Han et al	USA	NHANES	1988-2016	< 20 y, pregnant, BMI < 18.5 kg/m 2, history of cancer, heart attack, congestive heart failure, stroke	12,299	47	LS7	Cancer mortality
Hou et al	UK	UK Biobank	2006-2010	Baseline CVD or cancer	218,587	56	LE8	Incident cancer
Huether et al	USA	REGARDS	2003-2007	Races not Black/White, prevalent cancer, stroke, or CHD	11,385	65	LE8	Cancer mortality
Jiang et al	China	Kailuan study	2006-2020	Deaths, cancer at baseline	77,551	51	LE8	Incident cancer
Lau et al	USA	“FHS and PREVEND”	1979-2005	Prevalent end-stage renal disease, cancer, atrial fibrillation or major CVD	20,305	50	LS7	Incident cancer
Li et al	USA	NHANES	2005-2018	< 20 y, pregnant, viral hepatitis, autoimmune hepatitis, excessive alcohol consumption, Fatty liver Index < 60	10,050	50	LE8	Cancer mortality
Lin et al	USA; UK	NHANES; UK Biobank	2005-2018; 2006-2010	≤20 y, baseline cancer	17,076; 272,727	53; 56	LE8	Cancer mortality, Incident cancer
Ning et al	USA	NHANES	2007-2018	≥ 30 y, pregnant	21,062	52	LE8	Cancer mortality
Ogunmoroti et al	USA	MESA	2000-2015	History of CVD	6,506	62	LS7	Incident cancer
Peng et al	UK	UK Biobank	2006-2010	History of CVD or cancer	277,002	58 †	LE8	Incident cancer
Peng et al	UK	UK Biobank	2006-2010	Baseline cancer, CVD or T2D	277,997	56 †	LE8	Incident cancer
Rasmussen-Torvik et al	USA	ARIC	1987-2016	Race other than white or African American, baseline history of cancer	13,253	54 †	LS7	Incident cancer
Sun C. et al	USA	NHANES	2007-2012	< 20 y, not having baseline COPD	785	59	LE8	Cancer mortality
Sun M. et al	USA	NHANES	2005-2018	< 20 y, fatty liver index ≤60, pregnant women, alcoholism excessive, chronic viral hepatitis	9,094	52	LE8	Cancer mortality
Van Sloten et al	France	GAZEL	1989-2015	Prevalent cancer, CVD, BMI < 18.5 kg/m 2	13,933	45	LS7	Incident cancer
Wang et al	UK	UK Biobank	2006-2010	Female	25,656	NR	LC9	Incident cancer
Wu et al	UK	UK Biobank	2006-2010	Baseline tumor diagnoses	234,102	57	LE8	Incident cancer
Yang et al	UK	UK Biobank	2006-2010	Baseline cancer	332,417	58 †	LE8	Cancer mortality, incident cancer
Yu et al	UK	UK Biobank	2006-2010	History of noncommunicable chronic diseases	170,726	56	LE8	Incident cancer
Zhang et al	UK	UK Biobank	2006-2010	< 50 y, prevalent cancer	342,226	60	LS7	Incident cancer
Zhao et al	UK	UK Biobank	2006-2010	Baseline cancer, BMI < 18.5 kg/m 2, HRT users, male	277,002	56 †	LE8	Incident cancer
Zhou et al	USA	NHANES	2005-2018	Not having baseline metabolic syndrome	7,839	54	LE8	Cancer mortality

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