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Abstract
Objective Increasing number of clinical guidelines are adopting comprehensive cardiovascular risk assessment tools for treatment decision and disease management. Yet, little is known regarding cardiovascular risks associated with the length of favourable cardiometabolic profile. In this context, we examined whether the duration of strictly ideal cardiovascular health (CVH), based on body mass index, blood pressure, fasting glucose, total cholesterol, cigarette smoking, alcohol drinking and physical activity, in middle age is associated with risk of developing chronic kidney disease (CKD) and cardiovascular disease (CVD) in mid-to-late life.
Methods From the Korean Genome and Epidemiology Study Ansung-Ansan cohort, we included 8020 participants (median age 50.0 years, 47.9% male), of whom, 7854 without CKD and 7796 without CVD at baseline. Cox proportional hazards models were employed to assess CKD and CVD risks, adjusting for age, sex, education level, examination sites and renal markers.
Results Over a median follow-up of 15.0 years, 1401 cases of CKD and 493 cases of CVD were newly developed. Compared with participants with <5 years of ideal CVH duration, HR (95% CI) of those who maintained for 5–<10 years or ≥10 years had negatively graded risks for CKD (5–<10 years, 0.63 (0.39 to 0.93); ≥10 years, 0.33 (0.15 to 0.74)) and CVD (5–<10 years, 0.83 (0.54 to 1.27); ≥10 years, 0.22 (0.08 to 0.60)). In parallel, participants with delayed decline to suboptimal level had lower disease risks compared with counterparts with consistently suboptimal CVH.
Conclusion Our findings confer that maintaining favourable health behaviours and clinical risk factor levels in midlife will improve later-life cardiovascular outcomes.
- risk factors
- epidemiology
Data availability statement
Data are available upon reasonable request. The KoGES Ansung-Ansan data are available on reasonable request from the Korea Center for Disease Control and Prevention website.
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Introduction
In 2010, the American Heart Association has released cardiovascular health (CVH) metrics called the ‘Life’s Simple 7’1 based on modifiable risk factors. Concordantly, international clinical guidelines2 3 have adopted and actively used atherosclerotic cardiovascular disease (CVD) risk assessment algorithms that account for clinical and lifestyle risk factors. Such holistic tools are intended to aid surveillance and management of CVD, which remains the leading cause of mortality worldwide.4 Beyond this, timely and sustained management is expected to curtail life-years lost, to improve quality of life and to conserve healthcare costs.5
Previous literature has demonstrated the individual benefit of curbing obesity pandemic,6 blood pressure,7 cholesterol,8 and blood sugar9 lowering, smoking cessation,10 moderate alcohol consumption11 and regular physical activity12 in the context of primary and secondary prevention of CVD. Recent observational studies have illustrated the association between a single-occasion CVH measure and subclinical atherosclerosis based on coronary artery calcium progression13 and cardiac troponin T reduction.14 However, growing evidence underscores the novelty of repeated measures to capture lifetime burden.15
Little is known on the risk magnitude associated with duration spent in ideal CVH in middle-age, Asian population. Age-adjusted CVD mortality has declined significantly in the high-income, western and Asia-Pacific regions over the past decades, but the decline has relatively plateaued in recent years.4 Evaluating whether longer time spent in ideal CVH is associated with lower risk of target organ damage and cardiovascular events may improve the stagnant heart diseases hospitalisation and mortality rates.
In this context, we examined whether the duration of ideal CVH, based on body mass index, blood pressure, blood glucose, total cholesterol, cigarette smoking, alcohol drinking and physical activity, in middle age is associated with risk of developing chronic kidney disease (CKD) and CVD in mid-to-late life. To address this aim, we analysed data from the Korean Genome and Epidemiology Study (KoGES) Ansung-Ansan, an ongoing, prospective cohort in Republic of Korea.
Methods
Study population
The KoGES consortium is a platform designated to investigate the genetic, social and environmental aetiology of chronic diseases in Republic of Korea.16 It collected detailed information on demographics, lifestyle and healthcare utilisation and provided on-site anthropometric, blood and urine examinations.16
For this study, we selected the KoGES Ansung-Ansan, a community-based, prospective cohort in two suburban cities. Based on a two-stage cluster sampling recruitment, 10 030 participants, aged 40–69 years, underwent baseline examination between 2001 and 2002. Onwards, seven follow-up examinations were conducted every 2 years until 2015–2016. The KoGES Ansung-Ansan was administered, reviewed and approved by the Korea Center for Disease Control and Prevention. The present study was approved by the Institutional Review Board of Yonsei University Health System (Y-2020–0007). All participants provided written informed consent, and the study was conducted with strict adherence to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines.
Among the 10 030 participants, 912 participants who had not attended any follow-up examinations were excluded. Additionally, 1098 participants with incomplete CVH measurements were excluded (online supplementary table S1). Of the remaining 8020 participants, 166 participants with CKD at baseline were excluded in the final analyses with CKD as the outcome; likewise, 224 participants with CVD at baseline were excluded with CVD as the outcome (online supplementary figures 1 and 2).
Supplemental material
Ideal CVH duration
Each clinical and lifestyle CVH metric was assigned 0 (poor), 1 (intermediate) or 2 (ideal) points to yield a composite CVH score for each examination (table 1). Scores of 0–7, 8–11 or 12–14 points were regarded as having poor, intermediate or ideal CVH, respectively. The number of years lived in ideal CVH was calculated as a sum of duration with CVH score ≥12 between each examination. If a participant had not attended a particular follow-up examination, the ideal duration was calculated based on the most recently attended examination prior to the absent one by linearly regressing the score—referred to as the regressed model (online supplementary figure S3). For example, if person B scored 14 (ideal) at the second follow-up, did not attend the third follow-up, and scored 11 (intermediate) at the fourth follow-up (60 months from the second follow-up), he/she would hypothetically maintain ideal CVH for 40 months since the second follow-up, which thereafter, the score deteriorates below the ideal threshold. For all follow-up examinations, there was no partially incomplete CVH measurement.
Definition and scoring of cardiovascular health components
Outcomes
CKD was defined as having an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or self-reported diagnosis.17 Urine albumin-to-creatinine ratio (UACR) was defined as the ratio of the urine albumin (mg/dL) to creatinine (g/dL) concentrations. CVD was defined based on a self-reported diagnosis for coronary artery disease, cerebrovascular disease or heart failure. If a participant had >1 different type of event, the first event of each type was counted as an outcome.
Statistical analyses
Baseline characteristics of the study participants were reported as frequency and percentage or mean and SD then compared across the duration lived in ideal CVH.
The HR and 95% CI associated with each ideal CVH duration category were calculated using Cox proportional hazards models with discrete time intervals. The end of observation was defined as the date of event, last follow-up or 31 December 2016, whichever came first. HRs were adjusted for age, sex, education level, examination site; baseline eGFR and UACR were additionally adjusted with CKD as outcome. The proportional hazards assumption was not violated according to graphical inspection of log-minus-log plot and Schoenfeld residuals. Effect modification by cross-categories of sex and age (ie, male <50 years, female ≥50 years) was assessed using multiplicative interaction terms.
As a secondary analysis, we examined whether different rates at which ideal CVH deteriorates to suboptimal (intermediate or poor) levels are associated with CKD and CVD risks. In reference to participants with persistently suboptimal CVH, we assessed the risk differences across participants with early, incremental or no decline to suboptimal state based on latent class trajectory modelling (online supplemental methods).
Seven sensitivity analyses were performed. First, we examined the association of maintaining individual ideal CVH component for ≥5 years with CKD and CVD alongside their precursors—namely, hypertension, diabetes mellitus and hypercholesterolaemia. Second, we excluded incidence during the first follow-up to account for potential risk carryover. Third, to account for varied follow-up duration among participants, we examined the effects of relative CVH duration on outcomes by dividing the number of years lived in ideal CVH by total follow-up duration. Fourth, we assessed risks assuming no changes in CVH scores for missing examinations, referred to as the stagnant model; here, the most recent score is carried over and maintained until the subsequent follow-up attendance. Fifth, due to known J-shaped associations of very low clinical risk factor levels with CVD and all-cause mortality,18–21 we further excluded participants with (1) body mass index <18.5 kg/m2; (2) diastolic blood pressure <60 mm Hg; (3) low-density lipoprotein cholesterol <25 mg/dL; or (4) fasting glucose <70 mg/dL. Sixth, we examined whether the association persists for eGFR decline by 30% or greater from the baseline level in substitution for CKD. Lastly, we examined whether maintaining ideal or intermediate CVH (score ≥8) is also associated with CKD or CVD.
All statistical tests were two-sided, and statistical significance was set at a p value <0.05. All analyses were performed using R V.4.1.0 (R Foundation for Statistical Computing, Vienna, Austria) and SAS V.9.4 (SAS Institute).
Patient and public involvement
No participants were involved in design nor execution of the research. Results from the KoGES are publicly available through the Korea Disease Control and Prevention Agency website and routinely disseminated in media outlets.
Results
The study included 8020 participants (median age 50.0 years, 47.9% male), of whom, 7854 without CKD and 7796 without CVD at baseline. Among them, 110 (1.4%) had zero ideal CVH components, followed by 497 (6.2%) with one, 1152 (14.4%) with two, 1864 (23.2%) with three, 2018 (25.2%) with four, 1528 (19.1%) with five, 694 (8.7%) with six and 157 (2.0%) with seven ideal CVH components, respectively (online supplementary table S2). Participants with greater number of ideal CVH components at baseline were distinguishably of female sex (p value for sex difference <0.0001; figure 1, online supplementary tables S2 and S3).
Baseline number of ideal cardiovascular health (CVH) components by sex (left) and median age (right). The ideal level of each CVH component includes (1) never-smoking; (2) non-drinking; (3) ≥75 min of vigorous activity or ≥150 min of moderate-to-vigorous activity per week; (4) body mass index <23 kg/m2; (5) untreated systolic blood pressure <120 mm Hg and diastolic blood pressure <80 mm Hg; (6) untreated total cholesterol <200 mg/dL; and (7) untreated fasting glucose <100 mg/dL. P value for sex or age difference in the distributions of ideal number of CVH components were obtained from χ2 test.
Overall, 7156 (89.2%) participants had less than 5 years of ideal CVH, 525 (6.5%) had 5– <10 years of ideal CVH, and 339 (2.1%) had 10 or greater years of ideal CVH, respectively (table 2). Compared with participants with shorter ideal CVH duration, those who maintained ideal CVH for ≥10 years were more likely to be female, to attain high school degree, non-smokers and non-drinkers and less likely to have metabolic abnormalities.
Baseline characteristics by the duration lived in ideal cardiovascular health
During a median follow-up of 15.0 (25th–75th percentile, 14.2–15.6; minimum–maximum, 1.6–15.6) years, 1401 CKD events occurred (online supplementary figure S4). CKD incidence largely varied by the ideal number of clinical and lifestyle CVH components. Age- and sex-adjusted CKD incidence rates per 1000 person-years were 30.1 among participants with 0 vs 10.6 with seven ideal CVH components at baseline.
During a median follow-up of 15.1 (25th–75th percentile, 14.3–15.6; minimum–maximum, 1.7–15.6) years, 493 new CVD events occurred (online supplementary figure S5). Likewise, age- and sex-adjusted CVD incidence rates differed from 6.5 among participants with 0–2.7 per 1000 person-years with seven ideal CVH components at baseline.
Figure 2 illustrates disease risks associated with ideal CVH duration. CKD event rates were incrementally lower by the longer duration lived with ideal CVH (less than 5 years, 19.0%; 5– <10 years, 9.5%; ≥10 years, 6.9%). In fully adjusted model, 5– <10 (HR 0.63 (95% CI 0.39 to 0.93)) and ≥10 years (HR 0.33 (95% CI 0.15 to 0.74)) lived in ideal CVH were associated with lower CKD risk in reference to <5 years of maintenance (p trend, 0.0057).
Association of ideal cardiovascular health (CVH) duration and risk of chronic kidney disease and cardiovascular disease
Similarly, CVD event rates were the highest among participants lived with <5 years of ideal CVH (6.7%), followed by 5– <10 years (4.4%) and ≥10 years (1.2%) groups. In reference to the <5 years group, participants lived with 5– <10 years of ideal CVH had lower CVD risk (HR 0.83 (95% CI 0.54 to 1.27)) yet without statistical significance. However, living in ideal CVH for ≥10 years was associated with significantly lower CVD risk (HR 0.22 (95% CI 0.08 to 0.60)). By CVD subtypes, longer ideal CVH duration was associated with significantly lower risk for coronary artery disease (5– <10 years: HR 0.42 (95% CI 0.20 to 0.89), ≥10 years: HR 0.19 (95% CI 0.05 to 0.75)) and marginally lower risk for cerebrovascular disease (p trend, 0.0514). No significant effect measure modification by sex and age group was observed.
Secondary analysis
As a proxy to duration, we explored whether different rates at which optimal (ideal) CVH deteriorates to suboptimal (intermediate or poor) CVH are also meaningfully associated with both outcomes (figure 3). Compared with participants who mostly remained in suboptimal CVH, those who gradually declined to suboptimal CVH category had lower risk for CKD (HR 0.69 (95% CI 0.54 to 0.81)) and CVD (HR 0.65 (95% CI 0.51 to 0.79)). The risks were exceptionally lower among participants who consistently maintained optimal CVH.
Association of rate of cardiovascular health (CVH) change and risk of chronic kidney disease and cardiovascular disease.
Sensitivity analyses
We examined the association of maintaining ideal level of individual clinical and lifestyle risk factors for ≥5 years with CKD and CVD, alongside their established precursors (online supplementary table S4). In general, maintaining ideal clinical CVH for ≥5 years was consistently associated with lowered risks for all outcomes in reference to <5 years of maintenance. A notable exception was total cholesterol, which, alone, demonstrated no lowered effect on CKD (HR 0.94 (95% CI 0.79 to 1.13)) nor CVD (HR 1.01 (95% CI 0.84 to 1.22)).
After excluding events from the first follow-up, longer ideal CVH duration maintained negative associations with CKD (p trend, 0.0071) and CVD—specifically coronary artery disease (p trend, 0.0182) (online supplementary table S5). Furthermore, ideal CVH duration remained robustly associated with CKD and composite CVD events regardless of follow-up duration (online supplementary table S6).
Based on the stagnant model (online supplementary figure S6), no significant changes in the associations were observed (online supplementary table S7) despite moderate left-skewing of the CVH scores. We also restricted the analyses to participants within normal or high clinical risk factors range (online supplementary table S8). Notwithstanding blunted risk gradation, no significant changes were observed.
With 30% or greater eGFR decline as the outcome, the results were comparable to those of CKD (online supplementary table S9). Participants maintaining ideal CVH for 5– <10 years (HR 0.87 (95% CI 0.76 to 1.05)) or ≥10 years (HR 0.66 (95% CI 0.49 to 0.88)) had lower risk for adverse renal outcome.
We further expanded the analyses to more lenient definition of favourable CVH. Extending to ideal or intermediate level of CVH diminished the association strengths for all outcomes (online supplementary table S10). In reference to the <5 years group, those maintaining ideal or intermediate CVH for ≥10 years had significantly lower risk for composite (HR 0.61 (95% CI 0.49 to 0.75)) and all subtypes of CVD. However, maintaining ideal or intermediate CVH for 5– <10 years was not significantly associated with CKD nor CVD.
Discussion
In this study of middle-aged Korean adults, longer duration spent in ideal CVH was associated with incrementally lower CKD and CVD risks over a median follow-up of 15.0 years. Our findings bolster the utility of repeated CVH assessments to be incorporated into clinical guidelines and public health policies in devising long-term cardiometabolic health management strategies.
Our findings are consistent with previous literature. In the Framingham Offspring Study, worsening CVH over 20 years was associated with adverse echocardiographic atherosclerotic measures.22 Similarly, in a Korean hospital-based cohort of low-risk adults, higher baseline CVH score was negatively associated with coronary artery calcium development and progression.13 The maintenance of ideal CVH in midlife extends to favourable cardiovascular structure and function in later life. Compared with participants who had undergone ≥0.5 point/decade of CVH score increase, those with >1 point/decade decrease exhibited worse left ventricular structure, arterial function and myocardial stress.23 The benefits of sustained CVH are also projected to all CVD subtypes, regardless of age, sex, race and comorbidity.23 24 However, the aforementioned studies had a number of differences compared with the present analysis: (1) the participants were predominantly of non-Hispanic white/black race22 23; (2) a considerable proportion already had atherosclerotic lesion13; (3) outcomes were assessed in late life22; (4) a high proportion of participants had pre-diabetes/diabetes24; and (5) a single or very few CVH scores were considered with limited follow-up duration.13 22 Considering the heterogeneous distributions of each CVH component across sociodemographics,25 the current study advances the prior work by demonstrating that long-term CVH is associated with CVD and its preceding target organ damage in a low-risk, community-dwelling population.
To consider cumulative CVH, the Framingham Offspring Study team has investigated the association between duration of fair CVH and cardiometabolic outcomes. Among 1445 participants (mean age 60 years, 48% male), each 5-year duration with intermediate or ideal CVH was associated with lowered HRs (95% CIs) for CKD (0.75 (0.63 to 0.89)) and CVD (0.73 (0.63 to 0.85))26—analogous to our supplementary analyses of combined ideal and intermediate categories. However, several differences should be noted. First, our study substituted the traditional Life Simple 7’s diet score with alcohol drinking, as a nationwide study27 has reported age-varying rate of excessive alcohol consumption. Importantly, our primary analysis quantified the benefits of strictly ideal CVH duration, as our participants had significantly lower prevalence of hypertension (37% vs 67%) and diabetes mellitus (5% vs 21%) than the Framingham Offspring cohort26 even in the shortest ideal CVH duration category. Therefore, our results reflect promising cardiovascular outcomes in general population with predominantly low-to-moderate cardiometabolic risk. Regarding methodology, the aforementioned study26 calculated the duration by multiplying the number of examination cycles with available CVH score with mean interval (4 years) between follow-ups, whereas we summed the exact years between each examination. However, it remains undetermined whether deterioration or improvement in CVH can best be projected assuming linearity.
Nonetheless, our results illustrate how critical comprehensive lifestyle modification and pharmacological interventions in midlife are. Indeed, the absence of risk factors at 50 years of age was associated with very low lifetime CVD risk, longer survival and improved physical, mental and social functioning in older age.15 Beyond, prolongation of ideal CVH deems essential. Whereas maintaining ideal CVH for ≥5 years was associated with lower CKD risk, a brief maintenance was not meaningful. In light of these findings, public health programmes should aim to deter risk factor manifestation and progression earlier in life.
A major strength of our investigation was repeated assessments of CVH in general population. However, several limitations should be noted. Due to the nature of CVH scoring system, we were unable to pinpoint specific CVH component attributable for varied risks. As a previous study28 reported age-varying effects of CVD risk factors in both independent and interactive manner, a larger study is needed to adequately assess differential contributions of each component. As an observational study, we were unable to calculate absolute risk reduction from ideal CVH maintenance. Pragmatic trials may adequately yield real-world benefits of sustained CVH. Lastly, our findings may not be generalisable to populations with different age or race structure. Considering the geographic and racial/ethnic variations in CVH management status, population-specific metrics and cut-offs should be developed and validated.
In summary, our findings suggest that longer maintenance of ideal CVH in midlife is associated with lower CKD and CVD risks in mid-to-late life. Nationwide public health programmes should widen the opportunity window for early diagnosis across all age spectra. In healthcare settings, practitioners should actively cooperate with patients to evaluate their circumstances for lifestyle modifications, to identify potential barriers, to implement measurable goals and to monitor their progress.
Key messages
What is already known on this subject?
Single-occasion cardiovascular health (CVH) index is associated with subclinical atherosclerosis.
What might this study add?
Prolonged duration, but not brief maintenance, of ideal CVH is associated with lowered risks of chronic kidney disease and cardiovascular disease in healthy, middle-age, Korean population.
Routine CVH assessments and sustained lifestyle and pharmacological interventions in midlife can lower mid-to-late life cardiovascular risk.
How might this impact on clinical practice?
Nationwide public health programmes should widen the opportunity window for early diagnosis across all age spectra.
Health practitioners should actively cooperate with patients to evaluate their circumstances for lifestyle and treatment modifications, to identify potential barriers, to implement measurable goals and to monitor their progress throughout lifetime.
Data availability statement
Data are available upon reasonable request. The KoGES Ansung-Ansan data are available on reasonable request from the Korea Center for Disease Control and Prevention website.
Ethics statements
Patient consent for publication
Ethics approval
This study involved human participants and was approved by The KoGES Ansung-Ansan, and was administered, reviewed and approved by the Korea Center for Disease Control and Prevention. The present study was approved by the Institutional Review Board of Yonsei University Health System (Y-2020-0007). Participants gave informed consent to participate in the study before taking part.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors SMJC and HCK conceived and designed the study. SMJC performed statistical analyses. SMJC, JYJ, T-HY, H-YL, Y-HL and HCK interpreted the findings. SMJC drafted the manuscript. SMJC, JYJ, T-HY, H-YL, Y-HL and HCK made critical revision of the manuscript for key intellectual content. HCK takes full responsibility for the content of the manuscript, including data and analysis. All authors approved the final manuscript. HCK is the guarantor.
Funding This work was supported under the framework of international cooperation program managed by the National Research Foundation of Korea (NRF-2020K2A9A2A08000190).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.