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Associations of Life’s Simple 7 With Cerebral Small Vessel Disease

Originally publishedhttps://doi.org/10.1161/STROKEAHA.122.038838Stroke. 2022;53:2859–2867

Abstract

Background:

The purpose of this study is to examine the associations of Life’s Simple 7 (LS7) with risks of cerebral small vessel disease (CSVD) and its magnetic resonance imaging markers.

Methods:

Community-dwelling residents in Lishui city in China from the cross-sectional survey of the PRECISE study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) were included in this study from 2017 to 2019. LS7 was analyzed as the total score, medical score (derived from the 3 metrics based on medical history and testing), and behavioral score (based on 4 metrics based on behaviors), and categorized as poor, intermediate, or ideal. A CSVD score or a modified CSVD score was derived from 4 magnetic resonance imaging markers (lacunes, microbleeds, perivascular spaces, and white matter hyperintensity) at baseline. Binary logistic regression or ordinal logistic regression model was used to estimate the relationship of LS7 scores with CSVD and magnetic resonance imaging markers.

Results:

A total of 3061 participants were included in this study. Compared with poor total LS7 score, ideal LS7 total score was associated with reduced adjusted odds of higher CSVD score (common odds ratio [cOR], 0.73 [95% CI, 0.58–0.90]) and higher modified CSVD score (cOR, 0.78 [95% CI, 0.64–0.95]). Compared with poor LS7 medical score, ideal LS7 medical score was associated with reduced adjusted odds of higher CSVD score (cOR, 0.65 [95% CI, 0.53–0.80]) and higher modified CSVD score (cOR, 0.67 [95% CI, 0.56–0.81]). Higher total LS7 score and LS7 medical score were associated with a lower risk of white matter hyperintensities and lacunes. Higher LS7 behavioral score was associated with lower risk of lacunes.

Conclusions:

Ideal LS7 score, indicating excellent cardiovascular health, was associated with lower total CSVD burden. Optimizing the risk factors captured by LS7 may reduce the progression of CSVD.

See related article, p 2868

Cerebral small vessel disease (CSVD) refers to a group of pathological processes with various etiologies that affect the small arteries, arterioles, venules, and capillaries of the brain.1 It causes substantial cognitive, psychiatric, and physical disabilities in older people, and contributes to up to 45% of dementias2 and ~20% of all ischemic strokes.3 Its pathogenesis and risk factors are unknown. Although the significant associations of CSVD with dietary components, types of physical activity and other cardiovascular risk factors have been reported,4–6 it is unclear whether the overall improvement of lifestyle is associated with CSVD.

To improve cardiovascular health, the American Heart Association defined the ideal cardiovascular health, which is an overall score called Life’s Simple 7 (LS7). LS7 is composed of 4 behavioral (smoke, body mass index [BMI], physical activity, and diet) and 3 medical metrics (blood pressure, blood glucose, and total cholesterol).7 LS7, as a quantitative measure of cardiovascular health, has been used in the field of stroke.8–10 Previous studies suggested that a higher cardiovascular health score was associated with lower risk of stroke and mortality.8,9,11 Moreover, 2 recent cohort studies10,12 have shown that Life’s Simple 7 was associated with dementia, which may relate to CSVD. However, to our knowledge, few studies specifically investigate the association between LS7 and the risk of cerebral small vessel disease.

Using the data from the PRECISE study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events), we aimed to investigate whether LS7 score was associated with the risk of CSVD including total cerebral small vessel disease burden and magnetic resonance imaging (MRI) markers of CSVD.

Methods

Data Availability

The data are available to researchers on reasonable request from the corresponding author.

Study Design, Setting, and Participants

This study is based on baseline data from the PRECISE study (URL: https://www.clinicaltrials.gov; Unique identifier: NCT03178448). The rationale, design, and baseline participant characteristics of the PRECISE study have been described previously.13 Between May 2017 and September 2019, the PRECISE study, a population-based prospective cohort study in community-dwelling older adults, recruited 3067 subjects from 6 villages and 4 communities of Lishui city in China. In this study, intracranial and extracranial artery stenosis and plaque were evaluated comprehensively by advanced vascular imaging techniques. Exclusion criteria of this study included subjects with contraindications to MRI or computed tomography angiography, life expectancy ≤4 years due to advanced cancers and other diseases, and mental diseases.13 The protocol of this study was approved by ethics committee at Beijing Tiantan Hospital (IRB approval number: KY2017-010-01) and Lishui Hospital (IRB approval number: 2016-42). And all participants have provided written informed consents. The study adhered to the STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology; Supplemental Material).14

Data Sources

Data collection was performed at Lishui Hospital by well-trained researchers using a standard questionnaire. Information on demographics, medical history, concomitant medication, and behavioral subscale (diet, physical activity, smoking, and BMI) were collected through face-to-face interviews. The weight and height were measured through physical examination by researchers. BMI was calculated as the weight in kilograms divided by height in meters squared. In addition, the data of medical subscale (blood pressure, blood glucose, and total cholesterol) and renal function were obtained through medical examinations.

Life’s Simple 7

Life’s Simple 7 was based on 4 behavioral metrics (smoke, BMI, physical activity, and diet) and 3 medical metrics (blood pressure, blood glucose, and total cholesterol). Each metric was categorized into 3 levels (poor=0, intermediate=1, and ideal=2). We adjusted the categories of physical activity according to the IPAQ (International Physical Activity Questionnaire)15 and modified the categories of diet to reflect data available7 in the study (Table S1). Physical activity was classified into 3 categories: inactive, minimally active, and health-enhancing physical active. The metabolic equivalent was assessed with 4.0 for moderate-intensity activity and 8.0 for vigorous-intensity activity.16 We summed the LS7 score (0–14 points), medical score (0–6 points), and behavioral score (0–8 points). The total LS7 score was classified as poor (0–7), intermediate (8–9), or ideal (10–14) levels. The medical score was classified as poor (0–3), intermediate (4), or ideal (5–6) levels. The behavioral score was classified as poor (0–4), intermediate (5), or ideal (6–8) levels.

Assessment of Cerebral Small Vessel Disease

Acquisition of MRI images was performed at the baseline survey of the PRECISE (the same time as metrics of LS7) by well-trained investigators who followed a standardized protocol on a 3.0T scanner (Ingenia 3.0T, Philips, Best, the Netherlands) including 3-dimensional T1-weighted magnetization-prepared rapid-acquisition gradient-echo (3D T1w MPRAGE), axial T2-weighted, fluid-attenuated inversion recovery, and axial susceptibility-weighted imaging. The detailed scanner parameters were listed in Table S2. The imaging data, which were collected in digital imaging and communications in medicine format on discs analyzed by the imaging research center at Beijing Tiantan Hospital.

The MRI markers of CSVD were defined by the Standards for Reporting Vascular Changes on Neuroimaging Criteria.17 We used 2 criteria—total CSVD score18 and modified total CSVD score19—to assess cerebral small vessel disease and MRI markers, which include white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and perivascular spaces (PVS). WMH are lesions in the brain white matter that show up as areas of increased brightness on T2 images. The severity of periventricular WMH (PV-WMH) and the deep-WMH were rated by Fazekas rating scale.20 Lacunes are defined as rounded or ovoid, subcortical, fluid-filled cavities (signal similar to CSF) with diameter of 3 to 15 mm.17 CMBs are round or oval hypointense lesions with sizes of 2 to 10 mm on a gradient-recalled echo image or susceptibility-weighted image.17 PVSs are defined as small punctate with diameter smaller than 3 mm or linear hyperintensities on T2 images and PVS in the basal ganglia was rated with the semiquantitative rating scale developed by the Edinburg group.21 Imaging assessment of each MRI marker was performed by 2 well-trained raters (M. Zhou, Y. Chen, J. Pi, and M. Zhao, 1 rater was responsible for 2 MRI markers) who were blinded to patients’ clinical data. Images with inconsistent results were finally assessed by another senior neurologist (Y. Yang) who was blinded to initial results. The kappa coefficients of MRI markers between raters were 0.80 for the presence of lacune, 0.82 for Fazekas scale of WMH, 0.90 for the severity of EPVS, and 0.80 for the presence of CMB.

Total CSVD score was the sum of points awarded for the presence or absence of 4 MRI markers18: 1 point was awarded if lacunes were present, 1 point was awarded if CMBs were present, 1 point was awarded if there were moderate to severe PVS (>10) in the basal ganglia, and 1 point was awarded for either confluent deep WMH (Fazekas scale 2 or 3) or irregular PV-WMH extending into the deep white matter (Fazekas score 3). Modified total CSVD score was considered as the following 3 parts19: first, 1 point was allocated to frequent to severe (N>20) PVS in the basal ganglia or presence of lacunes. Second, burden of microbleeds was accounted for by assigning 1 point to patients with 1 to 4 microbleeds and 2 points to those with ≥5 microbleeds. Third, burden of total WMH (combined periventricular and subcortical WMH) was also accounted for by allocating 1 point to those with a moderate degree of WMH (combined score of 3 or 4) and 2 points to those with severe WMH (combined score of 5 or 6).

Statistical Methods

Only participants with complete data of MRI and LS7 were included in this analysis. We described continuous variables by mean with standard deviations or median with interquartile range (IQR) and categorical variables by percentage. We used Kruskal-Wallis Test to compare continuous data of the subjects and Pearson χ2 Test to compare categorical data. We first used the binary logistic regression analysis to assess whether the LS7 score was associated with presence of CSVD and to calculate odds ratio (OR) with their 95% CI. In addition, we examined the association of the LS7 score with total CSVD score by the ordinal logistic regression analysis and calculated the common odds ratio (cOR) with 95% CI. Two models were conducted for each outcome. Model 1 adjusted for age and sex and model 2 adjusted for age, sex, eGFR, antiplatelet, and anticoagulant drugs. The associations of LS7 score, medical score, and behavioral score with the risks of MRI markers were assessed by the binary or ordinal logistic regression analysis. All the data analyses were performed using SAS software version 9.4 (SAS Institute, Inc, Cary, NC). Statistical significance was set at a P<0.05.

Results

A total of 3067 subjects were included in the PRECISE study. We excluded 6 subjects because of the missing data of MRI or diet. Baseline characteristics of 3061 subjects stratified by LS7 score are presented in Table 1. Among the 3061 subjects, the mean age was 61.2 years (SD=6.7) and 1424 participants (46.5%) were men. There were 43.0% subjects with hypertension, 21.6% with diabetes, and 20.1% with dyslipidemia in this study.

Table 1. Baseline Characteristics of Study Subjects by LS7 Categories

VariablesLS7P value
Poor (0–7 points) (n=779)Intermediate (8–9 points) (n=1214)Ideal (10–14 points) (n=1068)
Demographic data
 Age, mean±SD61.7±6.961.7±6.660.3±6.5<0.001
 Male, n (%)518 (66.5)571 (47.0)335 (31.4)<0.001
 Current smoking, n (%)316 (40.6)238 (19.6)73 (6.8)<0.001
 Alcohol drinkers, n (%)239 (30.7)214 (17.6)120 (11.2)<0.001
 BMI, kg/m2, median (IQR)25.5 (23.0–27.3)23.7 (21.8–25.6)22.7 (21.0–24.1)<0.001
 FPG, mmol/L, median (IQR)6.0 (5.5–7.1)5.7 (5.3–6.2)5.3 (5.0–5.6)<0.001
 Total cholesterol, mmol/L, median (IQR)5.7 (5.2–6.4)5.3 (4.7–5.9)4.9 (4.4–5.4)<0.001
 HDL, mmol/L, median (IQR)1.3 (1.1–1.5)1.3 (1.1–1.6)1.4 (1.2–1.6)<0.001
 eGFR, mL/min per 1.73 m2), median (IQR)103.7 (94.4–109.5)104.0 (96.0–110.4)105.5 (98.0–110.9)<0.001
Medical history, n (%)
 History of heart disease69 (8.9)107 (8.8)73 (6.8)0.16
 Hypertension491 (63.0)578 (47.6)248 (23.2)<0.001
 Diabetes335 (43.0)267 (22.0)59 (5.52)<0.001
 Dyslipidemia196 (25.2)264 (21.8)154 (14.4)<0.001
Concomitant medication, n (%)
 Antihypertensive285 (36.6)367 (30.2)168 (15.7)<0.001
 Lipid lowering45 (5.8)56 (4.6)19 (1.8)<0.001
 Antidiabetic133 (17.1)109 (9.0)31 (2.9)<0.001
 Antiplatelet31 (4.0)36 (3.0)13 (1.2)<0.001
 Anticoagulants3 (0.4)1 (0.1)0 (0.0)0.06

BMI indicates body mass index; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HDL, high-density lipoprotein; IQR, interquartile range; and LS7, Life’s Simple 7.

The associations of total and modified CSVD score with LS7 score and LS7 subscales are shown in Figure 1. Better LS7 category was associated with less chance of having CSVD, defined as an original or modified CSVD score of 1 point or higher.

Figure 1.

Figure 1. Prevalence of cerebral small vessel disease (CSVD) in different categories of Life’s Simple 7 (LS7). *Total CSVD score: 1 point allocated for presence of lacunes, microbleeds, moderate to severe (>10) perivascular space in basal ganglia, periventricular white matter hyperintensity (WMH) Fazekas 3, or deep WMH Fazekas 2 to 3. Presence of CSVD was defined as patient with a total CSVD score ≥1 point. #Modified total CSVD score: 1 point allocated for presence of lacunes, 1 to 4 microbleeds, frequent to severe (>20) PVS in basal ganglia, moderate WMH (total periventricular+subcortical WMH grade 3–4), 2 points allocated for ≥5 microbleeds and severe WMH (total periventricular+subcortical WMH grade 5–6). Presence of CSVD was defined as patient with a modified total CSVD score ≥1 point.

Table 2 shows the adjusted odds of having CSVD, defined as 1 or more points on the CSVD score or modified CSVD score, according to LS7 category. After adjusting for age and sex (model 1), subjects in the ideal LS7 category had lower risk of having any CSVD (OR, 0.73 [95% CI, 0.58–0.91]). This association remained after additional adjustment for eGFR, antiplatelet, and anticoagulant drugs (Model 2). However, the association of ideal LS7 category with any CSVD based on the modified CSVD score was not significant (OR, 0.83 [95% CI, 0.67–1.02] in model 2). Ideal LS7 medical score, but not ideal LS7 behavioral score, was associated with lower risk of any CSVD based on either the original or modified CSVD score.

Table 2. Odds Ratio for Presence or Absence of CSVD According to the LS7 Score and Its Medical and Behavioral Subscales

OutcomeCategoriesNCSVD (n%)Unadjusted OR (95% CI)P valueModel 1*Model 2
Adjusted OR (95% CI)P valueAdjusted OR (95% CI)P value
Total CSVD scoreLS7 score
 Poor (0–7)779264 (33.9)RefRefRef
 Intermediate (8–9)1214418 (34.4)1.02 (0.85–1.24)0.801.08 (0.88–1.32)0.481.09 (0.89–1.33)0.43
 Ideal (10–14)1068252 (23.6)0.60 (0.49–0.74)<0.0010.73 (0.58–0.91)0.0060.74 (0.59–0.93)0.009
Medical score
 Poor (0–3)1390502 (36.1)RefRefRef
 Intermediate (4)884253 (28.6)0.71 (0.59–0.85)<0.0010.78 (0.65–0.95)0.010.79 (0.65–0.96)0.02
 Ideal (5–6)787179 (22.7)0.52 (0.43–0.64)<0.0010.63 (0.51–0.78)<0.0010.65 (0.52–0.80)<0.001
Behavioral score
 Poor (0–4)959299 (31.2)RefRefRef
 Intermediate (5)779244 (31.3)1.01 (0.82–1.23)0.951.05 (0.84–1.32)0.661.05 (0.84–1.32)0.66
 Ideal (6–8)1323391 (29.6)0.93 (0.77–1.11)0.401.06 (0.85–1.32)0.621.06 (0.85–1.33)0.62
Modified total CSVD score§LS7 score
 Poor (0–7)779332 (42.6)RefRefRef
 Intermediate (8–9)1214569 (46.9)1.19 (0.99–1.42)0.061.21 (1.00–1.47)0.0511.23 (1.02–1.50)0.03
 Ideal (10–14)1068370 (34.6)0.71 (0.59–0.86)<0.0010.81 (0.66–0.99)0.040.83 (0.67–1.02)0.07
Medical score
 Poor (0–3)1390663 (47.7)RefRefRef
 Intermediate (4)884344 (38.9)0.70 (0.59–0.83)<0.0010.77 (0.65–0.93)0.0060.78 (0.65–0.94)0.007
 Ideal (5–6)787264 (33.6)0.55 (0.46–0.66)<0.0010.68 (0.56–0.82)<0.0010.69 (0.57–0.84)<0.001
Behavioral score
 Poor (0–4)959388 (40.5)RefRefRef
 Intermediate (5)779320 (41.1)1.03 (0.85–1.24)0.791.01 (0.82–1.25)0.931.02 (0.82–1.26)0.87
 Ideal (6–8)1323563 (42.6)1.09 (0.92–1.29)0.321.13 (0.92–1.39)0.251.14 (0.92–1.41)0.22

CSVD indicates cerebral small vessel disease; LS7, Life’s Simple 7; and OR, odds ratio.

* Model 1: adjusted for age and sex.

† Model 2: adjusted for age, sex, eGFR, previous antiplatelet, and anticoagulant drugs use.

‡ Total CSVD score: one point allocated for presence of lacunes, microbleeds, moderate to severe (>10) PVS in basal ganglia, periventricular WMH Fazekas 3, or deep WMH Fazekas 2–3. Presence of CSVD was defined as patient with a total CSVD score ≥1 point.

§ Modified total CSVD score: 1 point allocated for presence of lacunes, 1–4 microbleeds, frequent to severe (>20) PVS in basal ganglia, moderate WMH (total periventricular+subcortical WMH grade 3–4), 2 points allocated for ≥5 microbleeds and severe WMH (total periventricular+subcortical WMH grade 5–6). Presence of CSVD was defined as patient with a modified total CSVD score ≥1 point.

Table 3 shows associations between LS7 categories and higher CSVD scores based on ordinal logistic regression. In these models, ideal LS7 category was associated with reduced odds of higher CSVD whether analyzed as the original score (model 2: cOR, 0.73 [95% CI, 0.58–0.90]) or the modified score (model 2: cOR, 0.78 [95% CI, 0.64–0.95]). For the LS7 medical score, both intermediate and ideal categories were associated with reduced odds of higher CSVD or modified CSVD scores. However, the behavioral score was not associated with reduced odds of higher CSVD scores.

Table 3. Ordinal Logistic Regression Analysis for the Association of LS7 With Total CSVD Score

OutcomeModel 1*Model2
CategoriesNUnadjusted cOR (95% CI)P valueAdjusted cOR (95% CI)P valueAdjusted cOR (95% CI)P value
Total CSVD scoreLS7 score
 Poor (0–7)779RefRefRef
 Intermediate (8–9)12141.00 (0.83–1.21)0.971.06 (0.87–1.29)0.541.07 (0.88–1.31)0.48
 Ideal (10–14)10680.58 (0.48–0.71)<0.0010.71 (0.57–0.88)0.0020.73 (0.58–0.90)0.004
Medical score
 Poor (0–3)1390RefRefRef
 Intermediate (4)8840.72 (0.60–0.86)<0.0010.81 (0.67–0.98)0.030.82 (0.68–0.99)0.04
 Ideal (5–6)7870.51 (0.42–0.62)<0.0010.64 (0.52–0.78)<0.0010.65 (0.53–0.80)<0.001
Behavioral score
 Poor (0–4)959RefRefRef
 Intermediate (5)7790.95 (0.77–1.16)0.580.93 (0.75–1.16)0.530.93 (0.75–1.16)0.52
 Ideal (6–8)13230.88 (0.73–1.05)0.140.94 (0.76–1.17)0.590.94 (0.76–1.17)0.58
Modified total CSVD score§LS7 score
 Poor (0–7)779RefRefRef
 Intermediate (8–9)12141.15 (0.97–1.37)0.111.19 (0.99–1.42)0.071.21 (1.01–1.45)0.04
 Ideal (10–14)10680.67 (0.55–0.80)<0.0010.76 (0.62–0.93)0.0070.78 (0.64–0.95)0.02
Medical score
 Poor (0–3)1390RefRefRef
 Intermediate (4)8840.69 (0.58–0.81)<0.0010.77 (0.65–0.91)0.0020.78 (0.65–0.92)0.004
 Ideal (5–6)7870.53 (0.45–0.64)<0.0010.66 (0.55–0.79)<0.0010.67 (0.56–0.81)<0.001
Behavioral score
 Poor (0–4)959RefRefRef
 Intermediate (5)7790.99 (0.82–1.20)0.930.96 (0.78–1.17)0.680.96 (0.78–1.17)0.67
 Ideal (6–8)13231.02 (0.86–1.20)0.831.04 (0.85–1.26)0.731.04 (0.85–1.27)0.70

cOR indicates common odds ratio; CSVD, cerebral small vessel disease; and LS7, Life’s Simple 7.

* Model 1: adjusted for age and sex.

† Model 2: adjusted for age, sex, eGFR, previous antiplatelet, and anticoagulants drugs use.

‡ Total CSVD score: 1 point allocated for presence of lacunes, microbleeds, moderate to severe (>10) PVS in basal ganglia, periventricular WMH Fazekas 3, or deep WMH Fazekas 2–3.

§ Modified total CSVD score: 1 point allocated for presence of lacunes, 1–4 microbleeds, frequent to severe (>20) PVS in basal ganglia, moderate WMH (total periventricular+subcortical WMH grade 3–4), 2 points allocated for ≥5 microbleeds and severe WMH (total periventricular+subcortical WMH grade 5–6).

As shown in Figure 2, the higher levels of LS7 score were associated with decreased risks of WMH burden (OR=0.59 [95% CI, 0.45–0.77]) and modified WMH burden (cOR, 0.70 [95% CI, 0.57–0.87]) in model 2. And the inverse association between LS7 score and lacunes (OR, 0.42 [95% CI, 0.27–0.67]) was also observed. Compared with poor LS7 score, subjects with intermediate LS7 score had higher risk of CMBs. Moreover, the medical score was inversely associated with the risks of WMH and lacunes, regardless of the criteria. Higher behavioral scores were also associated with a lower risk of lacunes.

Figure 2.

Figure 2. Odds ratio for magnetic resonance imaging (MRI) markers according to categories of Life’s Simple 7 (LS7). Odds ratio for cerebral small vessel disease image makers according to LS7 score, medical score, behavioral score adjusted for age, sex, eGFR, previous antiplatelet, anticoagulants drugs use. #White matter hyperintensity (WMH) burden was defined as either (early) confluent deep WMH (Fazekas score 2 or 3) or irregular periventricular WMH extending into the deep white matter (Fazekas score 3); modified WMH burden was classified into grade 0: total periventricular+subcortical WMH grades 1 and 2, grade 1: total periventricular+subcortical WMH grades 3 and 4 and grade 2: total periventricular+subcortical WMH grades 5 and 6. *Presence of cerebral microbleeds (CMBs) was defined as presence of any CMBs; CMBs burden was classified as grade 0: absent, grade 1: 1-4 microbleeds and grade 2: ≥5 microbleeds. &BG-enlarged perivascular space (EPVS; moderate to severe) indicated moderate to severe (>10) perivascular space in basal ganglia; BG-EPVS (severe) indicated frequent to severe (>20) perivascular space in basal ganglia. cOR indicates common odds ratio.

Discussion

In this large-scale population-based study, we found that the higher LS7 score and medical score were associated with the lower risk of total CSVD score and modified total CSVD score in community-based elderly adults. With regard to the MRI markers, ideal LS7 and medical scores were associated with lower odds of extensive WMH and lacune presence, while the behavioral score was associated with lower odds of lacune presence.

To our knowledge, few studies have specifically assessed the association between the LS7 and cerebral small vessel disease. Most studies8,10,12 reported the association of LS7 with stroke or dementia. A longitudinal study in the UK biobank12 has proved that the higher medical metric was associated with lower incident dementia risk. Previous studies22–24 have suggested that the LS7 score was inversely associated with risks of stroke. These findings supported that the LS7 and medical scores were associated with the risk of CSVD. Interestingly, the intermediate LS7 group was associated with higher odds of CSVD, while the ideal LS7 group was associated with lower odds of CSVD. These differences are driven by higher odds of CMB in the intermediate LS7 group and mainly driven by the behavioral factors. The mechanism of why intermediate LS7 was associated with higher odds of CMB was unclear. One potential explanation was that the intermediate LS7 also had a slight high proportion of individuals with smoking and obesity or overweight. Previous studies have shown that smoking, obesity and overweight may be associated with an increased risk of CMB via atherosclerosis, cerebral amyloid angiopathy, and hypertension.25,26 Second, the intermediate LS7 group had a high proportion of subjects with concomitant antiplatelet agents use. Last, this correlation may be due to chance or residual confounding and requires validation in further large scale studies. Moreover, this association was observed for modified total CSVD score but not for total CSVD score. The potential explanation was that compared with the total CSVD score, the modified total CSVD score may be closer to the real burden of CSVD. As the patients with 11 to 20 basal ganglia PVS were not at significantly increased risk of recurrent ischemic stroke or intracerebral hemorrhage and a clear increase in risk of CSVD was noted for the increasing burden of WMH, the cutoff for PVS was adjusted from >10 to >20 in the modified total CSVD score and the points of WMH were increased in scoring modified total CSVD score.19 In addition, studies about diet and physical activity have shown that specific nutrients and types of physical activity, such as dietary choline, vitamin D, and resistance training, were associated with MRI markers which are components of total CSVD score.27–30 Moreover, the previous studies25,31,32 showed that smoking and BMI were associated with the progress of WMH. However, there was no relationship between behavioral score and total CSVD score in our study, while the association of behavioral score with lacunes was significant. In contrast with our study, the different study populations were one possible reason to explain the inconsistency between these findings. Another explanation was that the behavioral metric needs to be translated into medical metric to have an impact on the human body. Overall, as the risk factors of CSVD were not identified, our study raises concern about the composite metric in the field of cerebral small vessel disease, although the LS7 was not originally developed for predicting CSVD. Considering the critical role of CSVD in stroke and dementia,33 it should be emphasized in clinical practice that the target is to attain ideal LS7, but not intermediate LS7. Future clinical trials should be considered to evaluate modifiable risk factors for reduction of CSVD and related outcomes.

Although the mechanism between LS7 and SCVD was unknown, previous studies34 have shown some hypothetical mechanisms between individual components and MRI markers. First, triglycerides (TGs) and visceral obesity may relate to MRI markers via inflammatory cytokines like CRP (C-reactive protein) and IL-6 (interleukin 6).35,36 Second, hyperlipidemia leads to microvascular hemodynamic regulation disorder, which increases viscosity and resistance of blood flow, and then impact WMH.31 Third, visceral obesity and hyperlipidemia may be related to diet, physical activity, and other vascular risk factors. The dietary pattern of Mediterranean was associated with improved endothelial function, adiposity, and lower levels of inflammatory markers,27 which may be potential mechanisms underlying the relationship between dietary patterns and MRI markers.

This study has several strengths. The major strength of the study was the population representativeness of the participant, which were based on cluster sampling. The demographics and medical histories of participants in the PRECISE study were similar to surveys of a nationwide sample,13 which enables the findings of this study to be generalized to general population. In addition, the relationship of LS7 and CSVD has been explored comprehensively in our study, which included delving into the associations of LS7 and its subscales with total CSVD score and MRI markers, besides examining the association between LS7 and the presence of CSVD. However, there are some limitations in our study. First, the current study was based on baseline data of the PRECISE study and we need a longitudinal study to validate the causal relationship between the level of LS7 and CSVD. Second, we modified the definition for diet for reflecting data available in the study. Because we did not include 2 dietary components (fiber-rich whole grains and sugar-sweetened beverages), which may lead to underestimation of the healthy diet level of participants in our study. Future studies with large sample sizes are needed to validate our results.

In conclusion, in this population-based study, the higher LS7 and medical score were associated with the lower presence of CSVD and the lower total CSVD score. The higher level medical or behavioral score were associated with the lower risks of lacunes. Meanwhile, the higher medical score was associated with the lower risks of WMH. Future studies are needed to determine the causal relationship between LS7 and CSVD and to examine the association of LS7 with progress of MRI markers of CSVD.

Article Information

Acknowledgments

We are grateful for the assistance of the staff, the participants and the other investigators of the PRECISE (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) study.

Supplemental Material

STROBE Statement

Tables S1–S2

Nonstandard Abbreviations and Acronyms

BMI

body mass index

CMB

cerebral microbleed

CRP

C-reactive protein

CSVD

cerebral small vessel disease

LS7

Life’s Simple 7

MRI

magnetic resonance imaging

OR

odds ratio

PRECISE

Polyvascular Evaluation for Cognitive Impairment and Vascular Events

PVS

perivascular space

WMH

white matter hyperintensity

Disclosures None.

Footnotes

*D. Liu and X. Cai contributed equally.

Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.122.038838.

For Sources of Funding and Disclosures, see page 2866.

Correspondence to: Yilong Wang, MD, PhD, No. 119, South 4th Ring West Rd, Fengtai District, Beijing 100070, China, Email
Yuesong Pan, PhD, No.119, South 4th Ring West Rd, Fengtai District, Beijing 100070, China, Email

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