Abstract 15837: Circulating Proneurotensin Concentrations Predict Cardiovascular Disease Events in the Community: The Framingham Heart Study

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
James Januzzi ◽  
Asya Lyass ◽  
Yuyin Liu ◽  
Hanna K Gaggin ◽  
April Trebnick ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Framingham Heart Study ◽  
Proportional Hazards ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cox Proportional Hazards ◽  
Amino Acid Peptide ◽  
Risk Reclassification ◽  
Heart Study

Introduction: Neurotensin is a 13-amino acid peptide whose receptor (SORT1) is strongly linked to cardiovascular disease (CVD) development through several mechanisms, including a role in hepatic low density lipoprotein (LDL) metabolism. We measured concentrations of proneurotensin (PNT; the stable pro-fragment of neurotensin) in subjects from the Framingham Heart Study (FHS) Offspring cohort. Hypothesis: Concentrations of PNT provide incremental information for incident CV events, possibly through interactions with LDL. Methods: Blood samples from 3439 fasting subjects (mean age 59.2 years, 47.1% male) were tested for PNT (Sphingotec, Hennigsdorf, GE). The primary outcome of interest was incident hard CVD (composite of myocardial infarction [MI], stroke, and CV death). Incident hard CHD (MI and CV death) was also examined. Results: Compared to subjects in PNT quartiles 1-3, those in the highest quartile were more likely to be younger and heavier, more likely to smoke (all P <0.007), and across PNT quartiles more likely to have prevalent CVD (from 24.4% to 31.1%; P =0.003) and diabetes mellitus (from 5.5% to 13.4%; P<0.001). No association between PNT and LDL concentrations was observed. In age and sex-adjusted Cox proportional hazards models, log-PNT concentrations predicted incident hard CVD (hazard ratio [HR] = 1.24 per one standard deviation [SD] change in log-PNT; 95% confidence intervals [CI] = 1.11-1.39; P <0.001). Greatest risk for incident hard CVD was observed in log-PNT quartile 4 (HR = 1.53 per one SD change in log-PNT vs quartile 1; P =0.005). In models adjusted for standard risk factors, log-PNT remained significantly associated with incident hard CVD (HR = 1.13 per one SD change in log-PNT; 95% CI = 1.01-1.27; P = 0.03). Addition of log-PNT to the FHS Risk Score resulted in modest risk reclassification (NRI = 0.024; 95% CI=-0.0008-0.048), and in Kaplan Meier analyses, shorter time to first event was seen in higher log-PNT values (log rank P = 0.02). Similar results were found for hard CHD. We did not observe effect modification by LDL. Conclusions: Higher concentrations of PNT are associated with a greater risk of incident hard CVD and CHD in the community independent of LDL concentrations and other risk factors.

Risk factors for cardiovascular diseases and development of prehypertension

2018 ◽  
pp. 37-43
Author(s):  
В.В. Шерстнев ◽  
М.А. Грудень ◽  
В.П. Карлина ◽  
В.М. Рыжов ◽  
А.В. Кузнецова ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Serum Levels ◽  
Left Ventricular ◽  
Optimal Blood Pressure

Цель - исследование взаимосвязи факторов риска сердечно-сосудистых заболеваний и развития предгипертонии. Методика. Проведен сравнительный и корреляционный анализы показателей модифицируемых и немодифицируемых факторов риска сердечно-сосудистых заболеваний у обследованных лиц в возрасте 30-60 лет с «оптимальным» артериальным давлением, (n = 63, АД <120/80 мм рт.ст.) и лиц с предгипертонией (n = 52, АД = 120-139/80-89 мм рт.ст.). Результаты. Показано, что лица с предгипертонией по сравнению с группой лиц, имеющих «оптимальное» артериальное давление характеризуются статистически значимо повышенным содержанием холестерина и холестерина липопротеидов низкой плотности, интеллектуальным характером трудовой деятельности, а также значимыми сочетаниями факторов риска: повышенный уровень холестерина липопротеидов низкой плотности с интеллектуальным характером трудовой деятельности; повышенное содержание креатинина с уровнем триглициридов; наследственная отягощенность по заболеваниям почек и интеллектуальным характером трудовой деятельности; наследственная отягощенность по сахарному диабету и гипертрофия левого желудочка сердца. У лиц с предгипертонией документированы перестройки структуры взаимосвязи (количество, направленность и сила корреляций) между показателями факторов риска в сравнении с лицами, имеющими «оптимальное» артериальное давление. Заключение. Выявленные особенности взаимосвязей факторов риска сердечно-сосудистых заболеваний при предгипертонии рассматриваются как проявление начальной стадии дизрегуляционной патологии и нарушения регуляции физиологических систем поддержания оптимального уровня артериального давления. The aim of the study was to investigate the relationship between risk factors for cardiovascular disease and development of prehypertension. Methods. Comparative and correlation analyses of modifiable and non-modifiable risk factors for cardiovascular disease were performed in subjects aged 30-60 with «optimal» blood pressure (n = 63, BP <120/80 mm Hg) and prehypertension (n = 52, BP = 120-139 / 80-89 mm Hg). Results. The group with prehypertension compared with the «optimal» blood pressure group had significantly increased serum levels of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, sedentary/intellectual type of occupation, and significant combinations of risk factors. The risk factor combinations included an increased level of LDL cholesterol and a sedentary/intellectual occupation; increased serum levels of creatinine and triglycerides; hereditary burden of kidney disease and a sedentary/intellectual occupation; hereditary burden of diabetes mellitus and cardiac left ventricular hypotrophy. In subjects with prehypertension compared to subjects with «optimal» blood pressure, changes in correlations (correlation number, direction, and strength) between parameters of risk factors were documented. Conclusion. The features of interrelationships between risk factors for cardiovascular disease observed in prehypertension are considered a manifestation of early dysregulation pathology and disordered regulation of physiological systems, which maintain optimal blood pressure.

scholarly journals The association between triglyceride-glucose index, cardio-cerebrovascular diseases, and death in Korean adults: A retrospective study based on the NHIS-HEALS cohort

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259212
Author(s):  
Joungyoun Kim ◽  
Sang-Jun Shin ◽  
Hee-Taik Kang
Keyword(s):  
Retrospective Study ◽  
Proportional Hazards ◽  
Smoking Status ◽  
Economic Status ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cerebrovascular Diseases ◽  
Cox Proportional Hazards ◽  
Tyg Index ◽  
All Cause Mortality

Background The triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance. We aimed to investigate the TyG index in relation to cardio-cerebrovascular diseases (CCVDs and mortality. Methods This retrospective study included 114,603 subjects. The TyG index was categorized into four quartiles by sex: Q1, <8.249 and <8.063; Q2, 8.249‒<8.614 and 8.063‒<8.403; Q3, 8.614‒< 8.998 and 8.403‒<8.752; and Q4, ≥8.998 and ≥8.752, in men and women, respectively. To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the primary outcomes (CCVDs and all-cause mortality) and secondary outcomes (cardiovascular diseases [CVDs], cerebrovascular diseases [CbVDs], CCVD-related deaths, or all-cause deaths), Cox proportional hazards regression models were adopted. Results Compared to Q1, the HRs (95% CIs) for the primary outcomes of Q2, Q3, and Q4 were 1.062 (0.981‒1.150), 1.110 (1.024−1.204), and 1.151 (1.058−1.252) in men and 1.099 (0.986−1.226), 1.046 (0.938−1.166), and 1.063 (0.954−1.184) in women, respectively, after adjusted for age, smoking status, drinking status, physical activity, body mass index, systolic blood pressure, low-density lipoprotein cholesterol, economic status, and anti-hypertensive medications. Fully adjusted HRs (95% CIs) for CVDs of Q2, Q3, and Q4 were 1.114 (0.969−1.282), 1.185 (1.031−1.363), and 1.232 (1.068−1.422) in men and 1.238 (1.017−1.508), 1.183 (0.971−1.440), and 1.238 (1.018−1.505) in women, respectively. The adjusted HRs (95% CIs) for ischemic CbVDs of Q2, Q3, and Q4 were 1.005 (0.850−1.187), 1.225 (1.041−1.441), and 1.232 (1.039−1.460) in men and 1.040 (0.821−1.316), 1.226 (0.981−1.532), and 1.312 (1.054−1.634) in women, respectively, while the TyG index was negatively associated with hemorrhagic CbVDs in women but not in men. The TyG index was not significantly associated with CCVD-related death or all-cause death in either sex. Conclusions Elevated TyG index was positively associated with the primary outcomes (CCVDs and all-cause mortality) in men and predicted higher risk of CVDs and ischemic CbVDs in both sexes.

Abstract MP35: Association Of Orthostatic Blood Pressure Response With Incident Heart Failure: The Framingham Heart Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Tara A Shrout ◽  
Vasan S Ramachandran ◽  
Vanessa Xanthakis
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Ejection Fraction ◽  
Framingham Heart Study ◽  
Proportional Hazards ◽  
Blood Pressure Response ◽  
The Elderly ◽  
Cox Proportional Hazards ◽  
Heart Study ◽  
Orthostatic Blood Pressure

Introduction: Orthostatic hypotension (OH) and hypertension (OHT) are associated with cardiovascular disease and mortality. The relation of OH and OHT with heart failure (HF) in the community is not well explored, particularly among the elderly and those with hypertension. Moreover, there remains a paucity of longitudinal data on the development of HF subtypes (HF with reduced ejection fraction [HFrEF] and HF with preserved ejection fraction [HFpEF]) in those with OH and OHT. Hypothesis: We hypothesized that OH and OHT are associated with a higher risk of HF. Methods: We evaluated 1914 Framingham Heart Study participants (mean age 72 years, 1159 women [61%]), with available orthostatic blood pressure (BP) measurements. OH was defined as a decrease and OHT as an increase of 20/10 mmHg in systolic/diastolic BP from supine to standing position, respectively. We used a categorical variable (OH, OHT, absence of OH and OHT [referent]). Using Cox proportional hazards regression, we related OH and OHT to risk of HF and its subtypes (HFrEF, HFpEF), compared to the referent group, adjusting for age, sex, body mass index, systolic BP, diastolic BP, hypertension treatment, smoking, and diabetes. Results: There were 275 participants with OH (181 women, 66%) and 411 with OHT (236 women, 57%). On median follow-up of 13 years, 492 developed HF (292 women, 59%). In multivariable-adjusted analyses, OH was associated with higher risk of HF (Hazards Ratio [HR] 1.47; 95% CI, 1.13-1.92; Figure ) compared to referent. Further, OH was associated with higher risk of HFrEF (HR 2.56; 95% CI, 1.46-4.48), but not HFpEF. OHT was not associated with incident HF. Conclusions: Assessment of orthostatic BP response in the elderly may identify future HF risk. Further studies are warranted to investigate mechanisms underlying the observed associations.

Abstract P345: Prediction of Cardiovascular Disease Events and Death using Multiple Biomarkers in African Americans: the Jackson Heart Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Solomon K Musani ◽  
Ramachandran Vasan ◽  
Aurelian Bidulescu ◽  
Jung Lee ◽  
Gregory Wilson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
African Americans ◽  
High Sensitivity ◽  
Serum Cortisol ◽  
Jackson Heart Study ◽  
Cvd Risk ◽  
Risk Reclassification ◽  
Heart Study ◽  
Traditional Risk Factors

Background: The usefulness of biomarkers from different biologic pathways for predicting cardiovascular disease (CVD) events among African Americans is not well understood. Methods: We evaluated prospectively 3,102 Jackson Heart Study participants (mean age 54 years; 64% women) with data on a panel of 9 biomarkers representing inflammation (high sensitivity C - reactive protein), adiposity (adiponectin, leptin), neurohormonal activation (B-type natriuretic peptide [BNP], aldosterone, and cortisol); insulin resistance (HOMA-IR); and endothelial function (endothelin and homocysteine). We used Cox proportional hazard regression to relate the biomarker panel to the incidence of CVD (stroke, coronary heart disease, angina, heart failure and intermittent claudication) adjusting for standard CVD risk factors. Results: On follow-up (median 8.2 years), 224 participants (141 women) experienced a first CVD event, and 238 (140 women) died. Circulating concentrations of aldosterone, BNP and HOMA-IR were associated with CVD (multivariable-adjusted hazard ratios [HR] and 95% confidence interval [CI] per standard deviation (SD) increase in log-biomarker) were, respectively 1.15, (95% CI 1.01-1.30, p=0.016), 1.97, (95% CI 1.22-2.41, p<0.0001), and 1.30, (95% CI 1.10-1.52, p=0.0064). Blood cortisol and homocysteine were associated with death (HR per SD increment log-biomarker, respectively, 1.17, (95% CI 1.01-1.35, p=0.042), and 1.24, (95% CI 1.10-1.40, pvalue=0.0005). Biomarkers improved risk reclassification by 0.135; 0.120 of which was gained in classification of participants that experienced CVD events and 0.015 from participants that did not. Also, biomarkers marginally increased the model c-statistic beyond traditional risk factors. Conclusions: In our community-based sample of African Americans, circulating aldosterone, BNP and HOMA-IR predicted CVD risk, whereas serum cortisol and homocysteine predicted death. However, the incremental yield of biomarkers over traditional risk factors for risk prediction was minimal.

Abstract 17: Association of Race and Sex with Cardiovascular Disease and Non-Cardiovascular Disease Mortality: The REasons for Geographic and Racial Differences in Stroke study

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Gabriel S Tajeu ◽  
Monika M Safford ◽  
George Howard ◽  
Rikki M Tanner ◽  
Paul Muntner
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Racial Differences ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Cvd Risk ◽  
Hazard Ratios ◽  
Stroke Study ◽  
Cvd Mortality

Introduction: Black Americans have higher rates of cardiovascular disease (CVD) mortality compared with whites. Differences in sociodemographic, psychosocial, CVD, and other risk factors may explain increased mortality risk. Methods: We analyzed data from 29,015 REasons for Geographic and Racial Differences in Stroke study participants to determine factors that may explain the higher hazard ratio for CVD and non-CVD mortality in blacks compared with whites. Cause of death was adjudicated by trained investigators. Within age-sex sub-groups, we used Cox proportional hazards regression with progressive adjustment to estimate black:white hazard ratios. Results: Overall, 41.0% of participants were black, and 54.9% were women. Over a mean follow-up of 7.1 years (maximum 12.3 years), 5,299 participants died (1,797 CVD and 3,502 non-CVD deaths). Among participants < 65 years of age, the age and region adjusted black:white hazard ratio for CVD mortality was 2.28 (95% CI: 1.68-3.10) and 2.32 (95% CI: 1.80-3.00) for women and men, respectively, and for participants ≥ 65 was 1.54 (95% CI: 1.30-1.82) and 1.35 (95% CI: 1.16-1.57) for women and men, respectively ( Table ). The higher black:white hazard ratios for CVD mortality were no longer statistically significant after multivariable adjustment, with the largest attenuation occurring with sociodemographic and CVD risk factor adjustment. Among participants < 65 years of age, the age and region adjusted black:white hazard ratios for non-CVD mortality were 1.51 (95% CI: 1.24-1.85) and 1.76 (95% CI: 1.46-2.13) for women and men, respectively, and for participants ≥ 65 was 1.12 (95% CI: 1.00-1.26) and 1.34 (95% CI: 1.20-1.49) for women and men, respectively. The higher black:white hazard ratios for non-CVD mortality were attenuated after adjustment for sociodemographics. Conclusions: Black:white differences are larger for CVD than non-CVD causes of death. The increased CVD mortality for blacks compared with whites is primarily explained by sociodemographic and CVD risk factors.

Abstract P181: Atherogenic Lipoproteins and Incident Atherosclerotic Cardiovascular Disease in the Framingham Offspring Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Hiroaki Ikezaki ◽  
Elise Lim ◽  
Ching-Ti Liu ◽  
L Adrienne Cupples ◽  
Bela F Asztalos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Significant Information ◽  
Ascvd Risk

Introduction: Elevated plasma low-density lipoprotein cholesterol (LDL-C), small-dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), triglycerides (TG), remnant-lipoprotein cholesterol (RLP-C), triglyceride-rich lipoprotein-C (TRL-C), very low-density lipoprotein cholesterol (VLDL-C), and lipoprotein(a) [Lp(a)] levels have been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. However, these parameters have not been included in risk factors for ASCVD in the pooled cohort equation (PCE). Hypothesis: We assessed the hypothesis that these atherogenic lipoprotein parameters add significant information for ASCVD risk prediction in the Framingham Offspring Study. Methods: We evaluated 3,147 subjects without ASCVD at baseline (mean age 58 years) from participants of Framingham Offspring Study cycle 6, 677 (21.5%) of whom developed inclusive ASCVD over 16 years. Biomarkers of risk were assessed in frozen plasma samples. Total cholesterol, TG, HDL-C, direct LDL-C, sdLDL-C, LDL-TG, Lp(a), RLP-C, and TRL-C were measured by standardized automated analysis. Calculated LDL-C, large buoyant low-density lipoprotein cholesterol (lbLDL-C), VLDL-C, and non-HDL-C values were calculated. Data were analyzed using Cox proportional regression analysis and net reclassification improvement (NRI) analysis to identify parameters significantly associated with the incidence of ASCVD after controlling for standard ASCVD risk factor and applying the PCE model. Results: All specialized lipoprotein parameters were significant ASCVD risk factors on univariate analysis, but only direct LDL-C, sdLDL-C, and Lp(a) were significant on multivariate analysis with standard risk factors in the model. Together these parameters significantly improved the model c statistic (0.716 vs 0.732, P < 0.05) and net risk reclassification (mean NRI 0.104, P < 0.01) for ASCVD risk. Using the ASCVD risk pooled cohort equation, sdLDL-C, TG, LDL-TG, LDL-C, RLP-C, and TRL-C individually added significant information, but no other parameter added significant information with sdLDL-C (hazard ratio 1.30 for 75th vs 25th percentile, P < 0.0001) in the model. Conclusions: In multivariate analysis, sdLDL-C, direct LDL-C, and Lp(a) contributed significantly to ASCVD risk, but only sdLDL-C added significant risk information to the PCE model, indicating that sdLDL-C may be the most atherogenic lipoprotein particle.

scholarly journals The Association of Breakfast Frequency and Cardiovascular Disease (CVD) Risk Factors among Adolescents in Malaysia

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 973 ◽  
Author(s):  
Norashikin Mustafa ◽  
Hazreen Abd Majid ◽  
Zoi Toumpakari ◽  
Harriet Amy Carroll ◽  
Muhammad Yazid Jalaludin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Longitudinal Research ◽  
Low Density Lipoprotein ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Diet History ◽  
Malaysian Adolescents

Breakfast frequency is associated with cardiovascular disease (CVD) risk in Western populations, possibly via the types of food eaten or the timing of food consumption, but associations in Malaysian adolescents are unknown. While the timing of breakfast is similar, the type of food consumed at breakfast in Malaysia differs from Western diets, which allows novel insight into the mechanisms underlying breakfast–CVD risk associations. We investigated foods eaten for breakfast and associations between breakfast frequency and CVD risk factors in the Malaysian Health and Adolescents Longitudinal Research Team study (MyHeARTs). Breakfast (frequency of any food/drink reported as breakfast in 7-day diet history interviews) and CVD risk factors (body mass index (BMI), waist circumference, fasting blood glucose, triacylglycerol, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and systolic and diastolic blood pressure) were cross-sectionally associated using linear regression adjusting for potential confounders (n = 795, age 13 years). Twelve percent of adolescents never ate breakfast and 50% ate breakfast daily, containing mean (SD) 400 (±127) kilocalories. Commonly consumed breakfast foods were cereal-based dishes (primarily rice), confectionery (primarily sugar), hot/powdered drinks (primarily Milo), and high-fat milk (primarily sweetened condensed milk). After adjustment, each extra day of breakfast consumption per week was associated with a lower BMI (−0.34 kg/m2, 95% confidence interval (CI) −0.02, −0.66), and serum total (−0.07 mmol/L 95% CI −0.02, −0.13) and LDL (−0.07 mmol/L 95% CI −0.02, −0.12) cholesterol concentrations. Eating daily breakfast in Malaysia was associated with slightly lower BMI and total and LDL cholesterol concentrations among adolescents. Longitudinal studies and randomized trials could further establish causality.

scholarly journals Cardiovascular health, genetic risk, and risk of dementia in the Framingham Heart Study

Neurology ◽  
2020 ◽  
Vol 95 (10) ◽  
pp. e1341-e1350 ◽  
Author(s):  
Gina M. Peloso ◽  
Alexa S. Beiser ◽  
Claudia L. Satizabal ◽  
Vanessa Xanthakis ◽  
Ramachandran S. Vasan ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Framingham Heart Study ◽  
Cardiovascular Health ◽  
Proportional Hazards ◽  
Genetic Risk Score ◽  
Cox Proportional Hazards ◽  
Ideal Cardiovascular Health ◽  
Heart Study ◽  
Common Genetic Variants ◽  
Ε4 Allele

ObjectiveTo determine the joint role of ideal cardiovascular health (CVH) and genetic risk on risk of dementia.MethodsWe categorized CVH on the basis of the American Heart Association Ideal CVH Index and genetic risk through a genetic risk score (GRS) of common genetic variants and the APOE ε4 genotype in 1,211 Framingham Heart Study (FHS) offspring cohort participants. We used multivariable Cox proportional hazards regression models to examine the association between CVH, genetic risk, and incident all-cause dementia with up to 10 years of follow-up (mean 8.4 years, 96 incident dementia cases), adjusting for age, sex, and education.ResultsWe observed that a high GRS (>80th percentile) was associated with a 2.6-fold risk of dementia (95% confidence interval [CI] of hazard ratio [HR] 1.23–5.29; p = 0.012) compared with having a low GRS (<20th percentile); carrying at least 1 APOE ε4 allele was associated with a 2.3-fold risk of dementia compared with not carrying an APOE ε4 allele (95% CI of HR 1.49–3.53; p = 0.0002), and having a favorable CVH showed a 0.45-fold lower risk of dementia (95% CI of HR 0.20–1.01; p = 0.0527) compared to having an unfavorable CVH when all 3 components were included in the model. We did not observe an interaction between CVH and GRS (p = 0.99) or APOE ε4 (p = 0.16).ConclusionsWe observed that both genetic risk and CVH contribute additively to dementia risk.

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