bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 5770: Abnormal Aortic Root Elastic Properties in Family Members of Bicuspid Aortic Valve Subjects, despite Normal Aortic Valve Morphology.
Authors: Rafique Asim , Biner Simon , Ray Indraneil , Cuk Olivera , Siegel Robert , Tolstrup Kirsten
Published: July 2021

Background:
Abnormal aorta dilatation and elastic properties have been documented in subjects with bicuspid aortic valve (BAV). 10% of first degree relatives (FDRs) of probands with BAV inherit this valvular abnormality. There is no data regarding the elastic properties of aortic root in family members of BAV subjects. We evaluated the elastic properties in FDRs with normal tricuspid aortic valves.

Methods:
Systolic and diastolic aortic root dimensions were measured by 2D echocardiography in BAV probands (n=48) their FDRs (n = 49) and controls without structural heart disease matched by age and gender (n=44) at sinuses of Valsalva level. In addition, systolic (SBP) and diastolic blood pressure (DBP) were measured to calculate aortic distensibility, stiffness index and strain.

Results:
Five subjects (10%) in FDR group were found to have BAV, thus they were included in BAV group. There was no difference in age, gender, SBP and DBP in the three groups. History of hypertension was less prevalent in FDRs when compared to BAV and controls (16% vs 43% and 33%, p=0.03). All three parameters of aortic elastic properties including distensibility ×10
−3
mmHg (1.2±1.0 and 1.5±1.1 vs 2.3±1.5, p<0.001), stiffness index (56.5±76.4 and 29.1±32.5 vs 12.6±9.2, p<0.001) and strain (2.9±2.4and 3.6±2.5 vs 6.0±3.6, p<0.001) were significantly worse in BAV and FDRs compared to controls (Figure

).

Conclusions:
Aortic root elastic properties are abnormal in the family members of subjects with BAV despite normal tricuspid aortic valve morphology. This finding supports the hypothesis that there is a common genetic basis for BAV and abnormal elastic properties of aorta.
Abstract 5772: The Impact of Aortic Plaque Morphology on Survival Rate and the Incidence of Subsequent Embolic Event: Very Long-Term Follow-Up Data
Authors: Izumi Chisato , Takahashi Shuichi , Hashiwada Sumiyo , Hanazawa Koji , Sakamoto Jiro , Yoshitani Kazuyasu , Miyake Makoto , Kaitani Kazuaki , Izumi Toshiaki , Gen Hiromitsu , Nakagawa Yoshihisa
Published: July 2021

Atheromatous plaques of the aorta have been regarded as a potential source of emboli, but there are few reports about the frequency and prognosis of patients with thoracic aortic plaques and about the relationship between plaque morphology and prognosis, especially long-term follow-up data. The purpose of this study is to clarify the impact of aortic atheromatous plaque morphology on survival rate and the incidence of subsequent embolic event. We retrospectively investigated 1570 consecutive patients who underwent transesophageal echocardiography between 1991 and 2003. The presence of severe plaque (>5mm in thickness) in the thoracic aorta were examined. Survival rate and subsequent embolic event rate were compared between patients with severe plaque and 109 control patients. The control patients were selected from the patients who showed no or mild plaque and as they were matched for age, gender, and risk factors of atherosclerosis with the patients with severe aortic plaque. The relationship between aortic plaque morphology and prognosis was also estimated, according to the presence of ulceration, calcification, hypoechoic plaques, and mobile plaques. Mean follow-up period was 8.7 years. Among 1570 patients, severe aortic plaque was detected in 92 patients (5.9%). These 92 patients showed significantly low survival rate and high subsequent embolic event rate compared with control patients (8-year survival rate, 50% vs 87%, 8-year embolic event free rate, 57% vs 90%). The relative risk of death was significantly increased for ulceration (2.4, 95% CI;1.1–5.2) and the relative risk of embolic events was significantly increased for mobile plaques (2.2, 95% CI;1.1–5.1). In conclusion, aortic plaque > 5mm in thickness was a predictor of a low survival rate and a high embolic event rate. Among patients with aortic plaque >5mm in thickness, ulceration was a predictor of a low survival rate and mobile plaque was a predictor of a high embolic event rate.
Abstract 005: Six-Minute Walk Test Predicts Heart Failure, Myocardial Infarction, and Death in Patients with Stable Ischemic Heart Disease: Data from the Heart and Soul Study
Authors: Beatty Alexis L , Schiller Nelson B , Whooley Mary A
Published: July 2021

Background:
The six-minute walk test (6MWT) is commonly used to assess functional exercise capacity in patients with heart or lung disease. However, its ability to predict events in patients with stable ischemic heart disease (IHD) is unknown.

Methods:
We measured 6MWT distance and treadmill exercise capacity in 556 outpatients with stable IHD between September 2000 and December 2002. Participants were followed for an average of 7.7 years to determine cardiovascular (CV) events (myocardial infarction, heart failure, or death). We used Cox proportional hazards models to evaluate 6MWT distance and treadmill exercise capacity as predictors of subsequent events.

Results:
Among the 556 patients, there were 82 heart failure hospitalizations, 63 myocardial infarctions, and 184 deaths from any cause. Patients in the lowest quartile of 6MWT distance (284-1375 ft) were 3 times as likely as patients in the highest quartile (1786-2746 ft) to experience CV events (62% vs. 22%, age-adjusted HR 3.15, 95%CI 1.98-5.03, p<0.0001). Each standard deviation (SD) decrease in 6MWT distance (342 ft) was associated with an 86% greater risk of heart failure (age-adjusted HR 1.86, 95%CI 1.51-2.31, p<0.0001), a 47% greater risk of myocardial infarction (age-adjusted HR 1.47, 95%CI 1.15-1.89, p=0.002), a 54% greater risk of death (age-adjusted HR 1.54, 95%CI 1.32-1.80, p<0.0001), and a 55% greater risk of any event (age-adjusted HR 1.55, 95%CI 1.35-1.78, p<0.0001). After adjustment for traditional risk factors and measures of cardiac disease severity (left ventricular ejection fraction, inducible ischemia, diastolic dysfunction, NT-proBNP and CRP), each SD decrease in 6MWT remained associated with a 38% greater risk of CV events (HR 1.38, 95%CI 1.10-1.74, p=0.005). 6MWT distance was similar to treadmill exercise capacity for predicting CV events (age-adjusted c-statistics 0.72 vs. 0.71, p=0.73 for comparison).

Conclusions:
Distance walked on 6MWT is as good as treadmill exercise capacity for predicting CV events in patients with stable IHD.
Abstract 008: Risk Factors for Type 2 Diabetes Mellitus Preceded by β-cell Dysfunction, Insulin Resistance, or Both: The Cardiovascular Health Study
Authors: Imamura Fumiaki , Mukamal Kenneth J , Meigs James B , Luchsinger Jose A , Ix Joachim H , Siscovick David S , Mozaffarian Dariush
Published: July 2021

Background:
Type 2 diabetes mellitus (DM) results from insulin resistance (IR), pancreatic β-cell dysfunction, or both. We hypothesized that risk factors could differ for DM preceded predominantly by IR, β-cell dysfunction, or both. This hypothesis is particularly important for older adults, in whom β-cell dysfunction may be relatively common.

Methods:
During 18 years of follow-up among 3,899 older adults free of DM (mean±sd age =73.0±5.8), we identified 274 incident DM cases by DM medication use, fasting glucose (≥126 mg/dL), or 2-hour post-challenge glucose (≥200 mg/dL), for whom homeostatic model assessments for IR (HOMA-IR) and β-cell function (HOMA-B) were assessed after baseline and before DM diagnosis. Using median cutoffs of the follow-up HOMA-IR and HOMA-B, we subclassified incident DM into DM preceded by IR only (n=112), β-cell dysfunction only (n=70), or both (n=77). Using multivariate competing-risk Cox models, we tested whether DM risk factors were differentially associated with risk of each DM subclass.

Results:
Elevated triglyceride levels (≥150 mg/dL) and impaired fasting glucose (100-125 mg/dL) were each positively associated with DM, irrespective of the DM subclass. Other DM risk factors of older age, overweight, obesity, low HDL cholesterol, and hypertension had substantially varying relationships with risk of different DM subclasses (p<0.001 for the variations). For example, overweight (BMI=25-29.9 kg/m2) and obesity (BMI≥30 kg/m2) were each positively associated with DM preceded by IR only (hazard ratio [95% CI]= 2.21 [1.25-3.92] and 5.02 [2.81-9.00], respectively), but with a significant inverse association with DM preceded by β-cell dysfunction only (0.61 [0.37-1.00] and 0.33 [0.14-0.80], respectively) (Figure).

Conclusions:
Among older adults, some DM risk factors differ substantially depending on HOMA-IR or HOMA-B subclassification. These findings support our hypothesis of heterogeneity in incident DM, especially among older adults.
Abstract 032: Examination of Cardiovascular Risk Factors and Rurality in Appalachian Children using Surveillance, Clustered Statistical Design and Geographic Information Systems (GIS) capabilities.
Authors: Ice Christa , Cottrell Lesley , Fedorko Evan , Neal William
Published: July 2021

Recent evidence suggests a strong link between rurality and obesity. Our hypothesis for this study is that children living in more rural areas will have higher percentages of body mass index (BMI) above the median; higher levels of total cholesterol (TC), triglycerides (TRIG) and low-density lipoprotein cholesterol (LDL); lower levels of high-density lipoprotein cholesterol (HDL); and higher systolic (SBP) and diastolic blood pressure (DBP) levels after controlling for individual covariates. Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) data was used; 65,531 5
th
grade children with home zip codes. Our statistical approach uses a clustered ANCOVA nesting individual children’s fasting lipid profile, BMI and BP results within their home zip coded using the Rural-Urban Continuum Code (RUCC) and controlling for child age, gender, race, and parent education. RUCC, a 9-point classification system, was reduced to 5 categories for this analysis (Figure 1). Significant nested effects were seen for all variables after controlling for covariates, including BMI, HDL, SBP, DBP, TRIG, LDL, and TC (p < 0.001). However, post-hoc comparisons disputed our hypothesis that rural areas would have significantly higher risk factors than urban or metro areas. In particular, Mid-sized metro areas had significantly higher BMI percent above ideal than Large or Small metro areas [21.45 v. 16.57 (p=0.035) and 16.65 (p=0.008)]; no differences between Rural or Urban areas. Large metro and Rural had significantly higher HDLs than Small metro, Urban, and Mid-sized metro areas. Mid-sized metro areas had higher SBP and LDL than Rural or Small Metro areas. This data directly contradicts previous literature suggesting a straight-forward link between rurality and cardiovascular risk factors. In general, Mid-sized metro areas presented the worst outcomes. Future research should include longitudinal design and mechanisms between cardiovascular risk factors and rurality, which could not be addressed in this study.
Abstract 055: Statins Raise Glucose Preferentially among Men Who are Older and at Greater Metabolic Risk
Authors: Golomb Beatrice A , Koperski Sabrina , White Halbert L
Published: July 2021

Background:
Several major statin trials have shown increased incident diabetes and/or modest average elevations in HbA1C (e.g. PROVE-IT, JUPITER) with statins, though average effects on glucose are small: There may be a vulnerable subset.

Hypothesis:
We hypothesized that advancing age and metabolic status would condition the rise in glucose on statins.

Design:
Sex-stratified randomized double-blind placebo-controlled trial of simvastatin 20mg, pravastatin 40mg or placebo for 6 months. We assessed glucose-change (from baseline to 6-months) on statins relative to placebo, as a function of age and metabolic markers (HDL30, SBP>130, triglycerides>130, glucose>100) in men (N=692).

Analysis:
Regression of statin-vs-placebo on glucose change was performed for subjects without and with metabolic markers. The effect of the number of metabolic markers present on the rise in glucose due to statins was examined, as measured by the interaction term of statins x #-metabolic-markers, as a function of age. Robust standard errors were used.

Results:
Statins showed little effect on glucose overall. Glucose elevation due to statins emerged in the presence of each metabolic marker (Table 1A), and increased with number of metabolic markers for both simvastatin and pravastatin in older age (Table 1B).

Conclusion:
Statins increase glucose particularly among persons who are older and have greater existing metabolic load.
Abstract MP001: Plasma Lipophilic Index and Risk of Coronary Heart Disease in US Men
Authors: Wu Hongyu , Ding Eric L , Rimm Eric B , Hu Frank B , Sun Qi
Published: July 2021

Background:
Lipophilicity of fatty acids plays a critical role in modulating the fluidity and function of cellular and lipoprotein membranes that are involved in the etiology of coronary heart disease (CHD). However, no data are available on the relationship between overall fatty acid lipophilicity and risk of CHD.

Objective:
To examine a novel index of fatty acid lipophilicity in relation to risk of CHD in men.

Methods:
In a prospective CHD case-control study nested in the Health Professionals Follow-up Study (HPFS), fatty acids in total plasma and erythrocyte membrane were measured by gas-liquid chromatography in 459 CHD cases and 879 matched controls. Plasma lipophilic index (LI) was computed by summing the products between relative density (proportion of total fatty acids) of 21 major fatty acids and their melting points. Erythrocyte LI was derived from 14 fatty acids using the same method.

Results:
Both plasma and erythrocyte LI summarized a pattern that featured high saturated fatty acids and low polyunsaturated fatty acids. Plasma C24:0, C22:0, C20:0, C23:0, C18:0 (all
P
<0.0001) were positively and C20:5n–3, C22:6n–3, and C20:4n–6 (all
P
<0.0001) were inversely associated with plasma LI, and these fatty acids jointly explained ∼71% of plasma LI variation among control participants. Among controls, higher plasma LI was significantly correlated with adverse profiles of CHD risk factors, including elevated levels of triglycerides, C-reactive protein, interlukin-6, and tumor necrosis factor α receptor 1 and 2, and lower level of HDL-cholesterol and adiponectin (all
P
<0.005). After multivariate adjustment of covariates including age, smoking status, body mass index, and physical activity, plasma LI was significantly associated with increased risk of total CHD: odds ratio (95% confidence interval) was 1.82 (1.16, 2.86;
P
for trend = 0.016) comparing extreme quintiles. The association was more pronounced for non-fatal myocardial infarction (OR=2.06, 95% CI 1.24, 3.42;
P
for trend = 0.004) than for fatal CHD (OR=1.04, 95% CI 0.31, 3.55;
P
for trend = 0.63). The association between erythrocyte LI and risk of CHD was not significant after multivariate adjustment (OR=1.18, 95% CI 0.71, 1.79;
P
for trend = 0.66).

Conclusions:
Our data indicate that the novel plasma lipophilic index, which summarizes overall lipophilicity of major fatty acids in plasma, is associated with an increased risk of CHD in men.
Abstract MP017: Television Viewing and Life Expectancy in the United States
Authors: Katzmarzyk Peter T , Lee I-Min
Published: July 2021

Introduction:
Sedentary behaviors such as television viewing are ubiquitous in modern society. Several prospective studies have demonstrated an association between television viewing and incident obesity and type 2 diabetes as well as cardiovascular disease and all-cause mortality.

Hypothesis:
We tested the null hypothesis that television viewing has no impact on life expectancy in the United States.

Methods:
A prevalence-based cause-deleted methodology was used to estimate the gains in life expectancy in the population that would be expected under current mortality patterns if television viewing was eliminated as a potential risk factor in the United States. The population attributable fraction (PAF, calculated using adjusted relative risk (RR) = ∑P(RR-1/RR)) was computed from the RR of all-cause mortality associated with television viewing (2–3.9 h and ≥4 h versus < 2 h) obtained from a meta-analysis of available prospective cohort studies, and the estimated case prevalence (P) of television viewing obtained from the U.S. National Health and Nutrition Examination Survey (2005–06) and the prospective cohort studies. The resulting PAF was applied to mortality rates among 18+ year olds living in the United States and an abridged life table analysis was used to estimate the potential gains in life expectancy.

Results:
Three prospective cohort studies contributed data to the meta-analysis, yielding summary RR estimates for all-cause mortality of 1.17 (95% CI: 1.04 – 1.32) and 1.49 (95% CI: 1.22–1.82) for 2–3.9 h and ≥4 h of television viewing versus <2 h, respectively. The estimated case prevalences of television viewing in the U.S. population were 23.8%, 45.7% and 37.2% for <2 h, 2–3.9 h and ≥4 h of television viewing, respectively. The estimated gain in life expectancy in the US population associated with television viewing was 1.38 years. The lower and upper limits from a sensitivity analysis which involved simultaneously varying the estimates of RR (using the upper and lower bounds of the 95% CI) and the prevalence of television viewing (± 20%) were 0.48 years and 2.50 years.

Conclusions:
Reducing sedentary behaviors such as television viewing has the potential to increase life expectancy in the United States.
Abstract MP026: Does the Replacement of Moderate-Intensity with Vigorous-Intensity Physical Activity Further Reduce All-Cause and Cardiovascular Mortality?
Authors: Shiroma Eric J , Sesso Howard D , Lee I-Min
Published: July 2021

The 2008 US federal guidelines require a minimum of 150 minutes/week of moderate-intensity, or 75 minutes/week of vigorous-intensity physical activity, or an equivalent combination of the two, for health benefits. Thus, they assume a 2:1 equivalence between the two intensities of activity; i.e., 2 minutes of moderate-intensity activity is equivalent to 1 minute of vigorous-intensity activity. However, no studies have specifically examined whether this assumption is correct.

Purpose:
To examine the effect of replacing 150 minutes/week of moderate-intensity with 75 minutes/week of vigorous-intensity physical activity on all-cause and cardiovascular disease (CVD) mortality.

Methods:
8,859 men (mean age, 66.4 yr) from the Harvard Alumni Health Study, free from CVD and cancer, were followed from 1988 to 2008. At baseline (1988) and in 1993, men reported physical activity (blocks walked, stairs climbed, and a listing of sports/recreational activities and participation time). Time spent per week in sports/recreational activities of moderate-intensity (3 to <6 METs, or multiples of resting metabolic rate) was summed and expressed as units (or fraction of units) of 150 minutes/week. Similarly, time spent in vigorous-intensity (≥6 METs) sports/recreational activities was summed, expressed as units (or fraction of units) of 75 min/week. Total and cause-specific mortality was identified from the National Death Index. Cox proportional hazards models calculated the risks of all-cause and CVD mortality, examining the effect of replacing 150 minutes/week of moderate-intensity with 75 minutes/week of vigorous-intensity physical activity, controlling for the total amount of physical activity.

Results:
During follow-up, 4,064 men died, including 1,192 from CVD. In multivariate analyses, controlling for the total physical activity, age, smoking, intakes of alcohol, vegetable, fruit, and saturated fat, and total caloric intake, replacing 150 minutes/week of moderate-intensity with 75 minutes/week of vigorous-intensity physical activity was associated with an additional 2% reduction in all-cause mortality (Hazard Ratio (95% confidence interval) = 0.98 (0.96, 1.00); p = 0.05), and an additional 5% reduction in CVD mortality (0.95 (0.92, 0.99); p = 0.02).

Conclusions:
The assumption that 2 minutes of moderate-intensity activity is equivalent to 1 minute of vigorous-intensity activity under current federal guidelines is not strictly correct. Vigorous-intensity physical activity is associated with additional risk reduction for CVD mortality compared to moderate-intensity physical activity. Although there is an added, statistically significant benefit of vigorous-intensity over moderate-intensity physical activity, the magnitude of benefit is small.
Abstract MP031: Birth Weight, Genetic-Susceptibility and Adulthood Risk of Type 2 Diabetes
Authors: Li Yanping , Qi Qibin , Workalemahu Tsegaselassie , Hu Frank B , Qi Lu
Published: July 2021

Background:
Both stressful intrauterine milieus and genetic susceptibility have been linked to later life diabetes risk. The present study aims to examine the interaction between low birth weight, a surrogate measure of stressful intrauterine milieus, and genetic susceptibility in relation to risk of type 2 diabetes in adulthood.

Methods:
The analysis included two independent, nested case-control studies of in total 2591 cases of type 2 diabetes and 3052 healthy controls from prospective cohorts: the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). We developed 2 genotype scores using susceptibility loci recently identified through Genome Wide Association Studies: 1) an ‘obesity genotype score’ based on 32 BMI-predisposing single nucleotide polymorphisms (SNPs); and 2) a ‘diabetes genotype score’ based on 35 diabetes-predisposing SNPs.

Results:
Both the obesity genotype score and diabetes genotype score showed consistently significant association with risk of type 2 diabetes in NHS and HPFS (
P
for trend < 0.01). In the pooled sample of the two cohorts, we found significant interaction between birth weight and obesity genotype score in relation to type 2 diabetes (
P
for interaction=0.017). In low birth weight individuals (≤ 2.5 kg), the multivariable-adjusted odds ratio (OR) was 2.55 (95% confidence interval [CI]: 1.34–4.84) in the comparison of the highest with the lowest quartile of the obesity genotype score, while the OR was 1.27 (95%CI: 1.04–1.55) among individuals with birth weight above 2.5kg. Diabetes genotype score also showed stronger association with type 2 diabetes risk in individuals with low birth weight than those with high birth weight. Comparing individuals of the highest with the lowest quartile of the diabetes genotype score, the multivariable-adjusted odds ratio was 3.80 (95%CI: 1.76–8.24) among individuals with low birth weight and was 2.27 (95%CI: 1.82–2.83) among those with high birth weight. However, test for interaction was marginal (
P
=0.16).

Conclusion:
Our data suggest low birth weight and genetic susceptibility to obesity may synergistically affect adulthood risk of type 2 diabetes.
Abstract MP035: Relative Attenuation of Visceral Adipose Tissue and Metabolic Risk: The Framingham Heart Study
Authors: Rosenquist Klara J , Pedley Alison , Massaro Joseph M , Murabito Joanne M , Hoffmann Udo , Fox Caroline S
Published: July 2021

Background:
Visceral abdominal tissue (VAT) is a unique pathogenic fat depot that is associated with cardiometabolic risk above and beyond overall body mass index (BMI). Higher lipid content of adipose tissue is associated with lower tissue attenuation (i.e. more negative) in computed tomography (CT) and is expressed as Hounsfield units (HU). Given this framework, we hypothesized that lower CT attenuation of adipose tissue is associated with more adverse metabolic risk.

Methods:
Framingham Heart Study participants (n=3198, mean age 51 years, 47% women) who participated in a computed tomography sub-study with volumetrically assessed VAT and documented HU were studied. Cardiovascular risk factors were measured using standard definitions. The association between HU and metabolic risk factors was assessed using sex-specific multivariable-adjusted regression models.

Results:
Mean visceral HU was −93.9 (Range −105.7 to −79.0). Mean HU were overall lower in men (−95.2) than women (−92.4). Lower HU correlated with higher BMI levels in women (age adjusted r = −0.51, p<0.001) and men (age adjusted r = −0.42, p<0.001). Risk factors levels were more adverse with decreasing HU levels. For example, the age-adjusted prevalence of metabolic syndrome ranged from 50% in the lowest negative tertile of visceral HU to 5.5% in the least negative tertile in women (p for trend across tertiles <0.001) with similar trends observed in men (p<0.001). In women, per 1 standard deviation (SD) decrease in visceral HU, the odds ratio (OR) for metabolic syndrome was 3.6 (95% CI 3.1 to 4.3, p<0.001), which persisted after adjustment for BMI (OR 2.5, p<0.001) and VAT (OR 1.5, p<0.001). Also in women, 1-SD decrease in visceral HU was associated with increased odds of hypertension (OR 1.8, 95% CI 1.6 to 2.1, p<0.001), impaired fasting glucose (OR 2.1, 95% CI 1.8 to 2.4, p<0.001) and insulin resistance (OR 3.3, 95% CI 2.8 to 4.0, p<0.001). These associations remained significant after adjustment for BMI (OR 1.4 to 2.3, all p<0.001). After adjustment for VAT, impaired fasting glucose (OR 1.5, p<0.001) and insulin resistance (OR 1.4, p=0.003) remained associated but hypertension did not (OR 1.2, p=0.19). Finally, per 1-SD decrease in visceral HU, HDL levels were 5.2 mg/dL lower (p <0.001) and log triglycerides were 0.20 mg/dL higher (p<0.001), both of which persisted after VAT adjustment. Similar findings were observed in men.

Conclusion:
Lower CT attenuation of visceral fat, a marker of higher lipid content of adipose tissue, is associated with increased adverse metabolic risk above and beyond total VAT volume. These findings highlight that both quantity and quality of fat depots may provide additional information regarding cardiometabolic risk.
Abstract MP052: Lifestyle Factors and Antihypertensive Treatment on the Risks of Ischemic and Haemorrhagic Stroke
Authors: Hu Gang , Zhang Yurong , Jousilahti Pekka , Wang Yujie , Antikainen Riitta , Tuomilehto Jaakko
Published: July 2021

Background
Although hypertension is a potential intermediate factor on the causal pathway of lifestyle factor with stroke risk, the joint relationship between healthy lifestyle and antihypertensive treatment with stroke risk is unclear.

Methods
We prospectively investigated the individual and joint effects of healthy lifestyle factors and antihypertensive treatment on total and type-specific stroke risk among 36,686 Finnish participants who were 25 to 74 years old and free of coronary heart disease and stroke at baseline. The Cox proportional hazards model was used to evaluate the associations between healthy lifestyle factors and hypertension subgroups with stroke risk.

Results
During a mean follow-up of 13.7 years, 1,478 people developed an incident stroke event (1,167 ischemic and 311 hemorrhagic). The risk of stroke was significantly decreased in people adhered to ≥3 healthy lifestyle factors (never smoking, normal weight, moderate/high level of physical activity, vegetable consumption ≥3 times/week, and light/moderate alcohol drinking) compared with those adhered to <3 healthy lifestyle factors and this association was present among participants with different hypertensive status. The risk of stroke was significantly increased in all hypertensive subgroups compared with the normotensive group. Compared with hypertensive subjects who did not use antihypertensive drugs and were adhered to ≥3 healthy lifestyle factors, the multivariable-adjusted hazard ratios in hypertensive subjects who used antihypertensive drugs and were adhered to <3 healthy lifestyle factors were 1.39 (95% CI 1.04-1.86) for total stroke, 1.42 (1.03-1.97) for ischemic stroke, 1.37 (0.72-2.58) for hemorrhagic stroke in men, and 2.27 (1.71-3.01) for total stroke, 2.31 (1.69-3.16) for ischemic stroke, 2.21 (1.16-4.23) for hemorrhagic stroke in women, respectively. Only hypertensive men but not women who used antihypertensive drugs and were adhered to ≥3 healthy lifestyle factors had decreased risks of total and ischemic stroke compared with those who did not use antihypertensive drugs and were adhered to <3 healthy lifestyle factors.

Conclusions
The present study demonstrates our study demonstrates that a healthy lifestyle significantly decreases the risks of total, ischemic and hemorrhagic stroke in different hypertensive status in both men and women. A healthy lifestyle may be more effective in preventing stroke than antihypertensive treatment in hypertensive subjects.
Abstract P051: Inflammation is Significantly Associated With High Blood Pressure in Females Only
Authors: Eckner Jenny , Larsson Charlotte A , Rastam Lennart , Lindblad Ulf
Published: July 2021

INTRODUCTION
The causes of high blood pressure are complex and based on an interaction between multiple biological factors and behaviours. Insulin resistance and inflammation are commonly acknowledged mechanisms in the development of CVD, while insulin resistance and relative body weight correspondingly predict the development of high blood pressure.

HYPOTHESIS
We aimed to compare insulin resistance, relative body weight, and inflammation in the association with SBP.

METHODS
In 2001-2005 a random sample of residents aged 30-74 years in the municipalities of Vara and Skövde, South-western Sweden, were invited to a survey of cardiovascular risk factors. In all 1811 participants in Vara (participation rate 81%) and 1005 participants in Skövde (70%) were enrolled. Subjects with a known history of hypertension were excluded for the current study. Specially trained nurses saw all subjects in the morning after a 10 hours over night fast, and venous blood samples were taken. A physical examination included body height and body weight (light cloths and no shoes), blood pressure was measured twice in a supine position after a 5 minutes rest (arm in heart level). The mean of the 2 measurements was used for statistical analyses. Hs-CRP and plasma insulin were analysed, and BMI and HOMA-index were calculated using standard algorithms. The log form of HOMA-ir was used in statistical analyses. Associations were explored in males and females separately using multivariate linear regression.

RESULTS
In all 2538 subjects, 1266 men (50%) and 1272 women (50%) without known hypertension were included. BMI and HOMA-ir were both significantly associated with SBP in both males and females, while hs-CRP was associated with SBP in women only. These factors were accordingly entered into a multivariate linear regression model also including age. In men HOMA-ir [regression coefficient, (95% confidence interval), and p-value] [5.4 (2.5-8.4), p<0.001], was significantly associated with SBP, while BMI [0.2 (-0.3-0.5), p=0.087], and CRP was not [0.02 (-0.1-0.1), p=0.138]. In women all three mechanisms came out significantly; HOMA-ir [5.4 (2.2-8.6), p<0.001], BMI [0.4 (0.2-0.5), p<0.001], and CRP [0.2 (0.02-0.4), p=0.031]. There were statistically significant interaction terms between gender and CRP (p=0.037), and gender and HOMA-ir (P=0.045), respectively, while no corresponding interaction was found for BMI. CONCLUSIONS Our study confirms a strong impact of insulin resistance and relative body weight on blood pressure levels in both men and women. However, a significant association between hs-CRP and systolic blood pressure in women was not seen in men. Gender differences in insulin resistance and inflammation were statistically confirmed by interaction terms. These findings have implications for future research and for development of clinical practice.
Abstract P052: The Effect of Re-designing Workflow and Introducing Automated Blood Pressure Devices in Community-based Primary Care Clinics
Authors: Boonyasai Romsai T , Prokopowicz Greg P , Charleston Jeanne , Carson Kathryn A , Noronha Gary J , Miller Edgar R , Cooper Lisa A
Published: July 2021

BACKGROUND:
Prior studies report that poor technique and terminal digit preference (TDP) can distort blood pressure (BP) estimates in clinical settings. These limitations may bias population BP estimates, increase clinician workload, and contribute to clinical inertia.

HYPOTHESIS:
We hypothesized that BP measurement training with an automated blood pressure measurement (aBPM) device would reduce TDP, reduce the number of times clinicians repeat staff-obtained measurements, and reduce average BP estimates within each site.

METHODS:
We replaced aneroid BP measurement devices in 6 community-based primary care clinics with aBPM devices (Omron HEM-907XL) and trained clinic staff with a standardized BP measurement protocol using 1 hour presentations and follow-up visits. We report mean weekly BP measured in the 8 weeks pre- and 4 weeks post-intervention at the first intervention site. Results are analyzed using chi-squared and paired t-tests.

RESULTS:
Clinic staff recorded 5796 BP readings in the 8 week pre-intervention period and 2321 readings in the 4 weeks post-intervention period. TDP and clinician workload improved after the intervention. Pre-intervention, 1941 of 4833 (40.2%) of systolic BP and 2199 of 4833 (45.5%) of diastolic BP ended in zero, in contrast to 216 of 2158 (10.0%) of systolic and 219 of 2158 (10.2%) of diastolic readings post-intervention (P<.001 for both SBP and DBP). Clinicians repeated BP obtained by staff in 963 of 5796 (16.6%) of visits pre-intervention but only in 163 of 2321 (7.0%) of visits post-intervention (P<.001). TDP persisted when clinicians repeated staff-obtained BP readings post-intervention: 58 of 163 (35.6%) systolic and 65 of 163 (35.7%) diastolic BP ended in zero (P=.32 for SBP and P=.35 for DBP in comparison with pre-intervention BP readings). Overall, BP estimates changed modestly following the intervention. Post-intervention, mean systolic BP rose 1.4 mmHg (P=.004) and diastolic BP declined 3.1 mmHg (P<.001). Among clinician-repeated BP readings, systolic BP rose 2.4 mmHg (P=.12 for pre/post change) and diastolic BP declined 0.4 mmHg (P=.72 for pre/post change).

CONCLUSIONS:
A standardized BP measurement protocol used with an aBPM device in community-based primary care settings can reduce TDP and clinician workload but is associated with only modest change in population BP estimates.
Abstract P056: Fructose Intake May Decrease Diastolic and Mean Arterial Blood Pressure: A Systematic Review and Meta-analysis of Controlled Feeding Trials
Authors: Ha Vanessa , Sievenpiper John L , de Souza Russell J , Chiavaroli Laura , Wang Dawei D , Cozma Adrian I , Mir-rahimi Arash , Yu Matthew , Carleton Amanda J , di Buono Marco , Jenkins Alexandra L , Leiter Lawrence A , Wolever Thomas M , Beyene Joseph , Kendall Cyril W , Jenkins David J
Published: July 2021

Background:
Concerns have been raised about the adverse effect of fructose on blood pressure. International dietary guidelines for the prevention of hypertension, however, have not addressed fructose intake directly.

Purpose:
A systematic review and meta-analysis was conducted to assess the effect of fructose in isocaloric exchange for other carbohydrate on systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MAP).

Hypothesis:
We hypothesized fructose intake in isocaloric and hypercaloric exchange for other carbohydrate sources would not have a significant effect on SBP, DBP, and MAP.

Methods:
Studies were identified using MEDLINE, EMBASE, and Cochrane databases (through September 29 2011). Human clinical trials that investigated isocaloric oral fructose exchange for other carbohydrate sources for at least 7 days were included in the analysis. A generic inverse variance method using random effects weighting was used to pool data. Pooled data were expressed as mean differences (MD) with 95% confidence intervals. Heterogeneity was assessed by the Q statistic and quantified by I2. Study quality was assessed using the Heyland Methodological Quality Score (MQS).

Results:
Thirteen isocaloric (n= 325 participants) and two hypercaloric (n= 24) trials met the eligibility criteria. Overall, fructose intake in isocaloric exchange for other carbohydrate decreased DBP (MD=−1.40 [95% CI: −2.69, −0.10]) and MAP (MD= −1.16 [95% CI: −2.11, −0.20]). There was no significant effect of fructose on SBP (MD= −1.05 [95% CI: −2.46, 0.36]). However, subgroup analyses revealed potentially important heterogeneous findings. In a priori subgroups, fructose format (fluid) was a significant modifier of the SBP effect. The effects of both DBP and MAP were modified by aspects of study design (non-randomization, parallel design) and study quality (MQS <8). Furthermore, the DBP effect was modified under conditions of follow-up >4weeks and MAP by carbohydrate comparator (high fructose corn syrup). The two hypercaloric fructose feeding trials found no significant MAP effect of fructose in comparison to other carbohydrate. Limitations: A small number of isocaloric trials and two hypercaloric trials were included, limiting the strength of the conclusion.

Conclusion:
Contrary to previous concerns, we found isocaloric substitution of fructose for other carbohydrate did not adversely affect SBP, DBP, or MAP in humans. Further larger and longer trials are needed to confirm results.
Abstract P059: Reproducibility of Blood Pressure Response to Cold Pressor Test: the GenSalt Study
Authors: Gu Dongfeng , Bazzano Lydia A , Cao Jie , Li Jianxin , Chen Jichun , Huang Jianfeng , Chen Jing , Kelly Tanika , Zhao Qi , Chen Chung-Shiuan , Hu Dongsheng , Ma Jixiang , Rice Treva , He Jiang
Published: July 2021

Higher blood pressure (BP) response to cold pressor test (CPT) is associated with increased risk of hypertension and cardiovascular diseases. However, it is unknown whether BP response to CPT is a stable and reproducible trait. We repeated the CPT among 568 Han Chinese who participated in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) four years after the original study. The same CPT protocol was applied in the original and repeated studies. BP was measured prior to and at 0, 1, 2, and 4 minutes after the participants immersed their hand in ice water (3
o
C to 5
o
C) for 1 minute using a standard mercury sphygmomanometer. On average, study participants were 39.0 years old and 54.0% of them were male. The mean body mass index was 23.6 kg/m
2
, systolic BP was 117.8 mmHg, and diastolic BP was 74.5 mmHg at baseline among study participants. The mean (standard deviation) of systolic BP responses at time 0 and 1 minutes, maximum responses, and area-under-the-curve during CPT were 13.3 (10.1), 4.2 (6.0), 13.6 (9.8) and 10.8 (17.6) mmHg in the original study and 11.1 (9.5), 4.1 (6.0), 11.7 (8.9), and 10.1 (17.1) mmHg in the repeated study. BP responses in the original and repeated studies were highly correlated. For example, the correlation coefficients for systolic BP responses to CPT were 0.4137 at time 0 minute, 0.3711 at time 1 minute, 0.4221 for the maximum responses, and 0.3641 for area-under-the-curve during CPT (all p<0.0001). These data indicate that BP response to CPT is a stable and reproducible trait. Furthermore, BP responses to CPT may be useful for identifying individuals at high risk for hypertension.
Abstract P060: Major Dietary Risk Factors for Chronic Diseases: A Systematic Review of the Current Evidence for Causal Effects and Effect Sizes
Authors: Khatibzadeh Shahab , Micha Renata , Afshin Ashkan , Rao Mayuree , Yakoob Mohammad Y , Mozaffarian Dariush
Published: July 2021

Background:
Diet habits contribute to development of CVD and diabetes. Estimating the impact of diet on these diseases requires identification and quantification of causal effects of dietary factors.

Objectives:
To assess major dietary risk factors for CVD and diabetes, evaluate current evidence for causal effects, and identify the best unbiased effect estimates on risk.

Methods:
For multiple dietary risk factors, we evaluated WHO and similar criteria as part of the Global Burden of Diseases (GBD) study to assess probable or convincing evidence for causal effects, including consistency, dose-response, plausibility, and temporality. We performed systematic searches of online databases from 2008 to 2011, including hand-searches of references and author contacts, to identify systematic reviews and meta-analyses of well-designed observational or interventional studies. Meta-analyses were evaluated based on number of studies, design, definition of diet factors and outcomes, sample size, number of events, length of follow-up, statistical methods, evidence of bias, and control for confounders. Meta-analyses with largest numbers of studies and events and least evidence for bias were identified. Effect sizes and uncertainty were quantified per defined units of exposure, including pooling of categorical dose-response estimates using fixed-effects generalized least squares for trend estimation (GLST).

Results:
We identified 15 dietary risk factors having probable or convincing evidence of causal effects on CVD or diabetes. For 13, data were identified to provide the best pooled unbiased effect size on disease (Table).

Conclusions:
This systematic evaluation provides the best evidence-based quantitative estimates of the effects of major dietary factors on CVD and diabetes. These findings enable estimation of quantitative impacts on diseases burdens of suboptimal intakes of these factors in specific populations, and also highlight gaps in knowledge related to causality or effect sizes of other dietary factors.
Abstract P070: The Relationship Between Weight and Fruit and Vegetable Consumption, Assessed by Serum Carotenoids and Self-Report: Results from the PREMIER Trial
Authors: Parker Jessie L , Chen Liwei , Mitchell Diane C , Yeh Hsin-Chieh , Anderson Cheryl , Appel Lawrence J
Published: July 2021

Background:
Increased intake of fruits and vegetables (F/V) may protect against adiposity, but effects on weight have been inconsistent. Our objective was to examine the relationship between fruit and vegetable intake and weight, using direct and indirect measures of dietary intake: self-reported 24-hour recall and serum carotenoid levels.

Methods:
Participants from the PREMIER lifestyle intervention trial were included in this analysis (n=554). Dietary measures included 24-hour dietary recalls and serum carotenoid levels, from a fasting blood sample. The outcome was weight in pounds. Nested linear mixed models were used to examine the association between F/V and weight.

Results:
Mean F/V increased from 4.6 (SD 2.4) to 5.6 (SD 3.2) (p=<.01), mean serum carotenoids increased from 53.2 (SD 31.9) to 68.1 (SD 42.5) (p=<.01). At 18 months, participants in the lowest quintile of fruit and vegetable change reported an average intake of 4.42.8 servings of fruits and vegetables, and those in the highest quintile of change reported an average intake of 7.73.2 servings. In a multivariate model adjusting for age, race, gender, intervention, energy, study site, and time, lower body weight was associated with higher F/V intake measured by dietary recall (−0.63 lbs, 95% CI −0.83 to −0.42, per 1 serving increase in F/V) and serum carotenoids (−0.13 lbs, 95% CI −0.15 to −0.11, per 1 ug/dl increase in carotenoids). Results were somewhat attenuated but consistent after additional adjustments for working heart rate, exercise, calories from sugar-sweetened beverages, marital and employment status, and alcohol use .

Conclusions:
Greater fruit and vegetable consumption was associated with decreased body weight. Results were consistent for both objective and self-reported measures of fruit and vegetable intake.
Abstract P071: The Effect of Menaquinone -7 Supplementation on Circulating Species of Matrix-Gla Protein
Authors: Dalmeijer Gerdien W , van der Schouw Yvonne T , Magdeleyns Elke , Vermeer Cees , Beulens Joline W
Published: July 2021

Background:
Menaquinones intake is associated with a reduced risk of coronary calcification and coronary heart disease. This association may be explained by increased carboxylation of matrix-Gla protein (MGP) by menaquinones. However, the effect of menaquinone supplementation on MGP carboxylation has not been investigated to date.

Objective:
To investigate if 180 µg/day and 360 µg/day menaquinone supplementation may increase carboxylation of MGP.

Design:
A randomized, double-blind, placebo-controlled trial was performed. Sixty subjects aged 40–65 years were randomly allocated to supplementation of 180 μg/d, 360 μg/d of menaquinone-7 (MK-7) or placebo during 12 weeks. At baseline, after 4 and 12 weeks, desphospho-uncarboxylated MGP (dp-ucMGP), desphospho-carboxylated MGP (dp-cMGP) and total uncarboxylated MGP (t-ucMGP) were measured by ELISA techniques. Furthermore, uncarboxylated osteocalcin (ucOC), carboxylated osteocalcin (cOC) and various cardiovascular risk factors were measured. The ratio of ucOC to cOC was used as proxy of vitamin K status.

Results:
Dp-ucMGP, decreased significantly and dose-dependently in the 180 μg and 360 mg MK-7 supplementation groups (
P
time*treatment <0.001) by 31% (400 pM to 276 pM) and 46% (391 pM to 210 pM) respectively after 12 weeks, while dp-ucMGP circulation levels remained unchanged after placebo treatment. The osteocalcin ratio also decreased significantly and dose-dependently in the 180 μg and 360 mg MK-7 treatment (
P
time*treatment <0.001) by 57% (0.44 to 0.19) and 74% (0.42 to 0.11) respectively after 12 weeks, while osteocalcin ratio remained unchanged after placebo treatment, showing improved vitamin K status and indicating good compliance to the study treatment. Changes over time of dp-cMGP (p=0.42) and t-ucMGP (p=0.23) levels did not differ between treatment arms. Also the prothrombin time did not differ between treatments arms (
P
time*treatment=0.92). Furthermore, changes over time in other risk factors of cardiovascular disease like blood lipid profile or blood pressure did not differ between treatments.

Conclusions:
Supplementation with MK-7 decreased dp-ucMGP with 31% to 46%. Like the osteocalcin ratio, dp-ucMGP can be used as a sensitive marker of vitamin K status. MK-7 supplementation has no effect on dp-cMGP and t-ucMGP concentrations.