bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin Cancer in Heart Transplant Recipients
Authors: Caforio Alida L. P. , Fortina Anna Belloni , Piaserico Stefano , Alaibac Mauro , Tona Francesco , Feltrin Giuseppe , Pompei Esmeralda , Testolin Luca , Gambino Antonio , Volta Sergio Dalla , Thiene Gaetano , Casarotto Dino , Peserico Andrea
Published: July 2021

Background
—The frequency of skin tumors of all types and specifically of squamous cell carcinoma (SCC) is increased in heart transplantation (HT), but the predisposing risk factors are controversial.

Methods and Results
—We studied 300 patients (age 49±15 years, 258 men, mean follow-up 4.6 years, follow-up range 1 month to 12 years) who were receiving standard double (cyclosporin plus azathioprine) or triple (cyclosporin plus azathioprine plus prednisone) therapy. The first-year rejection score was calculated for endomyocardial biopsy samples (International Society for Heart and Lung Transplantation grade 0=0, 1A=1, 1B=2, 2=3, 3A=4, 3B=5, and 4=6) and used as an indirect marker of the level of immunosuppression. Multivariate analysis (Cox regression) included age at HT, sex, skin type, first-year rejection score, presence of warts and solar keratosis, lifetime sunlight exposure, and first-year cumulative dose of steroids. The incidence of skin tumors of all types increased from 15% after 5 years to 35% after 10 years after HT according to life-table analysis. Age at HT of >50 years (
P
=0.03, RR=5.3), skin type II (
P
=0.05, RR=2.6), rejection score of 19 (
P
=0.003, RR=5.7), solar keratosis (
P
=0.001, RR=6.9), and lifetime sunlight exposure of >30 000 hours (
P
=0.0003, RR=7.6) were risk factors for SCC.

Conclusions
—Older age at HT, light skin type, solar keratosis, greater sunlight exposure, and high rejection score in the first year were independently associated with an increased risk of SCC. The progressive increase in cancer frequency during follow-up and the association with high rejection scores suggest that both the length and level of immunosuppression may be relevant. Because cumulative immunosuppressive load is cumbersome to calculate, a high rejection score in the first year may provide a useful predictor for patients at risk.
Zinc-Mediated Reduction of Apoptosis in Cardiac Allografts
Authors: Kown Murray H. , Van der Steenhoven Tim , Blankenberg Francis G. , Hoyt Grant , Berry Gerald J. , Tait Jonathan F. , Strauss H. William , Robbins Robert C.
Published: July 2021

Background
—Apoptosis is thought to occur during immune-mediated acute rejection of cardiac allografts. In vitro studies have shown that zinc inhibits the activity of the proapoptotic enzyme caspase-3. We hypothesized that ZnCl
2
would reduce acute cardiac rejection in vivo via the blockade of caspase-3–dependent apoptosis.
99m
Tc-labeled annexin V was used to measure apoptosis in cardiac allografts through nuclear imaging. Annexin V binds to phosphatidylserines, which are externalized to the outer membrane of apoptotic cells.

Methods and Results
—Twenty-seven PVG rat hearts were transplanted heterotopically into the abdomen of untreated ACI rats as controls (group 1). Fifteen were scanned and euthanized on postoperative day 4, and 12 were assessed for graft survival. Group 2 and 3 rats (n=15 each) received 1 and 5 mg/kg ZnCl
2
BID IP, respectively. Nine of each of these groups were scanned and euthanized on postoperative day 4, and 6 were studied for allograft survival. Group 4 rats (n=3) received isografts. Region-of-interest analysis demonstrated a dose-dependent reduction in
99m
Tc annexin uptake in ZnCl
2
-treated allografts: 2.43±0.37% for group 1, 1.97±0.41% for group 2, 1.21±0.47% for group 3, and 0.55±0.19% for group 4 (ANOVA,
P
=0.001). Graft survival times of 6.4±1.7, 9.3±3.0, and 11.5±3.4 days for groups 1, 2, and 3, respectively, were also observed (ANOVA,
P
=0.001). Caspase-3 activity in the allografts showed a 3.7-fold reduction in group 3 animals compared with group 1 animals (
P
=0.004).

Conclusions
—Apoptosis that occurs in acute cardiac allograft rejection is reduced with ZnCl
2
in a dose-dependent manner via caspase-3 inhibition.
Results of Immediate Surgical Treatment of All Acute Type A Dissections
Authors: Ehrlich Marek P. , Ergin M. Arisan , McCullough Jock N. , Lansman Steven L. , Galla Jan D. , Bodian Carol A. , Apaydin Anil , Griepp Randall B.
Published: July 2021

Background
—Surgery for acute type A aortic dissection is associated with a high mortality rate and incidence of postoperative complications. This study was designed to explore perioperative risk factors for death in patients with acute type A aortic dissection.

Methods and Results
—One hundred twenty-four consecutive patients with acute type A aortic dissection between 1984 and 1998 were reviewed. All underwent operation with resection of the intimal tear and open distal anastomosis: 107 patients had surgery within 24 hours and 17 patients had surgery within 72 hours of symptom onset. Median age was 62 years (23 to 89); 89 were men. Forty-three patients had ascending aortic replacement only, 72 had hemiarch repair, in 2 the entire arch was replaced, and in 7 replacement included the proximal descending aorta. The aortic valve was replaced in 54 patients, resuspended in 52, and untouched in 18. Hospital mortality rate was 15.3% (19 of 124): of these, 3 patients died during surgery, 4 had fatal rupture of the distal aorta before discharge, and 2 died of malperfusion-related complications. Multivariate analysis revealed age >60, hemodynamic compromise, and absence of hypertension as preoperative indicators of hospital death (
P
<0.05); the presence of new neurological symptoms was a significant preoperative risk factor in univariate analysis. Ominous intraoperative factors included contained hematoma and a comparatively low esophageal temperature but not cerebral ischemic time (mean 32 minutes). The site of the intimal tear did not influence outcome, but mortality rate was higher with more extensive resection: 43% with resection including the descending aorta died versus 14% with only ascending aorta or hemiarch replacement. Overall 5- and 10-year survival was 71% and 54%, respectively; among discharged patients (median follow-up 41 months) survival was 84% and 64% versus expected US survival of 92% and 79%.

Conclusions
—Immediate surgical treatment of all acute type A dissections with resection of the intimal tear and use of hypothermic circulatory arrest for distal anastomosis results in acceptable early mortality rates and excellent long-term survival.
Treatment of Iliac Artery Aneurysms by Percutaneous Implantation of Stent Grafts
Authors: Scheinert D. , Schröder M. , Steinkamp H. , Ludwig J. , Biamino G.
Published: July 2021

Background
—Iliac artery aneurysms have traditionally been treated by direct surgical reconstruction. Endovascular stent grafts have been developed to provide an effective but less invasive treatment option for patients with peripheral arterial aneurysms.

Methods and Results
—In 48 patients, a total of 53 endoprostheses (mean length 7.3 cm, mean diameter 8.1 mm) were implanted into the iliac arteries (common iliac artery n=29, external iliac artery n=19) for percutaneous exclusion of aneurysmal lesions. The technical success of complete exclusion of the aneurysm was achieved in 47 of 48 cases (97.9%). In 1 case, persistent perfusion through a collateral branch was detected; however, this aneurysm thrombosed spontaneously within 2 weeks. In all patients, graft patency was monitored by clinical examination, which included the standardized treadmill test with calculation of the ankle-brachial Doppler index and color-coded duplex ultrasound. Forty-two of the 48 patients (87.5%) underwent follow-up angiography. According to Kaplan-Meier life-table calculations, primary patency rates were 100% after 1 year, 97.9% after 2 years, 94.9% after 3 years, and 87.6% after 4 years. Serial contrast-enhanced spiral CT scans were performed to rule out late procedural failures and to assess growth progression of the lesions. No secondary leaks were observed. Furthermore, the aneurysm diameter had reduced from 24.8±8.0 mm to 23.1±6.6 mm at the last follow-up (
P
=NS).

Conclusions
—Stent grafts are a safe and effective treatment option for iliac artery aneurysms and provide good long-term patency of the graft.
Treatment of Acute Stanford Type B Aortic Dissection With a Novel Cylindrical Balloon Catheter in Dogs
Authors: Terai Hiromu , Tamura Nobushige , Nakamura Tatsuo , Nishimura Kazunobu , Tsutsui Norimasa , Shimizu Yasuhiko , Komeda Masashi
Published: July 2021

Background
—Despite recent progress in medical and surgical treatment, acute type B aortic dissection still carries a high mortality rate. We have developed a novel cylindrical balloon catheter for less invasive treatment to block the entry of the dissection and induce thrombotic occlusion of the false lumen. The balloon has the shape of a sheet when deflated but a double-cylinder shape when inflated. Therefore, aortic blood flow is maintained through the cylindrical lumen during balloon inflation.

Methods and Results
—Six beagle dogs underwent a left thoracotomy at the 6th intercostal space. An acute dissection of 4-cm length was created surgically on the descending aorta. The balloon catheter was inserted through the distal descending aorta and advanced to the entry site. The balloon catheter was inflated for 6 hours. The blood flow in the descending aorta and the position of the balloon was monitored by color Doppler echovasculography. Four dogs were killed humanely on the following day and 2 dogs 10 days after the surgery. The descending aorta was examined macroscopically and microscopically in all dogs. In all dogs, the false lumen was occluded by thrombi. Although no dog had clinical evidence of distal thromboembolism, 2 of the 4 dogs that were killed on the second postoperative day had fresh mural thrombi in the true lumen.

Conclusions
—The false lumen of the acute type B aortic dissection was effectively occluded by the novel cylindrical balloon catheter in the canine experimental model. The thrombus formation in the true lumen is the problem to be solved.
Selective Estrogen Receptor Modulator Idoxifene Inhibits Smooth Muscle Cell Proliferation, Enhances Reendothelialization, and Inhibits Neointimal Formation In Vivo After Vascular Injury
Authors: Yue Tian-Li , Vickery-Clark Lynne , Louden Calvert S. , Gu Juan-Li , Ma Xin L. , Narayanan Padma K. , Li Xiang , Chen Jun , Storer Barbara , Willette Robert , Gossett Kent A. , Ohlstein Eliot H.
Published: July 2021

Background
—Idoxifene (ID) is a tissue-selective estrogen receptor modulator (SERM). The pharmacological profile of ID in animal studies suggests that it behaves like an estrogen receptor (ER) agonist in bone and lipid metabolism while having negligible ER activity on the reproductive system. It is unknown whether ID retains the vascular protective effects of estrogen.

Methods and Results
—In cultured vascular smooth muscle cells (VSMCs), ID inhibited platelet-derived growth factor–induced DNA synthesis and mitogenesis with IC
50
values of 20.4 and 27.5 nmol/L, respectively. Treatment with ID resulted in S-phase cell cycle arrest in serum-stimulated VSMCs. ID 1 to 100 nmol/L significantly protected endothelial cells from tumor necrosis factor-α (TNF-α)–induced apoptosis in vitro. Virgin Sprague-Dawley rats ovariectomized 1 week before the study were treated with ID (1 mg · kg
−
1
· d
−
1
) or vehicle by gavage for 3 days before balloon denudation in carotid artery. The SMC proliferation in injured vessels was determined by immunostaining for proliferating cell nuclear antigen (PCNA). The number of PCNA-positive SMCs was reduced by 69%, 82%, and 86% in the media at days 1, 3 and 7, respectively, and by 78% in the neointima at day 7 after injury in ID- versus vehicle-treated group (
P
<0.01). ID significantly enhanced reendothelialization in the injured carotid arteries as determined by Evans blue stain and immunohistochemical analysis for von Willebrand factor. In the former assay, the reendothelialized area in injured vessels was 43% in ID-treated group versus 24% in the vehicle group (
P
<0.05); in the latter assay, the numbers of von Willebrand factor–positive cells per cross section increased from 24.8 (vehicle) to 60.5 (ID) (
P
<0.01) at day 14 after injury. In addition, the production of nitric oxide from excised carotid arteries was significantly higher in ID-treated than the vehicle group (8.5 versus 2.7 nmol/g,
P
<0.01). Finally, ID treatment reduced neointimal area and the ratio of intima to media by 45% and 40%, respectively (
P
<0.01), at day 14 after balloon angioplasty.

Conclusions
—The results indicate that ID beneficially modulates the balloon denudation–induced vascular injury response. Inhibition of VSMC proliferation and acceleration of endothelial recovery likely mediate this protective effect of ID.
Quality of Life After Aortic Valve Replacement at the Age of >80 Years
Authors: Sundt Thoralf M. , Bailey Marci S. , Moon Marc R. , Mendeloff Eric N. , Huddleston Charles B. , Pasque Michael K. , Barner Hendrick B. , Gay William A.
Published: July 2021

Background
—The optimal management of aortic valve disease in patients >80 years old depends on functional outcome as well as operative risks and late survival.

Methods and Results
—We retrospectively identified 133 patients (62 men, 71 women) aged 80 to 91 years (mean 84±3 years) who underwent aortic valve replacement alone or in combination with another procedure between January 1, 1993, and April 31, 1998. Demographics included hypertension 68%, diabetes mellitus 17%, and history of stroke 11%. Operative (30 day) mortality rate was 11%. Urgent or emergent surgery, aortic insufficiency, and perioperative stroke or renal dysfunction were risk factors for operative death by multivariable analysis. Intensive care unit and total hospital length of stay were prolonged at 6.2 and 14.7 days, respectively. Late follow-up between July 1, 1998, and November 1, 1999, was 98% complete. Actuarial survival at 1 and 5 years was 80% and 55%, respectively. Predictors of late mortality were preoperative or perioperative stroke, chronic obstructive pulmonary disease, aortic stenosis, and postoperative renal dysfunction. The mean New York Heart Association functional class for 65 long-term survivors improved from 3.1 to 1.7. Quality of life assessed with the Medical Outcomes Study Short Form-36 was comparable to that predicted for the general population >75 years old.

Conclusions
—Functional outcome after aortic valve replacement in patients >80 years old is excellent, the operative risk is acceptable, and the late survival rate is good. Surgery should not be withheld from the elderly on the basis of age alone.
The PR Interval is a Heritable Quantitative Trait with Evidence for Linkage to Chromosome 4 in a Genome-Wide Scan: the Framingham Heart Study
Authors: O’Donnell Christopher J. , Benjamin Emelia J. , Corey Diane , Newton-Cheh Christopher , Levy Daniel , D’Agostino Ralph B. , Larson Martin G.
Published: July 2021

P19

Introduction: Delayed atrioventricular conduction on the electrocardiogram (ECG), manifested by PR interval prolongation, can progress to heart block. Both heart-rate slowing drugs and environmental factors may lead to PR interval prolongation; however, the heritability of the PR interval has not been studied in the general population and genetic variants in the regulation of PR duration have not been characterized. Methods: We examined the heritability of the PR interval and we tested for evidence of linkage of the PR interval to chromosomal regions in a large population-based cohort. 12-lead ECGs were obtained routinely in adult Framingham Heart Study participants as part of the clinic examination. The PR interval was measured using digital calipers. We conducted a 10 cM genome wide scan in 328 extended families (1688 genotyped subjects, 2257 phenotyped subjects, 2028 phenotyped sibling pairs). Variance component methods were used to estimate heritability and to perform linkage analysis. Results: The PR interval (adjusted for age and RR-interval) was heritable [h

2

0.32 (95% confidence interval 0.26-0.37)]. The highest multipoint LOD score for the adjusted PR interval was found on chromosome 4 (LOD score was 2.16 at 123 cM). The next highest LOD score was 1.88 (chromosome 17 at 59 cM). Conclusion: These results suggest there are influential genetic regions contributing to variability in PR interval in the general population. Defining genetic determinants of PR duration may provide insights into the pathophysiology of heart block and may help identify persons with a high susceptibility to drug-induced heart block.
Ethical Issues in Human Genome Epidemiology: A Case Study Based on the Japanese American Family Study
Authors: Austin Melissa A
Published: July 2021

P21

The rapid advances in genetics and molecular biology are dramatically increasing our ability to understand genetic susceptibility to disease and to develop targeted prevention strategies using genetic and molecular epidemiology approaches. The implementation of these human genome epidemiology studies, however, raises serious ethical concerns. This analysis used a “case study” approach to explore ethical issues in the context on the ongoing Japanese American Family Study in Seattle, a population-based study of extended kindreds of Japanese descent living in a Western Culture that is examining genetic influences on risk factors for cardiovascular disease and diabetes. Issues related to study design, protocol implementation, and reporting study results were considered. Study design issues include the advanatages and disadvantages of using a genetically homogeneous group for study. Selecting such a population may decrease genetic heterogeneity and increase the possibilty of detecting genetics effects. However the potential social effects of such findings, including stigmatizing the group under study, must be considered. Further, whether or not it is appropriate to obtain community consent remains a controversial issue. In implementing a community-based family study, maintaining the confidentially of study data is essential, especially for individuals within families. Avoiding coercion of family members can be difficult in certain cultural settings, and informed consent for DNA banking requires specific informed consent procedures. Once the study results are available, investigators must make difficult decisions about whether or not to provide genotyping results to study participants, and when to involve genetic counselors. Finally, publishing the study results that include pedigrees, while avoiding identifying family information, is challenging. Careful analysis of ethical issues in study design, protocol implementation, and reporting study results can provide useful guidance for the successful completion of human genome epidemiology studies.
A Prospective Study of Persons with the Early Repolarization Normal Variant Electrocardiogram
Authors: Klatsky Arthur L. , Armstrong Mary Anne , Oehm Rudolph , Cooper Robert A. , Udaltsova Natalia
Published: July 2021

P30

Sometimes confused with abnormal electrocardiogram (ECG) patterns, especially acute myocardial infarction, the poorly understood “early repolarization normal variant” (VAR) ECG has been considered benign, but, to our knowledge, has not been studied in relationship to later cardiovascular (CV) problems. We collected 2081 possible VAR and normal (NORM) ECG’s from among those done at health examinations of 72,830 members of a pre-paid health care program in 1983-85. All ECG’s were reinterpreted independently as VAR, Borderline, or NORM by 2 cardiologists blinded to all identifying and clinical data; agreement by both was required for categorization as VAR. Comparisons of subsequent hospitalizations and deaths through 1998 among all 72,830 examinees used Cox proportional hazards models with 7 covariates. Outpatient diagnoses were available from 1995 through 1999 among a subset of 45,528 examinees still in the program in 1995; these were compared in sex & age-stratified groups by chi-square tests. The blinded readings yielded 670 VAR ECG s, 330 borderline ECG s, and 1081 NORM ECG s. Comparison of VAR to NORM showed increased VAR proportions of men, persons < 40 years old, and blacks or Asians (all with p<0.001). Among 21,826 persons hospitalized in the entire cohort there were 136 with VAR; among 7974 persons who died there were 37 with VAR; among 15,422 persons with outpatient diagnoses there were 95 with VAR. No significant differences in risk for VAR vs all persons were found for hospitalization or death for all causes, CV causes, or non-CV causes. For outpatient diagnoses, persons with VAR had lower rates/1000 persons than the entire population for any CV diagnosis (339/1000 for all; 256/1000 for VAR; p < 0.001). Diagnosis rates among VAR were significantly lower for hypertension (p < 0.02) arrhythmias (p < 0.01) and non-specific CV symptoms (p < 0.05) and also were nonsignificantly lower among VAR for coronary disease, cardiomyopathy, heart failure, stroke, and valvular disease. These data confirm the benign nature of VAR, suggesting that VAR not only carries no increased risk for development of CV conditions but may be associated with decreased CV risk.
Ethnicity, CVD Risk Factor Clustering and the Progression of Microvascular Disease: The Insulin Resistance and Atherosclerosis Study
Authors: Bell Ronny A. , Zaccaro Daniel J. , Wagenknecht Lynne E. , Mayer-Davis Elizabeth J.
Published: July 2021

P31

Ethnic disparities in cardiovascular disease (CVD) and end-stage renal disease exist in the US, with African Americans (AAs) and Hispanic Americans (HAs) being at greater risk compared to non-Hispanic whites (NHWs). This maybe related to variations in individual and/or clusters of CVD risk factors across ethnic groups. We have previously shown ethnic differences in cross-sectional analyses from the Insulin Resistance and Atherosclerosis Study (IRAS) data in the effect of CVD risk factor clustering, with AAs being more greatly affected for nephropathy risk, and NHWs being more affected for CVD. We examined the effect of CVD risk factor clustering on the 5-year progression of albuminuria, which itself is a known CVD risk factor. Data were analyzed from the IRAS study, a multi-center epidemiologic cohort study that included roughly similar numbers of persons with normal and impaired glucose tolerance and type 2 diabetes, at baseline and 5-year follow-up. Comparisons were made forAAs and NHWs (Oakland/LAclinics), and for HAs and NHWs (San Antonio/San Luis Valley clinics). Data were available on 1256 IRAS subjects on nephropathy progression status, of which about 10% progressed from normal, defined as albumin/creatinine ratio less than 30 mg/g, to microalbuminuria (ACR of ≥30 and < 300) or macroalbuminuria (ACR ≥300) or from microalbuminuria to macroalbuminuria. CVD risk factors (dyslipidemia, BMI, waist-hip ratio, PAI-1, hypertension, diabetes status) at baseline were dichotomized, and subjects were classified as having high (≥ risk factors) or low (< 3 risk factors) risk. Overall 30.9% of the sample were classified as high risk. After adjusting for age, gender, and baseline nephropathy status, risk factor clustering predicted nephropathy progression in both ethnic comparisons (OR 2.24, p< 0.001 in AAs/NHWs group; OR 2.81, p< 0.001 in the HAs/NHWs group). With risk status in the model, HAs were at no greater risk for progression compared to NHWs, but risk was about 80% greater for AAs compared to NHWs (p < 0.05). These data indicate a risk of nephropathy among AAs that extends beyond the traditional CVD risk factor clusters.
Current Practices and Attitudes Toward Cholesterol Management in Patients With Recent Acute Myocardial Infarction: A Survey of Community Physicians
Authors: Yarzebski Jorge L , Bujor Carmen , Goldberg Robert J , Spencer Frederick A , Lessard Darleen , Gore Joel M
Published: July 2021

P41

Background: Recurrent coronary events and mortality are associated with elevated serum cholesterol levels in patients with acute myocardial infarction (AMI). It’s unclear what physicians’ current attitudes and practices are toward the management of high cholesterol levels in patients with recent AMI. We carried out a survey of practicing physicians to examine factors that influence physicians prescription of lipid-lowering and dietary therapy in patients with recent AMI and threshold levels of cholesterol for intervention. Methods: Mailed questionnaire survey of general internists, cardiologists, and family physicians practicing and/or having admitting privileges to all Worcester (MA) metropolitan hospitals. Results: Among the 257 responding physicians, lipid lowering therapy was more likely to be initiated in younger patients at lower total and LDL-cholesterol levels than in older patients. Younger physicians were more likely to initiate dietary and lipid lowering drug therapy at lower total and LDL-cholesterol levels. General practice physicians were more likely to initiate dietary therapy at lower total cholesterol levels, but more likely to initiate lipid lowering drug therapy at higher total and LDL-cholesterol levels, than internists and cardiologists. The most important factors reported by physicians which interfered with patient’s use of lipid lowering drug therapy were their concerns about medication costs, issues related to polypharmacy, and failure to recognize the importance of lipid lowering drugs. Several physician associated factors including provider responsibility and importance of other cardiac drugs were associated with the more widespread use of these medications. Conclusions: Results of this survey in a representative sample of community physicians suggest that older physicians are less likely to implement recommended treatment guidelines in patients with recent AMI and high cholesterol. Additional efforts are needed to modify potential barriers to the implementation of effective long-term cholesterol management in patients with recent AMI.
Use of calcium channel blockers as antihypertensives in relation to mortality. A population based observational study.
Authors: Lindberg Gunnar , Lindblad Ulf , Low-Larsen Bent , Merlo Juan , Melander Arne , Rastam Lennart
Published: July 2021

P51

The beneficial effect of pharmacological treatment of hypertension is well established. However, the outcome may depend on the specific antihypertensive drug used. This study, aimed to compare mortality in users of calcium channel blockers (CCBs) with that in users of other antihypertensive drugs (AHDs), includes 719 patients on antihypertensive drugs at an outpatient clinic in primary care in 1989-90. They were classified as users of CCBs (mostly felodipine) or users of other ADHs according to status at inclusion. Co-morbidity, systolic blood pressure, and smoking data were derived from standardised patient records. The Swedish mortality register was used to follow patients until death or until the end of 1995. Odds ratios were calculated by Cox regression analysis (the

table). Although adjustment was made for confounders, mortality was higher in CCB users. This adds support to the view that CCBs may be inferior to other ADHs in reducing mortality when used to treat hypertension and should not be considered a first-line drug.

Table 1.
Serum Potassium is not Associated with Blood Pressure Tracking in the Framingham Heart Study
Authors: Walsh Craig R , Larson Martin G , Ramachandran Vasan S , Levy Danial
Published: July 2021

P52

Introduction Secondary and inherited, monogenic forms of hypertension (HTN) are often associated with low serum potassium (K). We hypothesized that low K may identify individuals at risk for progression of blood pressure (BP) stage. Methods 2358 participants (1066 men 1292 women) in the Framingham Heart Study free of HTN and not taking drugs affecting K who had K measured in 1979-83 were followed for progression of BP stage and development of HTN. Progression of BP stage was defined as increment of ≥1 JNC-VI BP category between baseline and follow-up exams. Results There were no differences in baseline systolic or diastolic BPs across K quartiles. Over 4 years of follow up, 36% progressed by ≥1 JNC-VI BP category. In a multivariable-adjusted logistic regression model, there was no significant association between K quartile and risk of BP progression (

table). During follow up, 14% progressed to HTN. After adjustment for multiple confounders, there was no significant association between K quartile and risk of progression to HTN (

table). Conclusions In our community-based sample, K was not associated with current BP, longitudinal BP tracking, or progression to HTN.

Table 1.
Blood Pressure Control & Incident Disability in Older Women:
Authors: Williamson Jeff D , Penninx Brenda , DiBari Mauro , Fried Linda P , Guralnik Jack M , Pahor Marco
Published: July 2021

P54

Cardiovascular disease is associated with disability & high B/P is a risk factor for CVD. Data is lacking on the relationship between B/P and disability and on the potential benefit of aggressive B/P control for prevention of disability in older adults. We report longitudinal data from the Women’s Health & Aging Study (WHAS) testing the hypothesis that high B/P and poor B/P control is a risk factor for disability in older women. Of the 1002 women at baseline, 388 were age 65-74, 311 age 75-84, and 303 women age 85+. Overall, 58.7% reported a diagnosis of hypertension. B/P was measured at baseline and every 6 months for 3 years by a nurse during an in-home standardized exam. Using “a lot of difficulty or unable to walk across a small room” as the dependent variable,

Table 1 shows the adjusted 3-year incidence of disability. At 3 years, women who were hypertensive on or off B/P meds at baseline (39.8%) had a disability RR of 1.44 (CI 1.07-1.94) compared to normotensive women on B/P meds (27.5%). These results show that SPB is strongly related to the incident disability. These data also provide epidemiologic evidence supporting SBP treatment goals to < 140 mmHg in older people. Given the prevalence of hypertension and poor B/P control in this population, aggressive treatment may provide an important pathway to reducing the burden of disability and institutionalization.

Table 1.
Birth weight and cardiovascular disease: The NHLBI Family Heart Study
Authors: Djousse Luc , Hong Yuling , Arnett Donna K , Minnesota University of , Hunt Steven C , Heiss Gerardo , Ellison R. Curtis
Published: July 2021

P66

Epidemiologic studies have been inconsistent on the association between low birth weight and increased risk of cardiovascular disease (CVD). Little is known about potential mechanisms by which determinants of low birth weight affect CVD. We used data collected on 2,540 participants of the NHLBI Family Heart Study to assess the relation of birth weight to CVD, hypertension, and diabetes mellitus. Birth weight was obtained by self report. CVD was defined as positive history of myocardial infarction, coronary angioplasty, coronary bypass surgery, congestive heart failure, or stroke. Hypertension was defined as systolic blood pressure of at least 140 mm Hg, or diastolic pressure of at least 90 mm Hg, or use of antihypertensive medication. Diabetes mellitus was ascertained by medical history and pathologic blood sugar levels. We used generalized estimating equations to assess the prevalence odds ratios, adjusting for age, risk group, anthropometric, metabolic, and lifestyle factors. Prevalence odds ratios (95% CI) are presented below. Low birth weight was associated with increased prevalence odds of CVD compared with normal and large babies (p=0.0012). The trend was suggestive of increased prevalence odds of hypertension (p=0.05) and diabetes mellitus (p=0.0012) from the highest to the lowest category of birth weight. In conclusion, low birth weight was associated with increased prevalence odds ratio of CVD, diabetes mellitus, and hypertension. Low birth weight may add to other traditional risk factors in identifying subjects at low and high risk of CVD.

Table 1.
The Relationship Between Syndrome X and Left Ventricular Hypertrophy: The Impact Of Different Methods of Adjusting Left Ventricular Mass.
Authors: Guyer Heidi M , Pladevall Manel , Yanez Aina M , Falces Carles , Sadurni Josep , Ribes Anna , Pare Carles
Published: July 2021

P67

Left ventricular hypertrophy is associated with the various elements of the insulin resistance syndrome (Syndrome X) including insulin resistance, hypertension, diabetes, dyslipidemia and obesity. There is no current consensus on the correct method of adjusting left ventricular mass (LVM). Objective: To determine the variation in the relationship between left ventricular hypertrophy (LVH)and Syndrome X when LVM is adjusted for height, height

2.7

and body surface area (BSA) in a population based study. Methods:LVM was measured echocardiographically in 442 participants aged 35 to 65 years. Results: The prevalence of LVH ranged from 15.6% to 33.9% depending on adjustment method. The correlation between LVH and Syndrome X components varied by adjustment criteria and by sex. In men, LVH was only correlated with blood pressure and obesity measurements. In women, LVH was correlated with all Syndrome X components except HDL cholesterol. Regardless of adjustment method, women with Syndrome X were more likely to have LVH than those without Syndrome X, although the magnitude of the relationship varied by LVM adjustment (LVM/height

2.7

:

OR 16.6, 95% CI: 6.7 41.1; LVM/BSA: OR 5.8, 95% CI: 2.6-12.9). In men, the relationship between Syndrome X and LVH was significant when LVM was adjusted for height

2.7

(OR 3.0, 95% CI: 1.4-6.7) but not when adjusted for BSA (OR 1.2, 95% CI: 0.4-3.5). Conclusions:Both the prevalence of LVH and the relationship between LVH and Syndrome X are dependent on the method used to adjust LVM. When LVM is adjusted for height

2.7

, LVH is more prevalent and the relationship with Syndrome X is stronger than when adjusted for BSA. Regardless of adjustment method, the relationship between Syndrome X and LVH is much stronger in women than men. The LVM adjustment method employed is important to take into account both in epidemiological studies and clinical practice.
Obesity and leisure time physical activity (LTPA) are strongly and inversely associated in men with the Lewis (a-b-) phenotype - not in men with other Lewis phenotypes
Authors: Hein Hans Ole , Suadicani Poul , Gyntelberg Finn
Published: July 2021

P73

Background Obesity is more prevalent among men with the Lewis (a-b-) phenotype than among others. It has recently been shown in the Copenhagen Male Study (CMS) that an excess risk of fatal IHD in Le(a-b-) men is strongly modified by LTPA. It has been disputed if LTPA is able to reduce or eliminate obesity. To elucidate this issue further, we hypothesized that a stronger inverse associaion exists between LTPA and obesity in Le(a-b-) men than in other men. Methods A historical prospective study of 2,824 Caucasian men free from overt IHD aged 53 to 75 years, examined in 1970 and 1985 in CMS. A low level of LTPA was defined as ≤4 hours/week moderate or ≤2 hour/week more vigorous physical activity. Main outcome: body mass index (BMI, kg/m

2

). Results 266 men had the Le(a-b-) phenotype, 2,558 had other Lewis phenotypes and were pooled for analytical purposes. Le(a-b-) men had a higher BMI than other Lewis phenotypes, 26.1 vs 25.6, p<0.05. The

table shows a strong inverse association between LTPA and BMI in Le(a-b-) men and an only weak association among others. Weight differences among sedentary men were 9.1 kg, among active 0.1 kg. Correlation coefficients for Le(a-b-) men: -0.27, for others: -0.07, a highly significant difference, p=0.008. Potential confounders did not explain this. Conclusions There was a strong inverse association between LTPA and BMI in Le(a-b-) men, an association not found among others. Public health and clinical implications may be important in eg US and Scandinavia, populations with a high prevalence of obesity, a predominantly sedentary lifestyle, and a high proportion of Le(a-b-) men.

Table 1.
Black-white differences in serum antioxidant concentrations reflect differences in food intake:
Authors: Gross Myron D , Yu Xinhua , Hilner Joan , Loria Cay , Steffen-Batey Lyn , Jacobs David R
Published: July 2021

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Blacks have been reported to have lower serum antioxidant vitamin concentrations than whites. We studied black-white patterns of antioxidant concentrations and food intake in 1985-86 (3477 nonusers of supplemental vitamins A, C, and E, 18-30 year old). Black men and women had lower levels than white men and women of serum alpha-tocopherol (aTOCO), alpha-carotene (aCARO) and beta-carotene (bCARO), but higher levels of gamma tocopherol (gTOCO) and similar levels of lycopene (LYCO), adjusted for age, plasma lipids, clinic, and smoking. Intake of minimally processed plant foods (MPPF: whole grain, fruits, vegetables, nuts, and

Table legumes processed to preserve nutrient content) was positively correlated with aTOCO, aCARO, and bCARO. Further adjustment for this and related food groups reduced differences in serum antioxidant concentrations between black and white women: aTOCO (0.09vs0.06), gTOCO (.022vs.011), aCARO (2.22vs1.42) and bCARO (3.96vs1.16), all still significant except gTOCO, with a similar pattern of reductions for men. Thus, low serum antioxidants, indicators of cardiovascular disease risk in blacks, reflect differences in food intake between blacks and whites. Culturally-specific dietary interventions may be necessary for an improvement in antioxidant status to reduce the risk of developing cardiovascular disease.

Table 1.
Neighboorhood Effects in Community Trials for Cardiovascular Disease
Authors: Oakes J. Michael , Kleinman Ken P. , Araujo Andre B.
Published: July 2021

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BACKGROUND:Cluster-randomized community trials are critically important to cardiovascular (CVD) epidemiology. While studies evaluating the effect of community education programs report favorable risk factor changes, including the Pawtucket Heart Health Program (PHHP), changes in hard CVD endpoints have been less common. Few have examined the effect of neighborhood on endpoints, especially controlling for individual characteristics. In short, overall effects may be confounded with neighborhood. METHODS:In the first study of this type, we geocoded PHHP neighborhoods to 1990 Census tracts, and randomly sampled 50% (n=521) of the observations from the 6th PHHP cross-sectional survey. Endpoints included CVD knowledge (number of correct risk factors mentioned), and total serum cholesterol. Income and percent working poor (households in a tract with income < 150% of the poverty-line) served as individual- and neighborhood-level SES, respectively. SAS Proc Mixed was used to fit multilevel models. Geographic Information Systems (GIS) methods map empirical Bayes estimates. RESULTS:Choropleth maps show variation in CVD knowledge and cholesterol across the 22 tracts of Pawtucket. Multilevel models reveal that income accounts for most of this neighborhood-level variation. However, a significant negative interaction between individual- and neighborhood-level SES (p < 0.10) was observed for CVD knowledge. Predicted values for CVD knowledge show that persons with a moderate income (level 5) living in a neighborhood with a large proportion (65%) of working poor would be expected to have a knowledge score of 2.34. This same person living in a neighborhood with a small proportion of working poor (15%) would be expected to have a knowledge score of 3.19. This represents a 14% difference due to the neighborhood effect. COMMENT: These results suggest that having more individual-level income is positively related to CVD knowledge; such effects are muted if one resides in a neighborhood with a larger proportion of working poor. It may be that future community trials for CVD may benefit by targeting, or concentrating more heavily on, not only poor persons but persons living in poor neighborhoods.
Attempts at Changing Diet and Exercise to Lower Risk of Coronary Heart Disease and Stroke: Who’s Doing What in the Community?
Authors: Thomas Randal J , Kottke Thomas E , Brekke Mark , Brandel Catherine , DeBoer Stephen
Published: July 2021

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Background and Methods:While only a minority of the population follows a low fat diet and does daily physical activity, it is unclear how much of the population is trying to improve these lifestyle habits. We carried out a telephone survey of 1232 adults, >20 years of age, from Olmsted County, MN to assess their attempts at improving their dietary and exercise habits to lower their risk of developing heart disease and stroke. Results: Fifty-nine percent of respondents reported making attempts to improve exercise habits, 71% reported attempts to improve their eating habits, and 50% reported trying to improve both habits. In all, 80% reported trying to improve exercise and/or dietary habits. Of those trying to change exercise habits, 69% reported at least some physical activity on a daily basis (Pearson correlation = 0.34). Of those attempting to change dietary habits, 31% reported eating at least five servings of fruits and vegetables each day (Pearson correlation = 0.14). After multivariate adjustment, attempts to change diet or exercise were highest in persons trying to lose or maintain weight, and persons who reported having received previous physician advice to change diet and exercise habits. Conclusions: The majority of people in Olmsted County, MN are attempting to change their exercise and dietary habits to reduce their risk of coronary heart disease and stroke. Still, only a minority are meeting recommended dietary and physical activity goals. Since most people are in the action phase of exercise and dietary behavioral change, health promotion messages should include information on how best to improve and maintain these health habits. Furthermore, since report of receiving physician advice is correlated with attempts to change lifestyle habits and since only 44% of the population reports receiving such advice, there is an opportunity for health care providers to impact their patients lives by advising them on how to make improvements in their dietary and exercise habits.
Cumulative Effects of Cholesterol and other Risk Factors on Coronary Artery Calcification in Men and Women:
Authors: O’Donnell Christopher J. , Larson Martin G. , Kupka Michelle , Manning Warren J. , Levy Daniel , Clouse Melvin E.
Published: July 2021

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Introduction: Coronary artery calcification (CAC) by electron beam computed tomography (EBCT) is associated with contemporaneous levels of traditional risk factors (RFs). The availability of repeated measures over 25 years allows a unique examination of relations of CAC with long-term RF levels in Framingham Heart Study subjects. Methods: Men and women free of symptomatic coronary disease underwent EBCT. Subjects were randomly sampled across quartiles of age and quintiles of Framingham coronary risk score. Longterm RFs were derived from 25-year averaged values. Logistic regression was used to relate long-term RFs to CAC. Results: In 167 men (35-76 yrs) and 160 women (35-77 yrs), age, long-term total cholesterol, and long-term systolic BP were related to Agatston CAC score ≥ 100 (

Table). In multivariable analyses, long-term total cholesterol was an independent predictor of CAC (p<0.02). Conclusion: Long-term exposure to coronary disease RFs is associated with increased risk for subclinical CAC. These studies may provide insights into differences in RFs for clinical coronary events and for atherosclerosis.

Table 1.
Plasma phospholipid n-3 polyunsaturated fatty acids, fatal ischemic heart disease, and non-fatal myocardial infarction in older adults.
Authors: Lemaitre Rozenn N , Siscovick David S , King Irena B , Kuller Lewis H , Tracy Russell P
Published: July 2021

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BACKGROUND. Studies in middle-aged populations suggest that the intake of both long-chain and intermediate chain n-3 polyunsaturated fatty acids (PUFAs) is associated with a reduction in fatal ischemic heart disease (IHD) but not with non-fatal myocardial infarction (MI). OBJECTIVES. To assess the associations of plasma phospholipid n-3 PUFAs, a biomarker of n-3 PUFA intake, with both incident fatal IHD and incident non-fatal MI in older adults. METHODS. We conducted a nested case-control study using data from the Cardiovascular Health Study, a prospective cohort study of adults 65 and older. We identified 54 incident cases of fatal IHD (fatal MI and coronary heart disease death) and 130 incident cases of non-fatal MI. Controls, randomly selected, were matched to the cases on age, gender, clinic, and month of blood draw at a ratio of 1:1. Sampled cases and controls were free of IHD or stroke at the time of the blood draw. Bloods were collected at the baseline CHS examination. Plasma phospholipid PUFAs were measured using gas chromatography. RESULTS. An increase of one standard deviation in plasma phospholipid levels of combined docosahexaenoic acid (22:6n3) and eicosapentaneoic acid (20:5n3) (1% of total fatty acids) was associated with a decreased risk of fatal IHD (Odds ratio: 0.38, 95% CI [0.18-0.82]) but was not associated with non-fatal MI (Odds ratio: 1.01, 95% CI [0.78-1.30]) after adjustment for age, education, systolic blood pressure, weight, and fasting plasma glucose levels. Similarly, an increase of one standard deviation in plasma phospholipid levels of linolenic acid (0.06% of total fatty acids) was associated with a decreased risk of fatal IHD (Odds ratio: 0.46, 95% CI [0.22-0.95]) but was not associated with non-fatal MI (Odds ratio: 1.00, 95% CI [0.76-1.31]). CONCLUSIONS. Higher plasma phospholipid levels of long-chain and intermediate chain n-3 PUFAs are associated with a decreased risk of incident fatal IHD but are not associated with incident non-fatal MI in older adults. These findings are consistent with studies suggesting an anti-arrhythmic effect of n-3 fatty acids.
LDL subclass distribution is associated with coronary calcification in postmenopausal women
Authors: Mackey Rachel H. , Kuller Lewis H. , Sutton-Tyrrell Kim , Matthews Karen A. , Evans Rhobert W. , Holubkov Richard , Otvos James D.
Published: July 2021

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Major lipoprotein classes consist of particles of various sizes, densities and composition. Associations between lipoprotein subclasses and coronary calcification were evaluated in 287 healthy women, 8 years post-menopause (age 56.9 to 65.4, mean=61.7 y). Coronary calcification score (CCS) was measured by electron beam CT and lipoprotein subclasses were determined by NMR spectroscopy. The mean CCS was 53 (range 0-1175) but 54% of the women had zero scores. CCS was analyzed as categories (CCS: 0, 1-99, ≥100). Current smoking was strongly associated with greater CCS but age and SBP were not significantly associated. Higher CCS was associated with higher triglycerides, total cholesterol and LDL-C, by NMR or usual methods, and total HDL-C by usual methods at the same visit (p < 0.05 for all). Large HDL and total HDL-C by NMR were weakly but not linearly related to CCS. Higher CCS was associated with higher levels of all VLDL subclasses categorized as small, medium or large (p<0.01). Only the smallest LDL subclass (L1) was related to CCS (p<0.01). Mean LDL particle size was smaller for higher CCS category (21.1 vs. 20.7 nm, p<0.01, for CCS = 0 vs CCS > 100). The number of LDL particles was also strongly related to CCS (p<0.001). Ordinal logistic regression was used to determine whether the lipoprotein subclasses were predictive of CCS category after adjustment for age, SBP, current smoking, and usual measures of LDL-C, HDL-C and triglycerides. Women with LDL particle concentrations ≥ 1800 nmol/L or levels of large VLDL > 27 mg/dL were more likely to be in a higher CCS category than those without these risk factors (OR = 2.09, 95% CI: 1.18, 3.70; OR= 2.21, 95% CI: 1.19,4.10, respectively.) After adjustment, higher CCS was still related to higher levels of small LDL (L1), but not to mean (LDL) particle size. These relationships were confirmed using linear regression with log-transformed variables. In postmenopausal women the size and number of LDL particles may be better predictors of atherosclerosis than total LDL-C. The level of large VLDL triglyceride contributes to decreased LDL size and increased number of LDL particles at a given level of LDL-C, via CETP and hepatic lipase.