1
EPIDEMIOLOGY/SPECIAL POPULATIONS P-134 A genetic variant of soluble guanylate cyclase is associated with higher plasma cholesterol and triglycerides in the general population Valentina Cannone, Christopher G. Scott, Kent R. Bailey, Timothy M. Olson, Jeanne L. Theis, Margaret M. Redfield, Richard J. Rodeheffer, John C. Burnett, Jr. Mayo Clinic, Rochester, MN, United States Nitric oxide (NO) is a vasodilator that also possesses lipogenic proper- ties. In rats, lipid accumulation and lipogenic enzymes are induced by NO and insulin-stimulated glucose uptake is dependent on intact NO synthesis in white adipose tissue. Mice in which the gene encoding inducible NO synthase was disrupted are protected from high-fat induced insulin resis- tance and NO inhibition in rodents on a high fat diet reduces hepatic lipid accumulation. These biological actions of NO are mediated by soluble guanylate cyclase (sGC) and importantly human adipocytes express the genes GUCY1A2, GUCY1A3, GUCY1B3 encoding for the alpha and beta subunits of sGC. The single nucleotide polymorphism rs13139571 is located within an intron of GUCY1A3 and its minor allele is associated with higher blood pressure and odds of hypertension in a recent genome wide association study. For the first time, we investigated the metabolic phenotype associated with rs13139571 in a random sample (n¼ 2007) of the general population from Olmsted County, MN. Frequencies of rs13139571 genotypes were CC: 59%, AC: 36%, AA: 5%. In age and gender adjusted analysis, carriers of the A minor allele had significantly higher plasma values of total cholesterol (CC: 202 36, AC: 20436, AA: 208 34 mg/dl, p value¼ 0.04) and triglycerides (CC: 14585, AC: 15086, CC: 169101 mg/dl, p value¼ 0.01). Metabolic syndrome trended toward increased prevalence in carriers of the minor allele (CC: 21%, AC: 23%, AA: 28%, p value¼ 0.06). Genotypes did not differ in terms of systolic blood pressure (CC: 132 22, AC: 134 21, CC: 132 21 mmHg, p value¼ 0.45), diastolic blood pressure (CC: 74 10, AC: 74 10, CC: 73 12 mmHg, p value¼ 0.77), BMI (CC: 28 5, 29 5, 28 5 Kg/m 2 , p value¼ 0.43) and percentage of subjects on antilipemic therapy (CC: 17%, AC: 19%, AA: 18%, p value¼ 0.56). These studies suggest that the minor allele of rs13139571 may be associated with increased NO activity and influence lipid metabolism by favoring lipid accumulation and insulin resistance. Alternatively, rs13139571 may be in linkage disequilibrium with another genetic locus that affects cardiome- tabolic phenotype. Additional studies are warranted to confirm our findings and further investigate the metabolic phenotype associated with this ge- netic variant. Keywords: soluble guanylate cyclase; nitric oxyde; cholesterol; triglycerides P-135 Assessing the incidence of probable ischemic colitis in treated adult hypertensive patients Dionne M. Hines , y ,1 Catherine B. McGuiness, 1 Raymond G. Schlienger, 2 Shawn Hallinan, 1 Charles Makin. 1 1 IMS Health, Alexandria, VA, United States; 2 Novartis Pharma AG, Basel, Switzerland Evidence suggests that antihypertensive (AHTN) therapy may be associ- ated with ischemic colitis. This study sought to evaluate the incidence of probable ischemic colitis (pIC) in treated hypertensive patients overall and by AHTN drug use (with a focus on aliskiren), as well as in a general population sample (non-hypertensive, without AHTN drug use). A cohort study was conducted using PharMetrics, a large US-based healthplan claims database. Patients with a hypertension diagnosis between Jan 1, 2006 and Mar 31, 2012, 1 claim for AHTN therapy within 180 days after or with day’s supply overlapping the diagnosis date, 18 years of age on the index date (date of first AHTN claim), and continuous health plan enrollment were included. Patients with a diagnosis of pIC during pre-in- dex or the first 30 days post-index, or with other data validity issues were excluded. Eligible patients were stratified into an incident (no AHTN claims pre-index), or prevalent AHTN treatment cohort (1 AHTN claim pre-index). Patients were further classified as monotherapy, dual, or triple- plus combination users based on AHTN drug use at index and on use within 30 days before the end of follow-up. Follow-up ended at earliest of: a recorded diagnosis of pIC or of a rule-out condition (e.g., diverticu- litis); end of enrollment; end of the study period (June 30, 2012). There were 996,357 and 1,359,869 patients included in the incident and prevalent groups; 2,356,226 patients comprised the general population. The inci- dence rate (IR) per 100,000 person-years (PYs) of pIC in the overall hyper- tensive population based on their index therapy was higher than in the general population (18.6, 95% CI: [17.6, 19.8] vs. 4.0, 95% CI: [3.4, 4.7]). The IR of pIC was 20.6 (95% CI: [19.2, 22.1]) for the prevalent, and 15.3 (95% CI: [13.8, 17.0]) per 100,000 PYs for the incident cohorts. Of all hypertensive patients, 20,274 (0.9%) used a regimen that included aliskiren. When analyzed by index regimen, the IRs for regimens contain- ing aliskiren were not different from all monotherapy, dual, or triple-plus combination regimens (table). When analyzed by therapy used prior to the end of follow-up, no events of pIC were observed for monotherapy or dual combination regimens that included aliskiren. Though limited by the rela- tively small number of aliskiren exposed patients, the data suggest that the risk of pIC with aliskiren is small when used as monotherapy or in a dual combination regimen. Regimen Number of patients Number of pIC events IR per 100,000 PYs 95% CI all monotherapy 1,641,979 727 17.5 16.2, 18.8 Aliskiren monotherapy 7,072 2 12.7 1.5, 45.8 All dual combination therapy 569,769 303 19.5 17.4, 21.8 Dual combination therapy including aliskiren 7,220 4 30.3 8.3, 77.5 All triple-plus combination therapy 144,478 109 27.7 22.7, 33.4 Triple-plus combination therapy including aliskiren 5,982 3 25.8 5.3, 75.5 Keywords: ischemic colitis; antihypertensive therapy; aliskiren; epidemiology P-136 Cardiovascular risk factors in centenarians Paulo Oliveira Duarte , 1 Mariana Garcia da Freiria Duarte, 1,2 Eduardo Ferriolli, 1 Julio Cesar Moriguti, 1 Elza Tiemi Sakamoto Hojo, 1 Nereida Kilza da Costa Lima. 1 1 School of Medicine of Ribeirao Preto – University of S~ ao Paulo - USP, Ribeir~ ao Preto, Brazil; 2 University of Ribeir~ ao Preto - UNAERP, Ribeir~ ao Preto, Brazil Study of Central European Jewish centenarians and their children found an increase in HDL cholesterol levels and lower LDL levels; lower prevalence 1933-1711/$ - see front matter Ó 2014 American Society of Hypertension. All rights reserved. Journal of the American Society of Hypertension 8(4S) (2014) e81–e91

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Page 1: Assessing the incidence of probable ischemic colitis in treated adult hypertensive patients

Journal of the American Society of Hypertension 8(4S) (2014) e81–e91

EPIDEMIOLOGY/SPECIAL POPULATIONS

P-134

A genetic variant of soluble guanylate cyclase is associated with

higher plasma cholesterol and triglycerides in the general population

Valentina Cannone, Christopher G. Scott, Kent R. Bailey,

Timothy M. Olson, Jeanne L. Theis, Margaret M. Redfield,Richard J. Rodeheffer, John C. Burnett, Jr. Mayo Clinic, Rochester, MN,

United States

Nitric oxide (NO) is a vasodilator that also possesses lipogenic proper-

ties. In rats, lipid accumulation and lipogenic enzymes are induced by NO

and insulin-stimulated glucose uptake is dependent on intact NO synthesis

in white adipose tissue. Mice in which the gene encoding inducible NO

synthase was disrupted are protected from high-fat induced insulin resis-

tance and NO inhibition in rodents on a high fat diet reduces hepatic lipid

accumulation. These biological actions of NO are mediated by soluble

guanylate cyclase (sGC) and importantly human adipocytes express the

genes GUCY1A2, GUCY1A3, GUCY1B3 encoding for the alpha and beta

subunits of sGC. The single nucleotide polymorphism rs13139571 is

located within an intron of GUCY1A3 and its minor allele is associated

with higher blood pressure and odds of hypertension in a recent genome

wide association study. For the first time, we investigated the metabolic

phenotype associated with rs13139571 in a random sample (n¼ 2007) of

the general population from Olmsted County, MN. Frequencies of

rs13139571 genotypes were CC: 59%, AC: 36%, AA: 5%. In age and

gender adjusted analysis, carriers of the A minor allele had significantly

higher plasma values of total cholesterol (CC: 202 � 36, AC: 204�36,

AA: 208 �34 mg/dl, p value¼ 0.04) and triglycerides (CC: 145�85,

AC: 150�86, CC: 169�101 mg/dl, p value¼ 0.01). Metabolic syndrome

trended toward increased prevalence in carriers of the minor allele (CC:

21%, AC: 23%, AA: 28%, p value¼ 0.06). Genotypes did not differ in

terms of systolic blood pressure (CC: 132 � 22, AC: 134 � 21, CC:

132 � 21 mmHg, p value¼ 0.45), diastolic blood pressure (CC: 74 �10, AC: 74 � 10, CC: 73 � 12 mmHg, p value¼ 0.77), BMI (CC: 28 �5, 29 � 5, 28 � 5 Kg/m2, p value¼ 0.43) and percentage of subjects on

antilipemic therapy (CC: 17%, AC: 19%, AA: 18%, p value¼ 0.56). These

studies suggest that the minor allele of rs13139571 may be associated with

increased NO activity and influence lipid metabolism by favoring lipid

accumulation and insulin resistance. Alternatively, rs13139571 may be

in linkage disequilibrium with another genetic locus that affects cardiome-

tabolic phenotype. Additional studies are warranted to confirm our findings

and further investigate the metabolic phenotype associated with this ge-

netic variant.

Keywords: soluble guanylate cyclase; nitric oxyde; cholesterol; triglycerides

P-135

Assessing the incidence of probable ischemic colitis in treated adult

hypertensive patients

Dionne M. Hines,y,1 Catherine B. McGuiness,1 Raymond G. Schlienger,2

Shawn Hallinan,1 Charles Makin.1 1IMS Health, Alexandria, VA, United

States; 2Novartis Pharma AG, Basel, Switzerland

Evidence suggests that antihypertensive (AHTN) therapy may be associ-

ated with ischemic colitis. This study sought to evaluate the incidence of

probable ischemic colitis (pIC) in treated hypertensive patients overall

and by AHTN drug use (with a focus on aliskiren), as well as in a general

population sample (non-hypertensive, without AHTN drug use). A cohort

1933-1711/$ - see front matter � 2014 American Society of Hypertension. All

study was conducted using PharMetrics, a large US-based healthplan

claims database. Patients with a hypertension diagnosis between Jan 1,

2006 and Mar 31, 2012, �1 claim for AHTN therapy within 180 days after

or with day’s supply overlapping the diagnosis date, �18 years of age on

the index date (date of first AHTN claim), and continuous health plan

enrollment were included. Patients with a diagnosis of pIC during pre-in-

dex or the first 30 days post-index, or with other data validity issues were

excluded. Eligible patients were stratified into an incident (no AHTN

claims pre-index), or prevalent AHTN treatment cohort (�1 AHTN claim

pre-index). Patients were further classified as monotherapy, dual, or triple-

plus combination users based on AHTN drug use at index and on use

within 30 days before the end of follow-up. Follow-up ended at earliest

of: a recorded diagnosis of pIC or of a rule-out condition (e.g., diverticu-

litis); end of enrollment; end of the study period (June 30, 2012). There

were 996,357 and 1,359,869 patients included in the incident and prevalent

groups; 2,356,226 patients comprised the general population. The inci-

dence rate (IR) per 100,000 person-years (PYs) of pIC in the overall hyper-

tensive population based on their index therapy was higher than in the

general population (18.6, 95% CI: [17.6, 19.8] vs. 4.0, 95% CI: [3.4,

4.7]). The IR of pIC was 20.6 (95% CI: [19.2, 22.1]) for the prevalent,

and 15.3 (95% CI: [13.8, 17.0]) per 100,000 PYs for the incident cohorts.

Of all hypertensive patients, 20,274 (0.9%) used a regimen that included

aliskiren. When analyzed by index regimen, the IRs for regimens contain-

ing aliskiren were not different from all monotherapy, dual, or triple-plus

combination regimens (table). When analyzed by therapy used prior to the

end of follow-up, no events of pIC were observed for monotherapy or dual

combination regimens that included aliskiren. Though limited by the rela-

tively small number of aliskiren exposed patients, the data suggest that the

risk of pIC with aliskiren is small when used as monotherapy or in a dual

combination regimen.

Regimen Number of Number of IR per 95% CI

rights reserved.

patients

pIC events 100,000 PYs

all monotherapy

1,641,979 727 17.5 16.2, 18.8

Aliskiren monotherapy

7,072 2 12.7 1.5, 45.8

All dual combination therapy

569,769 303 19.5 17.4, 21.8

Dual combination therapy

including aliskiren

7,220

4 30.3 8.3, 77.5

All triple-plus combination

therapy

144,478

109 27.7 22.7, 33.4

Triple-plus combination

therapy including

aliskiren

5,982

3 25.8 5.3, 75.5

Keywords: ischemic colitis; antihypertensive therapy; aliskiren;

epidemiology

P-136

Cardiovascular risk factors in centenarians

Paulo Oliveira Duarte,1 Mariana Garcia da Freiria Duarte,1,2

Eduardo Ferriolli,1 Julio Cesar Moriguti,1 Elza Tiemi Sakamoto Hojo,1

Nereida Kilza da Costa Lima.1 1School of Medicine of RibeiraoPreto – University of S~ao Paulo - USP, Ribeir~ao Preto, Brazil; 2University

of Ribeir~ao Preto - UNAERP, Ribeir~ao Preto, Brazil

Study of Central European Jewish centenarians and their children found an

increase in HDL cholesterol levels and lower LDL levels; lower prevalence