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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 PYsall monotherapy
1,641,979 727 17.5 16.2, 18.8Aliskiren monotherapy
7,072 2 12.7 1.5, 45.8All dual combination therapy
569,769 303 19.5 17.4, 21.8Dual combination therapy
including aliskiren
7,220
4 30.3 8.3, 77.5All triple-plus combination
therapy
144,478
109 27.7 22.7, 33.4Triple-plus combination
therapy including
aliskiren
5,982
3 25.8 5.3, 75.5Keywords: 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