Iyad N. Isseh

Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk Estimates: Effect on Low-Density Lipoprotein Cholesterol Levels (the MI-GENES Clinical Trial).

Background— Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods and Results— Participants (n=203, 45–65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS (+GRS). Participants in the +GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or +GRS (n=103). At the end of the study period, the +GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P=0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not participants with low GRS (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the +GRS group than in the CRS group (39% versus 22%, P<0.01). No significant differences in dietary fat intake and physical activity levels were noted. Conclusions— Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936675.Background— Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods and Results— Participants (n=203, 45–65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS (+GRS). Participants in the +GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or +GRS (n=103). At the end of the study period, the +GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P =0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants ( P =0.02) but not participants with low GRS (100.9±32.2 mg/dL; P =0.18). Statins were initiated more often in the +GRS group than in the CRS group (39% versus 22%, P <0.01). No significant differences in dietary fat intake and physical activity levels were noted. Conclusions— Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. Clinical Trial Registration— URL: . Unique identifier: [NCT01936675][1]. # CLINICAL PERSPECTIVE {#article-title-33} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01936675&atom=%2Fcirculationaha%2F133%2F12%2F1181.atom

Family history as a risk factor for peripheral arterial disease.

The association of a family history of peripheral arterial disease (PAD) with the presence of PAD is largely unknown. We conducted a case-control study of 2,296 patients with PAD (69 ± 10 years, 64% men) and 4,390 controls (66 ± 11 years, 62% men) identified from noninvasive vascular and stress testing laboratories at Mayo Clinic, Rochester, Minnesota, from October 2006 through June 2012. PAD was defined as an ankle brachial index of ≤ 0.9 at rest and/or after exercise, a history of lower extremity revascularization, or having poorly compressible leg arteries. Controls were patients with normal ankle brachial index or without a history of PAD. Family history of PAD was defined as having at least 1 first-degree relative who had undergone revascularization or stent placement for PAD before the age of 65 years. Logistic regression analyses were used to evaluate whether a family history of PAD was associated with the presence of PAD, independent of conventional risk factors. A family history of PAD was present more often in patients with PAD than in controls, with a resulting odds ratio (OR) of 2.20 (95% confidence interval [CI] 1.82 to 2.67). The association remained significant after adjustment for conventional risk factors (OR 1.97, 95% CI 1.60 to 2.42). The association was stronger in younger subjects (age <68 years; adjusted OR 2.46, 95% CI 1.79 to 3.38) than in older subjects (adjusted OR 1.61, 95% CI 1.22 to 2.12). A greater number of affected relatives with PAD was also associated with greater odds of presence of PAD (adjusted OR 1.86, 95% CI 1.48 to 2.33 and adjusted OR 2.56, 95% CI 1.60 to 4.11 for patients with 1 and ≥ 2 affected relatives with PAD, respectively). In conclusion, individuals with a family history of PAD have nearly double the odds of having PAD relative to those without such a history.

Family History as a Risk Factor for Carotid Artery Stenosis

Background and Purpose— We investigated whether family history of stroke or coronary heart disease (CHD) is associated with presence of carotid artery stenosis (CAS). Methods— The study cohort included 864 patients (72±8 years; 68% men) with CAS and 1698 controls (61±11 years; 55% men) referred for noninvasive vascular testing. CAS was defined as ≥70% stenosis in the internal carotid artery on ultrasound or history of carotid revascularization. Controls did not have CAS or history of cerebrovascular disease or CHD. Family history of stroke and CHD was defined as having ≥1 first-degree relative who had stroke or CHD before age 65 years. Logistic regression analysis was used to evaluate whether family history of stroke or CHD was associated with presence of CAS, independent of conventional risk factors. Results— Family history of stroke and CHD was present more often in patients with CAS than in controls, with a resulting odds ratios (95% confidence interval) of 2.02 (1.61–2.53) and 2.01 (1.70–2.37), respectively. The associations remained significant after adjustment for age, sex, body mass index, smoking, diabetes mellitus, hypertension, and dyslipidemia; odds ratios: 1.41 (1.06–1.90) and 1.69 (1.35–2.10), respectively. A greater number of affected relatives with stroke or CHD was associated with higher odds of CAS; adjusted odds ratios: 1.25 (0.91–1.72) and 1.46 (1.14–1.89) versus 2.65 (1.35–5.40) and 2.13 (1.57–2.90) for patients with 1 and ≥2 affected relatives with stroke and CHD, respectively. Conclusions— Family history of stroke and of CHD were each associated with CAS, suggesting that shared genetic and environmental factors contribute to the risk of CAS.

Incorporating a Genetic Risk Score into Coronary Heart Disease Risk Estimates: Effect on LDL Cholesterol Levels (the MIGENES Clinical Trial)

Background— Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods and Results— Participants (n=203, 45–65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS (+GRS). Participants in the +GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or +GRS (n=103). At the end of the study period, the +GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P=0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not participants with low GRS (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the +GRS group than in the CRS group (39% versus 22%, P<0.01). No significant differences in dietary fat intake and physical activity levels were noted. Conclusions— Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936675.Background— Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods and Results— Participants (n=203, 45–65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS (+GRS). Participants in the +GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or +GRS (n=103). At the end of the study period, the +GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P =0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants ( P =0.02) but not participants with low GRS (100.9±32.2 mg/dL; P =0.18). Statins were initiated more often in the +GRS group than in the CRS group (39% versus 22%, P <0.01). No significant differences in dietary fat intake and physical activity levels were noted. Conclusions— Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. Clinical Trial Registration— URL: . Unique identifier: [NCT01936675][1]. # CLINICAL PERSPECTIVE {#article-title-33} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01936675&atom=%2Fcirculationaha%2F133%2F12%2F1181.atom

Burden of hospitalization in clinically diagnosed peripheral artery disease: A community-based study

The burden and predictors of hospitalization over time in community-based patients with peripheral artery disease (PAD) have not been established. This study evaluates the frequency, reasons and predictors of hospitalization over time in community-based patients with PAD. We assembled an inception cohort of 1798 PAD cases from Olmsted County, MN, USA (mean age 71.2 years, 44% female) from 1 January 1998 through 31 December 2011 who were followed until 2014. Two age- and sex-matched controls (n = 3596) were identified for each case. ICD-9 codes were used to ascertain the primary reasons for hospitalization. Patients were censored at death or last follow-up. The most frequent reasons for hospitalization were non-cardiovascular: 68% of 8706 hospitalizations in cases and 78% of 8005 hospitalizations in controls. A total of 1533 (85%) cases and 2286 (64%) controls (p < 0.001) were hospitalized at least once; 1262 (70%) cases and 1588 (44%) controls (p < 0.001) ≥ two times. In adjusted models, age, prior hospitalization and comorbid conditions were independently associated with increased risk of recurrent hospitalizations in both groups. In cases, severe PAD (ankle–brachial index < 0.5) (HR: 1.25; 95% CI: 1.15, 1.36) and poorly compressible arteries (HR: 1.26; 95% CI: 1.16, 1.38) were each associated with increased risk for recurrent hospitalization. We demonstrate an increased rate of hospitalization in community-based patients with PAD and identify predictors of recurrent hospitalizations. These observations may inform strategies to reduce the burden of hospitalization of PAD patients.

Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk EstimatesCLINICAL PERSPECTIVE

Background— Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods and Results— Participants (n=203, 45–65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS (+GRS). Participants in the +GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or +GRS (n=103). At the end of the study period, the +GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P=0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not participants with low GRS (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the +GRS group than in the CRS group (39% versus 22%, P<0.01). No significant differences in dietary fat intake and physical activity levels were noted. Conclusions— Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936675.Background— Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods and Results— Participants (n=203, 45–65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS (+GRS). Participants in the +GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or +GRS (n=103). At the end of the study period, the +GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P =0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants ( P =0.02) but not participants with low GRS (100.9±32.2 mg/dL; P =0.18). Statins were initiated more often in the +GRS group than in the CRS group (39% versus 22%, P <0.01). No significant differences in dietary fat intake and physical activity levels were noted. Conclusions— Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. Clinical Trial Registration— URL: . Unique identifier: [NCT01936675][1]. # CLINICAL PERSPECTIVE {#article-title-33} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01936675&atom=%2Fcirculationaha%2F133%2F12%2F1181.atom

Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk EstimatesCLINICAL PERSPECTIVE: Effect on Low-Density Lipoprotein Cholesterol Levels (the MI-GENES Clinical Trial)

Background— Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods and Results— Participants (n=203, 45–65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS (+GRS). Participants in the +GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or +GRS (n=103). At the end of the study period, the +GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P=0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not participants with low GRS (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the +GRS group than in the CRS group (39% versus 22%, P<0.01). No significant differences in dietary fat intake and physical activity levels were noted. Conclusions— Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936675.Background— Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods and Results— Participants (n=203, 45–65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS (+GRS). Participants in the +GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or +GRS (n=103). At the end of the study period, the +GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P =0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants ( P =0.02) but not participants with low GRS (100.9±32.2 mg/dL; P =0.18). Statins were initiated more often in the +GRS group than in the CRS group (39% versus 22%, P <0.01). No significant differences in dietary fat intake and physical activity levels were noted. Conclusions— Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. Clinical Trial Registration— URL: . Unique identifier: [NCT01936675][1]. # CLINICAL PERSPECTIVE {#article-title-33} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01936675&atom=%2Fcirculationaha%2F133%2F12%2F1181.atom

HOSPITALIZATION AFTER DIAGNOSIS OF PERIPHERAL ARTERIAL DISEASE IN THE COMMUNITY

Cumulative burden and risk factors for hospitalization after diagnosis of peripheral arterial disease (PAD) are unknown. We identified all diagnosed cases of PAD in Olmsted County Minnesota between 1998 and 2011 and ascertained all hospitalizations for this cohort through 2013. For each case we

GENDER DIFFERENCES IN PERIPHERAL ARTERIAL DISEASE

On average, the ankle-brachial index (ABI) is lower in women than in men but whether this translates into higher prevalence of peripheral arterial disease (PAD) in women is unknown. We evaluated gender differences in the prevalence of PAD in patients referred to the vascular laboratory. A total of