A Case of Aortic Valve Infective Endocarditis with Dermatological Findings of Infective Endocarditis.

Infective endocarditis (IE) is associated with high morbidity and mortality. We present a case of a patient that presented with chest pain and had a workup focused on coronary artery disease and acute coronary syndrome. However, the patient had a history and, even more interestingly, physical exam findings, including Janeway lesions, Osler's nodes, and Splinter hemorrhages, indicative of infective endocarditis. We are sharing the findings that raised our suspicion for IE and a discussion on the pathophysiology of these findings in an effort to promote early recognition and treatment of IE.

Quadricuspid Aortic Valve Stenosis: Expanding Our Experience in Transcatheter Aortic Valve Implantation.

To our knowledge, this is the first documented case of successful TAVI for severe quadricuspid aortic valve (QAV) stenosis performed in the U.S. and the first documented Sapien 3 valve implantation in a severely stenotic QAV.

Using the ankle-brachial index to diagnose peripheral artery disease and assess cardiovascular risk.

The ankle-brachial index is valuable for screening for peripheral artery disease in patients at risk and for diagnosing the disease in patients who present with lower-extremity symptoms that suggest it. The ankle-brachial index also predicts the risk of cardiovascular events, cerebrovascular events, and even death from any cause. Few other tests provide as much diagnostic accuracy and prognostic information at such low cost and risk.

Association between cardiovascular disease risk factors and occurrence of venous thromboembolism. A time-dependent analysis.

Apart from obesity, it remains controversial whether atherosclerosis and its cardiovascular risk disease (CVD) factors are associated with risk of venous thromboembolism (VTE). Using data from the Atherosclerosis Risk in Communities study (ARIC), we evaluated associations between CVD risk factors and incident VTE in a cohort of 15,340 participants who were free a history of VTE and/or anticoagulant use on enrolment. The CVD risk factors were updated during the follow-up period. Over a mean follow-up time of 15.5 years (237,375 person-years), 468 participants had VTE events. Adjusting for demographic variables and body mass index (BMI), current smokers were at greater risk [HR of 1.44 (95% CI: 1.12-1.86)] compared to non-smokers. There was a positive monotonic association between BMI and VTE risk. Individuals with a BMI ≥35 kg/m² had a HR for VTE of 3.09 (95%CI: 2.26-4.23) compared to those with normal BMI (<25 kg/m²). Greater physical activity was associated with lower VTE risk in a demographic adjusted model; however, this association became non-significant following adjustment for BMI. Alcohol intake, diabetes, hypertension, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides were not associated with VTE risk. In conclusion, among the well-established CVD risk factors, only current smoking and obesity were independently associated with VTE risk in this large cohort where risk factors were updated serially during follow-up. This finding corroborates that the pathogenesis of venous disease differs from that of atherosclerotic disease.

Chronic kidney disease and venous thromboembolism: a prospective study.

BACKGROUND: The incidence of venous thromboembolism (VTE) is increased with severe kidney disease, but whether less-severe chronic kidney disease (CKD) increases the risk of VTE is less certain. METHODS: We studied this in a prospective cohort of 10 700 whites and African Americans, aged 53-75 years, attending Visit 4 (1996-98) of the Atherosclerosis Risk in Communities Study. Estimated glomerular filtration rate (eGFR) values were estimated from prediction equations based on serum creatinine (eGFR(creat)) or cystatin C (eGFR(cys)). Normal kidney function was defined as eGFR ≥90 ml/min/1.73 m(2), mildly decreased kidney function as eGFR between 60 and 89 ml/min/1.73 m(2) and Stage 3 to 4 CKD as eGFR between 15 and 59 ml/min/1.73 m(2). VTE occurrence (n = 228) was ascertained over a median of 8.3 years. RESULTS: For eGFR(cys), the age-, race- and sex-adjusted hazard ratios of total VTE were 1.0, 1.40 and 1.94 (P trend = 0.003) for normal kidney function, mildly impaired kidney function and Stage 3 to 4 CKD, respectively. These respective hazard ratios were moderately attenuated to 1.0, 1.26 and 1.60 (P trend = 0.04) with adjustment for hormone replacement therapy, diabetes and body mass index. Associations between CKD based on eGFR(cys) and VTE were slightly stronger for idiopathic VTE than for secondary VTE. In contrast, CKD based on eGFR(creat) was not associated with total VTE occurrence. CONCLUSIONS: Stage 3 to 4 CKD, based on eGFR(cys) but not eGFR(creat), was associated with an approximately 1.6-fold increased risk of VTE.

Chronic kidney disease and venous thromboembolism: epidemiology and mechanisms.

PURPOSE OF REVIEW: An estimated 13% of Americans have kidney disease. We sought to describe the association of kidney disease with risk of venous thromboembolism and discuss possible mechanisms explaining this association. RECENT FINDINGS: All severities of kidney disease appear to increase the risk of venous thromboembolism. In the general population the risk associated with mild to moderate kidney disease is 1.3-2-fold increased, and present even for microalbuminuria, although stage 1 chronic kidney disease itself has not been studied. End-stage renal disease is also associated with a 2.3-fold increased risk, compared to the general population. Although data are limited, risk increases after kidney transplant and with nephrotic syndrome as well. SUMMARY: Rates of kidney disease are increasing rapidly in the population and kidney disease is a risk factor for venous thromboembolism. An improved understanding of mechanisms linking kidney disease with venous thromboembolism will allow further study of best prevention efforts.

Relation of sleep-disordered breathing to carotid plaque and intima-media thickness.

BACKGROUND: Sleep-disordered breathing (SDB) is associated with clinical cardiovascular disease (CVD), but its relation to subclinical atherosclerosis remains to be determined. METHODS: We analyzed the cross-sectional associations of SDB, measured by the respiratory disturbance index (RDI), a hypoxemia index, and an arousal index, with carotid plaque and carotid intima-media thickness (IMT), measured by ultrasound. The sample included 985 participants in the Sleep Heart Health Study (mean age-62, median RDI-8.7) with no history of coronary heart disease and stroke, of whom 396 had evidence of a carotid plaque. RESULTS: As compared with the first quartile of the RDI (0-1.2), the crude odds ratio for carotid plaque was 1.14, 1.27, and 1.48 for the second (1.3-4.1), third (4.2-10.7), and fourth (>10.7) quartile, respectively. After adjustment for CVD risk factors, the corresponding odds ratios were reduced (1.00, 1.04, 1.07, and 1.25). Similarly, the unadjusted mean carotid IMT increased with RDI, but adjusted means (mm) were similar (0.84, 0.85, 0.84, 0.85). Spline regression models did not show monotonicity of the dose-response functions at the right end of the RDI distribution. Neither the hypoxemia index nor the arousal index was associated with carotid plaque or carotid IMT. CONCLUSION: The results of this study suggest that crude, positive associations between SDB and subclinical atherosclerosis can be attributed to confounding by CVD risk factors.

Chronic kidney disease increases risk for venous thromboembolism.

Chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease morbidity and mortality, but its association with incident venous thromboembolism (VTE) in non-dialysis-dependent patients has not been evaluated in a community-based population. With the use of data from the Longitudinal Investigation of Thromboembolism Etiology (LITE) study, 19,073 middle-aged and elderly adults were categorized on the basis of estimated GFR, and cystatin C (available in 4734 participants) was divided into quintiles. During a mean follow-up time of 11.8 yr, 413 participants developed VTE. Compared with participants with normal kidney function, relative risk for VTE was 1.28 (95% confidence interval [CI] 1.02 to 1.59) for those with mildly decreased kidney function and 2.09 (95% CI 1.47 to 2.96) for those with stage 3/4 CKD, when adjusted for age, gender, race, and center. After additional adjustment for cardiovascular disease risk factors, an increased risk for VTE was still observed in participants with stage 3/4 CKD, with a multivariable adjusted relative risk of 1.71 (95% CI 1.18 to 2.49). There was no significant association between cystatin C and VTE. In conclusion, middle-aged and elderly patients with CKD (stages 3 through 4) are at increased risk for incident VTE, suggesting that VTE prophylaxis may be particularly important in this population.

Kidney function and risk of peripheral arterial disease: results from the Atherosclerosis Risk in Communities (ARIC) Study.

Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular disease, but its association with peripheral arterial disease (PAD) is unclear. With the use of data from the Atherosclerosis Risk in Communities (ARIC) Study, 14,280 middle-aged adults were categorized on the basis of estimated GFR >/=90, 60 to 89, and 15 to 59 ml/min per 1.73 m(2) for normal kidney function, mildly decreased kidney function, and stages 3 to 4 CKD, respectively. Incident PAD was defined as a new onset of ankle-brachial index <0.9 assessed at regular examinations, new intermittent claudication assessed by annual surveillance, or PAD-related hospital discharges. Incidence rates and relative risks (RR) for PAD were compared across these categories. During a mean follow-up time of 13.1 yr (186,616 person-years), 1016 participants developed PAD. The incidence rates per 1000 person-years were 4.7, 4.9, and 8.6 for the normal kidney function, mildly decreased kidney function, and CKD groups, respectively. Compared with participants with normal kidney function, the age-, gender-, race-, and ARIC field center-adjusted RR for PAD was 1.04 (95% confidence interval [CI] 0.91 to 1.18) for those with mildly decreased kidney function and 1.82 (95% CI 1.34 to 2.47) for those with CKD. After additional adjustment for cardiovascular disease risk factors, an increase in risk for incident PAD still was observed in participants with CKD, with a multivariable adjusted RR of 1.56 (95% CI 1.13 to 2.14). Patients with CKD are at increased risk for incident PAD. Development of strategies for screening and prevention of PAD in this high-risk population seems warranted.

Clinical significance of a high ankle-brachial index: insights from the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: The clinical significance of a high ankle-brachial index (ABI), defined by the associated risk factor burden and ischemic risk, is largely unknown. METHODS: Using data from the Atherosclerosis Risk in Communities Study, we categorized 14,777 participants into normal (ABI between 0.9 and 1.3) and high ABI groups (ABI>1.3, >1.4, and >1.5) and compared the risk factor profile and CVD event rates of the normal ABI group to each high ABI group. RESULTS: The prevalence of high ABI was 5.5% for ABI>1.3, 1.2% for ABI>1.4, and 0.37% for ABI>1.5. Compared with participants with a normal ABI, those with ABI>1.3 had a lower prevalence of hypertension and current smoking. The ABI>1.3 group had a greater mean body mass index, but was characterized by fewer pack years of smoking and lower systolic and diastolic blood pressures than the normal ABI group. The prevalence of diabetes, left ventricular hypertrophy, claudication, and coronary heart disease and mean values of fibrinogen, factor VIII activity, von Willebrand factor, lipoprotein (a), and carotid and popliteal intimal-medial thickness were similar between the two ABI groups. The risk factor profiles of the ABI>1.4 and >1.5 groups were also not statistically significantly different from that of the normal ABI group. Over a mean follow-up time of 12.2 years, the age, sex, and race-adjusted CVD event rates per 1000 person years were 8.1 in the normal ABI group, 7.6 in the ABI>1.3 group, 7.6 in the ABI>1.4 group, and 7.4 in the ABI>1.5 group. The CVD event rates of the high ABI groups were similar to that of the normal ABI group. CONCLUSION: Individuals with a high ABI are not characterized by a more adverse atherosclerosis risk factor profile and do not suffer greater CVD event rates than those with a normal ABI.

Cardiovascular risk among adults with chronic kidney disease, with or without prior myocardial infarction.

OBJECTIVES: This study sought to determine whether chronic kidney disease (CKD) should be considered a coronary heart disease (CHD) risk equivalent for cholesterol treatment. BACKGROUND: It is unclear whether patients with CKD have a risk of CHD events or cardiovascular disease (CVD) mortality equivalent to patients with a prior myocardial infarction (MI). METHODS: Using data from the ARIC (Atherosclerosis Risk in Communities) study, we categorized nondiabetic participants based on their average level of kidney function (estimated glomerular filtration rate > or =60 or 30 to 59 ml/min/1.73 m2, which defines stage 3 CKD) and on prior MI (yes or no). Rates and relative risks (RR) of CHD (MI or fatal CHD) events (n = 653) and CVD mortality (n = 209) that occurred over 10 years were compared across these populations. RESULTS: Among 12,243 middle-age participants, 271 had stage 3 CKD. After adjustment for age, gender, race, and center, CHD incidence and CVD mortality rates per 1,000 person-years by presence of CKD and MI were 4.1 and 1.0 in the presence of neither condition, 8.0 and 3.4 in CKD only, 18.8 and 7.0 in MI only, and 30.8 and 18.0 in CKD and MI. After further adjustment for CVD risk factors, RR of CHD and CVD mortality were statistically significantly lower in subjects with CKD and no prior MI (RR = 0.44 [95% confidence interval (CI) 0.28 to 0.72] for CHD and RR = 0.46 [95% CI 0.24 to 0.90] for CVD mortality) than for subjects with no CKD and a prior MI. CONCLUSIONS: Stage 3 CKD confers CHD risk that is lower and not equivalent to a prior MI in this middle-aged, general, nondiabetic population.

HbA1c and peripheral arterial disease in diabetes: the Atherosclerosis Risk in Communities study.

OBJECTIVE: To assess the relation between HbA(1c) (A1C) and incident peripheral arterial disease (PAD) in a community-based cohort of diabetic adults from the Atherosclerosis Risk in Communities (ARIC) study. A second aim was to investigate whether the association was stronger for severe, symptomatic disease compared with PAD assessed by low ankle-brachial index (ABI). RESEARCH DESIGN AND METHODS: This was a prospective cohort study of 1,894 individuals with diabetes using ARIC visit 2 as baseline (1990-1992) with follow-up for incident PAD through 2002. We assessed the relation between A1C and incident PAD, defined by intermittent claudication, PAD-related hospitalization, or a low ABI (<0.9). RESULTS: During a mean follow-up of 9.8 years, the crude incidence rates were 2.1 per 1,000 person-years for intermittent claudication (n = 41), 2.9 per 1,000 person-years for PAD-related hospitalization (n = 57), and 18.9 per 1,000 person-years for low ABI at visit 3 or 4 (n = 123). The relative risk (RR) (95% CI) of an incident PAD event comparing the second and third tertiles of A1C to the first, respectively, after adjustment for cardiovascular risk factors was strongest for severe, symptomatic forms of disease, e.g., PAD-related hospitalization (RR = 4.56 [1.86-11.18] for the third A1C tertile compared with the first, P trend <0.001) than for low ABI (RR = 1.64 [0.94-2.87], P trend = 0.08). CONCLUSIONS: We found a positive, graded, and independent association between A1C and PAD risk in diabetic adults. This association was stronger for clinical (symptomatic) PAD, whose manifestations may be related to microvascular insufficiency, than for low ABI. Our results suggest that efforts to improve glycemic control in persons with diabetes may substantially reduce the risk of PAD.

Association of anger proneness, depression and low social support with peripheral arterial disease: the Atherosclerosis Risk in Communities Study.

There is mounting evidence to suggest that psychosocial factors, including anger proneness, depression and social isolation, are risk factors for cardiovascular disease. Nevertheless, evidence relating these factors to peripheral arterial disease (PAD) and intermittent claudication remains sparse. Using data from the Atherosclerosis Risk in Communities Study, we analyzed the relationship of psychosocial variables (Spielberger anger score, depression score from the Maastricht questionnaire, and a perceived social support scale) at study visit 2 with incident PAD (ankle-brachial index < or = 0.9; a hospital discharge diagnosis of PAD, leg amputation, or leg revascularization procedures; or intermittent claudication). In 12,965 middle-aged adults with no prior history of PAD, 854 developed PAD over a mean follow-up time of 9.7 years, yielding an incidence rate of 6.8 per 1000 person years. A modest, monotonic dose-response, positive association between anger proneness and incident PAD was observed in a multivariable model: relative risk (RR) = 1.15 (95% confidence interval (CI) 0.99-1.38) in the moderate anger group and RR = 1.38 (95% CI 1.08-1.76) in the high anger group, compared with the low anger group. When compared with a low level of depressive symptoms, moderate and high levels of depressive symptoms were also associated with greater incident PAD, with multi-variable RRs of 1.20 (95% CI 0.99-1.45) and 1.44 (95% CI 1.19-1.74) respectively. There was no association of perceived level of social support with the occurrence of PAD. Anger proneness and depressive symptoms may be associated with the occurrence of PAD, as for other atherosclerotic syndromes. These findings may warrant confirmation in further studies and, if causal, could serve as a unique target for a PAD prevention trial.

Risk factors for cardiovascular event recurrence in the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Numerous studies have identified risk factors and markers associated with incidence of cardiovascular disease (CVD). However, few studies have examined whether established risk factors, novel blood markers, carotid ultrasonography, or ankle-brachial index can predict recurrent CVD events. METHODS AND RESULTS: We analyzed the relation of established risk factors and markers of atherosclerosis with the risk of recurrent CVD in 766 participants. Over a mean of 8.7 years of follow-up, 70 women and 243 men had a recurrent CVD event (85.3% coronary heart disease and 23.7% stroke). Adjusting for age and sex, this study found that established risk factors were associated with recurrent CVD events in the anticipated direction. Being in the highest (vs lowest) quartiles of lipoprotein (a), fibrinogen, white blood cells, and creatinine at baseline were associated with 47%, 69%, 65%, and 81%, respectively, greater risk of a CVD event, and being in the highest quartile of albumin was associated with 39% lower risk. Being in the highest (vs lowest) quartile of carotid intima-media thickness (IMT) was associated with a doubling of risk, and having carotid plaque with acoustic shadowing (vs having no plaque) was associated with 83% increased risk of a CVD event. After adjustment for established risk factors, creatinine, albumin, and carotid IMT in the highest quartile (vs lowest quartile) and carotid plaque with acoustic shadowing (vs no plaque) were independently associated with recurrent CVD events. CONCLUSION: Established risk factors, but only a few of novel risk factors and markers, were independent predictors of recurrent CVD events.

Risk factors for peripheral arterial disease incidence in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Some risk factors for peripheral arterial disease (PAD) have been identified, but little information is available on PAD risk factors in individuals with diabetes. METHODS: Using data from the Atherosclerosis Risk in Communities (ARIC) Study, we assessed the relation of traditional and non-traditional risk factors with the risk of PAD in 1651 participants with diabetes, but not PAD, at baseline. Incident PAD was defined as an ankle-brachial index (ABI)<0.9 assessed at regular examinations; hospital discharge codes for PAD, amputation, or leg revascularization; or claudication assessed by annual questionnaire. RESULTS: Over a mean of 10.3 years of follow-up, 238 persons developed incident PAD identified, yielding a PAD event rate of 13.9 per 1000 person years. Adjusted for sex, age, race, and center, the risk of developing PAD was increased 1.87-fold (95% confidence interval (95% CI): 1.36-2.57) in persons who were current smokers versus non-smokers, 2.27-fold (95% CI: 1.57-3.26) for baseline coronary heart disease (CHD) versus no baseline CHD, and 1.75-fold (95% CI: 1.18-2.60) for the highest quartile versus lowest quartile of triglycerides. We found no evidence of an association with other blood lipids or hypertension. Compared with the lowest quartiles, comparably-adjusted relative risks for the highest quartiles were 1.60 (95% CI: 1.10-2.33) for waist-to-hip ratio, 2.52 (95% CI: 1.70-3.73) for fibrinogen, 1.70 (95% CI: 1.17-2.47) for factor VIII, 1.73 (95% CI: 1.18-2.54) for von Willebrand factor, 2.15 (95% CI: 1.43-3.24) for white blood cell count, 1.81 (95% CI: 1.19-2.74) for serum creatinine, 0.55 (95% CI: 0.37-0.83) for serum albumin, and 2.73 (95% CI: 1.77-4.22) for carotid intima-media thickness. Persons who had a prior history of diabetes and were taking insulin had a relative risk of 1.97 (95% CI: 1.35-2.87) for future PAD events, compared with those with newly identified diabetes at baseline. In our final multivariable model, current smoking, prevalent CHD, elevated fibrinogen and carotid IMT, and a prior history of diabetes with insulin treatment were independently associated with greater PAD incidence. CONCLUSION: These markers might be useful to identify individuals with diabetes at particular risk for PAD.