Background

Circulating lipids have been implicated as important modulators of immune response, and altered lipid levels correlate with the severity of infection. However, long-term prognostic implications of lipid levels regarding future infection risk remain unclear. The current project aims to explore whether baseline lipid levels are associated with risk of future serious infection, measured by hospitalization for pneumonia.

Methods

A retrospective analysis was performed in 13,478 participants selected from the Atherosclerosis Risk in Communities (ARIC) study, a large community-based longitudinal cohort in the United States with a median follow-up time of >20 years. First incident of hospitalization for pneumonia was identified through hospital discharge records. Cox proportional hazard models were used to assess the association of baseline major lipid levels (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides) with time to first pneumonia hospitalization.

Results

A total of 1969 (14.61%) participants had a pneumonia hospitalization during a median follow-up time of 21.5 years. The hazard ratio (HR) for pneumonia hospitalization was 0.90 (95% confidence interval, 0.87-0.92) for every 10-mg/dL increase in baseline HDL-C, and 1.02 (95% confidence interval, 1.02-1.03) for every 10-mg/dL increase in baseline triglycerides. HDL-C and triglycerides both remained significant predictors of pneumonia hospitalization after multivariable adjustment. Such associations were not seen with baseline LDL-C or total cholesterol levels.

Conclusion

Lower baseline HDL-C and higher triglyceride levels were strongly associated with increased risk of long-term pneumonia hospitalization in a large longitudinal US cohort.

Using data from the Multi-Ethnic Study of Atherosclerosis (United States, 2000-2015), 6,527 racially/ethnically diverse adults (mean age, 62 (standard deviation, 10) years) free of known cardiovascular (CVD) had ankle brachial index (ABI) assessment of their bilateral dorsalis pedis/posterior tibial arteries (4 vessels total) and were followed for total mortality and incident CVD events/mortality. Individuals were classified into categories of 0-, 1-, 2-, 3- or 4-vessel peripheral artery disease (PAD) (ABI of ≤0.9). There were 1,202 deaths (18%), 656 incident CVD events (10%), and 282 CVD deaths (4.3%). Of the 6,527 individuals, 5,711 (87.5%) had 0-, 460 (7.0%) had 1-, 218 (3.3%) had 2-, 69 (1.1%) had 3-, and 69 (1.1%) had 4-vessel PAD, respectively. In multivariable Cox models, higher number of vessels with PAD was associated with higher risk of mortality (P for trend <0.001), CVD events (P for trend = 0.002), and CVD mortality (P for trend = 0.001). Compared with individuals who had 0-vessel disease, hazard ratios for mortality were 1.29 (95% confidence interval (CI): 1.06, 1.59) for 1-, 1.45 (95% CI: 1.14, 1.86) for 2-, 1.58 (95% CI: 1.13, 2.21) for 3-, and 2.15 (95% CI: 1.58, 2.94) for 4-vessel disease. A similar pattern was seen for CVD events/mortality. These results suggest the importance of accounting for ABI values of all 4 leg arteries in clinical practice and research.

Chronic kidney disease (CKD) affects about 10% of all populations worldwide, with about 2 million people requiring dialysis. Although patients with CKD are at high risk of cardiovascular disease and events, they are often underrepresented or excluded in clinical trials, leading to important knowledge gaps about how to treat these patients. KDIGO (Kidney Disease: Improving Global Outcomes) convened the fourth clinical Controversies Conference on the heart, kidney and vasculature in Dublin, Ireland, in February 2020, entitled Central and Peripheral Arterial Diseases in Chronic Kidney Disease. A global panel of multidisciplinary experts from the fields of nephrology, cardiology, neurology, surgery, radiology, vascular biology, epidemiology, and health economics attended. The objective was to identify key issues related to the optimal detection, management, and treatment of cerebrovascular diseases, central aortic disease, renovascular disease, and peripheral artery disease in the setting of CKD. This report outlines the common pathophysiology of these vascular processes in the setting of CKD, describes best practices for their diagnosis and management, summarizes areas of uncertainty, addresses ongoing controversial issues, and proposes a research agenda to address key gaps in knowledge that, when addressed, could improve patient care and outcomes.

Background

The association of periodontal disease with atherosclerotic cardiovascular diseases is well known, but not specifically with incident peripheral artery disease (PAD). Therefore, we studied the associations of periodontal disease with incident PAD in a population-based setting.

Methods

Among 9,793 participants (aged 53-75 years) without prevalent PAD, self-reported history of periodontal disease was ascertained. Of these, 5,872 participants underwent full-mouth examinations from which periodontal status was defined using the US Centers for Disease Control and Prevention-American Academy of Periodontology (CDC-AAP) definition. We quantified the association of periodontal disease with incident PAD (defined by hospital admission diagnosis or procedures) using multivariable Cox regression models.

Results

During a median follow-up of 20.1 years, 360 participants (3.6%) developed PAD. In models accounting for potential confounders including diabetes and smoking pack-years, there was higher hazard of PAD in participants with self-reported tooth loss because of periodontal disease (hazard ratio:1.54 [95% CI:1.20-1.98]), history of periodontal disease treatment (1.37 [1.05-1.80]), and periodontal disease diagnosis (1.38 [1.09-1.74]), compared to their respective counterparts. The clinical measure of periodontal disease (n = 5,872) was not significantly associated with incident PAD in the fully adjusted model (e.g., 1.53 [0.94-2.50] in CDC-AAP-defined severe periodontal disease versus no disease).

Conclusion

We observed a modest association of self-reported periodontal disease, especially when resulting in tooth loss, with incident PAD in the general population. Nonetheless, a larger study with the clinical measure of periodontal disease is warranted.

Background and aims

Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function.

Methods

Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus).

Results

During a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3-8.3 for eGFR <30 and 2.4-3.5 for eGFR 30-59 vs. eGFR ≥90 mL/min/1.73 m²). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91-3.54] for B2M vs. 1.20 [0.91-1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11-1.94] in top quartile).

Conclusions

Kidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD.

eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta-analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of -6 versus 0 ml/min per 1.73 m(2) per year over the previous 3 years (a decline of 18 ml/min per 1.73 m(2) versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m(2) (a difference of 20 ml/min per 1.73 m(2)) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR<30 ml/min per 1.73 m(2).

Constipation is one of the most prevalent conditions in primary care settings and increases the risk of cardiovascular disease, potentially through processes mediated by altered gut microbiota. However, little is known about the association of constipation with CKD. In a nationwide cohort of 3,504,732 United States veterans with an eGFR ≥60 ml/min per 1.73 m², we examined the association of constipation status and severity (absent, mild, or moderate/severe), defined using diagnostic codes and laxative use, with incident CKD, incident ESRD, and change in eGFR in Cox models (for time-to-event analyses) and multinomial logistic regression models (for change in eGFR). Among patients, the mean (SD) age was 60.0 (14.1) years old; 93.2% of patients were men, and 24.7% were diabetic. After multivariable adjustments, compared with patients without constipation, patients with constipation had higher incidence rates of CKD (hazard ratio, 1.13; 95% confidence interval [95% CI], 1.11 to 1.14) and ESRD (hazard ratio, 1.09; 95% CI, 1.01 to 1.18) and faster eGFR decline (multinomial odds ratios for eGFR slope <-10, -10 to <-5, and -5 to <-1 versus -1 to <0 ml/min per 1.73 m² per year, 1.17; 95% CI, 1.14 to 1.20; 1.07; 95% CI, 1.04 to 1.09; and 1.01; 95% CI, 1.00 to 1.03, respectively). More severe constipation associated with an incrementally higher risk for each renal outcome. In conclusion, constipation status and severity associate with higher risk of incident CKD and ESRD and with progressive eGFR decline, independent of known risk factors. Further studies should elucidate the underlying mechanisms.

Background

The purpose of this document is to provide clinicians with guidance, using expert consensus, to help summarize evidence and offer practical recommendations.

Methods

Expert Consensus Documents are intended to provide guidance for clinicians in areas in which there are no clinical practice guidelines, especially for new and evolving tests such as arterial stiffness measurements, until any formal guidelines are released.

Results

This expert consensus document is intended as a source of information for decision-making and to guide clinician-patient discussions in various clinical scenarios.

Conclusions

The goal is to help clinicians and patients make a more informed decision together.

Background

Public statements about the effect of smoking on cardiovascular disease are predominantly based on investigations of coronary heart disease (CHD) and stroke, although smoking is recognized as a strong risk factor for peripheral artery disease (PAD). No study has comprehensively compared the long-term association of cigarette smoking and its cessation with the incidence of 3 major atherosclerotic diseases (PAD, CHD, and stroke).

Objectives

The aim of this study was to quantify the long-term association of cigarette smoking and its cessation with the incidence of the 3 outcomes.

Methods

A total of 13,355 participants aged 45 to 64 years in the ARIC (Atherosclerosis Risk In Communities) study without PAD, CHD, or stroke at baseline (1987 to 1989) were included. The associations of smoking parameters (pack-years, duration, intensity, and cessation) with incident PAD were quantified and contrasted with CHD and stroke using Cox models.

Results

Over a median follow-up of 26 years, there were 492 PAD cases, 1,798 CHD cases, and 1,106 stroke cases. A dose-response relationship was identified between pack-years of smoking and 3 outcomes, with the strongest results for PAD. The pattern was consistent when investigating duration and intensity separately. A longer period of smoking cessation was consistently related to lower risk of PAD, CHD, and stroke, but a significantly elevated risk persisted up to 30 years following smoking cessation for PAD and up to 20 years for CHD.

Conclusions

All smoking measures showed significant associations with 3 major atherosclerotic diseases, with the strongest effect size for incident PAD. The risk due to smoking lasted up to 30 years for PAD and 20 years for CHD. Our results further highlight the importance of smoking prevention and early smoking cessation, and indicate the need for public statements to take PAD into account when acknowledging the impact of smoking on overall cardiovascular health.