EAL

CKD: Hypertension and Hyperlipidemia (2001)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine clinical and laboratory parameters relevant to atherogenesis in a cohort of predialysis CRF patients and evaluate the incidence of CV atherosclerotic events over a 10-year period compared to that of the general French population.

Inclusion Criteria:

Progressive chronic kidney failure defined by a creatinine clearance between 20 and 50 ml/min/1.73m²

Exclusion Criteria:

Previous CV arterial occlusive accident

Description of Study Protocol:

Recruitment

Between January 1985 and December 1994, 233 patients referred from a Nephrology clinic, 147 gave consent to participate.

Design: Cohort Study

Blinding used (if applicable): not applicable

Intervention (if applicable): not applicable

Statistical Analysis

Comparisons used the x² test and the Fisher's exact test. Possible risk factors for CV accidents were examined with univariate Cox proportional hazard analysis. Covariates that correlated with the endpoints on univariate analysis (P<0.15) excluding age were also analyzed using a multivariate Cox analysis.

Data Collection Summary:

Timing of Measurements

Data collected between January 1985 and December 1994. 2 visits per year, or more depending on the degree of renal failure. Measurements taken on blood pressure, body weight, and serum creatinine. At yearly intervals, total cholesterol, HDL-C, triglycerides, apolipoproteins A1 and B, lipoprotein (a), and fibrinogen, and total homocysteine level were determined. During the 10-year period all acute atherosclerotic CV events occuring for the first time were recorded. Events were defined as MI or CVA.

Dependent Variables

MI : defined as a typical clinical history together with characteristic ECG changes, rise in enzyme levels, evidence of coronary artery stenosis on angiopraghy or coronary revascularization procedure
CVA : Non-fatal accident with focal neurological deficit with the absence of arterial embolism and evidence of infarction on CT or MRI

Independent Variables

Chronic Renal Failure

Control Variables

Blood pressure, body weight, and serum creatinine
Total cholesterol, HDL-chol, TG, Apolipoproteins A1 and B, lipoprotein (a), fibrinogen and total homocysteine.
Cigarette smoking

Description of Actual Data Sample:

Initial N: 223 patients recruited, 147 participants gave concent to participate. 99 male, 48 female

Attrition (Final N): Correlations analyzed in 138 patients not receiving hypolipemic therapy at referral.

Age: Mean age was 62.9 years (63.1 [SD 8.1] in males, 66[SD 3.2] in females)

Ethnicity: Not mentioned

Other relevant demographics:

Anthropometrics:

Location: France

Summary of Results:

Incidence of MI in 147 patients with CRF compared to the incidence for the French Population. Incidence given per 1000 patient years

Ages (years)	Males CRF	General French Population Male	Females CRF	General French Population Female
45-50	6.2^b	2.8	1.6	0.4
50-55	9.1^b	4.1	4.1^c	0.8
55-60	15.8^c	6.3	6.3^b	1.5
60-65	20.8^c	8.9	8.9^b	2.7
>= 65	27.8^c	10.4	12.7^a	8.1

^aP <0.05, ^bP<0.01, ^cP<0.001

Other Findings

The incidence of cardiovascular accidents was nearly 3 times higher in patients with CRF compared to the general French population.

There was a clear gender effect with incidence of myocardial infarction being nearly 2.5 times more frequent in male and in female CRF patients in all age groups, and a prominent adverse effect of age in both genders.

Heavier cigarette smoking, poorer blood pressure control, more marked hyperlipidemia: (low HDL-chol and increased degree of hyperfibrinogenaemia and hyperhomocysteinaemia) were found in CRF patients who subsequently developed atherosclerotic cardiovascular complications than those who remained free of such accidents.

Author Conclusion:

The present study provides evidence of a strikingly increased incidence of atherosclerotic CV complications in predialysis CRF patients when compared to gender- and age- matched subjects in the general population.

These findings are of potenital relevance in the management of uremic patients as several of these risk factors are amendable by specific therapeutic interventions. Prophylactic measures aimed at decreasing the risk of atherosclerotic complications should be considered long before the start of renal replacement therapy.

Funding Source:

University/Hospital:

Necker Hospital (Paris, France)

Reviewer Comments:

Study shows an association between progressive CRF and the incidence of MI or other CV accidents. It appears CRI/CRF patients with higher lipids and/or cigarette smokers have an increased risk for atherosclerotic complications.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	Yes
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	No
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	???
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	No
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		No
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes