EAL

CKD: Hypertension and Hyperlipidemia (2001)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to determine the prevalence of CVD and traditional CVD risk factors in subjects with mild renal insufficiency and to describe the relationships of mild renal insufficiency to incident CVD events and all-cause mortality.

Inclusion Criteria:

All original subjects of the Framingham Heart Study who participated in the 15^thbiennial exam (1977 through 1979, N=2632) and adult participants in the second exam of the Framingham Offspring Study (1979-1983, N=3853) were eligible.

Exclusion Criteria:

1. Missing data

2. Advanced kidney disease

Description of Study Protocol:

Recruitment

The Framingham Heart Study is a continuing study that started in 1948 when 5209 residents of Framingham, MA aged 28 to 62 yr were enrolled in a prospective epidemiological cohort study to identify traits or characteristics predisposing to the development of CVD.

Design: Cohort Study

Blinding Used (if applicable): not applicable

Intervention (if applicable): not applicable

Statistical Analysis:

Separate analyses were performed for men and women. Subjects were divided into 2 categories based on normal or mild renal insufficiency. Prevalence rates of traditional CVD risk factors for both categories were compared using the chi-square test. Crude event rates were calculated for both categories. Age-adjusted survival estimates were determined using Cox proportional hazards anlayses. Hazard ratios calculated using no adjustment, but for inferential purposes, hazard ratios were calculated with adjustment for age only and with adjustment for age and other clinical variables associated with CVD and mortality.

Data Collection Summary:

Timing of Measurements

Subjects were assessed every 2 yr by medical histories, physical exams and selected laboratory data.

Dependent Variables

CVD events and all cause mortality in subjects identified with mild renal insufficiency

Independent Variables

Renal insufficiency defined as serum creatinine 136 to 265 µmol/L in men and 120 to 265 µmol/L in women

Control Variables

Age
Height/weight and BMI
Diabetes defined as nonfasting blood glucose >11.1 mmol/L or fasting > 7.8 mmol/L or the use of insulin or oral hypoglycemic agents
Blood pressure: systolic and diastolic measurements; hypertension defined as >140/90 mm Hg or on antihypertensive medications
Blood lipids
Smoker defined by smoking >1 cigarette/d during the year before the exam

Description of Actual Data Sample:

Initial N: 516 with mild renal insufficiency

Attrition (Final N): 516

Age: see table below

Ethnicity: primarily Caucasian

Other relevant demographics and Anthropometrics:

Baseline characteristics of subjects with mild renal insufficiency:
	Men	Women
	N=246	n=270
Age, yr	54.4±15.8	66.4±13.3
BMI	27.2+3.7	25.6+4.8
Serum creatinine (µmol/L)	147+15	137+17
Blood pressure, mm Hg Systolic	131+19	135+22
Diastolic	80+11	75+11
Medications
Antihypertensive (%)	29.7	40.4
Cardiac, %	11.8	18.2
Diabetes. %	10.6	9.2
Smoker, %	26.0	19.3
CVD, %	17.9	20.4
CHD, %	14.2	16.3
CHF, %	2.0	2.6
LVH, %	2.9	3.7

Location: Framingham, Massachusetts

Summary of Results:

Other Findings

The mean follow-up was 11 yr in men and 11.6 yr in women. In men, there were 544 incident CVD events and 709 deaths, 3 deaths were secondary to renal failure. In women, there were 456 CVD events and 697 deaths, 7 of those were attributed to renal disease.

Hazards Ratio:

In women, mild renal insufficiency was not associated with increased risk for CVD events 1.04 for all-cause mortality. For men, mild renal insufficiency showed no significant associations with CVD events, 1.17 but it was associated with all cause mortality in age-adjusted 1.42 and multivariable adjusted analyses 1.31.

Author Conclusion:

CVD is relatively common in subjects with mild renal insufficiency and the associated CVD risk factors are more prevalent when compared with subjects with normal renal function. Although mild renal insufficiency is associated with increased risk for death in men, it does not contribute to increased risk for death in women when traditional risk factors are considered, particularly age.

Further research is needed to determine the role of CVD in the development and progression of renal insufficiency.

Funding Source:

Government:

NIH/NHLBI

Reviewer Comments:

In this cohort, the differences in CVD in those with renal insufficiency compared to normal renal function were impressive, with ~ 2 times the prevalence in those with renal insufficiency for the following:

Use of cardiac medications and antihypertensive medications for both men and women and the prevalence of CVD in women.

Authors note that serum creatinine as a marker for impaired renal function has limitations.

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)	N/A
	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)	N/A

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?		???
	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?	N/A
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		N/A
	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?	N/A
	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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	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?		N/A
	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.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	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?	N/A
	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?		???
	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?	???
	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?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes